MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Journal of NeuroImmune Pharmacology' source. Mon, 15 Mar 2010 14:19:31 +0100 http://www.medworm.com/index.php?rid=3328537&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff63195v773126634%2F Content Type Journal ArticleCategory BRIEF REPORTDOI 10.1007/s11481-010-9196-9Authors Guy A Cabral, Virginia Commonwealth University School of Medicine Richmond VA USA Journal Journal of Neuroimmune PharmacologyOnline ISSN 1557-1904Print ISSN 1557-1890 (Source: Journal of NeuroImmune Pharmacology) Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=3328537 Tue, 02 Mar 2010 10:06:44 +0100 3328537 http://www.medworm.com/index.php?rid=3304000&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fftv34576875un640%2F Content Type Journal ArticleCategory Guest CommentaryDOI 10.1007/s11481-010-9195-xAuthors Guy A. Cabral, Virginia Commonwealth University Department of Microbiology and Immunology, School of Medicine Richmond VA USAThomas J. Rogers, Temple University School of Medicine Fels Institute for Cancer Research and Molecular Biology, Center for Substance Abuse Research, Center for Inflammation, Translational and Clinical Lung Research Philadelphia PA USA Journal Journal of Neuroimmune PharmacologyOnline ISSN 1557-1904Print ISSN 1557-1890 (Source: Journal of NeuroImmune Pharmacology) Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=3304000 Tue, 23 Feb 2010 07:59:34 +0100 3304000 http://www.medworm.com/index.php?rid=3304001&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fxk1302g019w19562%2F In this study, we examined the role of central nervous system (CNS) expression of IRF-1 in the natural course of EAE. In an effort to dissect the CNS effects from the peripheral immune effects of IRF-1, we generated bone marrow chimera mice that differentially expressed IRF-1 in the CNS and in the immune system. We found that mice lacking IRF-1 in the CNS developed significantly milder clinical symptoms and shorter disease duration compared to those with wild-type background. Based on these results, we concluded that the CNS expression of IRF-1 regulates the disease process in EAE. Our findings are relevant to the inflammatory mechanisms involved in multiple sclerosis and may provide a basis for development of novel therapeutic targets of the disease. Content Type Journal Articl... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=3304001 Tue, 23 Feb 2010 07:59:33 +0100 3304001 http://www.medworm.com/index.php?rid=3281180&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fcn332j5426268517%2F In this study, we examined the effects of two non-selective HDACi, trichostatin A and valproic acid, on antiviral and cytokine gene expression in primary human microglia and astrocytes stimulated with TLR3 or TLR4 ligand. HDACi potently suppressed the expression of innate antiviral molecules such as IFNβ, interferon-simulated genes, and proteins involved in TLR3/TLR4 signaling. HDACi also suppressed microglial and astrocytic cytokine and chemokine gene expression, but with different effects on different groups of cytokines. These results have important implications for the clinical use of HDACi. Content Type Journal ArticleCategory ORIGINAL ARTICLEDOI 10.1007/s11481-010-9192-0Authors Hyeon-Sook Suh, Albert Einstein College of Medicine Department of Pathology 1300 Morris Park A... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=3281180 Tue, 16 Feb 2010 06:44:51 +0100 3281180 http://www.medworm.com/index.php?rid=3264146&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F03m497932l486665%2F Content Type Journal ArticleCategory Guest CommentaryDOI 10.1007/s11481-010-9194-yAuthors Howard S. Fox, University of Nebraska Medical Center Department of Pharmacology and Experimental Neuroscience Omaha NE 68198-5880 USA Journal Journal of Neuroimmune PharmacologyOnline ISSN 1557-1904Print ISSN 1557-1890 (Source: Journal of NeuroImmune Pharmacology) Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=3264146 Mon, 08 Feb 2010 17:20:23 +0100 3264146 http://www.medworm.com/index.php?rid=3232990&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F47274q72l8q2662v%2F Abstract  Nociceptin/orphanin FQ (N/OFQ), added in vitro to murine spleen cells in the picomolar range, suppressed antibody formation to sheep red blood cells in a primary and a secondary plaque-forming cell assay. The activity of the peptide was maximal at 10−12 M, with an asymmetric U-shaped dose–response curve that extended activity to 10−14 M. Suppression was not blocked by pretreatment with naloxone. Specificity of the suppressive response was shown using affinity-purified rabbit antibodies against two N/OFQ peptides and with a pharmacological antagonist. Antisera against both peptides were active, in a dose-related manner, in neutralizing N/OFQ-mediated immunosuppression, when the peptide was used at concentrations from 10−12.3 to 10−11.6 M. In... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=3232990 Mon, 01 Feb 2010 06:47:39 +0100 3232990 http://www.medworm.com/index.php?rid=3228929&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F61778108u386746r%2F Abstract  Transmissible spongiform encephalopathies (TSE) are neurodegenerative diseases caused by an infectious agent with viral properties. Host prion protein (PrP), a marker of late stage TSE pathology, is linked to a similar protein called Shadoo (Sho). Sho is reduced in mice infected with the RML scrapie agent, but has not been investigated in other TSEs. Although PrP is required for infection by TSE agents, it is not known if Sho is similarly required. Presumably Sho protects cells from toxic effects of misfolded PrP. We compared Sho and PrP changes after infection by very distinct TSE agents including sporadic CJD, Asiatic CJD, New Guinea kuru, vCJD (the UK epidemic bovine agent) and 22L sheep scrapie, all passaged in standard mice. We found that Sho reductions were ... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=3228929 Fri, 29 Jan 2010 12:06:11 +0100 3228929 http://www.medworm.com/index.php?rid=3224015&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ftq547532n348p8pg%2F Abstract  Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are autoimmune demyelinating diseases of the central nervous system (CNS). Interferon-γ-producing Th1 and interleukin-17-producing Th17 CD4+ T helper (Th) cells mediate disease pathogenesis in EAE and likely in MS as well. However, the relative contribution of each Th subset to autoimmune processes in the CNS remains unclear. Emerging data suggest that both Th1 and Th17 cells contribute to CNS autoimmunity, albeit through different mechanisms. A better understanding of the roles that Th1 and Th17 cells play in autoimmune inflammation will be helpful in developing new therapeutic approaches. In this review, we discuss recent findings on the roles of Th1 and Th17 cells in ... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=3224015 Wed, 27 Jan 2010 19:59:01 +0100 3224015 http://www.medworm.com/index.php?rid=3206024&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0747mv55p5uv42n0%2F In this study we evaluated the therapeutic efficacy of GSNO in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Oral administration of GSNO (0.5 or 1.0 mg/kg) reduced disease progression in chronic models (SJL and C57BL/6) of EAE induced with PLP(139–151) or MOG(35–55) peptides, respectively. GSNO attenuated EAE disease by reducing the production of IL17 (from Thi or Th17 cells) and the infiltration of CD4 T cells into the central nervous system without affecting the levels of Th1 (IFNγ) and Th2 (IL4) immune responses. Inhibition of IL17 was observed in T cells under normal as well as Th17 skewed conditions. In vitro studies showed that the phosphorylation of STAT3 and expression of RORγ, key regulators of IL17 signaling, were reduced ... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=3206024 Thu, 21 Jan 2010 11:08:04 +0100 3206024 http://www.medworm.com/index.php?rid=3190786&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F943t2t2229q02618%2F Abstract  Until recently, knowledge of the impact of abused drugs on gene and protein expression in the brain was limited to less than 100 targets. With the advent of high-throughput genomic and proteomic techniques, investigators are now able to evaluate changes across the entire genome and across thousands of proteins in defined brain regions and generate expression profiles of vulnerable neuroanatomical substrates in rodent and nonhuman primate drug abuse models and in human post-mortem brain tissue from drug abuse victims. The availability of gene and protein expression profiles will continue to expand our understanding of the short- and long-term consequences of drug addiction and other addictive disorders and may provide new approaches or new targets for pharmacothera... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=3190786 Mon, 18 Jan 2010 18:23:22 +0100 3190786 http://www.medworm.com/index.php?rid=3168871&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg7ml2p2341q3011u%2F Abstract  Immunotherapy against the Aß peptide is increasingly viewed as an effective means of preventing and even decreasing Aß deposition in transgenic mouse models and human cases of Alzheimer's disease. A prior active immunization trial was halted due to adverse events which occurred subsequent to a change in the adjuvant used in the vaccine preparation. Although widely used in experimental studies, adjuvants available for use in vaccines intended for humans are limited. We compared two vaccine preparations in which an immunogenic bacteriophage was conjugated with either an N-terminal (Aß1-9) or C-terminal (Aß28-40) peptide sequence from the Aß molecule. We found that both produced significant antibody titers without use of additional adjuvants. Surprisingly, the r... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=3168871 Mon, 11 Jan 2010 18:23:32 +0100 3168871 http://www.medworm.com/index.php?rid=3105993&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F00kx372010848733%2F Abstract  There are currently no consistent objective biochemical markers of alcohol abuse and alcoholism. Development of reliable diagnostic biomarkers that permit accurate assessment of alcohol intake and patterns of drinking is of prime importance to treatment and research fields. Diagnostic biomarker development in other diseases has demonstrated the utility of both open, systems biology, screening for biomarkers and more rational focused efforts on specific biomolecules or families of biomolecules. Long-term alcohol consumption leads to altered inflammatory cell and adaptive immune responses with associated pathologies and increased incidence of infections. This has led researchers to focus attention on identifying cytokine biomarkers in models of alcohol abuse. Alcoho... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=3105993 Fri, 18 Dec 2009 07:15:33 +0100 3105993 http://www.medworm.com/index.php?rid=3105994&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff216g5725m10p871%2F Abstract  CD4+ T cell subsets play an important role in the adaptive immune response in human autoimmune diseases and in animal models of autoimmunity. In recent years, our knowledge of CD4+ T cell differentiation has increased significantly, and new subsets continue to be recognized. Of significant importance is the recent discovery of Th9 cells, the CD4 + T cell subset that produces Interleukin-9. IL-9 has largely been regarded as a Th2 cytokine; however, it is now known that under specific conditions, Tregs, Th1, Th17 and the Th9 subset of T cells also produce IL-9. The STAT family of proteins plays a major role in the signaling pathways of these CD4+T subsets. Biological actions of IL-9 and the STATs signaling pathways in autoimmune diseases are continuing to be clarified... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=3105994 Fri, 18 Dec 2009 07:15:31 +0100 3105994 http://www.medworm.com/index.php?rid=3105995&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx0384jk165q866p2%2F Abstract  HIV and simian immunodeficiency virus (SIV) have a formidable capacity for mutation and adaptation, a characteristic that has contributed to the extensive genetic variability. Evolutionary pressures imposed within the host and the viral capacity to mutate lead to the generation of such variants. To date, very little information is available regarding the evolution of HIV with drug abuse as a cofounding factor. Using our macaque model of drug dependency and AIDS, we have investigated the dynamics of SIV mutations in the genes tat, vpr, envelope, and nef. The results presented in this review, from our laboratory and others, contribute to the overall understanding of how drugs of abuse might influence immune selective pressure contribution to variation in different SI... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=3105995 Wed, 16 Dec 2009 07:04:45 +0100 3105995 http://www.medworm.com/index.php?rid=3064435&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F6704v38r05x32435%2F Abstract  The endogenous neurotransmitter noradrenaline (NA) is known to exert potent anti-inflammatory effects in glial cells, as well as provide neuroprotection against excitatory and inflammatory stimuli. These properties raise the possibility that increasing levels of NA in the central nervous system (CNS) could provide benefit in neurological diseases and conditions containing an inflammatory component. In the current study, we tested this possibility by examining the consequences of selectively modulating CNS NA levels on the development of clinical signs in experimental autoimmune encephalomyelitis (EAE). In mice immunized with myelin oligodendrocyte glycoprotein peptide to develop a chronic disease, pretreatment to selectively deplete CNS NA levels exacerbated clini... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=3064435 Thu, 03 Dec 2009 12:53:35 +0100 3064435 http://www.medworm.com/index.php?rid=2986476&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F841u48g2752044k2%2F Abstract  The development of antigen-specific therapies for the selective tolerization of autoreactive T cells remains the Holy Grail for the treatment of T-cell-mediated autoimmune diseases such as multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). This quest remains elusive, however, as the numerous antigen-specific strategies targeting myelin-specific T cells over the years have failed to result in clinical success. In this review, we revisit the antigen-based therapies used in the treatment of myelin-specific CD4+ T cells in the context of the functional avidity and the strength of signal of the encephalitogenic CD4+ T cell repertoire. In light of differences in activation thresholds, we propose that autoreactive T cells are no... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2986476 Wed, 11 Nov 2009 06:58:16 +0100 2986476 http://www.medworm.com/index.php?rid=2971490&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd46965736446n760%2F Abstract  Multidrug resistance-associated protein 1 (MRP-1) is a ubiquitously expressed member of the ATP-binding cassette transporter family. MRP-1 is one of the primary transporters of glutathione and glutathione conjugates. This protein also transports antiretroviral therapeutics, such as HIV-1 protease inhibitors (PI). We hypothesized that inflammatory mediators that activate macrophages would modify the expression and activity of MRP-1 in macrophages. Real-time PCR assays, western blots, and calcein efflux assays were used to show that exposure of macrophage cell line RAW 264.7 to lipopolysaccharide (LPS) increased expression of MRP-1 at the levels of mRNA, protein, and functional activity. Treatment of macrophages with LPS resulted in 2-fold increases of MRP-1 express... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2971490 Thu, 05 Nov 2009 18:37:51 +0100 2971490 http://www.medworm.com/index.php?rid=2971491&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fvq31158786t75614%2F Abstract  Theiler’s murine encephalomyelitis virus (TMEV) infection of mice is an experimental model for multiple sclerosis (MS). TMEV induces a biphasic disease in susceptible mouse strains. During the acute phase, 1 week after infection, TMEV causes polioencephalomyelitis characterized by infection and apoptosis of neurons in the gray matter of the brain. During the chronic phase, about 1 month after infection, virus infects glial cells and macrophages, and induces inflammatory demyelination with oligodendrocyte apoptosis and axonal degeneration in the white matter of the spinal cord. Although antibody, CD4+, and CD8+ T cell responses against TMEV capsid proteins play important roles in neuropathogenesis, infectious virus with persistence is necessary to induce... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2971491 Thu, 05 Nov 2009 18:37:50 +0100 2971491 http://www.medworm.com/index.php?rid=2921641&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr212375432uk4k16%2F Abstract  The molecular mechanism of action of Δ9-tetrahydrocannabinol (THC), the psychotropic constituent of Cannabis, has been a puzzle during the three decades separating its characterization, in 1964, and the cloning, in the 1990s, of cannabinoid CB1 and CB2 receptors. However, while these latter proteins do mediate most of the pharmacological actions of THC, they do not seem to act as receptors for other plant cannabinoids (phytocannabinoids), nor are they the unique targets of the endogenous lipids that were originally identified in animals as agonists of CB1 and CB2 receptors, and named endocannabinoids. Over the last decade, several potential alternative receptors for phytocannabinoids, endocannabinoids, and even synthetic cannabimimetics, have been proposed, often b... