Brain Pathology via MedWorm.com

Transient Peripheral Immune Response and Central Nervous System Leaky Compartmentalization in a Viral Model for Multiple Sclerosis

Brain Pathology — Tue, 09 Mar 2010 00:00:00 +0100

Theiler's virus-induced demyelination represents an important animal model to study the chronic-progressive form of multiple sclerosis (MS). The aim of the present study was to identify specific genes and pathways in the deep cervical lymph node (cLN) and spleen of experimentally infected SJL-mice, using DNA microarrays. Analyses identified 387 genes in the deep cLN and only 6 genes in the spleen of infected animals. The lymph node presented 27.4% of genes with fold changes ±1.5 at 14 days post infection (dpi) and a reduced transcription at later time points. K-means clustering analyses resulted in five clusters. Accordingly, functional annotation revealed that the B-cell immune response pathway was the most up-regulated cluster at the early phase. Additionally, an increase of CD68- and l...

John j. kepes, md, frsm: the loss of a colleague, mentor and friend

Brain Pathology — Fri, 05 Mar 2010 00:00:00 +0100

(Source: Brain Pathology)

Telomerase Inhibition as a Novel Therapy for Pediatric Ependymoma

Brain Pathology — Fri, 19 Feb 2010 00:00:00 +0100

Ependymomas are the third most common pediatric brain tumor with an overall survival of [sim]50%. Recently, we showed that telomerase [human telomerase reverse transcriptase (hTERT)] expression is a predictor of poor outcome in pediatric ependymoma. Thus, we hypothesized that ependymomas with functional telomerase may behave more aggressively and that these patients may benefit from anti-telomerase therapy. To address our hypothesis, we investigated the effect of telomerase inhibition on primary ependymoma cells harvested at the time of surgery, as no animal models or established cell lines are readily available for this tumor. The cells were characterized for glial fibrillary acidic protein (GFAP) and hTERT expression, initial telomere length and telomerase activity. They were then subjec...

Status of ICN 2010

Brain Pathology — Wed, 17 Feb 2010 00:00:00 +0100

(Source: Brain Pathology)

The Utility and Limitations of Neurosphere Assay, CD133 Immunophenotyping and Side Population Assay in Glioma Stem Cell Research

Brain Pathology — Fri, 05 Feb 2010 00:00:00 +0100

The newly proposed glioma stem cell (GSC) hypothesis may re-model the way we diagnose and treat the tumor, which highlights the need for a complete knowledge on the genetic and epigenetic "blueprints" of GSCs. To identify the true "stemness" signatures, pure GSC populations are primarily needed. Reliable in vitro methods enriching for GSCs and thereby identifying the key stem-like characteristics constitute the preliminary step forward. We discuss in this review the current widely used methods for enriching and isolating GSCs, namely neurosphere assay, CD133 Immunophenotyping and side population assay, and detail their limitations and potential pitfalls that could complicate interpretation of corresponding results. (Source: Brain Pathology)

Glioma Pathophysiology: Insights Emerging from Proteomics

Brain Pathology — Wed, 13 Jan 2010 00:00:00 +0100

Proteomics is increasingly employed in both neurological and oncological research to provide insight into the molecular basis of disease but rarely has a coherent, novel pathophysiological insight emerged. Gliomas account for >50% of adult primary intracranial tumors, with malignant gliomas (anaplastic astrocytomas and glioblastoma multiforme) being the most common. In glioma, the application of proteomic technology has identified altered protein expression but without consistency of these alterations or their biological significance being established. A systematic review of multiple independent proteomic analyses of glioma has demonstrated alterations of 99 different proteins. Importantly 10 of the 99 proteins found differentially expressed in glioma [PHB, Hsp20, serum albumin, epidermal ...

Hypothermia-Induced Neurite Outgrowth is Mediated by Tumor Necrosis Factor-Alpha

Brain Pathology — Wed, 13 Jan 2010 00:00:00 +0100

Systemic or brain-selective hypothermia is a well-established method for neuroprotection after brain trauma. There is increasing evidence that hypothermia exerts beneficial effects on the brain and may also support regenerative responses after brain damage. Here, we have investigated whether hypothermia influences neurite outgrowth in vitro via modulation of the post-injury cytokine milieu. Organotypic brain slices were incubated: deep hypothermia (2 h at 17°C), rewarming (2 h up to 37°C), normothermia (20 h at 37°C). Neurite density and cytokine release (IL 1beta, IL-6, IL-10, and TNF-alpha) were investigated after 24 h. For functional analysis mice deficient in NT-3/NT-4 and TNF-alpha as well as the TNF-alpha inhibitor etanercept were used. Hypothermia led to a significant increase of...

Higher Soluble Amyloid β Concentration in Frontal Cortex of Young Adults than in Normal Elderly or Alzheimer's Disease

Brain Pathology — Tue, 12 Jan 2010 00:00:00 +0100

Little is known about the relationship between soluble amyloid [beta] (A[beta]) and age. We have measured soluble and insoluble A[beta] by enzyme-linked immunosorbent assay (ELISA) in post-mortem frontal cortex in normal brains (16[ndash]95 years) and AD. Insoluble A[beta] increased with age, and was significantly higher in Alzheimer's disease (AD) than age-matched controls. However, levels of soluble A[beta] declined with age and were significantly greater in younger adults than older adults with or without AD. In AD, insoluble : soluble A[beta] ratio was much higher than in age-matched controls. The high levels of soluble A[beta] in young adults included oligomeric species of A[beta]1-42. These observations do not preclude A[beta] oligomers as neurotoxic mediators of AD but suggest that ...

Changes with Age in the Activities of β-secretase and the Aβ-degrading Enzymes Neprilysin, Insulin-degrading Enzyme and Angiotensin-converting Enzyme

Brain Pathology — Tue, 12 Jan 2010 00:00:00 +0100

We recently found that insoluble A[beta] increases, but soluble A[beta] decreases with age in normal brains. We now report the changes in activities of [beta]-secretase (BACE-1) and A[beta]-degrading enzymes with age, and their relationships to concentrations of soluble and insoluble A[beta]. We measured BACE-1 activity and the levels and activities of neprilysin (NEP), insulin-degrading enzyme (IDE) and angiotensin-converting enzyme (ACE) in normal control brains (16 years[ndash]95 years). We also compared the measurements to those in AD. BACE-1 activity correlated closely with age in controls and was significantly higher in AD. In controls, NEP and IDE activities (but not protein levels) increased with age but ACE activity and level did not. BACE-1 activity correlated directly with insol...

Expression of KIT Receptor Tyrosine Kinase in Endothelial Cells of Juvenile Brain Tumors

Brain Pathology — Fri, 18 Dec 2009 00:00:00 +0100

KIT receptor tyrosine kinase is expressed in tumor endothelial cells of adult glioblastomas, but its expression in pediatric brain tumor endothelial cells is unknown. We assessed expression of KIT, phosphorylated KIT, stem cell factor (SCF) and vascular endothelial growth factor receptor-2 (VEGFR-2) in 35 juvenile pilocytic astrocytomas and 49 other pediatric brain tumors using immunohistochemistry, and KIT messenger RNA (mRNA) using in situ hybridization. KIT and phospho-KIT were moderately or strongly expressed in tumor endothelia of 37% and 35% of pilocytic astrocytomas, respectively, whereas marked SCF and VEGFR-2 expression was uncommon. KIT mRNA was detected in tumor endothelial cells. Tumor endothelial cell KIT expression was strongly (P < 0.01) associated with endothelial cell phos...

Vasopressin Synthesis by the Magnocellular Neurons is Different in the Supraoptic Nucleus and in the Paraventricular Nucleus in Human and Experimental Septic Shock

Brain Pathology — Tue, 15 Dec 2009 00:00:00 +0100

This study shows that both in human and experimental septic shock, AVP posttranscriptional synthesis and transport are differently modified in the magnocellular neurons of the supraoptic and paraventricular nuclei. This may account for the inappropriate AVP release in septic shock and suggests that distinct pathogenic mechanisms operate in these nuclei. (Source: Brain Pathology)

Chronic Cortical and Subcortical Pathology with Associated Neurological Deficits Ensuing Experimental Herpes Encephalitis

Brain Pathology — Tue, 08 Dec 2009 00:00:00 +0100

Long-term neurological sequela is common among herpes simplex encephalitis (HSE) survivors. Animal models for HSE are used to investigate mechanisms of acute disease, but little has been done to model chronic manifestations of HSE. The current study presents a detailed, systematic analysis of chronic neuropathology, including characterization of topography and sequential progression of degenerative lesions and inflammation. Subsequent to intranasal HSV-1 infection, inflammatory responses that were temporally and spatially distinct persisted in infected cortical and brain stem regions. Neutrophils were present exclusively within the olfactory bulb and brain stem regions during the acute phase of infection, while the chronic inflammation was marked by plasma cells, lymphocytes and activated ...

Genomic Landscape of Meningiomas

Brain Pathology — Fri, 20 Nov 2009 00:00:00 +0100

Meningiomas are one of the most common adult brain tumors. For most patients, surgical excision is curative. However, up to 20% recur. Currently, the molecular determinants predicting recurrence and malignant transformation are lacking. We performed retrospective global genetic and genomic analysis of 85 meningioma samples of various grades. Copy number alterations were assessed by 100K single-nucleotide polymorphism arrays and correlated with gene expression, proliferation indices and clinical outcome. In addition to chromosome 22q loss, which was detected in the majority of clinical samples, chromosome 6q and 14q loss was significantly more common in recurrent tumors and was associated with anaplastic histology. Five "classes" of meningiomas were detected by gene expression analysis that...

Hypermethylation and Transcriptional Downregulation of the TIMP3 Gene Is Associated with Allelic Loss on 22q12.3 and Malignancy in Meningiomas

Brain Pathology — Wed, 18 Nov 2009 00:00:00 +0100

The gene for the tissue inhibitor of metalloproteinase 3 (TIMP3) on 22q12.3 had been reported to be inactivated by promoter methylation in various types of cancers, with controversial findings in meningiomas. We performed direct sodium bisulfite sequencing in a series of 50 meningiomas, including 27 benign meningiomas [World Health Organization (WHO) grade I], 11 atypical meningiomas (WHO grade II) and 12 anaplastic meningiomas (WHO grade III), and found hypermethylation of TIMP3 in 67% of anaplastic meningiomas, but only 22% of atypical and 17% of benign meningiomas. Moreover, TIMP3 methylation scores were significantly inversely correlated with TIMP3 mRNA expression levels (P = 0.0123), and treatment of the meningioma cell line Ben-Men-1 with demethylating agents induced an increased TIM...

Neuropathology of Olfactory Ensheathing Cell Transplantation into the Brain of Two Amyotrophic Lateral Sclerosis (ALS) Patients

Brain Pathology — Tue, 17 Nov 2009 00:00:00 +0100

In conclusion, the present neuropathologic analysis does not support a beneficial effect of fetal OEC implantation into the frontal lobes of ALS patients. (Source: Brain Pathology)

Gene Expression Analysis of Tuberous Sclerosis Complex Cortical Tubers Reveals Increased Expression of Adhesion and Inflammatory Factors

Brain Pathology — Thu, 12 Nov 2009 00:00:00 +0100

Cortical tubers in patients with tuberous sclerosis complex are associated with disabling neurological manifestations, including intractable epilepsy. While these malformations are believed to result from the effects of TSC1 or TSC2 gene mutations, the molecular mechanisms leading to tuber formation, as well as the onset of seizures, remain largely unknown. We used the Affymetrix Gene Chip platform to provide the first genome-wide investigation of gene expression in surgically resected tubers, compared with histological normal perituberal tissue from the same patients or autopsy control tissue. We identified 2501 differentially expressed genes in cortical tubers compared with autopsy controls. Expression of genes associated with cell adhesion, for example, VCAM1, integrins and CD44, or wit...

Characterization of R132H Mutation-specific IDH1 Antibody Binding in Brain Tumors

Brain Pathology — Mon, 09 Nov 2009 00:00:00 +0100

Heterozygous point mutations of isocitrate dehydrogenase (IDH)1 codon 132 are frequent in grade II and III gliomas. Recently, we reported an antibody specific for the IDH1R132H mutation. Here we investigate the capability of this antibody to differentiate wild type and mutated IDH1 protein in central nervous system (CNS) tumors by Western blot and immunohistochemistry. Results of protein analysis are correlated to sequencing data. In Western blot, anti-IDH1R132H mouse monoclonal antibody mIDH1R132H detected a specific band only in mutated tumors. Immunohistochemistry of 345 primary brain tumors demonstrated a strong cytoplasmic and weaker nuclear staining in 122 cases. Correlation with direct sequencing of 186 cases resulted in consensus of 177 cases. Genetic retesting of cases with confli...

Purple Sweet Potato Color Alleviates D-galactose-induced Brain Aging in Old Mice by Promoting Survival of Neurons via PI3K Pathway and Inhibiting Cytochrome C-mediated Apoptosis

Brain Pathology — Wed, 28 Oct 2009 00:00:00 +0100

Purple sweet potato color (PSPC), a class of naturally occurring anthocyanins, protects brain function against oxidative stress induced by D-galactose (D-gal) (Sigma-Aldrich, St. Louis, MO, USA). Our data showed that PSPC enhanced open-field activity, decreased step-through latency, and improved spatial learning and memory ability in D-gal-treated old mice by decreasing advanced glycation end-products' (AGEs) formation and the AGE receptor (RAGE) expression, and by elevating Cu,Zn-superoxide dismutase (Cu,Zn-SOD) (Sigma-Aldrich) and catalase (CAT) expression and activity. Cleavage of caspase-3 and increased terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end-labeling (TUNEL)-positive cells in D-gal-treated old mice were inhibited by PSPC, which mi...

Upregulation of Immunoglobulin-related Genes in Cortical Sections from Multiple Sclerosis Patients

Brain Pathology — Fri, 16 Oct 2009 00:00:00 +0100

This study demonstrates that genes involved in the synthesis of Igs are upregulated in MS patients and that this activation is caused by a small number of meningeal plasma cells that are not infected by EBV. The findings indicate that the Ig-producing B-cells found in the cerebrospinal fluid (CSF) of MS patients could have meningeal origin. (Source: Brain Pathology)

FUS-Immunoreactive Intranuclear Inclusions in Neurodegenerative Disease

Brain Pathology — Mon, 12 Oct 2009 23:00:00 +0100

The objective of the present study was to determine the range of neurodegenerative disorders characterized by FUS-positive NIIs. Immunostaining for FUS revealed intense reactivity of NIIs in FTLD-IF and FTLD-UPS as well as in Huntington's disease, spinocerebellar ataxias 1 and 3, and neuronal intranuclear inclusion body disease. In contrast, there was no FUS staining of NIIs in inherited forms of FTLD-TDP caused by GRN and VCP mutations, fragile-X-associated tremor ataxia syndrome, or oculopharyngeal muscular dystrophy. In a cell culture model of Huntington's disease, NIIs were intensely FUS-positive. NII-bearing cells displayed loss of the normal diffuse nuclear pattern of FUS staining. This suggests that sequestration of nuclear FUS by NIIs may interfere with its normal nuclear localizat...

Unique Molecular Characteristics of Pediatric Myxopapillary Ependymoma

Brain Pathology — Tue, 29 Sep 2009 23:00:00 +0100

Myxopapillary ependymoma (MEPN) generally can be cured by gross total surgical resection and usually manifest a favorable prognosis. However, surgery is less curative in tumors that are large, multifocal or extend outside the thecal sac. Late recurrences may occur, particularly in pediatric patients. The role of adjuvant therapy is unclear in the clinical management of recurrent tumors. Clinical trial design requires a better understanding of tumor biology. Unique molecular features of MEPN were investigated by using microarray technology to compare the gene expression of five pediatric MEPN to 24 pediatric intracranial ependymoma (EPN). The upregulation of three genes of interest, homeobox B13 (HOXB13), neurofilament, light polypeptide (NEFL) and PDGFR[alpha], was further studied by immun...

Recent Insights into PDGF-Induced Gliomagenesis

Brain Pathology — Thu, 24 Sep 2009 23:00:00 +0100

Gliomas are aggressive and almost incurable glial brain tumors which frequently display abnormal platelet-derived growth factor (PDGF) signaling. Evidence gained from studies on several in vivo animal models has firmly established a causal connection between aberrant PDGF signaling and the formation of some gliomas. However, only recently has significant knowledge been gained regarding crucial issues such as the glioma cell of origin and the relationship between the transforming stimulus and the cellular characteristics of the resulting tumor. Based on recent evidence, we propose that PDGF can bias cell-fate decisions, driving the acquisition of cell type-specific features by the progeny of multipotent neural progenitors, thus determining the shape and direction of the transformation path....

Identification and Functional Characterization of microRNAs Involved in the Malignant Progression of Gliomas

Brain Pathology — Wed, 23 Sep 2009 23:00:00 +0100

Diffuse astrocytoma of World Health Organization (WHO) grade II has an inherent tendency to spontaneously progress to anaplastic astrocytoma WHO grade III or secondary glioblastoma WHO grade IV. We explored the role of microRNAs (miRNAs) in glioma progression by investigating the expression profiles of 157 miRNAs in four patients with primary WHO grade II gliomas that spontaneously progressed to WHO grade IV secondary glioblastomas. Thereby, we identified 12 miRNAs (miR-9, miR-15a, miR-16, miR-17, miR-19a, miR-20a, miR-21, miR-25, miR-28, miR-130b, miR-140 and miR-210) showing increased expression, and two miRNAs (miR-184 and miR-328) showing reduced expression upon progression. Validation experiments on independent series of primary low-grade and secondary high-grade astrocytomas confirme...

Brain Neurons Express Ornithine Decarboxylase-Activating Antizyme Inhibitor 2 with Accumulation in Alzheimer's Disease

Brain Pathology — Mon, 21 Sep 2009 23:00:00 +0100

Polyamines are small cationic molecules that in adult brain are connected to neuronal signaling by regulating inward-rectifier K+-channels and different glutamate receptors. Antizyme inhibitors (AZINs) regulate the cellular uptake of polyamines and activate ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine synthesis. Elevated levels of ODC activity and polyamines are detected in various brain disorders including stroke and Alzheimer's disease (AD). We originally reported a novel brain- and testis-specific AZIN, called AZIN2, the distribution of which we have now studied in normal and diseased human brain by in situ hybridization and immunohistochemistry. We found the highest accumulation of AZIN2 in a pearl-on-the-string-like distribution along the axons in both the whit...

Impact of Morphology, MIB-1, p53 and MGMT on Outcome in Pilocytic Astrocytomas

Brain Pathology — Sun, 20 Sep 2009 23:00:00 +0100

Pilocytic astrocytoma (PA) is the most common glioma in the pediatric population. PAs can exhibit variable behavior that does not always correlate with location, yet at present there is no way to predict which tumors will be more aggressive. To address this problem, an institutional cohort of 147 PAs (118 with outcome data) from both cerebellar and noncerebellar locations (spine, diencephalon, midbrain, brainstem and cortex) was utilized. Parameters included quantification of characteristic morphologic variables as well as genes previously shown to be of relevance in high-grade gliomas, including MIB-1, p53 and MGMT. In this cohort, the classic biphasic appearance was most common in cerebellar tumors, whereas noncerebellar tumors were predominantly microcystic. Associations with outcome su...

PCR- and Restriction Endonuclease-Based Detection of IDH1 Mutations

Brain Pathology — Thu, 10 Sep 2009 23:00:00 +0100

Hotspot mutations in codon 132 of the gene encoding isocitrate dehydrogenase 1 (IDH1) have emerged as the most frequent DNA alteration in astrocytomas, oligodendrogliomas and oligoastrocytomas. These mutations have been shown to be of significant diagnostic and prognostic value. So far, assessment of IDH1 mutation relied on DNA sequencing techniques. We generated a set of primers suitable for endonuclease-based detection of hotspot mutations in codon 132 of IDH1. This primer set will allow determining these mutations without the need of DNA sequencing. One set of primer sets is designed to detect the presence or absence of IDH1 mutations in codon 132, while the other primer sets individually recognize the R132H, R132C, R132S, R132G and R132L mutations. (Source: Brain Pathology)

Protein Targets of Oxidative Damage in Human Neurodegenerative Diseases with Abnormal Protein Aggregates

Brain Pathology — Wed, 02 Sep 2009 23:00:00 +0100

Human neurodegenerative diseases with abnormal protein aggregates are associated with aberrant post-translational modifications, solubility, aggregation and fibril formation of selected proteins which cannot be degraded by cytosolic proteases, ubiquitin[ndash]protesome system and autophagy, and, therefore, accumulate in cells and extracellular compartments as residual debris. In addition to the accumulation of "primary" proteins, several other mechanisms are involved in the degenerative process and probably may explain crucial aspects such as the timing, selective cellular vulnerability and progression of the disease in particular individuals. One of these mechanisms is oxidative stress, which occurs in the vast majority of, if not all, degenerative diseases of the nervous system. The pres...

Axonal Pathology and Loss Precede Demyelination and Accompany Chronic Lesions in a Spontaneously Occurring Animal Model of Multiple Sclerosis

Brain Pathology — Tue, 25 Aug 2009 23:00:00 +0100

Axonal damage has been highlighted recently as a cause of neurological disability in various demyelinating diseases, including multiple sclerosis, either as a primary pathological change or secondary due to myelin loss. To characterize and quantify axonal damage and loss in canine distemper demyelinating leukoencephalomyelitis (DL), formalin-fixed paraffin-embedded cerebella were investigated histochemically and immunohistochemically using the modified Bielschowsky's silver stain as well as antibodies against nonphosphorylated (n-NF), phosphorylated neurofilament (p-NF) and [beta]-amyloid precursor protein ([beta]-APP). Injured axons characterized by immunoreactivity against n-NF and [beta]-APP were detected in early distemper lesions without demyelination. In subacute and chronic demyelin...