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2921641 Wed, 21 Oct 2009 23:01:30 +0100 2921641 http://www.medworm.com/index.php?rid=2896256&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl146086265074246%2F Abstract  The attrition rate of new drugs for central nervous system diseases including multiple sclerosis (MS) is very high. A widely recognized bottleneck in the selection of promising central nervous system drug candidates from the development pipeline is the lack of sufficiently predictive animal models. Here, we review how the experimental autoimmune encephalomyelitis (EAE) model in the Neotropical primate “common marmoset” can help to bridge the gap between rodent EAE models and MS. The EAE model in the marmoset closely resembles MS in the clinical as well as pathological presentation and can be used for fundamental research into immunopathogenic mechanisms and for therapy development. We discuss recent insights arising from this model, both on novel therapeutics ... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2896256 Tue, 13 Oct 2009 20:40:05 +0100 2896256 http://www.medworm.com/index.php?rid=2884079&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft238022514613201%2F Abstract  During the last two decades, a wealth of animal and human studies has implicated inflammation-derived oxidative stress and cytokine-dependent neurotoxicity in the progressive degeneration of the dopaminergic nigrostriatal pathway, the hallmark of Parkinson’s disease (PD). In this review, we discuss the various hypotheses regarding the role of microglia and other immune cells in PD pathogenesis and progression, the inflammatory mechanisms implicated in disease progression from pre-clinical and clinical studies, the recent evidence that systemic inflammation can trigger microglia activation in PD-relevant central nervous system regions, the synergism between gene products linked to parkinsonian phenotypes (α-synuclein, parkin, Nurr1, and regulator of G-protein si... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2884079 Sat, 10 Oct 2009 07:31:01 +0100 2884079 http://www.medworm.com/index.php?rid=2848185&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F58452206t1304148%2F We report that RTL551 therapy can reverse disease progression and reduce demyelination and axonal damage induced by rhMOG without suppressing the anti-MOG antibody response. This result suggests that T cell-mediated inflammation and associated blood–brain barrier dysfunction are the central contributors to EAE pathogenesis and that successful regulation of these key players restricts potential damage by demyelinating antibodies. The results of our study lend support for the use of RTL therapy for treatment of MS subjects whose disease includes inflammatory T cells as well as those with an additional antibody component. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s11481-009-9175-1Authors Sushmita Sinha, Portland VA Medical Center Neuroimmunology Research 3710... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2848185 Tue, 29 Sep 2009 16:57:15 +0100 2848185 http://www.medworm.com/index.php?rid=2810799&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy51253m6051k1742%2F Abstract  Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system (CNS) can result in neurological dysfunction with devastating consequences in a significant proportion of individuals with acquired immune deficiency syndrome. HIV-1 does not infect neurons directly but induces damage indirectly through the accumulation of activated macrophage/microglia (M/M) cells, some of which are infected, that release neurotoxic mediators including both cellular activation products and viral proteins. One mechanism for the accumulation of activated M/M involves the development in infected individuals of an activated peripheral blood monocyte population that traffics through the blood–brain barrier, a process that also serves to carry virus into CNS and estab... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2810799 Fri, 18 Sep 2009 16:25:27 +0100 2810799 http://www.medworm.com/index.php?rid=2810800&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2560489725426068%2F Content Type Journal ArticleCategory Guest CommentaryDOI 10.1007/s11481-009-9173-3Authors Gary E. Landreth, Case Western Reserve University School of Medicine Alzheimer Research Laboratory, Department of Neurosciences 10900 Euclid Ave. Cleveland OH 44106 USA Journal Journal of Neuroimmune PharmacologyOnline ISSN 1557-1904Print ISSN 1557-1890 (Source: Journal of NeuroImmune Pharmacology) Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2810800 Fri, 18 Sep 2009 06:16:05 +0100 2810800 http://www.medworm.com/index.php?rid=2810801&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff4545748342w3317%2F Abstract  Marijuana cannabinoids, the endocannabinoids, and cannabinoid cell receptors have been shown to play important roles in immune regulation particularly as potent modulators of anti-inflammatory cytokines. The predominant cannabinoid receptor involved in this immune regulation is cannabinoid receptor 2 (CB2), which is predominantly expressed in B lymphocytes. However, the promoter region and mechanisms of CB2 gene regulation are unknown in this immune cell type. Utilizing a combination of bioinformatics, 5′ rapid amplification of cDNA ends (5′ RACE), real-time reverse transcription-polymerase chain reaction, DNA sequencing, and luciferase reporter assays, we show that human B cells express one CB2 transcript while mouse B cells express three CB2 transcripts, with ... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2810801 Tue, 15 Sep 2009 21:54:41 +0100 2810801 http://www.medworm.com/index.php?rid=2810802&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7w068j3352207514%2F Abstract  Many facets of transcriptional and translational regulation contribute to the proper functioning of the nervous system. Dysfunctional control of mRNA and protein expression can lead to neurodegenerative conditions. Recently, a new regulatory control element—small noncoding RNAs—has been found to play a significant role in many physiologic systems. Here, we review the microRNA (miRNA) field as it pertains to discovery-based and mechanistic studies on the brain and specifically in neurodegenerative disorders. Understanding the role of miRNAs in the brain will aid to open new avenues to the field of neuroscience and, importantly, neurodegenerative disease research. Content Type Journal ArticleCategory Invited ReviewDOI 10.1007/s11481-009-9172-4Authors Sowmya ... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2810802 Tue, 15 Sep 2009 21:54:40 +0100 2810802 http://www.medworm.com/index.php?rid=2810803&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn825389639431330%2F Abstract  Inflammation, including microglial activation and T cell infiltration, is a neuropathological hallmark of amyotrophic lateral sclerosis (ALS), a rapidly progressing neurodegenerative disease. The identification of mutations in the gene for Cu2+/Zn2+ superoxide dismutase (SOD1) from patients with an inherited form of ALS enabled the creation of transgenic mice overexpressing mutant forms of SOD1 (mSOD1) which develop a motoneuron disease that resembles the disease seen in ALS patients. These transgenic mice display similar inflammatory reactions at sites of motoneuron injury as detected in ALS patients, enabling the observation that this inflammation is not simply a late consequence of motoneuron degeneration, but actively contributes to the balance between neuropro... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2810803 Tue, 15 Sep 2009 21:54:39 +0100 2810803 http://www.medworm.com/index.php?rid=2767256&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr73uq28188673488%2F Abstract  Microglia are the resident macrophage population in the central nervous system (CNS) parenchyma and, as such, are poised to provide a first line of defense against invading pathogens. Microglia are endowed with a vast repertoire of pattern recognition receptors that include such family members as Toll-like receptors and phagocytic receptors, which collectively function to sense and eliminate microbes invading the CNS parenchyma. In addition, microglial activation elicits a broad range of pro-inflammatory cytokines and chemokines that are involved in the recruitment and subsequent activation of peripheral immune cells infiltrating the infected CNS. Studies from several laboratories have demonstrated the ability of microglia to sense and respond to a wide variety of... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2767256 Thu, 03 Sep 2009 06:36:06 +0100 2767256 http://www.medworm.com/index.php?rid=2723672&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp421054837822v81%2F Abstract  Astrocytes are the major cellular component of the central nervous system (CNS), and they play multiple roles in brain development, normal brain function, and CNS responses to pathogens and injury. The functional versatility of astrocytes is linked to their ability to respond to a wide array of biological stimuli through finely orchestrated changes in cellular gene expression. Dysregulation of gene expression programs, generally by chronic exposure to pathogenic stimuli, may lead to dysfunction of astrocytes and contribute to neuropathogenesis. Here, we review studies that employ functional genomics to characterize the effects of HIV-1 and viral pathogenic proteins on cellular gene expression in astrocytes in vitro. We also present the first microarray analysis of... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2723672 Fri, 21 Aug 2009 10:52:28 +0100 2723672 http://www.medworm.com/index.php?rid=2717606&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft542601x4q8v1276%2F Abstract  Infection of the central nervous system with human immunodeficiency virus type 1 (HIV-1) can produce morphological changes in the neocortical synaptodendritic arbor that are correlated with neurocognitive impairment. To determine whether HIV-1 infection influences the protein composition of human synapses, a proteomic study of isolated nerve endings was undertaken. Synaptosomes from frontal neocortex were isolated using isopyknic centrifugation from 19 human brain specimens. Purity and enrichment were assessed by measuring pre- and postsynaptic protein markers. Two-dimensional polyacrylamide gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry was used to screen for proteins differentially expressed in HIV/AIDS. The ... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2717606 Wed, 19 Aug 2009 18:45:43 +0100 2717606 http://www.medworm.com/index.php?rid=2706359&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd90p4m3574552361%2F Abstract  The importance of microglial cells in the maintenance of a well-functioning central nervous system (CNS) cannot be overstated. As descendants of the myelomonocytic lineage they are industrious housekeepers and watchful sentries that safeguard a homeostatic environment through a number of mechanisms designed to provide protection of fastidious neurons at all times. Microglia become particularly active after homeostasis has been perturbed by physical injury or other insults and they enter into a state of activation which is determined largely by the nature and severity of the lesion. Microglial activation is the main cellular event in acute neuroinflammation and essential for wound healing in the CNS. Recent studies from this laboratory have been focused on microgli... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2706359 Fri, 14 Aug 2009 18:46:50 +0100 2706359 http://www.medworm.com/index.php?rid=2697392&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft4501v0168381301%2F Abstract  While the central nervous system (CNS) was once thought to be excluded from surveillance by immune cells, a concept known as “immune privilege,” it is now clear that immune responses do occur in the CNS—giving rise to the field of neuroimmunology. These CNS immune responses can be driven by endogenous (glial) and/or exogenous (peripheral leukocyte) sources and can serve either productive or pathological roles. Recent evidence from mouse models supports the notion that infiltration of peripheral monocytes/macrophages limits progression of Alzheimer's disease pathology and militates against West Nile virus encephalitis. In addition, infiltrating T lymphocytes may help spare neuronal loss in models of amyotrophic lateral sclerosis. On the other hand, CNS leukoc... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2697392 Tue, 11 Aug 2009 01:45:23 +0100 2697392 http://www.medworm.com/index.php?rid=2697393&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj142968l04665740%2F Abstract  A variety of studies have documented increased presence of reactive microglia in the brains of not only Alzheimer’s disease (AD) patients but its transgenic mouse models. Since these cells are often characterized in association with fibrillar Aβ peptide-containing plaques, it has been assumed that plaque interaction provides one stimulus for the phenotype observed. The growing appreciation that microglia phenotype changes with age and that resident immune cells are comingled with blood-derived macrophage has complicated understanding of the behavior of these cells in AD. In addition, comparison of microglia within AD brains and the many rodent models suggests that there are population phenotype differences among these cells within any given brain during disease... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2697393 Tue, 11 Aug 2009 01:45:20 +0100 2697393 http://www.medworm.com/index.php?rid=2679884&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy401l5q746109t84%2F Abstract  The immune response in the brain has been widely investigated and while many studies have focused on the proinflammatory cytotoxic response, the brain’s innate immune system demonstrates significant heterogeneity. Microglia, like other tissue macrophages, participate in repair and resolution processes after infection or injury to restore normal tissue homeostasis. This review examines the mechanisms that lead to reduction of self-toxicity and to repair and restructuring of the damaged extracellular matrix in the brain. Part of the resolution process involves switching macrophage functional activation to include reduction of proinflammatory mediators, increased production and release of anti-inflammatory cytokines, and production of cytoactive factors involved in... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2679884 Tue, 04 Aug 2009 21:55:39 +0100 2679884 http://www.medworm.com/index.php?rid=2476903&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff33238m257117211%2F Abstract  It is important to determine how a candidate drug is distributed and metabolized within the body in early phase of drug discovery. Recently, matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS; also referred to as mass spectrometry imaging) has attracted great interest for monitoring drug delivery and metabolism. Since this emerging technique enables simultaneous imaging of many types of metabolite molecules, MALDI-IMS can visualize and distinguish the parent drug and its metabolites. As another important advantage, changes in endogenous metabolites in response to drug administration can be mapped and evaluated in tissue sections. In this review, we discuss the capabilities of current IMS techniques for imaging metabolite molecules a... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2476903 Wed, 10 Jun 2009 11:21:51 +0100 2476903 http://www.medworm.com/index.php?rid=2432801&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq7x4724127352166%2F Abstract  HIV-1-associated neurocognitive disorders (HAND) remains a significant source of morbidity in the era of wide spread use of highly active antiretroviral therapy. Disease is precipitated by low levels of viral growth and glial immune activation within the central nervous system. Blood borne macrophage and microglia affect a proinflammatory response and release viral proteins that affects neuronal viability and leads to death of nerve cells. Increasing evidence supports the notion that HAND is functional channelopathy, but proof of this concept remains incomplete. Based on their role in learning and memory processes, we now posit that voltage-gated potassium (Kv) channels could be a functional substrate for disease. This was tested in the severe combined immunodefici... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2432801 Fri, 22 May 2009 05:49:41 +0100 2432801 http://www.medworm.com/index.php?rid=2429438&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw3h76807732g0q60%2F Abstract  The National Institute of Mental Health in cooperation with the National Institute on Drug Abuse and the National Institute of Neurological Disorders and Stroke organized a meeting on July 24–25, 2008 to develop novel research directions for neuroAIDS research. The deliberations of this meeting are outlined in this brief report. Several critical research areas in neuroAIDS were identified as areas of emphasis. Opportunities for collaborations between large NIH-funded projects were also discussed. Content Type Journal ArticleCategory Brief ReportDOI 10.1007/s11481-009-9159-1Authors Jeymohan Joseph, National Institutes of Health HIV Pathogenesis, Neuropsychiatry and Treatment Branch, Center for Mental Health Research on AIDS, National Institute of Mental Health ... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2429438 Wed, 20 May 2009 06:14:53 +0100 2429438 http://www.medworm.com/index.php?rid=2418797&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa4m44u26382x7ng6%2F Abstract  Methamphetamine (METH) addiction is prevalent among individuals with HIV infection. We hypothesize that HIV-positive individuals are more prone to METH use and to the development of METH dependence. To test this hypothesis, we examined the effects of METH (daily intraperitoneal injection 2.5 mg/kg for 6 days) on rearing and head movement in 12–13-week-old male HIV-1 transgenic (HIV-1Tg) rats compared to F344 control rats as an indicator of behavioral sensitization, also representing neural adaptation underlying drug dependence and addiction. Body and brain weights were also recorded. The involvement of the dopaminergic system was investigated by examining dopamine receptors 1 (D1R) and 2 (D2R) and dopamine transporter (DAT) expression in the striatum a... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2418797 Fri, 15 May 2009 05:59:54 +0100 2418797 http://www.medworm.com/index.php?rid=2418798&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1716hg80552834h0%2F In this study, we found that curcumin imparts neuroprotection in vitro, probably by decreasing cellular reactive oxygen species level, restoration of cellular membrane integrity, decreasing pro-apoptotic signaling molecules, and modulating cellular levels of stress-related proteins. We have also shown that curcumin, by inhibition of ubiquitin–proteasome system causes reduction in infective viral particle production from previously infected neuroblastoma cells. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s11481-009-9158-2Authors Kallol Dutta, National Brain Research Centre Manesar Haryana 122050 IndiaDebapriya Ghosh, National Brain Research Centre Manesar Haryana 122050 IndiaAnirban Basu, National Brain Research Centre Manesar Haryana 122050 India Jour... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2418798 Tue, 12 May 2009 06:07:16 +0100 2418798 http://www.medworm.com/index.php?rid=2400230&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr3n3744t5504v058%2F Abstract  Metabolomics is the characterization, identification, and quantitation of metabolites resulting from a wide range of biochemical processes in living systems. Its rapid development over the past few years has increased the demands for bioinformatics and cheminformatics resources that span from data processing tools, comprehensive databases, statistical tools, and computational tools for modeling metabolic networks. With the wealth of information that is being amassed, new types of metabolomic databases are emerging that are not only designed to store, manage, and analyze metabolomic data but are also designed to serve as gateways to the vast information space of metabolism in living systems. At present, metabolomics is underpinned by a number of freely and commerci... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2400230 Wed, 06 May 2009 06:01:36 +0100 2400230 http://www.medworm.com/index.php?rid=2391757&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe771216264rr2877%2F Content Type Journal ArticleCategory Guest CommentaryDOI 10.1007/s11481-009-9155-5Authors Tsuneya Ikezu, University of Nebraska Medical Center Department of Pharmacology and Experimental Neuroscience, Center for Neurodegenerative Disorders 985880 Nebraska Medical Center Omaha NE 68198-5880 USA Journal Journal of Neuroimmune PharmacologyOnline ISSN 1557-1904Print ISSN 1557-1890 (Source: Journal of NeuroImmune Pharmacology) Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2391757 Tue, 05 May 2009 05:53:27 +0100 2391757 http://www.medworm.com/index.php?rid=2383882&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fpw52u72280n4234h%2F Abstract  Assessment of a biological system by means of global and non-targeted metabolite profiling—metabolomics or metabonomics—provides the investigator with molecular information that is close to the phenotype in question in the sense that metabolites are an ultimate product of gene, mRNA, and protein activity. Over the last few years, there has been a rapidly growing number of metabolomics applications aimed at finding biomarkers which could assist diagnosis, provide therapy guidance, and evaluate response to therapy for particular diseases. Also, within the fields of drug discovery, drug toxicology, and personalized pharmacology, metabolomics is emerging as a powerful tool. This review seeks to update the reader on analytical strategies, biomarker findings, and im... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2383882 Tue, 28 Apr 2009 13:28:34 +0100 2383882 http://www.medworm.com/index.php?rid=2354830&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3067m66n70454864%2F Abstract  The human immunodeficiency virus (HIV) invades the central nervous system early in the course of infection and establishes a protected viral reservoir. However, neurocognitive consequences of HIV infection, known collectively as HIV-associated neurocognitive disorders (HAND), develop in only a small portion of infected patients. The precise mechanisms of pathogenesis involved in HIV-induced central nervous system injury are still not completely understood. In particular, most theories of HAND pathogenesis cannot account for either the selective vulnerability of specific neuronal populations to HIV-induced neurodegeneration or why only a subset of patients develop clinically detectable nervous system disease. Epidemiological and virological studies have identified ... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2354830 Fri, 17 Apr 2009 07:07:07 +0100 2354830 http://www.medworm.com/index.php?rid=2333059&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn5qr21j261j75764%2F Abstract  In our previous studies, CB1 cannabinoid receptor agonists stimulated production of cyclic GMP and translocation of nitric oxide (NO)-sensitive guanylyl cyclase in neuronal cells (Jones et al., Neuropharmacology 54:23–30, 2008). The purpose of these studies was to elucidate the signal transduction of cannabinoid-mediated neuronal nitric oxide synthase (nNOS) activation in neuronal cells. Cannabinoid agonists CP55940 (2-[(1S,2R,5S)-5-hydroxy-2-(3-hydroxypropyl) cyclohexyl]-5-(2-methyloctan-2-yl)phenol), WIN55212-2 (R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate), and the metabolically stable analog of anandamide, (R)-(+)-methanandamide stimulated NO production in N18TG2 cells over a 20-min peri... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2333059 Tue, 14 Apr 2009 05:56:35 +0100 2333059 http://www.medworm.com/index.php?rid=2333060&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4317q2p221m753mp%2F Abstract  TNF-α is a highly pleiotropic cytokine and plays an important role in regulating HIV-1 replication. It may compromise the integrity of the blood-brain-barrier and, thus, may contribute to the neurotoxicity of HIV-1-infection. Both intravenous drug abuse (IDU) and HIV infection can increase TNF-α activity, but little information is available on the effects of a combination of these factors on TNF-α. We investigated plasma TNF-α levels and mRNA in the peripheral monocytes of 166 men and women in three groups: HIV-1-positive IDUs, HIV-1-negative IDUs, and HIV-negative non-IDU control participants. HIV-1-positive IDUs had higher TNF-α levels than HIV-1-negative IDUs who, in turn, had higher levels than controls. TNF-α mRNA expression in peripheral monocytes was ... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2333060 Sun, 05 Apr 2009 13:03:10 +0100 2333060 http://www.medworm.com/index.php?rid=2276987&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F325h81822q301371%2F Abstract  In recent years, human immunodeficiency virus (HIV)-infected patients under highly active anti-retroviral therapy (HAART) regimens have shown a markedly improved general clinical status; however, the prevalence of mild cognitive disorders has increased. We propose that increased longevity with HIV-mediated chronic inflammation combined with the secondary effects of HAART may increase the risk of early brain aging as shown by intraneuronal accumulation of abnormal protein aggregates like amyloid β (Aβ), which might participate in worsening the neurodegenerative process and cognitive impairment in older patients with HIV. For this purpose, levels and distribution of Aβ immunoreactivity were analyzed in the frontal cortex of 43 patients with HIV (ages 38–60) and... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2276987 Mon, 16 Mar 2009 05:43:49 +0100 2276987 http://www.medworm.com/index.php?rid=2276988&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F60815hh3708u4112%2F Abstract  The use of antiretroviral therapy for HIV infection has extended the survival of individuals living with HIV. However, the effects of chronic HIV infection and aging are introducing another facet of HIV complications. HIV therapy can calm the immune system and lower viral replication to undetectable but the virus is still present. In the brain, amyloid beta (Aβ) increases during normal aging but Aβ accumulation appears to accelerate in HIV infection. HIV Tat protein inhibits the major Aβ-degrading enzyme neprilysin with the cysteine-rich domain of Tat being essential for this inhibition. In this minireview, we also include new data that the β chemokine, CCL2/MCP-1, associated with HIV migration to the brain, also causes an increase in Aβ. These findings may e... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2276988 Sat, 14 Mar 2009 12:16:14 +0100 2276988 http://www.medworm.com/index.php?rid=2264128&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn15x3q6vw8g25h00%2F Abstract  Our work characterizes the effects of opiate (morphine) dependence on auditory brainstem and visual evoked responses in a rhesus macaque model of neuro-AIDS utilizing a chronic continuous drug delivery paradigm. The goal of this study was to clarify whether morphine is protective, or if it exacerbates simian immunodeficiency virus (SIV)-related systemic and neurological disease. Our model employs a macrophage tropic CD4/CCR5 coreceptor virus, SIVmac239 (R71/E17), which crosses the blood-brain barrier shortly after inoculation and closely mimics the natural disease course of human immunodeficiency virus infection. The cohort was divided into three groups: morphine only, SIV only, and SIV + morphine. Evoked potential (EP) abnormalities in subclinically infected macaq... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2264128 Fri, 13 Mar 2009 10:42:11 +0100 2264128 http://www.medworm.com/index.php?rid=2239088&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa54pp81301q75440%2F In this report, we present evidence that activation of CB2 receptors, by selective CB2 agonists, reduces inflammatory responses that contribute to CNS injury. The studies demonstrate neuroprotective effects in experimental autoimmune encephalomyelitis, a model of multiple sclerosis, and in a murine model of cerebral ischemia/reperfusion injury. In both cases, CB2 receptor activation results in reduced white cell rolling and adhesion to cerebral microvessels, a reduction in immune cell invasion, and improved neurologic function after insult. In addition, administration of the CB1 antagonist SR141716A reduces infarct size following ischemia/reperfusion injury. Administration of both a selective CB2 agonist and a CB1 antagonist has the unique property of increasing blood flow to the brain... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2239088 Tue, 03 Mar 2009 11:08:35 +0100 2239088 http://www.medworm.com/index.php?rid=2186818&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu606420755101851%2F In this study, we found that production of CX3CL1 by human astrocytes stimulated with interleukin (IL)-1β was inhibited in a concentration-dependent manner following pretreatment with the synthetic cannabinoid WIN55,212-2. The CB2 receptor selective antagonist SR144528 significantly inhibited WIN55,212-2-mediated suppression of CX3CL1, suggesting a CB2-receptor-related mechanism. IL-1β triggered the activation of p38 and ERK1/2 (p44/42) MAP kinase (MAPK) signaling pathways, but WIN55,212-2 mainly inhibited p38 MAPK phosphorylation. This finding was mirrored in experiments using known inhibitors of these MAPKs, suggesting that the suppression of CX3CL1 production by WIN55,212-2 involves inhibition of signaling via p38 MAPK. Our results support the concept that synthetic cannabinoids h... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2186818 Fri, 13 Feb 2009 08:23:54 +0100 2186818 http://www.medworm.com/index.php?rid=2172062&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc454x70245vt2k40%2F Abstract  Patients infected with human immunodeficiency virus (HIV) have a higher risk of developing major depressive disorder (MDD) than the general population. Immunophilins FKBP51 and FKBP52 are expressed in cortical neurons and regulate the function of the glucocorticoid receptor (GR). Previous reports have shown that genetic variants in the FKBP5 gene encoding FKBP51 are linked to psychiatric disorders. We sought to determine whether immunophilins are upregulated in HIV infection. To determine whether FKBP52 and FKBP51 are associated with MDD and/or HIV, we compared protein and gene expression in autopsy tissues from the frontal cortical gray matter. The study cases were divided into five groups: control, MDD, MDD with psychosis, HIV+, and HIV+ with MDD. Gene expression... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2172062 Sat, 07 Feb 2009 10:20:13 +0100 2172062 http://www.medworm.com/index.php?rid=2159900&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb69307401g6733ju%2F Abstract  Opioids are known to exert direct effects on the immune system, and the expression of functional opioid receptors has been reported on several immune cell types. Dendritic cells (DCs) are important inducers and regulators of immune responses. In this study, we investigated whether murine dendritic cells express functional mu opioid receptors (MOR). RT-PCR analysis and double immunofluorescence staining revealed the expression of MOR in activated murine dendritic cells. We also studied the dynamic expression of MOR messenger RNA in murine dendritic cells in response to different Toll-like receptor ligands. Functionally, treatment of DCs with endomorphin 1 (EM1), a specific agonist of MOR, can inhibit the forskolin-induced formation of cyclic adenosine monophosphate... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2159900 Tue, 03 Feb 2009 07:08:53 +0100 2159900 http://www.medworm.com/index.php?rid=2134294&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F722643k38185807m%2F Abstract  Writing this editorial is especially pleasing. First, it provides us an opportunity to introduce new directives to the field of Neuroimmune Pharmacology and to explain why the field of nanomedicine is likely an important part of its future growth and development. Second, it is an opportunity to showcase research in this area currently operative in Russia that may not be readily accessible to the readership. Third, it is a platform to better explain why the Journal Editorial leadership was enthusiastic about the science and its relationship to the Society on NeuroImmune Pharmacology strategic goals. All are brought to bear in this issue of the Journal of Neuroimmune Pharmacology. The issue includes articles presented at a recent joint US–Russian workshop entitled, �... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2134294 Sat, 24 Jan 2009 12:20:24 +0100 2134294 http://www.medworm.com/index.php?rid=2032440&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh21vx407467765r2%2F Abstract  Cognitive impairment and neurodegeneration still occur despite highly active antiretroviral therapy (HAART). While there are many potential reasons for this, there is increasing evidence that such impairment occurs in the absence of a clear cause. Furthermore, there are data that some neurodegenerative diseases, especially Alzheimer’s or an Alzheimer-like illness, are becoming more common in the context of HAART-treated human immunodeficiency virus (HIV) disease. This review will critically examine the evidence underpinning these observations. Potential mechanisms will be discussed with particular emphasis on the effect of ageing and how it overlaps with the effects of HIV disease itself thereby leading to neurodegeneration. The nature of this overlap will then ... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2032440 Wed, 10 Dec 2008 08:01:34 +0100 2032440 http://www.medworm.com/index.php?rid=2016396&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F803vk51366n4r037%2F Abstract  Microglial activation is an important pathogenic component of neurodegenerative disease processes. This state of increased inflammation is associated not only with neurotoxic consequences but also neuroprotective effects, e.g., phagocytosis and clearance of amyloid in Alzheimer’s disease. In addition, activation of microglia appears to be one of the major mechanisms of amyloid clearance following active or passive immunotherapy. Imaging techniques may provide a minimally invasive tool to elucidate the complexities and dynamics of microglial function and dysfunction in aging and neurodegenerative diseases. Imaging microglia in vivo in live subjects by confocal or two/multiphoton microscopy offers the advantage of studying these cells over time in their native env... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=2016396 Thu, 04 Dec 2008 07:14:30 +0100 2016396 http://www.medworm.com/index.php?rid=1998488&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk86m2148x3v33343%2F Abstract  P-glycoprotein (P-gp) is a brain-to-blood efflux system that controls the ability of many drugs and endogenous substances to access the brain. In vitro work has shown that inflammatory states mediated through lipopolysaccharide (LPS) and tumor necrosis factor-alpha first impair and then stimulate P-gp activity. Here, we determined whether LPS can affect P-gp function in vivo. Mice treated with a single intraperitoneal injection of LPS (3 mg/kg) showed an inhibition of P-gp function. As assessed by brain perfusion, inhibition began 18 h after LPS administration and lasted until 36 h after administration. P-gp protein was increased by 44%, consistent with P-gp inhibition occurring through post-translational mechanisms. Unlike other effects of LPS on b... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1998488 Fri, 28 Nov 2008 13:59:34 +0100 1998488 http://www.medworm.com/index.php?rid=1995701&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F55r68w6x8tmn4686%2F Abstract  Progressive human immunodeficiency virus (HIV)-1 infection and virus-induced neuroinflammatory responses effectuate monocyte-macrophage transmigration across the blood–brain barrier (BBB). A key factor in mediating these events is monocyte chemotactic protein-1 (MCP-1). Upregulated glial-derived MCP-1 in HIV-1-infected brain tissues generates a gradient for monocyte recruitment into the nervous system. We posit that the inter-relationships between MCP-1, voltage-gated ion channels, cell shape and volume, and cell mobility underlie monocyte transmigration across the BBB. In this regard, MCP-1 serves both as a chemoattractant and an inducer of monocyte-macrophage ion flux affecting cell shape and mobility. To address this hypothesis, MCP-1-treated bone marrow-deri... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1995701 Wed, 26 Nov 2008 19:50:23 +0100 1995701 http://www.medworm.com/index.php?rid=1995700&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm2xk747484m1v582%2F Abstract  As part of the innate immune defense against HIV infection, OTK18, a zinc finger protein, is upregulated in human macrophages and reduces viral replication through suppression of viral long-terminal repeat promoter activity. Although we know that the processing products of OTK18 accumulate in the cytoplasm of brain perivascular macrophages in advanced HIV encephalitis cases, the molecular mechanisms behind its post-translational processing are still poorly understood. To characterize OTK18 processing, we assessed a panel of protease inhibitors to identify the candidates involved in the OTK18 processing using human monocyte-derived macrophages (MDM) overexpressing OTK18 by recombinant adenoviral gene transfer. Viral infection of MDM strongly increased the processin... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1995700 Wed, 26 Nov 2008 19:50:23 +0100 1995700 http://www.medworm.com/index.php?rid=1995703&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4583rv8677583j11%2F Abstract  OTK18 is a C2H2 type zinc finger protein involved in the regulation of HIV-1 replication in human mononuclear phagocytes. Previously, we reported OTK18 expression in brain perivascular macrophages but not in microglia in HIV encephalitis brain. We have cloned the OTK18 promoter region proximal to the transcriptional start site and determined the region responsible (−884/+1) for the basal transcriptional activity in a microglia cell line. Sequential deletion mutation analyses reveal three important response elements: Yingyang-1 (YY1; −805/−777), an HIV-1 response element for promoter activation; FoxD3 (−743/−725), a negative regulatory element; and Ets response element (−725/−707), a basal transcriptional activity response element. HIV-1 infection-indu... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1995703 Wed, 26 Nov 2008 19:50:22 +0100 1995703 http://www.medworm.com/index.php?rid=1995702&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl1q5784g9m2j1806%2F Abstract  Neuronal loss, reactive astrocytes, and other abnormalities are seen in the brain of individuals with acquired immune deficiency syndrome-associated Dementia Complex (ADC). Human immunodeficiency virus-1 (HIV-1) is believed to be the main agent causing ADC. However, little is known about the molecular and cellular mechanisms of HIV-1 neurotoxicity considering that HIV-1 does not infect post-mitotic neurons and that viral load does not necessarily correlate with ADC. Various viral proteins, such as the envelope protein gp120 and the transcription activator Tat, have been shown to induce neuronal apoptosis through direct and indirect mechanisms both in vitro and in vivo. Progeny HIV-1 virions can also cause neuronal death. However, it has not been fully established ... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1995702 Wed, 26 Nov 2008 19:50:22 +0100 1995702 http://www.medworm.com/index.php?rid=1984337&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ftl7011246505g743%2F This study examines the role of NF-κB in the regulation of TNFα production by morphine in microglia. Using reverse transcriptase polymerase chain reaction, we demonstrated the presence of morphine receptors in these cells. We next demonstrated the ability of morphine to promote TNFα production and secretion by these cells using a cytokine array assay. Transient transfection experiments led to the identification of the region located between nucleotides −751 and −615 within the TNFα promoter as being responsive to morphine treatment. The DNA sequence of this region contains a motif indicative of a potential NF-κB binding site. The use of a small interfering RNA directed against p65, a subunit of NF-κB, demonstrated that TNFα induction by morphine is NF-κB-dependent. All of... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1984337 Fri, 21 Nov 2008 07:13:31 +0100 1984337 http://www.medworm.com/index.php?rid=1974324&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F828h7mw753532823%2F Abstract  Although the introduction of highly active antiretroviral therapy (HAART) has led to a strong reduction of HIV-associated dementia (HAD) incidence, the prevalence of minor HIV-1-associated neurocognitive disorder (HAND) is rising among AIDS patients. HAART medication has shifted neuropathology from a subacute encephalitic condition to a subtle neurodegenerative process involving synaptic and dendritic degeneration, particularly of hippocampal neurons that are spared prior to HAART medication. Considerable neuroinflammation coupled with mononuclear phagocyte activation is present in HAART-medicated brains, particularly in the hippocampus. Accumulating evidence suggests that the resultant elevated secretion of pro-inflammatory cytokines such as interferon-γ, tumor ... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1974324 Wed, 19 Nov 2008 19:03:48 +0100 1974324 http://www.medworm.com/index.php?rid=1954804&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F8v12r51262508685%2F Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s11481-008-9134-2Authors Huangui Xiong, University of Nebraska Medical Center Department of Pharmacology and Experimental Neuroscience 985880 Nebraska Medical Center Omaha NE 68198-5880 USASulie L. Chang, Seton Hall University Institute of Neuroimmune Pharmacology, The College of Arts and Science South Orange NJ 07079 USAShilpa Buch, University of Kansas Medical Center Department of Molecular and Integrative Physiology Kansas City KS 66160 USASabita Roy, University of Minnesota Division of Infection, Inflammation and Vascular Biology, Department of Surgery and Pharmacology 420 Delaware Street SE Minneapolis MN 55455 USAWenzhe Ho, University of Pennsylvania School of Medicine Department of Pediatrics Philadelphia PA 19... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1954804 Tue, 11 Nov 2008 08:02:15 +0100 1954804 http://www.medworm.com/index.php?rid=1920527&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv5w04347023m7218%2F We report that Meth enhances HIV-1 infectivity of dendritic cells as measured by multinuclear activation of a galactosidase indicator (MAGI) cell assay, p24 assay, and LTR-RU5 amplification. Meth induces increased HIV-1 infection in association with an increase in the HIV-1 coreceptors, CXCR4 and CCR5, and infection is mediated by downregulation of extracellular-regulated kinase (ERK2) and the upregulation of p38 mitogen-activated protein kinase (MAPK). A p38 inhibitor (SB203580) specifically reversed the Meth-induced upregulation of the CCR5 HIV-1 coreceptor. The dopamine D2 receptor antagonist RS ± sulpiride significantly reversed the Meth-induced upregulation of CCR5, demonstrating that the Meth-induced effect is mediated via the D2 receptor. These studies report for th... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1920527 Wed, 29 Oct 2008 07:03:10 +0100 1920527 http://www.medworm.com/index.php?rid=1905161&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv322875737107857%2F Abstract  Alzheimer’s disease (AD) is a critical health care problem that has considerable social and economic impact on society. Effective treatments have been elusive. One major causal factor for the disease is believed to be the deposition of amyloid fibrils in the brain, which ultimately leads to neurodegeneration and cognitive dysfunction. Based on the amyloid hypothesis of Alzheimer’s disease, many therapies presently target the amyloid beta (Aβ) peptide, the monomeric protein fragment that assembles to form fibrils. This video article takes the form of a debate between Dr. Morgan and Dr. Landreth on the merits and drawbacks of an Alzheimer’s disease vaccine. Click on Supplemental Material to watch the streaming video. Content Type Journal ArticleCategory Vid... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1905161 Thu, 23 Oct 2008 05:54:22 +0100 1905161 http://www.medworm.com/index.php?rid=1894133&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq731864542662082%2F Abstract  The development of novel immune-based therapeutics for neurodegenerative diseases is an area of intense focus. Neurodegenerative diseases represent a particular challenge since in many cases the onset of symptoms occurs after considerable degeneration has ensued. Based on human genetic and histopathological evidence from patients with neurodegenerative diseases, animal models that recapitulate specific pathologic features have been developed. Utilizing these animal models in combination with viral vector-based gene therapeutics, specific epochs of disease can be targeted. One common feature of several neurodegenerative diseases is misfolded proteins. The mechanism by which these altered protein conformers lead to neurodegeneration is not completely understood but ... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1894133 Sat, 18 Oct 2008 11:06:15 +0100 1894133 http://www.medworm.com/index.php?rid=1867845&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb334537606812562%2F Abstract  Spider dragline silk possesses impressive mechanical and biochemical properties. It is synthesized by a couple of major ampullate glands in spiders and comprises of two major structural proteins—spidroins 1 and 2. The relationship between structure and mechanical properties of spider silk is not well understood. Here, we modeled the complete process of the spider silk assembly using two new recombinant analogs of spidroins 1 and 2. The artificial genes sequence of the hydrophobic core regions of spidroin 1 and 2 have been designed using computer analysis of existing databases and mathematical modeling. Both proteins were expressed in Pichia pastoris and purified using a cation exchange chromatography. Despite the absence of hydrophilic N- and C-termini, both puri... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1867845 Wed, 08 Oct 2008 10:51:12 +0100 1867845 http://www.medworm.com/index.php?rid=1855491&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm05220l7520798p4%2F Abstract  Potassium ion channels play critical roles in cell function, providing the maintenance of the membrane, repolarization of action potentials, and the regulation of firing frequency. Mutations in genes that interfere with Kv ion channel function cause severe inherited diseases, such as episodic ataxia type 1, deafness, epilepsy, or cardiac arrhythmia. Because of their critical role in the central nervous system, all ion channels are targets for multiple pharmacologically active compounds. Better understanding of the structure and function of Kv channels may eventually contribute to a more effective design of drugs. In this review, we show the recent data about domain organization of eukaryotic potassium voltage-gated ion channels. We are giving special attention to th... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1855491 Sat, 04 Oct 2008 09:29:59 +0100 1855491 http://www.medworm.com/index.php?rid=1847476&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F02212l1734460gt6%2F Abstract  Manufactured nanoparticles of aluminum oxide (nano-alumina) have been widely used in the environment; however, their potential toxicity provides a growing concern for human health. The present study focuses on the hypothesis that nano-alumina can affect the blood-brain barrier and induce endothelial toxicity. In the first series of experiments, human brain microvascular endothelial cells (HBMEC) were exposed to alumina and control nanoparticles in dose- and time-responsive manners. Treatment with nano-alumina markedly reduced HBMEC viability, altered mitochondrial potential, increased cellular oxidation, and decreased tight junction protein expression as compared to control nanoparticles. Alterations of tight junction protein levels were prevented by cellular enri... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1847476 Wed, 01 Oct 2008 09:25:11 +0100 1847476 http://www.medworm.com/index.php?rid=1832554&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp71t8573017p6528%2F Abstract  To assess the role of CC-chemokine ligand 5 (CCL5)/RANTES in opiate drug abuse and human immunodeficiency virus type 1 (HIV-1) comorbidity, the effects of systemic morphine and intrastriatal HIV-1 Tat on macrophage/microglial and astroglial activation were assessed in wild-type and CCL5 knockout mice. Mice were injected intrastriatally with vehicle or Tat and assessed after 7 days. Morphine was administered to some Tat-injected mice via time-release implant (5 mg/day, s.c. for 5 days) starting at 2 days post injection. Glial activation was significantly reduced in CCL5(−/−) compared to wild-type mice at 7 days following combined Tat and morphine exposure. Moreover, the percentage of 3-nitrotyrosine immunopositive macrophages/microglia w... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1832554 Thu, 25 Sep 2008 07:34:58 +0100 1832554 http://www.medworm.com/index.php?rid=1805719&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg332021787710648%2F Abstract   Legionella pneumophila infection of mice induces proinflammatory cytokines and Th1 immunity as well as rapid increases in serum levels of IL-12 and IFNγ and splenic IL-12Rβ2 expression. Delta-9-tetrahydrocannabinol (THC) treatment prior to infection causes a shift from Th1 to Th2 immunity and here we demonstrate that CB1 and CB2 cannabinoid receptors mediate different aspects of the shift. Using cannabinoid receptor antagonists and cannabinoid receptor gene deficient mice (CB1 −/− and CB2 −/−), we showed that both CB1 and CB2 receptors were involved in the THC-induced attenuation of serum IL-12 and IFNγ. IFNγ production is dependent upon signaling through IL-12Rβ2 (β2) and THC treatment suppressed splenic β2 message; moreover, this effect was CB1 ... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1805719 Tue, 16 Sep 2008 09:40:44 +0100 1805719 http://www.medworm.com/index.php?rid=1774941&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw5q10647u35154t5%2F Abstract  There is a large body of experimental evidence in research animals and in vitro models that opioids suppress the immune system. If this effect occurs in acute human disease, then patients cared for in Intensive Care Units (ICUs) would be a particularly vulnerable population. ICU patients have the most severe forms of acute infection, have the greatest risk of acquiring new infections in the hospital, and are exposed to high doses of opioids for long periods of time. We review the epidemiology of ICU infections and the pharmacoepidemiology of opioid use in critically ill patients. We critique the limited human research examining the relationship between opioids and infection and make recommendations on designing future clinical studies that could close the knowledg... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1774941 Fri, 05 Sep 2008 15:24:37 +0100 1774941 http://www.medworm.com/index.php?rid=1774940&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe121072q03h1423l%2F Abstract  OTK18 is a C2H2 type zinc finger protein expressed by human macrophages following HIV infection. OTK18 possesses antiretroviral activity, and its processing products accumulate in the cytoplasm of perivascular brain macrophages in advanced HIV encephalitis cases. Since the regulation of OTK18 expression in living patients following human immunodeficiency virus-1 (HIV-1) infection is unknown, our objective is to investigate the first cohort study on OTK18 protein levels in living patients. We assessed OTK18 levels in plasma and cerebrospinal fluid (CSF) in 44 living patients with or without HIV-1 infection, with diverse demographic and clinical background. A novel high-sensitivity OTK18 ELISA system was developed to measure OTK18 levels in CSF and plasma using cust... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1774940 Fri, 05 Sep 2008 15:24:37 +0100 1774940 http://www.medworm.com/index.php?rid=1768132&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F97j4w53t94239q40%2F Abstract  Glioblastoma is the most common high-grade glioma characterized by strikingly poor therapeutic outcome with survival time of about a year. This makes a search for new therapeutic approaches to glioblastoma treatment an area of great clinical importance. The present study aims to explore the potential of targeted delivery of 125I-radiolabeled antibodies, specific to glial fibrillary acidic protein (GFAP) and AMVB1 (antigen of abluminal membrane of endotheliocytes predominantly expressed in glioblastoma microvessels) as a strategy for in vivo tumor targeting. Rat C6 glioma model was used to test this hypothesis. Tumor bearing animals, injected with radiolabeled monoclonal antibodies to GFAP or AMVB1, were compared to control group, which received nonspecific mouse Ig... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1768132 Thu, 04 Sep 2008 08:39:15 +0100 1768132 http://www.medworm.com/index.php?rid=1729153&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F25271687441l734t%2F Content Type Journal ArticleCategory Guest CommentaryDOI 10.1007/s11481-008-9122-6Authors Thomas W. Klein, University of South Florida Department of Molecular Medicine 12901 Bruce B. Downs Blvd Box 07 Tampa FL 33626 USAPhillip Peterson, University of Minnesota Minneapolis MN USAGuy Cabral, Virginia Commonwealth University Richmond VA USANorbert Kaminski, Michigan State University East Lansing MI USAMartin Adler, Temple University Philadelphia PA USA Journal Journal of Neuroimmune PharmacologyOnline ISSN 1557-1904Print ISSN 1557-1890 (Source: Journal of NeuroImmune Pharmacology) Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1729153 Fri, 22 Aug 2008 12:38:00 +0100 1729153 http://www.medworm.com/index.php?rid=1713471&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk27762m7vwx57t37%2F Abstract  Methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) are amphetamine derivatives with high abuse liability. These amphetamine-related drugs of abuse mediate their effects through the acute activation of both dopaminergic and serotonergic neurons. Long-term abuse of these amphetamine derivatives, however, results in damage to both dopaminergic and serotonergic terminals throughout the brain. This toxicity is mediated in part by oxidative stress, metabolic compromise, and inflammation. The overall objective of this review is to highlight experimental evidence that METH and MDMA increase oxidative stress, produce mitochondrial dysfunction, and increase inflammation that converge and culminate in the long-term toxicity to dopaminergic and serot... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1713471 Sat, 16 Aug 2008 08:41:35 +0100 1713471 http://www.medworm.com/index.php?rid=1713470&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F45g16g1127230802%2F Abstract  Chronic infection with HIV is associated with neuroinflammation. Prior diffusion tensor imaging (DTI) studies demonstrated increased mean diffusion (MD) and decreased fractional anisotropy (FA) in the white matter (WM) and subcortical brain regions of HIV patients. The current study aims to detect whether there are greater than age-related brain changes in HIV patients after a 1-year follow-up period using DTI. Thirty-nine antiretroviral-stable HIV subjects and 32 HIV-seronegative (SN) controls were evaluated, with neuropsychological tests and DTI, at baseline and after 1 year. MD and FA in the genu and splenium of the corpus callosum and in six other subcortical and white matter regions were evaluated bilaterally. Compared to SN controls, HIV subjects had si... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1713470 Sat, 16 Aug 2008 08:41:35 +0100 1713470 http://www.medworm.com/index.php?rid=1678946&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj504uu60mu60u2x3%2F Abstract  A synthetic amphiphilic block copolymer Pluronic P85 (P85) was shown to be among the most potent inhibitors of Pgp efflux system in the blood–brain barrier (BBB) and capable of enhancing delivery of Pgp substrates to the brain. The purpose of this work is to evaluate the effects of P85 on amino acid transport in BBB. Primary bovine brain microvessel endothelial cells (BBMEC) grown on membrane inserts were used as an in vitro BBB model. Expression of amino acid transporters, like large neutral amino acid transporter 1, cationic amino acid transporter 1, and small neutral amino acid transporter 1, were confirmed by reverse transcriptase polymerase chain reaction. Effects of P85 on amino acid transporters were examined using their substrates: 3H-phenylalanine, 3H-l... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1678946 Sat, 02 Aug 2008 07:02:54 +0100 1678946 http://www.medworm.com/index.php?rid=1676750&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F9q27054332622k02%2F Abstract  Phagocytosis is an essential mechanism for clearance of pathogens, dying cells, and other unwanted debris in order to maintain tissue health in the body. Macrophages execute this process in the peripheral immune system but in the brain microglia act as resident macrophages to accomplish this function. In the peripheral immune system, macrophages secrete Milk Fat Globule Factor-E8 (MFG-E8) that recognizes phosphatidylserine “eat me” signals expressed on the surface of apoptotic cells. MFG-E8 then acts as a tether to attach the apoptotic cell to the macrophage and trigger a signaling cascade that stimulates the phagocyte development, allowing the macrophage to engulf the dying cell. When this process becomes disrupted, inflammation and autoimmunity can result. M... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1676750 Fri, 01 Aug 2008 06:20:22 +0100 1676750 http://www.medworm.com/index.php?rid=1656980&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu013n671m99p567g%2F Abstract  Neurokinin-1 receptor (NK-1R) antagonists suppress HIV-1 infection of macrophages in vitro. We have further investigated the anti-HIV-1 activity of aprepitant, a Food and Drug Administration-approved NK-1R antagonist, and its cytotoxic effect in the macrophage/microglia system. Aprepitant inhibited infection of macrophages with primary HIV-1 R5 strains (subtypes A, D, and H; UG275, BZ163, and BCF-KITA), while it had little effect on primary HIV-1 X4 strains (subtypes B and D, BZ167 and SE365). Aprepitant, when added to microglia cultures infected with CSF-derived HIV-1 strains (JAGO or JRFL), significantly inhibited viral replication. Aprepitant also enhanced the anti-HIV-1 activity of enfuvirtide (an HIV-1 fusion inhibitor) in HIV-1-infected macrophages. Over a c... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1656980 Fri, 25 Jul 2008 06:58:23 +0100 1656980 http://www.medworm.com/index.php?rid=1651943&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff4805g7v7qn571t6%2F We report here on a new bacterial cell-based system, which is suitable for study of interactions between ligands and ligand-binding sites of eukaryotic Kv1.3 and Kv1.1 channels. To create this system, high-level expression of KcsA-Kv1.3 and KcsA-Kv1.1 hybrid proteins (ligand-binding sites of Kv1.3 or Kv1.1 fused with prokaryotic KcsA potassium channel) was achieved in the plasma membrane of Escherichia coli. An efficient procedure of E. coli conversion to intact spheroplasts was developed. We demonstrate that fluorescently labeled agitoxin 2 binds specifically to high-affinity and lower-affinity sites of KcsA-Kv1.3 and KcsA-Kv1.1, respectively, at the membrane of spheroplasts. Number of binding sites per cell is estimated to be (1.0 ± 0.6) ×105 and (0.3 ± 0.2) ×105 for... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1651943 Wed, 23 Jul 2008 06:26:42 +0100 1651943 http://www.medworm.com/index.php?rid=1637231&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fkw77626472n8186t%2F Abstract  Misfolding and aggregation of proteins are common threads linking a number of important human health problems, including various neurodegenerative disorders such as Parkinson’s disease in particular. The first and perhaps most important elements in most neurodegenerative processes are misfolding and aggregation of specific proteins. Despite the crucial importance of protein misfolding and abnormal interactions, very little is currently known about the molecular mechanism underlying these processes. Factors that lead to protein misfolding and aggregation in vitro are poorly understood, in addition to the complexities involved in the formation of protein nanoparticles with different morphologies (e.g. nanopores and other species) in vivo. A clear understanding of ... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1637231 Thu, 17 Jul 2008 06:39:55 +0100 1637231 http://www.medworm.com/index.php?rid=1605248&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4g8143x21n732626%2F Abstract  Anti-Aβ antibody administration to amyloid-depositing transgenic mice can reverse amyloid pathology and restore memory function. However, in old mice, these treatments also increase vascular leakage and promote formation of vascular amyloid deposits. Deglycosylated antibodies with reduced affinity for Fcγ receptors and complement are associated with reduced vascular amyloid and microhemorrhage while retaining amyloid-clearing and memory-enhancing properties of native intact antibodies. In the current experiment, we investigated the effect of 3, 10, or 30 mg/kg of deglycosylated antibody (D-2H6) on amyloid pathology and cognitive behavior in old Tg2576 mice. We found that low doses of deglycosylated antibody appear more efficacious than higher doses in reduc... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1605248 Tue, 08 Jul 2008 08:18:58 +0100 1605248 http://www.medworm.com/index.php?rid=1574968&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe63288t8xk7485l2%2F Abstract  While methamphetamine-induced changes in brain neurotransmitters, their receptors, and transporters are well studied, the means by which methamphetamine abuse results in cognitive and behavioral abnormalities is unknown. Here, we administered methamphetamine chronically, in doses relevant to recreational usage patterns, to nonhuman primates. Neurostructural analysis revealed decreased dendritic material and loss of spines in frontal lobe neurons. Molecular examination demonstrated that type I interferons (interferon-alpha and interferon-beta) increased in the frontal lobe in response to chronic methamphetamine treatment, in correlation with the neuronal changes. Chronic methamphetamine thus results in significant changes in the primate brain, inducing cytokines an... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1574968 Wed, 02 Jul 2008 15:35:05 +0100 1574968 http://www.medworm.com/index.php?rid=1559871&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr5864r0w4816xu04%2F Abstract  The human immunodeficiency virus (HIV) invades the central nervous system early after viral exposure but causes progressive cognitive, behavior, and motor impairments years later with the onset of immune deficiency. Although in the brain, HIV preferentially replicates productively in cells of mononuclear phagocyte (MP; blood borne macrophage and microglia), astrocytes also can be infected, at low and variable frequency, particularly in patients with encephalitis. Among their many functions, astrocytes network with microglia to provide the first line of defense against microbial infection; however, very little is known about astrocytes’ consequences on MP. Here, we addressed this question using co-culture systems of HIV-infected mouse astrocytes and microglia. Ps... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1559871 Sat, 28 Jun 2008 08:11:47 +0100 1559871 http://www.medworm.com/index.php?rid=1552868&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh5k5016056gp822q%2F In this study, we examined LPS-induced cytokine production in the brain of morphine-tolerant rats. The animals were implanted with two and four morphine (75 mg) pellets on days 1 and 2, respectively. On either day 4 or 5, 250 μg/kg LPS was administered (i.p.). Animals implanted with placebo and injected with saline were used as the control. The animals were sacrificed either 16 or 2 h post-injection, respectively, and TNF-α, IL-1β, and IL-6 mRNA levels in the brain were determined by reverse transcriptase polymerase chain reaction. IL-1β mRNA increased 2 h post-LPS treatment, whereas IL-6 decreased. At 16 h, TNF-α expression mRNA increased. These data suggest that the inflammatory response in the brain is heightened during morphine tolerance. Content T... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1552868 Fri, 27 Jun 2008 06:00:44 +0100 1552868 http://www.medworm.com/index.php?rid=1550777&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F055146432gw1v157%2F Abstract  CD38 is a 45-kD ectoenzyme involved in the synthesis of potent calcium (Ca2+)-mobilizing agents, cyclic adenosine diphosphate-ribose (cADPR), and nicotinic acid adenine dinucleotide phosphate (NAADP+). In HIV-1-infected patients, increased CD38 expression on CD8+ T cells is linked to immune system activation and progression of HIV-1 infection. However, the role of CD38 upregulation in astrocyte function and HIV-1-associated dementia (HAD–now called HAND: HIV-1-associated neurocognitive disorder) neuropathogenesis is unclear. To these ends, we used interleukin (IL)-1β and HIV-1gp120 to activate primary human astrocytes and measured CD38 expression using real-time polymerase chain reaction and CD38 function by ADP-ribosyl cyclase activity. We also determined cADPR... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1550777 Thu, 26 Jun 2008 06:23:13 +0100 1550777 http://www.medworm.com/index.php?rid=1521689&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ffkp218n2ut4p627w%2F Content Type Journal ArticleCategory Book ReviewDOI 10.1007/s11481-008-9109-3Authors Shilpa J. Buch, Kansas University Medical Center Kansas City KS 66160 USARachel Williams, Kansas University Medical Center Kansas City KS 66160 USA Journal Journal of Neuroimmune PharmacologyOnline ISSN 1557-1904Print ISSN 1557-1890 (Source: Journal of NeuroImmune Pharmacology) Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1521689 Sat, 14 Jun 2008 05:56:27 +0100 1521689 http://www.medworm.com/index.php?rid=1493976&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3057717nt05657wl%2F Abstract  Methamphetamine (METH) is a stimulant drug that is toxic primarily to dopaminergic and serotonergic neurons and may lead to inflammatory changes in the brain. Additionally, the glutamatergic system is altered following METH exposure. Therefore, concentrations of brain glutamate + glutamine (GLX) were assessed during abstinence from chronic METH abuse. Twenty-five subjects with a history of METH dependence (age 31.8 ± 7.4 years, 14 women and 11 men) and 28 control subjects without a history of drug abuse (age 32.6 ± 8.8 years, 14 women) were enrolled. Twelve of the METH subjects were followed and rescanned 5 months later. METH users had used the drug 5.9 ± 1.7 times per week, for 109 ± 69 months, and had been abstinent for... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1493976 Tue, 03 Jun 2008 06:12:17 +0100 1493976 http://www.medworm.com/index.php?rid=1425774&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F152854p28l342561%2F Abstract  Human immunodeficiency virus type-1 (HIV-1)-associated dementia (HAD), a severe form of HIV-associated neurocognitive disorders (HAND), describes the cognitive impairments and behavioral disturbances which afflict many HIV-infected individuals. Although the precise mechanism leading to HAD is incompletely understood, it is commonly accepted its progression involves a critical mass of infected and activated mononuclear phagocytes (brain perivascular macrophages and microglia) releasing immune and viral products in the brain. These cellular and viral products induce neuronal dysfunction and injury via various signaling pathways. Emerging evidence indicates voltage-gated potassium (Kv) channels, key regulators of cell excitability and animal behavior (learning and mem... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1425774 Tue, 06 May 2008 16:13:59 +0100 1425774 http://www.medworm.com/index.php?rid=1425775&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy3n423505m44j6w0%2F Content Type Journal ArticleCategory LetterDOI 10.1007/s11481-008-9107-5Authors Howard E. Gendelman, University of Nebraska Medical Center Omaha NE 68198-5880 USA Journal Journal of Neuroimmune PharmacologyOnline ISSN 1557-1904Print ISSN 1557-1890 (Source: Journal of NeuroImmune Pharmacology) Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1425775 Mon, 05 May 2008 21:02:27 +0100 1425775 http://www.medworm.com/index.php?rid=1411299&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7q1809138k7471l0%2F Content Type Journal ArticleCategory ErratumDOI 10.1007/s11481-008-9104-8Authors Heng Zhao, Stanford University School of Medicine Department of Neurosurgery MSLS Bldg., P306 1201 Welch Rd., P306 Stanford CA 94305-5327 USA Journal Journal of Neuroimmune PharmacologyOnline ISSN 1557-1904Print ISSN 1557-1890 (Source: Journal of NeuroImmune Pharmacology) Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1411299 Tue, 29 Apr 2008 06:21:58 +0100 1411299 http://www.medworm.com/index.php?rid=1287172&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu6636m421147k655%2F Abstract  Neurodegenerative and infectious disorders related to host genetics, aging, and environment are rapidly increasing. Drugs, vaccines, or regenerative proteins offer “real” possibilities for positively affecting disease outcomes but are limited by access across the blood-brain barrier. New developments in nanomedicine and cell based drug delivery are becoming available. These discoveries can lead to improved neurological disease outcomes. Such obstacles include the toxicities inherent in the delivery systems de novo such as immuno- and neurological dysfunctions and perturbations of blood-brain barrier function. This debate by leading experts in the field highlights the promise and perils of CNS drug delivery. Content Type Journal ArticleCategory Video DebateDO... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1287172 Thu, 06 Mar 2008 16:50:18 +0100 1287172 http://www.medworm.com/index.php?rid=1241342&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm752324025124667%2F Abstract  The inducible isoform of nitric-oxide synthase (iNOS) is involved in neuropathogenesis associated with infection and disease in the brain. Hence, there is considerable interest in the identification of therapeutic interventions to prevent iNOS-mediated pathology. Astroglia are a major site of iNOS expression during neuropathogenesis. To mimic a key component of neuroinflammation, human A172 astroglial cells were exposed in vitro to a cytokine mixture containing interferon γ, tumor necrosis factor α, and interleukin-1β, resulting in significant iNOS expression. Next, we assessed the effects of the mu opioid receptor antagonist, β-funaltrexamine (β-FNA), on cytokine induced iNOS expression in human astroglia. β-FNA dose-dependently inhibited iNOS expression. β... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1241342 Sun, 17 Feb 2008 05:27:51 +0100 1241342 http://www.medworm.com/index.php?rid=1175816&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F207r151256504871%2F Abstract  Neurodegenerative disorders including Alzheimer’s and Parkinson’s diseases, amyotrophic lateral sclerosis, and stroke are rapidly increasing as population ages. The field of nanomedicine is rapidly expanding and promises revolutionary advances to the diagnosis and treatment of devastating human diseases. This paper provides an overview of novel nanomaterials that have potential to improve diagnosis and therapy of neurodegenerative disorders. Examples include liposomes, nanoparticles, polymeric micelles, block ionomer complexes, nanogels, and dendrimers that have been tested clinically or in experimental models for delivery of drugs, genes, and imaging agents. More recently discovered nanotubes and nanofibers are evaluated as promising scaffolds for neuroregene... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1175816 Tue, 22 Jan 2008 15:55:44 +0100 1175816 http://www.medworm.com/index.php?rid=1162996&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr5680j73088l1867%2F Abstract  Microglial neuroinflammatory responses affect the onset and progression of Parkinson’s disease (PD). We posit that such neuroinflammatory responses are, in part, mediated by microglial interactions with nitrated and aggregated α-synuclein (α-syn) released from Lewy bodies as a consequence of dopaminergic neuronal degeneration. As disease progresses, secretions from α-syn-activated microglia can engage neighboring glial cells in a cycle of autocrine and paracrine amplification of neurotoxic immune products. Such pathogenic processes affect the balance between a microglial neurotrophic and neurotoxic signature. We now report that microglia secrete both neurotoxic and neuroprotective factors after exposure to nitrated α-syn (N-α-syn). Proteomic (surface enhanc... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1162996 Fri, 18 Jan 2008 16:18:22 +0100 1162996 http://www.medworm.com/index.php?rid=1162997&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fyg7470133673w4j4%2F Content Type Journal ArticleCategory Guest CommentaryDOI 10.1007/s11481-008-9101-yAuthors Shilpa Buch, University of Kansas Medical Center Department of Molecular and Integrative Physiology 5000 Wahl Hall East, Mail Stop 3029, 3901 Rainbow Blvd Kansas City KS 66160 USABarry T. Rouse, University of Tennessee Department of Pathobiology Knoxville TN USAHoward E. Gendelman, University of Nebraska Medical Center Department of Pharmacology and Experimental Neuroscience Omaha NE USAM. Christine Zink, Johns Hopkins University School of Medicine Department of Comparative Medicine Baltimore MD USAJanice E. Clements, Johns Hopkins University School of Medicine Department of Molecular and Comparative Pathobiology Baltimore MD USA Journal Journal of NeuroImmune PharmacologyOnline ISSN 1557-1... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1162997 Fri, 18 Jan 2008 16:16:56 +0100 1162997 http://www.medworm.com/index.php?rid=1083944&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl01374568413366x%2F Abstract  Microglial cells respond to the herpes simplex virus (HSV)-1 by producing proinflammatory cytokines and chemokines. After this inflammatory burst, these cells undergo apoptotic cell death. We have recently demonstrated that both virus-induced immune mediator production and apoptosis were induced through Toll-like receptor 2 (TLR2) signaling. Based upon these findings, we hypothesized that the inhibition of TLR2 signaling may serve as a means to alleviate excessive neuroinflammation. In the present study, we cloned four vaccinia virus (VV) proteins, which have been reported to disrupt either TLR signaling or NF-κB activation, and overexpressed them in HEK293T cells stably expressing murine TLR2 and in primary murine microglia. Using an NF-κB-driven luciferase rep... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1083944 Sat, 08 Dec 2007 19:05:12 +0100 1083944 http://www.medworm.com/index.php?rid=1074449&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fdg5280h712143645%2F In this study, we demonstrated the constitutive expression of nicotinic acetylcholine receptor mRNA in primary human microglial cells and showed that the pretreatment of microglia with nicotine increased HIV-1 expression in a concentration-dependent manner, as measured by p24 antigen levels in culture supernatants. We also found that nicotine robustly altered the gene expression profile of HIV-1-infected microglia and that the transforming growth factor-β1 is involved in the enhanced expression of HIV-1 by nicotine. Content Type Journal ArticleCategory Brief ReportDOI 10.1007/s11481-007-9098-7Authors R. Bryan Rock, University of Minnesota Medical School Center for Infectious Diseases and Microbiology Translational Research, Division of Infectious Diseases and International Medici... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1074449 Tue, 04 Dec 2007 20:58:20 +0100 1074449 http://www.medworm.com/index.php?rid=1062387&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F746l65m727383741%2F The objective of the present study was to explore the effects of cocaine on BBB permeability using human brain microvascular endothelial cells (HBMECs). Additionally, because the chemokine CCL2 and its receptor CCR2 play a crucial role in the recruitment of inflammatory cells into the central nervous system in HAD brains, we tested for the effect of cocaine in modulating the CCL2/CCR2 axis. Our findings suggest that exposure of HBMECs to cocaine correlated with the breakdown of ZO-1 tight junction protein and reorganization of the cytoskeleton resulting in stress fiber formation. Furthermore, cocaine also modulated upregulation of the CCL2/CCR2 axis in monocytes. These findings conform to the multifaceted effects of cocaine leading to accelerated progression of HIV-1 neuropathogenesi... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1062387 Thu, 29 Nov 2007 16:36:49 +0100 1062387 http://www.medworm.com/index.php?rid=1029768&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fqj72682556209662%2F Abstract  Substances of abuse, such as opiates, and astroglial-derived proinflammatory cytokines, such as interleukin (IL)-1β, likely contribute to the neuroinflammatory and neurodegenerative processes observed in NeuroAIDS in injection drug users. Furthermore, uncontrolled synthesis and activation of complement component C3 in the brain can also lead to inflammation and neurodegeneration. We hypothesized that morphine may alter regulation of the C3 gene by IL-1β in astrocytes. Our studies demonstrate that IL-1β induces C3 promoter activity in a CAAT/enhancer-binding protein (C/EBP)-dependent manner. Inhibition of IL-1β mediated C3 promoter activation by the dominant negative mutant of p38-α mitogen-activated protein kinase suggests that IL-1β induces C3 expression th... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=1029768 Wed, 14 Nov 2007 16:05:41 +0100 1029768 http://www.medworm.com/index.php?rid=981829&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F185135832h33817g%2F Abstract  Chemokine and opioid receptors are G-protein-coupled receptors that play important roles in both the central nervous system and the immune system. The long-term goal of our research is to establish whether opioids regulate the activity of the chemokine receptor CXCR4 (one of the major HIV co-receptors) in the brain. In this research, we studied the anatomical distribution of functional receptors in young and adult animals by using the [35S]GTPγS “binding” assay as an indication of G-protein activation by CXCL12 (the natural CXCR4 ligand) or by μ-opioid agonists. Brain slices or homogenates from Holtzmann rats of different ages (from 2 to 21 days old and adult animals) were treated with CXCL12 (0.001–100 nM), d-ala2,MePhe4,gly-ol5]enkephalin (DAMGO... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=981829 Thu, 25 Oct 2007 15:07:16 +0100 981829 http://www.medworm.com/index.php?rid=973508&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv63560822h351003%2F Abstract  HIV-associated dementia (HAD) is a chronic neuroinflammatory disease that remains an important clinical problem without available rational treatment. As HIV does not infect neurons, the pathogenesis of HAD is thought to be secondary to the impact of infected leukocytes, including parenchymal microglia, which can secrete inflammatory mediators and viral products that alter the function of surrounding uninfected cells. We previously reported that the transcription factor p53 accumulates in neurons, microglia, and astrocytes of HAD patients. We have also shown that microglia from p53-deficient mice fail to induce neurotoxicity in response to the HIV coat protein gp120 in a coculture system, supporting the hypothesis that p53 plays a pathogenic role in the chronic neu... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=973508 Sun, 21 Oct 2007 00:06:48 +0100 973508 http://www.medworm.com/index.php?rid=955786&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh02168371253l072%2F Abstract Objective  The purpose of this paper was to determine whether antiretroviral medications, especially the nucleoside analogue reverse transcriptase inhibitors, lead to altered brain activation due to their potential neurotoxic effects in patients with human immunodeficiency virus (HIV) infection. Methods  Forty-two right-handed men were enrolled in three groups: seronegative controls (SN, n = 18), HIV subjects treated with antiretroviral medications (HIV+ARV, n = 12), or not treated with antiretroviral medications (HIV+NARV, n = 12). Each subject performed a set of visual attention tasks with increasing difficulty or load (tracking two, three or four balls) during functional magnetic resonance imaging. Results  HIV subject... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=955786 Sat, 13 Oct 2007 19:16:21 +0100 955786 http://www.medworm.com/index.php?rid=946702&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg53r6153581305m6%2F Conclusions  Low CSF leptin levels are associated with poorer performance in learning and memory among HIV-infected men adjusting for usual predictors of HIV-associated neurocognitive impairment. This association is consistent with prior in vitro and animal data suggesting leptin has a trophic or facilitatory role in the hippocampus, above and beyond its role in hypothalamic regulation. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s11481-007-9093-zAuthors J. S. Huang, University of California Department of Pediatrics San Diego USAS. Letendre, University of California Department of Medicine San Diego USAJ. Marquie-Beck, University of California HIV Neurobehavioral Research Group San Diego USAM. Cherner, University of California Department of Psychiat... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=946702 Thu, 11 Oct 2007 15:14:43 +0100 946702 http://www.medworm.com/index.php?rid=944165&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F55301825x4267357%2F We report that Gas6 induces phagocytosis in microglia through a novel non-classical phagocytic mechanism. Gas6 stimulates a type-II-related phagocytic response, but requires Vav phosphorylation and Rac activation, distinguishing it from the classical type II mechanism. Importantly, Gas6 suppressed lipopolysaccharide-induced expression of the inflammatory molecules IL-1β and iNOS. Gas6 inhibited iNOS expression through suppression of promoter activity. The present data provide direct evidence for the role of Gas6 receptors in mediating an anti-inflammatory response to ligands found on apoptotic cells with the simultaneous stimulation of phagocytosis. These data provide a mechanistic explanation for the phenotype observed in animals lacking Axl/Mer receptors. Content Type Journal A... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=944165 Wed, 10 Oct 2007 16:23:25 +0100 944165 http://www.medworm.com/index.php?rid=944164&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv44t55537hjp2307%2F Abstract  Opioid modulation of host resistance to infectious diseases is well documented; however, not much is known during visceral leishmaniasis (VL). Low doses of morphine, administered subcutaneously in Leishmania donovani-infected BALB/c mice, on days 0 and +15, significantly (p < 0.05) suppressed (1 mg/kg/day) or even sterile-cleared (2 mg/kg/day) the infection; paradoxically, high doses (10 and 30 mg/kg/day) exacerbated the infection. In vitro, low concentration (1 � 10−9 and 1 � 10−11 M) morphine treatment of L. donovani-infected mouse peritoneal macrophages (PM), endowed them with significant (p < 0.05) leishmanicidal activity, whereas a high-concentration (1 � 10−5 M) treatment augmented intramacropha... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=944164 Wed, 10 Oct 2007 16:23:22 +0100 944164 http://www.medworm.com/index.php?rid=910914&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fan33137x22432822%2F Abstract  Marijuana cannabinoid treatment increases Th2 activity, and previous reports showed that B cells express the highest level of CB2 mRNA relative to other immune cells, suggesting that cannabinoids play a critical role in B cell activation and maturation. We previously reported evidence of Th2 biasing and class switching in cannabinoid-treated and antigen-challenged mice. We now explore the possibility that cannabinoids directly influence B cell antibody class switching. Mouse splenic B cells were purified by negative selection and cultured with IL4 and anti-CD40 in the presence or absence of the nonselective cannabinoid agonist, CP55940, or the CB1 selective cannabinoid agonist, methanandamide, and analyzed at different days by flow cytometry for surface expression ... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=910914 Thu, 27 Sep 2007 15:52:06 +0100 910914 http://www.medworm.com/index.php?rid=887776&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F44j8387372137574%2F This article reviews the protective effects of postconditioning against ischemia from the heart to the brain and provides insights on how studies of postconditioning in the field of heart ischemia have shed light on postconditioning of the brain. Because brain ischemia has many mechanisms in common with heart ischemia, it is logical to test whether postconditioning protects against brain ischemia as well. A few groups have reported that postconditioning reduces infarct size in focal cerebral ischemia and improves deficits of short-term memory and motor coordination after global cerebral ischemia. However, many outstanding issues remain elusive regarding the protective effects of postconditioning against cerebral ischemia. Future studies should further identify parameters that generat... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=887776 Tue, 18 Sep 2007 21:03:34 +0100 887776 http://www.medworm.com/index.php?rid=881824&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl1556271r4p70480%2F We report here that human CD14+ monocytes expresses the mRNA for ORL1. Our results also demonstrate that nociceptin can suppress the production of CCL2/MCP-1 and CCL5/RANTES chemokine protein in both primary CD14+ human monocytes and monocyte-like cell lines. However, nociceptin does not appear to regulate the expression of these chemokines at the level of transcription, as CCL2/MCP-1 and CCL5/RANTES mRNA levels following nociceptin treatment of monocytes were essentially normal. Although the mechanism of chemokine regulation by nociceptin is as yet unknown, it is evident that the ORL1/nociceptin system plays a role in regulating chemotactic responses of leukocytes through chemokine suppression. Finally, these data may provide the initial basis for the development of ORL1 agonists and... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=881824 Mon, 17 Sep 2007 17:48:18 +0100 881824 http://www.medworm.com/index.php?rid=871538&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fat0l73u3m8153m85%2F Abstract  Morphine is known to prevent the development of cell-mediated immune (CMI) responses and enhance expression of the CCR5 receptor in monocyte macrophages. We undertook a study to determine the effect of morphine on the neuropathogenesis and immunopathogenesis of simian immunodeficiency virus (SIV) infection in Indian Rhesus Macaques. Hypothetically, the effect of morphine would be to prevent the development of CMI responses to SIV and to enhance the infection in macrophages. Sixteen Rhesus Macaques were divided into three experimental groups: M (morphine only, n = 5), VM (morphine + SIV, n = 6), and V (SIV only, n = 5). Animals in groups M and VM were given 2.5 mg/kg of morphine sulfate, four times daily, for up to 59 weeks. Groups VM and V wer... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=871538 Thu, 13 Sep 2007 06:57:47 +0100 871538 http://www.medworm.com/index.php?rid=852915&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft258002068212416%2F Abstract  The extensively innervated intestinal mucosa encompasses a vast surface exposed to an array of potentially infectious microorganisms. We investigated the role of enteric nerves in modulating intracellular internalization of a multidrug-resistant Salmonella typhimurium DT104 field isolate in mucosa–submucosa sheets from the porcine ileum, a biomedical model for the human intestine. The effects of transmural electrical stimulation and drugs on intracellular internalization of Salmonella over 90 min was determined by a gentamicin-resistance assay relative to untreated tissues from the same animal serving as controls. The actin inhibitor cytochalasin D reduced internalization of Salmonella, and the mucus-disrupting agent dithiothreitol decreased its mucosal adhere... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=852915 Sat, 08 Sep 2007 07:07:28 +0100 852915 http://www.medworm.com/index.php?rid=852914&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa8343n84k5348826%2F This study demonstrates dysregulation of glutamate uptake in human astrocytes infected with both variants of HHV-6, A and B, with differential effects of HHV-6 in acute and persistently infected cells. Whereas astrocytes acutely infected with HHV-6 demonstrated increased glutamate uptake, cells persistently infected with HHV-6A and HHV-6B demonstrated impaired glutamate uptake. Functional dysregulation of glutamate uptake was associated with early increases in mRNA and protein expression of the glial glutamate transporter EAAT-2 followed by a sustained decrease in mRNA expression in astrocytes infected with both HHV-6A and HHV-6B. Dysregulated glutamate uptake and transporter expression suggests a mechanism for dysregulation of glutamate levels in vivo and a potential mechanism for v... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=852914 Sat, 08 Sep 2007 07:07:28 +0100 852914 http://www.medworm.com/index.php?rid=756418&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft3016n864t878328%2F Content TypeJournal Article JournalJournal of NeuroImmune PharmacologyOnline ISSN 1557-1904Print ISSN 1557-1890 (Source: Journal of NeuroImmune Pharmacology) Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=756418 Tue, 24 Jul 2007 07:14:57 +0100 756418 http://www.medworm.com/index.php?rid=747579&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg6q07228x56h7434%2F This study explores the effect of Parkin downregulation on dopaminergic cells in Parkinson’s disease. We generated small interfering RNA plasmids that target the parkin gene and transfected them into PC12 cells to mimic in vivo loss-of-function. We found that these small plasmids were able to effectively inhibit endogenous Parkin expression in PC12 cells. Downregulation of Parkin decreased the amount of glutathione and superoxide dismutase activity without affecting the amount of malondialdehyde. Moreover, Parkin knockdown rendered PC12 cells more susceptible to cell death induced by the proteasome inhibitor lactacystin. These results indicate that downregulation of Parkin may damage the antioxidation defenses of dopaminergic cells and increase their susceptibility to proteasome in... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=747579 Fri, 20 Jul 2007 06:53:16 +0100 747579 http://www.medworm.com/index.php?rid=729539&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn5n6342814358123%2F Abstract  The chemotactic response of murine peritoneal macrophages to RANTES/CCL5 was inhibited significantly following pretreatment with delta-9-tetrahydrocannabinol (THC), the major psychoactive component in marijuana. Significant inhibition of this chemokine directed migratory response was obtained also when the full cannabinoid agonist CP55940 was used. The CB2 receptor-selective ligand O-2137 exerted a robust inhibition of chemotaxis while the CB1 receptor-selective ligand ACEA had a minimal effect. The THC-mediated inhibition was reversed by the CB2 receptor-specific antagonist SR144528 but not by the CB1 receptor-specific antagonist SR141716A. In addition, THC treatment had a minimal effect on the chemotactic response of peritoneal macrophages from CB2 knockout mice. C... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=729539 Wed, 11 Jul 2007 15:34:12 +0100 729539 http://www.medworm.com/index.php?rid=704112&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fax7g521120362u67%2F Abstract  We review the literature for Ran Binding Protein in the Microtubule-Organizing Center (RanBPM; RanBP9), a 90-kDa protein that possesses many characteristics of a scaffolding protein, including protein-interaction motifs, a cytoskeletal-binding domain, and multiple canonical docking sites for signaling intermediates. We focus on studies that have examined functional interactions between RanBPM and other proteins. These studies suggest that RanBPM provides a platform for the interaction of a variety of signaling proteins, including cell surface receptors, nuclear receptors, nuclear transcription factors, and cytosolic kinases. These studies indicate that RanBPM acts as a scaffolding protein and is important in regulating cellular function in both the immune system an... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=704112 Thu, 28 Jun 2007 13:40:49 +0100 704112 http://www.medworm.com/index.php?rid=701808&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fpnj4507651883861%2F In this study, we investigated the expression of CXCL12 and CXCR4 during neural progenitor cells (NPC) differentiation by microarray analysis and reverse transcriptase-polymerase chain reaction (RT-PCR) using human fetal NPC as a model system. The production of CXCL12 was measured by enzyme-linked immunosorbent assay (ELISA). CXCR4 expression was determined by florescence-activated cell sorting (FACS) analysis, immunocytochemical staining, and CXCR4-mediated inhibition of cyclic AMP (cAMP) accumulation. Our data demonstrated that CXCR4 expression is significantly upregulated when NPC are differentiated into neuronal precursors, whereas CXCL12 is upregulated when differentiated into astrocytes. We also provide evidence that CXCR4 localization changes as neurons mature. In neuronal pre... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=701808 Wed, 27 Jun 2007 07:21:22 +0100 701808 http://www.medworm.com/index.php?rid=691806&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1378039411905315%2F Abstract  HIV-1 infection of the central nervous system impairs neural, cognitive, and behavioral functioning in patients despite antiretroviral therapy. However, studying mechanisms underlying HIV-1-related neurological and cognitive dysfunction has been limited without an adequate animal model. A novel, noninfectious HIV-1 transgenic (HIV-1Tg) rat model was recently created that expresses an HIV-1 provirus with a deletion of functional gag and pol genes. This HIV-1Tg rat reportedly develops clinical manifestations of human HIV disease and thus appears to mimic the persistent infection that results from the presence of HIV viral proteins in the host. We evaluated the HIV-1Tg rat model using the Morris water maze, a popular paradigm for testing learning and memory deficits i... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=691806 Fri, 22 Jun 2007 07:14:28 +0100 691806 http://www.medworm.com/index.php?rid=622040&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fmm3p43jp14xlgk39%2F Abstract  Despite progress in our understanding molecular mechanisms of neuronal cell death in many central nervous system (CNS) diseases, widely effective treatments remain elusive. Recent studies have shown that neural stem cells (NSCs) are present in the subventricular zone (SVZ) lining the lateral ventricles and the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG) in adult mouse, rat, nonhuman primate, and human brain. Newly generated cells in the SGZ can differentiate into mature, functional neurons and integrate into the DG as granule cells, which are involved in memory formation. In addition, many CNS diseases can stimulate the proliferation of neuronal stem/progenitor cells located in the SVZ and SGZ of the adult rodent brain, and the resulting newborn c... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=622040 Fri, 18 May 2007 07:30:26 +0100 622040 http://www.medworm.com/index.php?rid=622039&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd0g7750260820814%2F Abstract  The role of CD200–CD200R signaling in immune regulation of the central nervous system has become a popular field of research in recent years. Many studies have shown that there is a close correlation between CD200–CD200R, microglia activation, and Parkinson’s disease (PD). This review discusses the above relationship, highlighting (1) the gene mapping and molecular structure of CD200 and CD200R, (2) the distribution and expression of CD200 and CD200R in the nervous system, (3) the effect of CD200–CD200R signaling on microglia activation, and (4) the role of microglia activation in the pathogenesis and progression of PD. Finally, we discuss the status of current studies on the regulation of microglia activation in PD and strongly suggest that it is very pro... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=622039 Fri, 18 May 2007 07:30:23 +0100 622039 http://www.medworm.com/index.php?rid=603693&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa582h0801k41673n%2F Abstract  Parkinson’s disease is one of the most common neurodegenerative diseases caused by the loss of dopaminergic neurons in the substantia nigra pars compacta. Pharmacological therapies are valuable but suffer from two main drawbacks: side effects and loss of efficacy with disease progression. Surgical treatment is no better than drugs. Transplantation of embryonic mesencephalic tissue has emerged as a therapeutic alternative, but the unstable efficiency and the shortage of embryonic donors limit its clinical application. Recent advances in stem cell research inspire our hope that stem cell transplantation to replace degenerated neurons may be a promising therapy for Parkinson’s disease. There are three sources of stem cells currently in testing: embryonic stem cel... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=603693 Wed, 09 May 2007 14:31:49 +0100 603693 http://www.medworm.com/index.php?rid=588566&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy17l578805660l37%2F Abstract  In the normal mature brain, blood vessel formation is tightly downregulated. However, pathologic processes such as ischemia can induce cerebral vascular regeneration. Angiogenesis is one of the major styles of new vessel formation. In this article, we summarize the major angiogenic factors in the brain, discuss the significant changes of angiogenic factors and endothelial progenitor cells (EPCs) in response to brain ischemia, and finally, review the therapeutic potential of angiogenic factors and EPCs in experimental cerebral ischemia based on the concept of neurovascular unit. Content TypeJournal Article JournalJournal of NeuroImmune PharmacologyOnline ISSN 1557-1904Print ISSN 1557-1890 (Source: Journal of NeuroImmune Pharmacology) Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=588566 Tue, 01 May 2007 07:21:08 +0100 588566 http://www.medworm.com/index.php?rid=522059&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq7671561436430t8%2F Abstract  Members of the Toll-like receptor (TLR) family play critical roles as regulators of innate and adaptive immune responses. TLRs function by recognizing diverse molecular patterns on the surface of invading pathogens. In the brain, microglial cells generate neuroimmune responses through production of proinflammatory mediators. The upregulation of cytokines and chemokines in response to microbial products and other stimuli has both beneficial and deleterious effects. Emerging evidence demonstrates a central role for TLRs expressed on microglia as a pivotal factor in generating these neuroimmune responses. Therefore, understanding the basis of TLR signaling in producing these responses may provide insights into how activated microglia attempt to strike a balance betwe... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=522059 Tue, 03 Apr 2007 09:05:00 +0100 522059 http://www.medworm.com/index.php?rid=516527&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F046174751885033q%2F Abstract  Proinflammatory cytokines and chemokines have been implicated in the pathogenesis of several neurological and neurodegenerative disorders. Prominent among such factors is the pleiotropic cytokine, tumor necrosis factor (TNF)-α. Under normal physiological conditions, TNF-α orchestrates a diverse array of functions involved in immune surveillance and defense, cellular homeostasis, and protection against certain neurological insults. However, paradoxical effects of this cytokine have been observed. TNF-α is elicited in the brain following injury (ischemia, trauma), infection (HIV, meningitis), neurodegeneration (Alzheimer’s, Parkinson’s), and chemically induced neurotoxicity. The multifarious identity for this cytokine appears to be influenced by several mecha... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=516527 Sat, 31 Mar 2007 06:51:46 +0100 516527 http://www.medworm.com/index.php?rid=516525&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F8r8566r847163122%2F Abstract  Macrophages play an important role in brain immune and inflammatory responses. They are also critical cells in mediating the pathology of neurodegenerative disorders such as HIV-associated dementia. This is largely through their capacity to secrete a variety of bioactive molecules such as cytokines, leading to neuronal dysfunction and/or death. Accumulating evidence indicates that voltage-gated potassium (Kv) channels play a pivotal role in the modulation of macrophage proliferation, activation, and secretion. Blockade of Kv channels by specific antagonists decreases macrophage cytokine production and ameliorates macrophage-associated neuronal injury. These results suggest that Kv channels might become a potential target for the development of new therapeutic stra... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=516525 Sat, 31 Mar 2007 06:51:46 +0100 516525 http://www.medworm.com/index.php?rid=508725&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp3386546617444w4%2F Abstract  Inflammation has been argued to play a fundamental role in the pathogenesis of Alzheimer’s disease. Mice transgenic for mutant human amyloid precursor protein (APP) develop progressive amyloid deposition, gliosis, and cognitive impairment. Paradoxically, intracranial administration of lipopolysaccharide (LPS) to promote neuroinflammation results in a reduction in amyloid-β peptide (Aβ) burden concurrent with the inflammatory response. To determine whether microglia mediate Aβ clearance after LPS, we used dexamethasone to inhibit the microglial response. Amyloid precursor protein mice were injected intrahippocampally with either LPS or saline and were allowed to survive for 7 days with or without dexamethasone cotreatment. Brain tissue was then analyzed by immu... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=508725 Tue, 27 Mar 2007 06:55:49 +0100 508725 http://www.medworm.com/index.php?rid=465713&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy18q613w2267p421%2F Content TypeJournal Article JournalJournal of NeuroImmune PharmacologyOnline ISSN 1557-1904Print ISSN 1557-1890 (Source: Journal of NeuroImmune Pharmacology) Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=465713 Sun, 11 Mar 2007 08:18:27 +0100 465713 http://www.medworm.com/index.php?rid=460879&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx443662577618k77%2F This study underlines the importance of neutral sphingomyelinase?ceramide pathway in mediating oxidative stress-induced apoptosis and cell death of human primary oligodendrocytes. Various oxidative stress-inducing agents, such as, superoxide radical produced by hypoxanthine and xanthine oxidase, hydrogen peroxide, aminotriazole capable of inhibiting catalase and increasing intracellular level of H2O2, or reduced glutathione-depleting diamide induced the activation of neutral sphingomyelinase and the production of ceramide. It is interesting to note that antisense knockdown of neutral but not acidic sphingomyelinase ablated oxidative stress-induced apoptosis and cell death in human primary oligodendrocytes. This study identifies neutral but not acidic sphingomyelinase as a target for possib... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=460879 Thu, 08 Mar 2007 08:01:55 +0100 460879 http://www.medworm.com/index.php?rid=460880&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F9612047wn4848668%2F Content TypeJournal Article JournalJournal of NeuroImmune PharmacologyOnline ISSN 1557-1904Print ISSN 1557-1890 (Source: Journal of NeuroImmune Pharmacology) Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=460880 Wed, 07 Mar 2007 07:45:24 +0100 460880 http://www.medworm.com/index.php?rid=455705&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F423x485433183025%2F Abstract??Neuroblastoma (NB) is a common and aggressive tumor of early childhood. To date, treatment with chemotherapy, surgery, and radiation therapy has resulted in suboptimal outcomes in those with advanced disease. Immune-based treatments hold promise for patients with recurrent or advanced NB. Here, recent preclinical studies and early stage (phase I) clinical trials using cellular therapeutic approaches for NB are reviewed, including studies of natural killer cells, ?? T cells, chimeric receptor expressing T cells, dendritic cells, and allogeneic hematopoietic cell transplant. Content TypeJournal Article JournalJournal of NeuroImmune PharmacologyOnline ISSN 1557-1904Print ISSN 1557-1890 (Source: Journal of NeuroImmune Pharmacology) Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=455705 Mon, 05 Mar 2007 22:13:19 +0100 455705 http://www.medworm.com/index.php?rid=455706&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F16780755v3003001%2F Abstract??The phospholipid mediator platelet-activating factor (PAF), an endogenous modulator of glutamatergic neurotransmission, can also be secreted by brain mononuclear phagocytes during HIV-1 infection. Platelet-activating factor can induce neuronal apoptosis by NMDA receptor-dependent and independent mechanisms. We now demonstrate that acute administration of sublethal doses of PAF to striatal slices augments synaptic facilitation in striatal neurons following high-frequency stimulation, which can be blocked by PAF receptor antagonists, suggesting that striatal synaptic facilitation can be augmented by PAF receptor agonism. We also demonstrate that repeated sublethal doses of PAF during tetanic stimulation can greatly increase the magnitude of postsynaptic potentials and action potent... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=455706 Fri, 02 Mar 2007 08:49:33 +0100 455706 http://www.medworm.com/index.php?rid=414570&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn31807m1p7672868%2F This article is written to provide an overview about the information suggesting significant roles of NAD+and NADH in neuronal death in certain neurological diseases. Our latest studies have suggested that intranasal administration with NAD+can profoundly decrease ischemic brain damage. These observations suggest that NAD+administration may be a novel therapeutic strategy for some neurological diseases. Content TypeJournal Article JournalJournal of NeuroImmune PharmacologyOnline ISSN 1557-1904Print ISSN 1557-1890 (Source: Journal of NeuroImmune Pharmacology) Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=414570 Tue, 13 Feb 2007 18:30:13 +0100 414570 http://www.medworm.com/index.php?rid=360803&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv259205587624211%2F Abstract??Pharmacotherapy in human immunodeficiency virus (HIV)-infected patients and the development of safe and effective antiretroviral dosing regimens has been hindered by numerous issues, including the rapid development of viral resistance to drug therapy, the narrow therapeutic window of the drug compounds, and lack of fundamental knowledge concerning the sources of variation in exposure and response to antiretroviral agents. Sources of variation may include factors such as interpatient differences in genetic expression, immunological response, pathogenesis, epidemiologic and socioeconomic factors, and demographics. Modeling and simulation (M&S) techniques have become valuable tools to identify and quantify variability in exposure and response to antiretroviral agents throughout the ... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=360803 Wed, 17 Jan 2007 07:48:21 +0100 360803 http://www.medworm.com/index.php?rid=355169&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq4344236624g417l%2F Abstract??On May 15 and 16, 2006, the National Institute of Mental Health sponsored a workshop designed to facilitate discussion and collaboration between basic and clinical investigators in neuroAIDS. Day 2 of the meeting featured a series of talks by clinical investigators. Three of these (those by J. McArthur, P. Tebas, and C. Flexner) are described in detail here. The remaining four talks (those by R. Ellis, R. Price, S. Letendre, and R. Robertson) are briefly introduced here, and full-length papers may be found elsewhere in this issue of theJournal. Content TypeJournal Article JournalJournal of NeuroImmune PharmacologyOnline ISSN 1557-1904Print ISSN 1557-1890 (Source: Journal of NeuroImmune Pharmacology) Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=355169 Sat, 13 Jan 2007 07:28:54 +0100 355169 http://www.medworm.com/index.php?rid=355170&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx588qk468171q2l8%2F Conclusion??Aprepitant is active against HIV drug-resistant isolates and enhances the anti-HIV activity of the antiretrovirals. Aprepitant downregulates CCR5 expression on macrophages. NK-1R antagonists merit further investigation as potential HIV therapeutic and immunomodulatory agents. Content TypeJournal Article JournalJournal of NeuroImmune PharmacologyOnline ISSN 1557-1904Print ISSN 1557-1890 (Source: Journal of NeuroImmune Pharmacology) Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=355170 Fri, 12 Jan 2007 07:46:57 +0100 355170 http://www.medworm.com/index.php?rid=350527&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq142p4251wk20756%2F In conclusion, an innovative design can provide solutions to challenging practical issues in trials with multiple treatment options. Content TypeJournal Article JournalJournal of NeuroImmune PharmacologyOnline ISSN 1557-1904Print ISSN 1557-1890 (Source: Journal of NeuroImmune Pharmacology) Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=350527 Wed, 10 Jan 2007 08:03:13 +0100 350527 http://www.medworm.com/index.php?rid=350528&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1052176gp5q65241%2F Abstract??Intranasal (IN) delivery of HIV-1 Tat in aging mice was investigated as a possible model for HIV-1 infection in the brain. After IN administration, the distribution of [125I]-labeled Tat in the brains of Swiss Webster mice was evaluated by autoradiography and gamma counting. [125I]-labeled Tat was detected at the highest concentrations in the olfactory bulb, cervical nodes, and trigeminal nerve tract. In another experiment, APPSw transgenic mice were used to model chronic Tat exposure. The mice were treated intranasally with 6??g Tat (n?=?4) or vehicle (n?=?4) three times per week for 4?weeks. Total RNA was isolated from the frontal cortex, and differential gene expression analysis was performed using gene microarrays. Gene ontology profiles indicated innate immunity, inflammator... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=350528 Tue, 09 Jan 2007 07:48:43 +0100 350528 http://www.medworm.com/index.php?rid=350529&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fqj7502371324mm87%2F Abstract??The goals of this component were to discuss the potential for NeuroAIDS therapeutics. The presentations included discussions of biomarkers, pathogenic mechanisms of disease, laboratory models, and the development of adjunctive therapies for neuroinflammatory and neurodegenerative disorders with a focus on NeuroAIDS. Talks by Dana Giulian on the use of CSF biomarkers for therapeutic trial design in dementia, Howard Fox on the SIV model of NeuroAIDS, Christine Zink on minocycline and its antiretroviral activities, and Katrina L. Mealey on the means to improve drug access to the brain by regulation P-glycoprotein, rounded out the session. It was acknowledged that although a number of compounds including selegiline, nimodipine, and memantine were studied in clinical trials and showed... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=350529 Tue, 09 Jan 2007 07:48:42 +0100 350529 http://www.medworm.com/index.php?rid=350530&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg62x778217w17216%2F Abstract??The goal of this component of the meeting was to discuss novel therapeutics that attenuate inflammatory pathways, enhance drug delivery into the brain and/or bypass the blood?brain barrier (BBB). Presentations included discussions of (i) antiretroviral drugs packaged into nanoparticles by Howard Gendelman, (ii) how to engage the nasal epithelium and its closely associated neural fibers as a route for drug entry to the brain, by William H. Frey and Lynn Pulliam, and (iii) antioxidant gene delivery to neurons using vector systems that can protect neurons against HIV-associated toxicity, by David Strayer. The session was capped by active discourse among leaders in the field of adjunctive therapies in a broad range of scientific disciplines. Content TypeJournal Article JournalJ... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=350530 Tue, 09 Jan 2007 07:48:41 +0100 350530 http://www.medworm.com/index.php?rid=347315&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe0n7468334j82h3u%2F Abstract??The prevalence of HIV-associated brain disorders is reportedly increasing due, in part, to the prolonged life span of individuals who are surviving well on highly active antiretroviral treatments (HAART). While clinicians report CNS-related deficits that are more subtle in presentation than the frank dementia evident in the pre-HAART era, the milder presentation continues to substantively reduce an individual?s quality of life. The development of novel drugs or therapeutic strategies for treating HIV-related CNS disease is important as most investigators agree that the brain is a sanctuary for latent virus, local viral recrudescence, and associated brain inflammatory responses. The prolonged chronic and cumulative effects on the brain of living with HIV-related inflammatory proce... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=347315 Sat, 06 Jan 2007 13:28:16 +0100 347315 http://www.medworm.com/index.php?rid=343153&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe32210474474p537%2F Abstract??HIV infection results in a neurodegenerative disorder for which currently there is no effective therapy available. Currently, available antiretroviral therapy has no impact on the production of early regulatory HIV proteins once the virus is integrated. Of these proteins, Tat was shown to be toxic to neurons. We, thus, used an in vitro neuronal culture system to determine if immunophilin ligands could protect against Tat-induced neurotoxicity. We found that GPI 1046 had potent neuroprotective effects in this model. The compound was able to protect the neurons even though it only partially obliterated Tat-induced oxidative stress in neurons, suggesting that other mechanisms may be important in mediating its neuroprotective effect. Furthermore, GPI 1046 showed inhibition of HIV rep... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=343153 Wed, 03 Jan 2007 18:22:48 +0100 343153 http://www.medworm.com/index.php?rid=343152&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F64673j165353u750%2F Conclusions??SRIs may reduce HIV replication in CSF and improve NP performance. This was particularly true for three SRIs?supporting differences in antiviral efficacy between drugs?in individuals who were not taking ART. In contrast, statins were not associated with lower HIV replication in CSF in multivariate analyses and were not associated with better NP performance. These analyses support the value of large observational cohort studies in identifying FDA-approved drugs that may be worth further investigation. Content TypeJournal Article JournalJournal of NeuroImmune PharmacologyOnline ISSN 1557-1904Print ISSN 1557-1890 (Source: Journal of NeuroImmune Pharmacology) Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=343152 Wed, 03 Jan 2007 18:22:48 +0100 343152 http://www.medworm.com/index.php?rid=343151&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw3767503u23036t6%2F Abstract??The global burden of the HIV epidemic is staggering, but in the short term, it is largely unfelt in the developed world. Almost one million people have been infected with HIV in North America, and the results of effective antiretroviral therapy have dramatically improved survival and quality of life. However, there are 25 million infected in sub-Saharan Africa alone, and antiretroviral treatment is scarce. Ninety-five percent of new infections occur in the developing world where resources are limited. Very little is known about NeuroAIDS in the developing world where few studies have been conducted on the neurologic and neurocognitive effects of antiretroviral treatment. HIV Clade differences and other factors could have dramatic effects on treatment effectiveness. There are a nu... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=343151 Wed, 03 Jan 2007 18:22:47 +0100 343151 http://www.medworm.com/index.php?rid=343150&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm76u2421jk204q02%2F Content TypeJournal Article JournalJournal of NeuroImmune PharmacologyOnline ISSN 1557-1904Print ISSN 1557-1890 (Source: Journal of NeuroImmune Pharmacology) Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=343150 Wed, 03 Jan 2007 18:22:47 +0100 343150 http://www.medworm.com/index.php?rid=327881&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn34lg571k4210646%2F Abstract??Highly active antiretroviral therapy (HAART) has made a significant impact on the lives of people living with HIV-1 infection. The incidence of neurologic disease associated with HIV-1 infection of the CNS plummeted between 1996?2000, but unfortunately the number of people currently HIV-1 infected (i.e., prevalence) with associated cognitive impairment has been steadily rising. While the reasons for this may be multifactorial, the implication is clear: there is a pressing need for adjunctive therapy directed at reversing or preventing damage to vulnerable pathways in the central nervous system (CNS) from HIV-1 infection. Using a team of preclinical and clinical investigators, we have focused our efforts on defining how proinflammatory mediators and secretory neurotoxins from HIV-... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=327881 Mon, 18 Dec 2006 13:56:02 +0100 327881 http://www.medworm.com/index.php?rid=313659&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb732662221214827%2F Abstract??Representative, reproducible, and high-throughput models of human cells and tissues are critical for a meaningful evaluation of host?pathogen interactions and are an essential component of the research developmental pipeline. The most informative infection models?animals, organ explants, and human trials?are not suited for extensive evaluation of pathogenesis mechanisms and screening of candidate drugs. At the other extreme, more cost-effective and accessible infection models such as conventional cell culture and static coculture may not capture physiological and three-dimensional (3-D) aspects of tissue biology that are important in assessing pathogenesis, effectiveness, and cytotoxicity of therapeutics. Our lab has used innovative bioengineering technology to establish biologic... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=313659 Thu, 07 Dec 2006 08:45:49 +0100 313659 http://www.medworm.com/index.php?rid=313658&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk7266v5243588wv1%2F Abstract??This is a brief summary of the animal models session held during the 12th Annual Meeting of the Society on NeuroImmune Pharmacology, Santa Fe, NM, USA. This session provided important information for participants on availability and utility of animal models for the studies of HIV-1 central nervous system infection and drug abuse. It highlighted animal model relevance to human disease/condition, its utility for the studies of pathogenesis, potential importance for the development of therapeutics, and demonstrated limitations/pitfalls. Content TypeJournal Article JournalJournal of NeuroImmune PharmacologyOnline ISSN 1557-1904Print ISSN 1557-1890 (Source: Journal of NeuroImmune Pharmacology) Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=313658 Thu, 07 Dec 2006 08:45:49 +0100 313658 http://www.medworm.com/index.php?rid=313660&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft606126715784660%2F Abstract??Accumulating evidence suggests that bone-marrow (BM)-derived mononuclear phagocytes have an important role in the clearance of soluble and aggregated amyloid-? peptides (A?) in Alzheimer?s disease (AD) brains. However, the exact kinetics of A? clearance in mononuclear phagocytes derived from transgenic animal models of AD expressing ?-amyloid precursor protein (APP) mutants have been poorly characterized. We have examined whether CCL2 and APP expression affects the clearance of A? in conjunction with our control, acetylated low-density lipoprotein (AcLDL), using primary cultured BM-derived macrophages derived from adult APP, CCL2, APP/CCL2, and control littermates. Pulse-chase analysis demonstrated three distinct destinations for A?40 and AcLDL: intracellular retention, degradati... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=313660 Wed, 06 Dec 2006 04:31:35 +0100 313660 http://www.medworm.com/index.php?rid=298780&cid=s_33363_13_f&fid=33363&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm6x2178748q556q7%2F Abstract??Invasion of human immunodeficiency virus (HIV) into the central and peripheral nervous system produces a wide range of neurological symptoms, which continue to persist even with adequate therapeutic suppression of the systemic viremia. The development of therapies designed to prevent the neurological complications of HIV require a detailed understanding of the mechanisms of virus penetration into the nervous system, infection, and subsequent neuropathogenesis. These processes, however, are difficult to study in humans. The identification of animal lentiviruses similar to HIV has provided useful models of HIV infection that have greatly facilitated these efforts. This review summarizes contributions made fromin vitroandin vivostudies on the infectious and pathological interactions... Journal of NeuroImmune Pharmacology journals http://www.medworm.com/rss/comments.php?id=298780 Tue, 28 Nov 2006 08:16:30 +0100 298780