Loss of Inhibitor of Growth (ING-4) Is Implicated in the Pathogenesis and Progression of Human Astrocytomas

Brain Pathology — Wed, 05 Aug 2009 23:00:00 +0100

Inhibitor of growth 4 (ING-4) is a tumor suppressor gene that interacts with nuclear factor-kappaB (NF-[kappa]B) and represses its transcriptional activity. Several lines of evidence suggest that the tumor suppressor gene ING-4, the transcription factor NF-[kappa]B and its target genes matrix metalloproteases MMP-2, MMP-9 and urokinase plasminogen activator (u-PA) are critically involved in tumor invasion. The aim of the present study was to investigate immunohistochemically the expression pattern of ING-4, NF-[kappa]B and the NF-[kappa]B downstream targets MMP-2, MMP-9 and u-PA in human astrocytomas from 101 patients. We found that ING-4 expression was significantly decreased in astrocytomas, and ING-4 loss was associated with tumor grade progression. Expression of p65, a NF-[kappa]B subu...

Leptin and Its Receptor Are Overexpressed in Brain Tumors and Correlate with the Degree of Malignancy

Brain Pathology — Sun, 19 Jul 2009 23:00:00 +0100

Although leptin and its receptor (ObR) have emerged as important cancer biomarkers, the role of the leptin system in brain tumor development remains unknown. We screened 87 human brain tumor biopsies using immunohistochemistry and detected leptin and ObR in 55.2% and 60.9% cases, respectively. In contrast, leptin and ObR were absent in 14 samples of normal brain tissue. The presence of leptin correlated with ObR with overall concordance 80.5%. The leptin/ObR system was highly expressed in glioblastomas and anaplastic astrocytomas, while lower expression of both markers was noted in low-grade astrocytomas and gangliogliomas. The association between leptin/ObR and the degree of tumor malignancy was highly significant (P < 0.001). Using double immunofluorescence of glioblastoma tissues, we fo...

Oligomeric Aβ in Alzheimer's Disease: Relationship to Plaque and Tangle Pathology, APOE Genotype and Cerebral Amyloid Angiopathy

Brain Pathology — Wed, 15 Jul 2009 23:00:00 +0100

Despite accumulating evidence of a central role for oligomeric amyloid [beta] (A[beta]) in the pathogenesis of Alzheimer's Disease (AD), there is scant information on the relationship between the levels and distribution of oligomeric A[beta] and those of other neurodegenerative abnormalities in AD. In the present study, we have found oligomeric A[beta] to be associated with both diffuse and neuritic plaques (mostly co-localized with A[beta]1[ndash]42) and with cerebrovascular deposits of A[beta] in paraffin sections of formalin-fixed human brain tissue. The amount of oligomeric A[beta] that was labeled in the sections correlated with total A[beta] plaque load, but not phospho-tau load, cerebral amyloid angiopathy (CAA) severity or APOE genotype. Although soluble, oligomeric and insoluble A...

Cerebral Microinfarcts Associated with Severe Cerebral β-Amyloid Angiopathy

Brain Pathology — Wed, 15 Jul 2009 23:00:00 +0100

Cerebral amyloid angiopathy (CAA) is common in elderly individuals, especially those affected with Alzheimer's disease. Eighteen brains with severe SCAA (SCAA) were compared with 21 brains with mild CAA (MCAA) to investigate whether the presence of SCAA in the brains of demented patients was associated with a higher burden of old microinfarcts than those with MCAA. Immunohistochemistry for CD68 was employed to highlight old microinfarcts in tissue blocks from various brain regions. Old microinfarcts, manually counted by light microscopy, were present in 14 of 18 SCAA brains and in 7 of 21 MCAA brains (P = 0.01, two-tailed Fisher's exact test). The average number of old microinfarcts across geographic regions in each brain ranged from 0 to 1.95 (mean rank 24.94, sum of ranks 449) in the SCA...

A Topographic Study of Minicolumnar Core Width by Lamina Comparison between Autistic Subjects and Controls: Possible Minicolumnar Disruption due to an Anatomical Element In-Common to Multiple Laminae

Brain Pathology — Tue, 07 Jul 2009 23:00:00 +0100

This study further characterizes this cortical deficit by comparing minicolumnar widths across layers. Brains from seven autistic patients and an equal number of age-matched controls were celloidin embedded, serially sectioned at 200 µm and Nissl stained with gallocyanin. Photomicrograph mosaics of the cortex were analyzed with computerized imaging methods to determine minicolumnar width at nine separate neocortical areas: Brodmann Area's (BA) 3b, 4, 9, 10, 11, 17, 24, 43 and 44. Each area was assessed at supragranular, granular and infragranular levels. Autistic subjects had smaller minicolumns whose dimensions varied according to neocortical area. The greatest difference between autistic and control groups was observed in area 44. The interaction of diagnosis × cortical area × lamina ...

N-CAM Dysfunction and Unexpected Accumulation of PSA-NCAM in Brain of Adult-Onset Autosomal-Dominant Leukodystrophy

Brain Pathology — Wed, 24 Jun 2009 23:00:00 +0100

Previously, myelin from cerebral white matter (CWM) of two subjects of a family with orthochromatic adult-onset autosomal-dominant leukodystrophy (ADLD) was disclosed to exhibit defective large isoform of myelin-associated glycoprotein (L-MAG) and patchy distribution only in the elder subject. L-MAG and neural cell adhesion molecule (N-CAM) (N-CAM 180, 140, and 120) are structurally related and concur to myelin/axon interaction. In early developmental stages, in neurons and glia N-CAM is converted into polysialylated (PSA)-NCAM by two sialyltransferases sialyltransferase-X (STX) and polysialyltransferase-1 (PST). Notably, PSA-NCAM disrupts N-CAM adhesive properties and is nearly absent in the adult brain. Here, CWM extracts and myelin of the two subjects were searched for the expression pa...

Central Nervous System Primitive Neuroectodermal Tumors: A Clinicopathologic and Genetic Study of 33 Cases

Brain Pathology — Wed, 24 Jun 2009 23:00:00 +0100

Central nervous system (CNS) primitive neuroectodermal tumors (PNETs) include supratentorial, brain stem, and spinal cord tumors with medulloblastoma-like histopathology. The prognostic impact of various pathologic and genetic features has not been thoroughly investigated. After re-diagnosis of three infantile cases as atypical teratoid/rhabdoid tumor (AT/RT), 33 remaining CNS PNETs were retrieved for clinicopathologic and fluorescence in situ hybridization studies. Anaplastic and/or large cell features were seen in 18 of 33 (55%) examples and survival was decreased in these patients (P = 0.036). MYCN or MYCC gene amplifications were noted in about half, with a trend towards decreased survival (P = 0.112). Polysomies of chromosomes 2 and 8 were each individually associated with decreased s...

Association Between Lifetime Cigarette Smoking and Lewy Body Accumulation

Brain Pathology — Tue, 16 Jun 2009 04:00:00 +0100

Cigarette smoking has been associated repeatedly in observational studies with decreased risk of Parkinson's disease (PD), but its relationship to the risk of dementia or Alzheimer's disease (AD) is inconsistent. All of these studies have used clinical diagnoses of disease. We tested the hypothesis that lifetime cigarette use might be associated with reduced risk of neuropathologic changes of Lewy-related pathology (LRP) in multiple brain regions or with reduced risk of consensus neuropathologic changes of AD in a prospective community-based study of brain aging and dementia, the Adult Changes in Thought (ACT) study. We observed that heavy lifetime cigarette smoking (>50 pack years) was associated with significantly reduced relative risk (RR) for LRP, but not AD-type pathologic changes, af...

PET of Brain Prion Protein Amyloid in Gerstmann–Sträussler–Scheinker Disease

Brain Pathology — Mon, 08 Jun 2009 23:00:00 +0100

In vivo amyloid PET imaging was carried out on six symptomatic and asymptomatic carriers of PRNP mutations associated with the Gerstmann[ndash]Sträussler[ndash]Scheinker (GSS) disease, a rare familial neurodegenerative brain disorder demonstrating prion amyloid neuropathology, using 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([F-18]FDDNP). 2-Deoxy-2-[F-18]fluoro-d-glucose PET ([F-18]FDG) and magnetic resonance imaging (MRI) scans were also performed in each subject. Increased [F-18]FDDNP binding was detectable in cerebellum, neocortex and subcortical areas of all symptomatic gene carriers in close association with the experienced clinical symptoms. Parallel glucose metabolism ([F-18]FDG) reduction was observed in neocortex, basal ganglia and/or thalam...

NG2+/Olig2+ Cells Are the Major Cycle-Related Cell Population of the Adult Human Normal Brain

Brain Pathology — Thu, 28 May 2009 04:00:00 +0100

A persistent cycling cell population in the normal adult human brain is well established. Neural stem cells or neural progenitors have been identified in the subventricular zone and the dentate gyrus subgranular layer (SGL), two areas of persistent neurogenesis. Cycling cells in other human normal brain areas, however, remains to be established. Here, we determined the distribution and identity of these cells in the cortex, the white matter and the hippocampal formation of adult patients with and without chronic temporal lobe epilepsy using immunohistochemistry for the cell cycle markers Ki-67 (Mib-1) and minichromosome maintenance protein 2. Rare proliferative neuronal precursors expressing the neuronal antigen neuronal nuclei were restricted to the SGL. In contrast, the oligodendrocyte p...

Diffuse Leptomeningeal Glioneuronal Tumors: A New Entity?

Brain Pathology — Wed, 27 May 2009 04:00:00 +0100

The peculiar radiological and pathological findings of four pediatric cases admitted to the University Hospital of Padua between 1990 and 2007 are described. In all cases, the contrast-enhanced head and spine magnetic resonance images revealed thickened and abnormally enhancing subarachnoid spaces particularly at the level of basal cisterns and interhemispheric fissure. Furthermore, small cystic lesions scattered throughout the brain and mainly in the cerebellum were also visible. All patients were missing a well-defined intraparenchymal mass, although during the follow-up a small intramedullary lesion appeared within the cervical spine in two and subsequently in the frontal horn of the left lateral ventricle in one of those. All patients presented an indolent long-term follow-up. Histolog...

Differential Expression of Utrophin-A and -B Promoters in the Central Nervous System (CNS) of Normal and Dystrophic mdx Mice

Brain Pathology — Wed, 27 May 2009 04:00:00 +0100

Utrophin (Utrn) is the autosomal homolog of dystrophin, the Duchene Muscular Dystrophy (DMD) locus product and of therapeutic interest, as its overexpression can compensate dystrophin's absence. Utrn is transcribed by Utrn-A and -B promoters with mRNAs differing at their 5' ends. However, previous central nervous system (CNS) studies used C-terminal antibodies recognizing both isoforms. As this distinction may impact upregulation strategies, we generated Utrn-A and -B promoter-specific antibodies, Taqman Polymerase chain reaction (PCR)-based absolute copy number assays, and luciferase-reporter constructs to study CNS of normal and dystrophic mdx mice. Differential expression of Utrn-A and -B was noted in microdissected and capillary-enriched fractions. At the protein level, Utrn-B was pred...

Neuropathogenesis of Naturally Occurring Encephalitis Caused by Listeria monocytogenes in Ruminants

Brain Pathology — Thu, 21 May 2009 03:39:20 +0100

This study investigates the neuropathogenesis of listeric encephalitis in over 200 natural cases in cattle, sheep and goats by analyzing anatomical distribution, severity, bacterial load and temporal evolution of the lesions. Our results suggest that LM gains access to the brainstem of all three species via axonal migration not only along the trigeminal nerve, but also along other nerves. The ensuing encephalitis does not remain restricted to the brainstem. Rather, LM spreads further from the brainstem into rostral brain regions likely by intracerebral axonal migration. Significant differences in severity of the lesions and bacterial load were found between cattle and small ruminants, which may be caused by species-specific properties of antibacterial immune responses. As histopathological...

Mitotic Epitopes Are Incorporated into Age-dependent Neurofibrillary Tangles in Niemann–Pick Disease Type C

Brain Pathology — Wed, 20 May 2009 04:00:00 +0100

The mechanism underlying neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) and other neurodegenerative disorders remains elusive. Niemann[ndash]Pick disease type C (NPC) is a kind of genetic neurovisceral disorder in which the intracellular sequestration of cholesterol and other lipids in neurons, NFT formation and neuronal degeneration in brain are the neuropathology hallmarks. The age of onset and progression of the disease vary dramatically. We have analyzed the hippocampus from 17 NPC cases, aged from 7 months to 55 years, to depict the temporal characteristics of NFT formation. Unexpectedly, classic NFT was observed in about 4-year-old NPC brain, suggesting that NFT is not aging dependent, and that juvenile brain neurons satisfy the requirements for NFT formation. NFT in the ...

Fetal Hydrocephalus Caused by Cryptic Intraventricular Hemorrhage

Brain Pathology — Wed, 20 May 2009 04:00:00 +0100

Cryptic intracerebral hemorrhage as an etiological factor in fetal hydrocephalus has been postulated but not described at autopsy. Four fetuses with overt hydrocephalus diagnosed by in utero ultrasound examination were examined at autopsy at 19[ndash]22 weeks gestation. Although a hemorrhagic etiology was not evident on ultrasound, hemosiderin-containing macrophages and associated reactive changes were found to obstruct the otherwise well-formed cerebral aqueduct in all four. Coagulopathy due to thrombocytopenia was implicated in one case. Anomalies involving other parts of the body were identified in two cases, although a direct link to the hydrocephalus was not obvious. The abnormality was isolated in one case. In three cases, possible sites of hemorrhage in the ventricles were identifie...

Alterations of Zinc Transporter Proteins ZnT-1, ZnT-4 and ZnT-6 in Preclinical Alzheimer's Disease Brain

Brain Pathology — Sat, 18 Apr 2009 04:00:00 +0100

Our previous studies demonstrate alterations of zinc (Zn) transporter proteins ZnT-1, ZnT-4 and ZnT-6 in vulnerable brain regions of subjects with mild cognitive impairment (MCI), and early and late stage Alzheimer's disease (AD), suggesting disruptions of Zn homeostasis may play a role in the pathogenesis of AD. A preclinical stage of AD (PCAD) has been described in which subjects show no overt clinical manifestations of AD, but demonstrate significant AD pathology at autopsy. To determine if alterations of ZnT proteins occur in PCAD, we measured ZnT-1, ZnT-4 and ZnT-6 in the hippocampus/parahippocampal gyrus (HPG) and cerebellum (CER) of seven PCAD subjects and seven age-matched normal control (NC) subjects using Western blot analysis and immunohistochemistry. Our results show a signific...

Galectins and Gliomas

Brain Pathology — Thu, 09 Apr 2009 04:00:00 +0100

Malignant gliomas, especially glioblastomas, are associated with a dismal prognosis. Despite advances in diagnosis and treatment, glioblastoma patients still have a median survival expectancy of only 14 months. This poor prognosis can be at least partly explained by the fact that glioma cells diffusely infiltrate the brain parenchyma and exhibit decreased levels of apoptosis, and thus resistance to cytotoxic drugs. Galectins are a family of mammalian beta-galactoside-binding proteins characterized by a shared characteristic amino acid sequence. They are expressed differentially in normal vs. neoplastic tissues and are known to play important roles in several biological processes such as cell proliferation, death and migration. This review focuses on the role played by galectins, especially...

Pi3K-mTOR Signaling and AMOG Expression in Epilepsy-associated Glioneuronal Tumors

Brain Pathology — Thu, 09 Apr 2009 04:00:00 +0100

Gangliogliomas (GGs) and dysembryoplastic neuroepithelial tumors (DNTs) represent the most frequent type of neoplasms in pediatric medically intractable epilepsy. Several data suggest a pathogenetic relationship between GGs and other glioneuronal malformations of cortical development (MCDs), including activation of the Pi3K-mTOR signaling pathway. To further reveal these pathogenetic similarities, we investigated immunocytochemically the expression of phosphorylated (p)-PDK1, p-AKT, p-mTOR, p-4E-BP1, p-eIF4G, p-p70S6K and p-S6, the effector proteins ERM (ezrin/radixin/moesin) and the pathway regulator AMOG (adhesion molecule on glia) in both GGs and DNTs. Components of the Pi3K-mTOR signaling pathway were observed in a higher percentage of neuronal cells in GGs compared with control cortex...

Cerebellar Cortical Demyelination in the Murine Cuprizone Model

Brain Pathology — Thu, 09 Apr 2009 04:00:00 +0100

In multiple sclerosis, demyelination occurs beside the white-matter structures and in the cerebral and cerebellar cortex. We have previously shown that, in the cuprizone model, demyelination is present not only in the corpus callosum but also in the cerebral cortex. Here, we have performed a detailed analysis of the dynamics of de- and remyelination in the cerebellar cortex and white matter at nine timepoints in two cerebellar regions. To induce demyelination, C57BL/6 mice were fed with 0.2% cuprizone for 12 weeks followed by a recovery of 8 weeks. Both cortex and white-matter structures were significantly demyelinated after 12 weeks of cuprizone feeding. Remyelination occurred after withdrawal of cuprizone but was less prominent in the more caudal cerebellar region. Microglia infiltration...

TDP-43 Redistribution Is an Early Event in Sporadic Amyotrophic Lateral Sclerosis

Brain Pathology — Tue, 17 Mar 2009 04:00:00 +0100

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder consisting of progressive loss of motor neurons. TDP-43 has been identified as a component of ubiquitin-immunoreactive inclusions of motor neurons in ALS. We focused on the diffuse cytoplasmic TDP-43 immunoreactivity in ALS neurons, and quantitatively assessed it in comparison with skein/round TDP-43 and ubiquitin immunostaining in motor neurons of 30 sporadic ALS cases. The percentage of spinal motor neurons with cytoplasmic TDP-43 immunoreactivity was higher than that of ubiquitin-immunoreactive ones. The percentage of TDP-43-positive motor neurons was independent of neuron counts in anterior horns, while the percentage of ubiquitinated neurons was inversely correlated. Aiming to define the cytosolic localization of TDP-...

Neuroprotective Effects of Calmodulin Peptide 76-121aa: Disruption of Calmodulin Binding to Mutant Huntingtin

Brain Pathology — Wed, 11 Mar 2009 04:00:00 +0100

Huntington's disease (HD) is a neurodegenerative disease caused by mutant huntingtin protein containing an expanded polyglutamine tract, which may cause abnormal protein[ndash]protein interactions such as increased association with calmodulin (CaM). We previously demonstrated in HEK293 cells that a peptide containing amino acids 76-121 of CaM (CaM-peptide) interrupted the interaction between CaM and mutant huntingtin, reduced mutant huntingtin-induced cytotoxicity and reduced transglutaminase (TG)-modified mutant huntingtin. We now report that adeno-associated virus (AAV)-mediated expression of CaM-peptide in differentiated neuroblastoma SH-SY5Y cells, stably expressing an N-terminal fragment of huntingtin containing 148 glutamine repeats, significantly decreases the amount of TG-modified ...

Array-Based Genomics in Glioma Research

Brain Pathology — Fri, 06 Mar 2009 05:00:00 +0100

Over the years, several relevant biomarkers with a potential clinical interest have been identified in gliomas using various techniques, such as karyotype, microsatellite analysis, fluorescent in situ hybridization and chromosome comparative genomic hybridization. Despite their pivotal contribution to our understanding of gliomas biology, clinical application of these approaches has been limited by technological and clinical complexities. In contrast, genomic arrays (array-based comparative genomic hybridization and single nucleotide polymorphisms array) have emerged as promising technologies for clinical use in the setting of gliomas. Indeed, their feasibility and reliability have been rigorously assessed in gliomas and are discussed in this review. The well-known genomic biomarkers in gl...

Lithium Restores Neurogenesis in the Subventricular Zone of the Ts65Dn Mouse, a Model for Down Syndrome

Brain Pathology — Wed, 04 Mar 2009 05:00:00 +0100

Down syndrome (DS), a high-incidence genetic pathology, involves brain hypoplasia and mental retardation. Emerging evidence suggests that reduced neurogenesis may be a major determinant of brain underdevelopment in DS. To establish whether it is possible to improve neurogenesis in DS, Ts65Dn mice[mdash]the most widely used model for DS[mdash]and euploid mice were treated with control or lithium chow for 1 month. During the last 3 days animals received one daily injection of 5-bromo-2-deoxyuridine (BrdU)[mdash]a marker of proliferating cells[mdash]and were sacrificed 24 h after the last injection. Neurogenesis was examined in the subventricular zone (SVZ), a region that retains a neurogenic potential across life. We found that Ts65Dn mice had less ([minus]40%) BrdU+ cells than euploid mice,...

Mitochondrial ATP-Synthase in the Entorhinal Cortex Is a Target of Oxidative Stress at Stages I/II of Alzheimer's Disease Pathology

Brain Pathology — Sat, 28 Feb 2009 05:00:00 +0100

In this study, we investigate whether brain proteins are locally modified by oxidative stress at the first stages of AD-related pathology when morphological lesions are restricted to the entorhinal and transentorhinal cortices of neurofibrillary pathology (stages I/II of Braak). Using a proteomic approach, we show that the [alpha] subunit of the mitochondrial adenosine triphosphate (ATP)-synthase is distinctly lipoxidized in the entorhinal cortex at Braak stages I/II compared with age-matched controls. In addition, ATP-synthase activity is significantly lower in Braak stages I/II than age-matched control, while electron transport chain, expressed by the mitochondrial complex I activity, remains not affected. This is the first study showing oxidative damage in the first stage, and clinicall...

Morpho-Physiologic Characteristics of Dorsal Subicular Network in Mice after Pilocarpine-Induced Status Epilepticus

Brain Pathology — Fri, 27 Feb 2009 05:00:00 +0100

The goal of this study was to examine the morpho-physiologic changes in the dorsal subiculum network in the mouse model of temporal lobe epilepsy using extracellular recording, juxtacellular and immunofluorescence double labeling, and anterograde tracing methods. A significant loss of total dorsal subicular neurons, particularly calbindin, parvalbumin (PV) and immunopositive interneurons, was found at 2 months after pilocarpine-induced status epilepticus (SE). However, the sprouting of axons from lateral entorhinal cortex (LEnt) was observed to contact with surviving subicular neurons. These neurons had two predominant discharge patterns: bursting and fast irregular discharges. The bursting neurons were mainly pyramidal cells, and their dendritic spine density and bursting discharge rates ...

Lesion Profiling at Primary Isolation in RIII Mice Is Insufficient in Distinguishing BSE from Classical Scrapie

Brain Pathology — Thu, 26 Feb 2009 05:00:00 +0100

Primary isolation of bovine spongiform encephalopathy (BSE) in RIII mice generates a lesion profile believed to be reproducible and distinct from that produced by classical scrapie. This profile, which is characterized by peaks at gray matter areas 1, 4 and 7 (dorsal medulla, hypothalamus and septal nuclei), is used to diagnose BSE on primary isolation. The aim of this study was to investigate whether the BSE agent could be present in sheep diagnosed with classical scrapie, using lesion profiles in RIII mice as a discriminatory method. Sixty-two positive scrapie field cases were collected from individual farms between 1996 and 1999 and bioassayed in RIII mice. Fifty-five of these isolates transmitted successfully to at least one mouse. Of the 31 that produced adequate data to allow lesion ...

Global Expression Profiling in Epileptogenesis: Does It Add to the Confusion?

Brain Pathology — Thu, 26 Feb 2009 05:00:00 +0100

Since the inception of global gene expression profiling platforms in the mid-1990s, there has been a significant increase in publications of differentially expressed genes in the process of epileptogenesis. In particular for mesial temporal lobe epilepsy, the presence of a latency period between the first manifestation of seizures to chronic epilepsy provides the opportunity for therapeutic interventions at the molecular biology level. Using global expression profiling techniques, approximately 2000 genes have been published demonstrating differential expression in mesial temporal epilepsy. The majority of these changes, however, are specific to laboratory or experimental conditions with only 53 genes demonstrating changes in more than two publications. To this end, we review the current s...

A2B5 Cells from Human Glioblastoma have Cancer Stem Cell Properties

Brain Pathology — Sun, 22 Feb 2009 05:00:00 +0100

Glioblastomas, like other cancers, harbor small cell populations with the capability of sustaining tumor formation. These cells are referred to as cancer stem cells. We isolated cells expressing the surface marker A2B5 from three human glioblastomas (GBM) and showed that after grafting into nude mice, they generated dense and highly infiltrative tumors. Then, we extensively studied A2B5+ cells isolated from 11 human GBM. These cells display neurosphere-like, self-renewal, asymmetrical cell division properties and have multipotency capability. Stereotactic xenografts of dissociated A2B5+-derived secondary spheres revealed that as few as 1000 cells produced a tumor. Moreover, flow cytometry characterization of A2B5+-derived spheres revealed three distinct populations of cells: A2B5+/CD133+, ...

Reduced Activity of CD13/Aminopeptidase N (APN) in Aggressive Meningiomas Is Associated with Increased Levels of SPARC

Brain Pathology — Fri, 20 Feb 2009 05:00:00 +0100

In this study, we examined the expression and function of the membrane alanyl-aminopeptidase [mAAP, aminopeptidase N (APN), CD13, EC3.4.11.2] zinc-dependent ectopeptidase in meningiomas and meningioma cell lines, based on its prior association with tumor invasion in colorectal and renal carcinomas. We found a significant reduction of APNmRNA and protein expression, as well as enzymatic activity, in high-grade meningiomas. While meningioma tumor cell proliferation was not affected by either pharmacologic APN inhibition or siRNA-mediated APN silencing, APN pharmacologic and siRNA knockdown significantly reduced meningioma cell invasion in vitro. Next, we employed pathway-specific cDNA microarray analyses to identify extracellular matrix and adhesion molecules regulated by APN, and found that...

Claudin 6 Is a Positive Marker for Atypical Teratoid/Rhabdoid Tumors

Brain Pathology — Wed, 11 Feb 2009 05:00:00 +0100

Atypical teratoid/rhabdoid tumors (AT/RTs) are highly aggressive pediatric brain tumors characterized by the presence of rhabdoid cells and negative immunostaining for INI1 (BAF47). Histogenesis is unknown and diagnosis can be challenging because of their extreme morphological and immunophenotypic heterogeneity. Currently no signature markers other than INI1 loss have been identified. To search for possible candidate proteins of interest in AT/RTs, Affymetrix GeneChip® microarrays were utilized to investigate nine AT/RTs vs. 124 other tumor samples. The most distinctive gene identified was claudin 6 (CLDN6), a key component of tight junctions. CLDN6 showed moderate or higher mRNA expression in eight of nine AT/RTs, with little to no expression in 114 of 115 other tumors. Average expressio...

Computer- and Internet-Based Tools for Neuropathology in the 21st Century

Brain Pathology — Wed, 04 Feb 2009 04:27:07 +0100

(Source: Brain Pathology)

Modified C-Reactive Protein Is Expressed by Stroke Neovessels and Is a Potent Activator of Angiogenesis In Vitro

Brain Pathology — Thu, 22 Jan 2009 04:10:55 +0100

Native C-reactive protein (nCRP) is a pentameric oligo-protein and an acute phase reactant whose serum expression is increased in patients with inflammatory disease. We have identified by immunohistochemistry, significant expression of a tissue-binding insoluble modified version or monomeric form of CRP (mCRP) associated with angiogenic microvessels in peri-infarcted regions of patients studied with acute ischaemic stroke. mCRP, but not nCRP was expressed in the cytoplasm and nucleus of damaged neurons. mCRP co-localized with CD105, a marker of angiogenesis in regions of revascularisation. In vitro investigations demonstrated that mCRP was preferentially expressed in human brain microvessel endothelial cells following oxygen-glucose deprivation and mCRP (but not column purified nCRP) assoc...

Immunolocalization of Fascin, an Actin-Bundling Protein and Glial Fibrillary Acidic Protein in Human Astrocytoma Cells

Brain Pathology — Thu, 15 Jan 2009 05:00:00 +0100

In this report, we investigate fascin in astrocytomas. We show that fascin is expressed in astrocytes and in a panel of human astrocytoma cell lines. Immunofluorescence analysis demonstrates that fascin and the intermediate filament protein, glial fibrillary acidic protein (GFAP), are both expressed in the perinuclear region and within cytoplasmic processes of astrocytes and astrocytoma cells. Amino acid residues within the NH2 terminus of GFAP can undergo phosphorylation; these modifications regulate intermediate filament disassembly and occur during cytokinesis. We show that fascin and specific phosphorylated species of GFAP colocalize within dividing cells. Finally, we demonstrate that fascin co-immunoprecipitates with GFAP and that immunocomplex formation is preferential for GFAP phosp...

Reduction of Cerebral Oxidative Stress Following Environmental Enrichment in Mice with Alzheimer-Like Pathology

Brain Pathology — Thu, 08 Jan 2009 05:00:00 +0100

This study identifies a thus far undescribed antagonizing effect of environmental stimulation on Alzheimer's disease-related oxidative damage. (Source: Brain Pathology)

Analysis of the Repressor Element-1 Silencing Transcription Factor/Neuron-Restrictive Silencer Factor Occupancy of Non-Neuronal Genes in Peripheral Lymphocytes from Patients with Huntington's Disease

Brain Pathology — Wed, 07 Jan 2009 04:00:55 +0100

We have previously demonstrated that the transcription of neuronal repressor element-1/neuron-restrictive silencer element (RE1/NRSE)-regulated genes is reduced in the brain of subjects with Huntington's disease (HD) as a result of increased binding of the repressor element-1 silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) to its RE1/NRSE targets. As specific non-neuronal REST/NRSF-regulated genes have been identified in the human genome, we exploited the possibility that the binding of REST/NRSF to its target RE1/NRSE sites may also be altered in the peripheral tissues of HD patients. Our results show that REST/NRSF occupancy is increased in lymphocytes from HD subjects, thus indicating for the first time that the activity of the RE1/NRSE sites is dysfunction...

Spinal Cord Neuronal Pathology in Multiple Sclerosis

Brain Pathology — Sun, 21 Dec 2008 05:00:00 +0100

The objective of this study was to assess neuronal pathology in the spinal cord in multiple sclerosis (MS), both within myelinated and demyelinated tissue. Autopsy material was obtained from 38 MS cases and 21 controls. Transverse sections were taken from three spinal cord levels and stained using Luxol Fast Blue/Cresyl Violet and myelin protein immunohistochemistry. Measurements of neuronal number and size were made for all neurons within the anterior horns of the gray matter. Neurons were classified as motoneurons or interneurons according to size criteria. In comparison with controls, both motoneuron and interneuron number were reduced in MS cases at the upper cervical (interneuron P = 0.0549; motoneuron P = 0.0073) and upper thoracic (interneuron P = 0.0507; motoneuron P = 0.0144), but...

Ependymoblastoma: Dear, Damned, Distracting Diagnosis, Farewell!*

Brain Pathology — Sat, 20 Dec 2008 04:43:37 +0100

Ependymoblastoma is a diagnostic label that has been applied to a variety of rare central nervous system (CNS) tumors over the last eight decades. Consequently, there is uncertainty about whether such an entity exists and what its characteristic features might be. The current study, based on 14 cases from our institutional archives and identified by the search terms "ependymoblastoma,""ependymoblastomatous,""ependymoblastic" or "PNET with ependymal differentiation," aimed to test the hypothesis that the ependymoblastoma is a distinct and recognizable entity. Ependymoblastic rosettes are a key diagnostic feature and were present in 11/14 (79%) tumors, eight (73%) of which were embryonal tumors with abundant areas of neuropil-like differentiation. Three other cases showed rare ependymoblasti...

Expression Sites of Colligin 2 in Glioma Blood Vessels

Brain Pathology — Sun, 07 Dec 2008 04:14:55 +0100

In a previous study using state-of-the-art proteomic techniques, we identified colligin 2 (HSP47) as a glioma blood vessel-specific protein. In the present study we precisely localized the expression of colligin 2 in the blood vessels of diffusely infiltrating gliomas and relate the expression to the distinct cellular components of the vessels by using multiple immunolabeling and confocal microscopy. We grouped the glioma blood vessels into morphological categories ranging from normal looking capillaries to vessels with hypertrophic and sclerotic changes. The expression patterns of various markers of endothelial and pericytic differentiation were correlated with the position of the cells in the vessels and the expression of colligin 2. We found that colligin 2 is expressed in all categorie...

Autophagy and Cell Death of Purkinje Cells Overexpressing Doppel in Ngsk Prnp-deficient Mice

Brain Pathology — Tue, 25 Nov 2008 04:29:39 +0100

In this study, Western blotting and immunohistofluorescence show that both before and during significant PC loss, the scrapie-responsive gene 1 (Scrg1)[mdash]potentially associated with autophagy[mdash]and the autophagic markers LC3B and p62 increased in the NP0/0 PCs whereas RT-PCR shows stable mRNA expression, suggesting that the degradation of autophagic products is impaired in NP0/0 PCs. At the ultrastructural level, autophagic-like profiles accumulated in somatodendritic and axonal compartments of NP0/0, but not wild-type PCs. The most robust autophagy was observed in NP0/0 PC axon compartments in the deep cerebellar nuclei suggesting that it is initiated in these axons. Our previous and present data indicate that Dpl triggers autophagy and apoptosis in NP0/0 PCs. As observed in amylo...

Modeling the Association between 43 Different Clinical and Pathological Variables and the Severity of Cognitive Impairment in a Large Autopsy Cohort of Elderly Persons

Brain Pathology — Thu, 20 Nov 2008 05:00:00 +0100

We evaluated the association between mini-mental status examination (MMSE) scores proximal to death and the values of 43 different clinical and pathological parameters. Studies were performed using data from 334 elderly, longitudinally evaluated research subjects who had undergone autopsy and satisfied inclusion criteria from an initial study group of 501. Interindividual variance in MMSE scores was used as a surrogate for the severity of cognitive impairment linked to aging (CILA). A statistical linear regression-based model provided a framework for assessing the parameters with significant, direct impact on CILA severity. Strong association between CILA and Alzheimer's disease (AD) pathology, especially isocortical neurofibrillary tangles, was evident. The pattern of association between ...

Molecular Changes in White Matter Adjacent to an Active Demyelinating Lesion in Early Multiple Sclerosis

Brain Pathology — Sat, 01 Nov 2008 04:00:00 +0100

A stereotactic biopsy of a 17-year-old woman revealed an active inflammatory demyelinating lesion compatible with pattern III multiple sclerosis (MS) according to Lucchinetti et al. The biopsy included a white matter region distant from the active inflammatory demyelinating lesion with abnormal MRI signal, lacking histopathological signs of demyelination and/or oligodendrocyte apoptosis. Expression analysis of this area revealed a strong up-regulation of neuronal nitric oxide synthase (nNOS). Furthermore, detection of nitrotyrosine provided evidence for reactive nitrogen species (RNS)-mediated damage to oligodendrocytes. Concomitantly, genes involved in neuroprotection against oxidative stress such as heme oxygenase 1 were up-regulated. Even though a single case report, this study shows ea...

Interferon-Related Transcriptome Alterations in the Cerebrospinal Fluid Cells of Aicardi-Goutières Patients†

Brain Pathology — Fri, 24 Oct 2008 04:00:00 +0100

Aicardi[ndash]Goutières syndrome (AGS) is a rare interferon (IFN)-related encephalopathy with onset during the first year of life. AGS, is clinically characterized by progressive microcephaly, bilateral basal ganglia calcification, cerebral atrophy, cerebrospinal fluid (CSF), lymphocytosis, delayed development of psychomotor abilities with pyramidal[ndash]extrapyramidal syndrome and mimics congenital viral infections. Microarray analysis examining the expression of 18 880 human genes has been applied to the CSF lymphocytes of 20 AGS cases (age 4.5 ± 4.4 years, mean ± standard deviation) characterized by high IFN-alpha levels in CSF and 20 matched controls (age 4.4 ± 4.3 years, mean ± standard deviation). Gene-expression data reveal significant differences between AGS cases and control...

Duplication of 7q34 in Pediatric Low-Grade Astrocytomas Detected by High-Density Single-Nucleotide Polymorphism-Based Genotype Arrays Results in a Novel BRAF Fusion Gene

Brain Pathology — Wed, 22 Oct 2008 04:00:00 +0100

In the present study, DNA from 28 pediatric low-grade astrocytomas was analyzed using Illumina HumanHap550K single-nucleotide polymorphism oligonucleotide arrays. A novel duplication in chromosome band 7q34 was identified in 17 of 22 juvenile pilocytic astrocytomas and three of six fibrillary astrocytomas. The 7q34 duplication spans 2.6 Mb of genomic sequence and contains approximately 20 genes, including two candidate tumor genes, HIPK2 and BRAF. There were no abnormalities in HIPK2, and analysis of two mutation hot-spots in BRAF revealed a V600E mutation in only one tumor without the duplication. Fluorescence in situ hybridization confirmed the 7q34 copy number change and was suggestive of a tandem duplication. Reverse transcription polymerase chain reaction-based sequencing revealed a f...

SJL Mice Exposed to Cuprizone Intoxication Reveal Strain and Gender Pattern Differences in Demyelination

Brain Pathology — Wed, 22 Oct 2008 04:00:00 +0100

The role of mouse strain and the influence of gender on demyelination were explored for the first time in SJL mice using the cuprizone intoxication model. We document here that SJL mice display a unique pattern of demyelination that did not follow the profile that is well-characterized in C57BL/6 mice. The SJL mice did not readily demyelinate at the midline within the corpus callosum but showed greater demyelination immediately lateral to midline. During continuous exposure to cuprizone, demyelination was not complete and appeared to plateau after week 7. Importantly, female mice were partially resistant to demyelination, whereas male mice were more severely demyelinated. Differences in the number of mature oligodendrocytes were consistent with the extent of demyelination; however, microgl...

Astrocytes are More Resistant to Focal Cerebral Ischemia Than Neurons and Die by a Delayed Necrosis

Brain Pathology — Fri, 10 Oct 2008 04:00:00 +0100

Several recent reports proposed that astrocyte death might precede neuronal demise after focal ischemia, contrary to the conventional view that astrocytes are more resistant to injury than neurons. Interestingly, there are findings supporting each of these opposing views. To clarify these controversies, we assessed astrocyte viability after 2-h middle cerebral artery occlusion in mice. In contrast to neighboring neurons, astrocytes were alive and contained glycogen across the ischemic area 6 h after reperfusion, and at the expanding outer border of the infarct at later time points. These glycogen-positive astrocytes had intact plasma membranes. Astrocytes lost plasmalemma integrity much later than neurons: 19 ± 22 (mean ± standard deviation), 58 ± 14 and 69 ± 3% of astrocytes in the pe...

Galectin-1 Is Implicated in the Protein Kinase C ε/Vimentin-Controlled Trafficking of Integrin-β1 in Glioblastoma Cells

Brain Pathology — Thu, 09 Oct 2008 04:00:00 +0100

Cell motility and resistance to apoptosis characterize glioblastoma (GBM) growth and malignancy. In our current work we report that galectin-1, a homodimeric adhesion molecule and carbohydrate-binding protein with affinity for [beta]-galactosides, is linked with cell surface expression of integrin [beta]1 and the process of integrin trafficking. Using immunofluorescence, depletion of galectin-1 through both stable knockdown and transient-targeted small interfering RNA (siRNA) treatment induces an intracellular accumulation of integrin-[beta]1 coincident with a diminution of integrin-[beta]1 at points of cellular adhesion at the cell membrane. Galectin-1 depletion does not alter the gene expression level of integrin-[beta]1. Transient galectin-1 depletion effectuates as well the perinuclear...

Development of the WHO Classification of Tumors of the Central Nervous System: A Historical Perspective

Brain Pathology — Thu, 04 Sep 2008 04:00:00 +0100

The classification of brain tumors has undergone numerous changes over the past half century. The World Health Organization has played a key role in the effort. Four versions of its Classification of Tumours of the Central Nervous System have been published. The present work chronicles their progress, placing emphasis on the historical context of the earliest effort. (Source: Brain Pathology)

Hippocampal Sclerosis: Progress Since Sommer

Brain Pathology — Sat, 30 Aug 2008 04:00:00 +0100

Hippocampal sclerosis (HS) continues to be the most common pathology identified in patients with refractory temporal lobe epilepsy undergoing surgery. Wilhelm Sommer described this characteristic pattern of neuronal loss over 120 years ago through his post-mortem studies on patients with epilepsy. Neuropathological post-mortem studies in the 20th century proceeded to contribute significantly to the understanding of this disease process, with regard to the varying patterns of HS and involvement of adjacent limbic structures. From studies of surgical temporal lobe specimens from the 1950s onwards it was recognized that an early cerebral injury could act as the precipitant for the sclerosis and epilepsy. Modern neuropathological studies have focused on aspects of neuronal injury, loss of spec...

Interphase Cytogenetics for 1p19q and t(1;19)(q10;p10) may Distinguish Prognostically Relevant Subgroups in Extraventricular Neurocytoma

Brain Pathology — Sun, 17 Aug 2008 04:00:00 +0100

Co-deletion of chromosome arms 1p and 19q, characteristic of oligodendroglial tumors, was recently found to be mediated by t(1;19)(q10;p10). To evaluate the prevalence of 1p19q co-deletion and t(1;19) in extraventricular neurocytomas (EVN), we studied tumors from 23 patients, including 13 females and 10 males (median age at diagnosis 34 years, range 2[ndash]76 years). Fluorescence in situ hybridization (FISH) studies were performed with probes targeting 1p36/1q25 and 19q13/19p13 to assess for 1p19q co-deletion, as well as chromosome 1 [alpha]-satellite and 19p12 to detect t(1;19)(q10;p10). FISH was successful in 21 (91%) cases and demonstrated 1p19q co-deletion in five cases (24%) or isolated 1p loss in two cases (10%). Evidence for t(1;19) was found in four (of five) cases with 1p19q co-d...

Dynamics of Trace Element Concentration During Development and Excitotoxic Cell Death in the Cerebellum of Lurcher Mutant Mice

Brain Pathology — Thu, 14 Aug 2008 04:00:00 +0100

Elevated concentrations of Zn, Cu and Fe, observed in biopsied or post-mortem tissue from diseased human brains, have often been considered as some of the major factors in the etiology of excitotoxic neuronal death but without any direct evidence for the causal role of metals. Although elevated metal concentrations that precede or coincide with the onset of neurodegeneration may provide such evidence, the dynamics of metal concentrations during excitotoxic cell death has never been established. Hence, we measured time-resolved Zn, Cu and Fe concentrations during the course of excitotoxic cell death in the Lurcher (Lc/+) mutant mouse with neutron activation analysis. In the Lc/+ cerebellum, Fe and Zn but not Cu concentrations were substantially lower than in normal cerebellum before the ons...

A Comparative Study of α-Dystroglycan Glycosylation in Dystroglycanopathies Suggests that the Hypoglycosylation of α-Dystroglycan Does Not Consistently Correlate with Clinical Severity

Brain Pathology — Sun, 10 Aug 2008 04:00:00 +0100

Hypoglycosylation of [alpha]-dystroglycan underpins a subgroup of muscular dystrophies ranging from congenital onset of weakness, severe brain malformations and death in the perinatal period to mild weakness in adulthood without brain involvement. Mutations in six genes have been identified in a proportion of patients. POMT1, POMT2 and POMGnT1 encode for glycosyltransferases involved in the mannosylation of [alpha]-dystroglycan but the function of fukutin, FKRP and LARGE is less clear. The pathological hallmark is reduced immunolabeling of skeletal muscle with antibodies recognizing glycosylated epitopes on [alpha]-dystroglycan. If the common pathway of these conditions is the hypoglycosyation of [alpha]-dystroglycan, one would expect a correlation between clinical severity and the extent ...

Glioblastoma with Adipocyte-Like Tumor Cell Differentiation—Histological and Molecular Features of a Rare Differentiation Pattern

Brain Pathology — Thu, 07 Aug 2008 04:00:00 +0100

We report on three adult patients with primary glioblastomas showing prominent adipocytic (lipomatous) differentiation, hence referred to as "glioblastomas with adipocyte-like tumor cell differentiation." Histologically, the tumors demonstrated typical features of glioblastoma but additionally contained areas consisting of glial fibrillary acidic protein (GFAP)-positive astrocytic tumor cells resembling adipocytes, that is, containing large intracellular lipid vacuoles. Comparative genomic hybridization (CGH) and focused molecular genetic analyses demonstrated gains of chromosomes 7, losses of chromosomes 9 and 10, as well as homozygous deletion of p14ARF in one of the tumors. The second tumor showed gains of chromosomes 3, 4, 8q and 12 as well as losses of chromosomes 10, 13, 15q, 19 and ...

Transglutaminases and Transglutaminase-Catalyzed Cross-Links Colocalize with the Pathological Lesions in Alzheimer's Disease Brain

Brain Pathology — Sat, 02 Aug 2008 04:00:00 +0100

Alzheimer's disease (AD) is characterized by pathological lesions, in particular senile plaques (SPs), cerebral amyloid angiopathy (CAA) and neurofibrillary tangles (NFTs), predominantly consisting of self-aggregated proteins amyloid beta (A[beta]) and tau, respectively. Transglutaminases (TGs) are inducible enzymes, capable of modifying conformational and/or structural properties of proteins by inducing molecular covalent cross-links. Both A[beta] and tau are substrates for TG cross-linking activity, which links TGs to the aggregation process of both proteins in AD brain. The aim of this study was to investigate the association of transglutaminase 1 (TG1), transglutaminase 2 (TG2) and TG-catalyzed cross-links with the pathological lesions of AD using immunohistochemistry. We observed immu...

Brain Extracellular Matrix in Neurodegeneration

Brain Pathology — Sat, 26 Jul 2008 04:00:00 +0100

The role of extracellular matrix (ECM) in neurological development, function and degeneration has evolved from a simplistic physical adhesion to a system of intricate cellular signaling. While most cells require ECM adhesion to survive, it is now clear that differentiated function is intimately dependent upon cellular interaction with the ECM. Therefore, it is not surprising that the ECM is increasingly found to be involved in the enigmatic process of neurodegeneration. Descriptive studies of human neurodegenerative disorders and experimental studies of animal models of neurodegeneration have begun to define potential mechanisms of ECM disruption that can lead to synaptic and neuronal loss. (Source: Brain Pathology)

Genetically Altering Aβ Distribution from the Brain to the Vasculature Ameliorates Tau Pathology

Brain Pathology — Fri, 25 Jul 2008 04:00:00 +0100

The inheritance of the [epsilon]4 allele of the apolipoprotein E (apoE) gene is the major genetic risk factor for developing late-onset Alzheimer disease. In transgenic mice overexpressing amyloid precursor protein (APP), replacing the endogenous mouse apoE gene with the human apolipoprotein E4 (apoE4) gene alters the distribution of amyloid-[beta] (A[beta]) deposits from the brain parenchyma to the vasculature. However, the effects of this distribution on the onset and progression of tau pathology remain to be established. To address this issue, we used a genetic approach to replace the endogenous apoE gene with the human apoE4 allele in the 3xTg-AD mice. We showed that changing A[beta] distribution from the parenchyma to the vasculature drastically reduces the tau pathology. The 3xTg-AD ...

Quantitation and Mapping of Cerebral Detergent-Insoluble Proteins in the Elderly

Brain Pathology — Thu, 24 Jul 2008 04:00:00 +0100

Accumulation of abnormal protein aggregates, detergent-insoluble (DI) proteins and amyloid in the brain are shared features of many neurodegenerative diseases. Previous studies correlating DI proteins and cognitive performance are limited. We addressed these limitations using two sets of autopsy brains, one selected from our Alzheimer's Disease Research Center and the other an unselected series from Adult Changes in Thought (ACT), a population-based study of brain aging. We observed concentrations of 11 proteins and 6 protein variants that can be grouped into three highly correlated clusters: amyloid (A)[beta], tau and alpha-synuclein ([alpha]-syn). While abnormal proteins from each cluster independently correlated with cognitive performance in ACT participants, only increased soluble A[be...

Chordoid Glioma: A Case Report and Molecular Characterization of Five Cases

Brain Pathology — Thu, 24 Jul 2008 04:00:00 +0100

We reported a case of chordoid glioma in a 41-year-old man with obstructive hydrocephalus. Histologically, the tumor consisted of polygonal epithelioid cells admixed with elongated cells in a myxoid stroma. A prominent lymphoplasmacytic infiltrate was present. The tumor cells expressed glial fibrillary acidic protein (GFAP), epithelial membrane antigen (EMA), vimentin, CD31, CD34, epidermal growth factor receptor (EGFR) and S100 but were negative for pankeratin and E-cadherin. The percentage of Ki67 positive cells was approximately 3%. Weak p53 immunoreactivity was seen in less than 10% of the cells. Array comparative genomic hybridization performed on this case, as well as on four other archived cases, showed losses at several loci. Fluorescence in situ hybridization (FISH) confirmed cons...

Melatonin Attenuates Hypoxia-Induced Ultrastructural Changes and Increased Vascular Permeability in the Developing Hippocampus

Brain Pathology — Wed, 16 Jul 2008 04:00:00 +0100

We examined the hippocampus of neonatal Wistar rats subjected to hypoxia for VEGF and NO production. The mRNA and protein expression of hypoxia inducible factor-1[alpha], endothelial, neuronal, inducible nitric oxide synthase and VEGF was found to be up-regulated significantly after the hypoxic exposure. Tissue VEGF concentration and NO production were also increased. By electron microscopy, swollen dendrites, vacuolated axons and hypertrophic astrocyte end feet associated with blood vessels were observed in hypoxic animals. In hypoxic rats, the passage of rhodamine isothiocyanate (RhIC) and horseradish peroxidase, administered intraperitoneally or intravenously, was observed through vascular walls. Furthermore, immunoglobulin G was localized in the neuropil and neurons. We suggest that in...

Gene Expression Profiles of Meningiomas are Associated with Tumor Cytogenetics and Patient Outcome

Brain Pathology — Tue, 15 Jul 2008 04:00:00 +0100

Cytogenetic analysis is a powerful tool for predicting recurrence in meningiomas, even among histologically benign/grade I tumors. Despite this, no study has been reported in which the impact of tumor cytogenetics on the gene expression profiles (GEP) has been analyzed in meningiomas. Here, we analyzed the GEP of 47 tumors and correlated them with the most clinical relevant cytogenetic subgroups of meningiomas, as confirmed through the analysis of 172 patients. Additionally three normal meningeal samples were also studied. Overall, our results show a clear association between the clinically relevant cytogenetic subgroups of meningiomas including diploid tumors (n = 18), isolated [minus]22/22q[minus] (n = 12), del(1p36) alone (n = 4) and complex karyotypes associated with del(1p36) and/or [...

MiR-92b and miR-9/9* Are Specifically Expressed in Brain Primary Tumors and Can Be Used to Differentiate Primary from Metastatic Brain Tumors

Brain Pathology — Sun, 13 Jul 2008 04:00:00 +0100

A recurring challenge for brain pathologists is to diagnose whether a brain malignancy is a primary tumor or a metastasis from some other tissue. The accurate diagnosis of brain malignancies is essential for selection of proper treatment. MicroRNAs are a class of small non-coding RNA species that regulate gene expression; many exhibit tissue-specific expression and are misregulated in cancer. Using microRNA expression profiling, we found that hsa-miR-92b and hsa-miR-9/hsa-miR-9* are over-expressed, specifically in brain primary tumors, as compared to primary tumors from other tissues and their metastases to the brain. By considering the expression of only these two microRNAs, it is possible to distinguish between primary and metastatic brain tumors with very high accuracy. These microRNAs ...

Monocyte Chemoattractant Protein-1 Plays a Dominant Role in the Chronic Inflammation Observed in Alzheimer's Disease

Brain Pathology — Thu, 10 Jul 2008 04:00:00 +0100

Chronic neuroinflammation correlates with cognitive decline and brain atrophy in Alzheimer's disease (AD), and cytokines and chemokines mediate the inflammatory response. However, quantitation of cytokines and chemokines in AD brain tissue has only been carried out for a small number of mediators with variable results. We simultaneously quantified 17 cytokines and chemokines in brain tissue extracts from controls (n = 10) and from patients with and without genetic forms of AD (n = 12). Group comparisons accounting for multiple testing revealed that monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6) and interleukin-8 (IL-8) were consistently upregulated in AD brain tissue. Immunohistochemistry for MCP-1, IL-6 and IL-8 confirmed this increase and determined localization of thes...

Spontaneous In Vitro Transformation of Adult Neural Precursors into Stem-Like Cancer Cells

Brain Pathology — Thu, 10 Jul 2008 04:00:00 +0100

Recent studies have found that cellular self-renewal capacity in brain cancer is heterogeneous, with only stem-like cells having this property. A link between adult stem cells and cancer stem cells remains, however, to be shown. Here, we describe the emergence of cancer stem-like cells from in vitro cultured brain stem cells. Adult rat subventricular zone (SVZ) stem cells transformed into tumorigenic cell lines after expansion in vitro. These cell lines maintained characteristic features of stem-like cells expressing Nestin, Musashi-1 and CD133, but continued to proliferate upon differentiation induction. Karyotyping detected multiple acquired chromosomal aberrations, and syngeneic transplantation into the brain of adult rats resulted in malignant tumor formation. Tumors revealed streak ne...

RASSF1A, BLU, NORE1A, PTEN and MGMT Expression and Promoter Methylation in Gliomas and Glioma Cell Lines and Evidence of Deregulated Expression of de novo DNMTs

Brain Pathology — Wed, 09 Jul 2008 04:00:00 +0100

Methylation of CpG islands in gene promoters can lead to gene silencing. Together with deletion or mutation, it may cause a loss of function of tumor suppressor genes. RASSF1A (3p21.3), NORE1A (1q32.1) and BLU (3p21.3) have been shown to be downregulated by methylation in cancer, and PTEN (10q23.3) and MGMT (10q26.1) are located in areas commonly deleted in astrocytomas. MGMT methylation predicts a better response and a longer overall survival in patients with glioblastomas treated with temozolomide. We analyzed 53 astrocytoma samples and 10 high-grade glioma cell lines. Gene expression was assessed by RT-PCR. Bisulfite sequencing, MSP and a melting curve analysis-based real-time PCR were performed to detect promoter methylation. Treatments with 5'-aza-2'-deoxicitidine were applied to rest...

Inter-Laboratory Assessment of PrPSc Typing in Creutzfeldt–Jakob Disease: A Western Blot Study within the NeuroPrion Consortium

Brain Pathology — Tue, 08 Jul 2008 04:00:00 +0100

Molecular typing is of considerable importance for the surveillance and epidemiology of human transmissible spongiform encephalopathies (TSEs). It relies on the detection of distinct protease-resistant prion protein (PrPSc) core fragments that differ in molecular mass and/or glycoform ratio. In this collaborative study, we tested the inter-laboratory agreement in TSE molecular typing. Sixteen characterized brain specimens from sporadic TSEs and variant Creutzfeldt-Jakob disease (vCJD) cases were distributed blindly to seven laboratories for molecular characterization by a defined protocol and classification. Agreement between laboratories in the classification of samples was excellent. In particular, there were no differences in the distinction between PrPSc type 1, type 2A, and type 2B wi...

Detergent-Insoluble EAAC1/EAAT3 Aberrantly Accumulates in Hippocampal Neurons of Alzheimer's Disease Patients

Brain Pathology — Tue, 08 Jul 2008 04:00:00 +0100

Disturbed glutamate homeostasis may contribute to the pathological processes involved in Alzheimer's disease (AD). Once glutamate is released from synapses or from other intracellular sources, it is rapidly cleared by glutamate transporters. EAAC1 (also called EAAT3 or SLC1A1) is the primary glutamate transporter in forebrain neurons. In addition to transporting glutamate, EAAC1 plays other roles in regulating GABA synthesis, reducing oxidative stress in neurons, and is important in supporting neuron viability. Currently, little is known about EAAC1 in AD. To address whether EAAC1 is disturbed in AD, immunohistochemistry was performed on tissue from hippocampus and frontal cortex of AD and normal control subjects matched for age and gender. While EAAC1 immunostaining in cortex appeared com...

FTY720 Rescue Therapy in the Dark Agouti Rat Model of Experimental Autoimmune Encephalomyelitis: Expression of Central Nervous System Genes and Reversal of Blood-Brain-Barrier Damage

Brain Pathology — Sat, 07 Jun 2008 18:47:19 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract FTY720 (fingolimod) is an oral sphingosine-1 phosphate (S1P) receptor modulator in phase III development for the treatment of multiple sclerosis. To further investigate its mode of action, we analyzed gene expression in the central nervous ... (Source: Brain Pathology)

Target Gene Activation of the Wnt Signaling Pathway in Nuclear β-Catenin Accumulating Cells of Adamantinomatous Craniopharyngiomas

Brain Pathology — Fri, 06 Jun 2008 18:46:09 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract Activating β-catenin (CTNNB1) mutations can be identified in the majority of adamantinomatous craniopharyngiomas (adaCP), suggesting an aberrant Wnt signaling pathway in this histopathologically peculiar tumor entity. However, there is no proven ... (Source: Brain Pathology)

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Brain Pathology — Mon, 02 Jun 2008 17:14:52 +0100

Brain Pathology, Volume 18, Issue 3, Page 464-467, July 2008. (Source: Brain Pathology)

A GBM by Any Other Name?

Brain Pathology — Mon, 02 Jun 2008 17:13:46 +0100

Brain Pathology, Volume 18, Issue 3, Page i-iii, July 2008. (Source: Brain Pathology)

The 2007 WHO Classification of Tumors of the Nervous System: Controversies in Surgical Neuropathology

Brain Pathology — Mon, 02 Jun 2008 17:13:11 +0100

Brain Pathology, Volume 18, Issue 3, Page 307-316, July 2008. Abstract Controversy surrounds the recent 2007 WHO Classification of Tumours of the Nervous System. A number of nosologic issues remain to be resolved, some a reflection of conceptual disagreement, others the result of inadequate data to permit their ... (Source: Brain Pathology)

An Antibody to the Aggregated Synthetic Prion Protein Peptide (PrP106–126) Selectively Recognizes Disease-Associated Prion Protein (PrPSc) from Human Brain Specimens

Brain Pathology — Tue, 27 May 2008 22:48:01 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract Human prion diseases are characterized by the conversion of the normal host cellular prion protein (PrPC) into an abnormal misfolded form [disease-associated prion protein (PrPSc)]. Antibodies that are capable of distinguishing between PrPC and ... (Source: Brain Pathology)

Activity-Regulated Cytoskeleton-Associated Protein in Rodent Brain is Down-Regulated by High Fat Diet in vivo and by 27-Hydroxycholesterol in vitro

Brain Pathology — Fri, 23 May 2008 10:23:03 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract Growing evidence strongly suggests that high fat diet (HFD) has an important role in some neurodegenerative disorders, including Alzheimer's disease (AD). To identify new cellular pathways linking hypercholesterolemia and neurodegeneration, we ... (Source: Brain Pathology)

Hypocretin and Melanin-Concentrating Hormone in Patients with Huntington Disease

Brain Pathology — Thu, 22 May 2008 18:12:40 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract To evaluate whether hypocretin-1 (orexin-A) and melanin-concentrating hormone (MCH) neurotransmission are affected in patients with Huntington disease (HD), we immunohistochemically stained hypocretin and MCH neurons and estimated their total ... (Source: Brain Pathology)

Substantial Archaeocortical Atrophy and Neuronal Loss in Multiple Sclerosis

Brain Pathology — Tue, 20 May 2008 18:13:33 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract Recent studies have revealed extensive neocortical pathology in multiple sclerosis (MS). The hippocampus is a unique archaeocortical structure understudied in MS. It plays a central role in episodic and anterograde memory—the most frequently ... (Source: Brain Pathology)

A Lack of Amyloid β Plaques Despite Persistent Accumulation of Amyloid β in Axons of Long-Term Survivors of Traumatic Brain Injury

Brain Pathology — Mon, 19 May 2008 18:11:06 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract Traumatic brain injury (TBI) is a risk factor for developing Alzheimer's disease (AD). Additionally, TBI induces AD-like amyloid β (Aβ) plaque pathology within days of injury potentially resulting from massive accumulation of amyloid precursor ... (Source: Brain Pathology)

EGR-1 is Regulated by N-Methyl-D-Aspartate-Receptor Stimulation and Associated with Patient Survival in Human High Grade Astrocytomas

Brain Pathology — Fri, 16 May 2008 18:10:19 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract Early growth response-1 (EGR-1) is considered a central regulator in tumor cell proliferation, migration and angiogenesis and a promising candidate for gene therapy in human astrocytomas. However, conflicting data have been reported suggesting ... (Source: Brain Pathology)

Cell Cycle Elongation Impairs Proliferation of Cerebellar Granule Cell Precursors in the Ts65Dn Mouse, an Animal Model for Down Syndrome

Brain Pathology — Wed, 14 May 2008 18:10:44 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract Mental retardation, the hallmark of Down syndrome (DS), has been attributed to the reduced number of neurons populating the DS brain. The Ts65Dn mouse model of DS displays several anomalies analogous to those in individuals with DS, including ... (Source: Brain Pathology)

Analysis of Gene Expression in Parkinson's Disease: Possible Involvement of Neurotrophic Support and Axon Guidance in Dopaminergic Cell Death

Brain Pathology — Wed, 07 May 2008 18:11:00 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra. We have studied alterations in gene expression in the substantia nigra, the caudate nucleus and ... (Source: Brain Pathology)

Common Polymorphisms in the MDM2 and TP53 Genes and the Relationship between TP53 Mutations and Patient Outcomes in Glioblastomas

Brain Pathology — Tue, 06 May 2008 18:11:33 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract MDM2 SNP309 is associated with younger age of tumor onset in patients with Li-Fraumeni syndrome, and TP53 codon 72 polymorphism decreases its apoptotic potential. Glioblastomas frequently show genetic alterations in the TP53 pathway. In the ... (Source: Brain Pathology)

Clinicopathological Outline of Dementia with Lewy Bodies Applying the Revised Criteria: The Hisayama Study

Brain Pathology — Tue, 06 May 2008 12:31:41 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract To explore the validity of the criteria for dementia with Lewy bodies (DLB) revised in 2005, we examined community based consecutive autopsy cases. 10.3% of the non-demented subjects and 31.2% of the demented subjects showed the Lewy body ... (Source: Brain Pathology)

Delineation of Early Changes in Cases with Progressive Supranuclear Palsy-Like Pathology. Astrocytes in Striatum are Primary Targets of Tau Phosphorylation and GFAP Oxidation

Brain Pathology — Tue, 06 May 2008 12:31:37 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract Progressive supranuclear palsy (PSP) is a complex tauopathy usually confirmed at post-mortem in advanced stages of the disease. Early PSP-like changes that may outline the course of the disease are not known. Since PSP is not rarely associated ... (Source: Brain Pathology)

Expression of Interleukin-16 in Sciatic Nerves, Spinal Roots and Spinal Cords of Experimental Autoimmune Neuritis Rats

Brain Pathology — Tue, 06 May 2008 12:31:33 +0100

In this study, we studied the spatiotemporal expression of interleukin-16 (IL-16) in the nervous system of EAN rats and pharmacological effects of ... (Source: Brain Pathology)

Malignant Gliomas with Primitive Neuroectodermal Tumor-like Components: A Clinicopathologic and Genetic Study of 53 Cases

Brain Pathology — Wed, 30 Apr 2008 18:22:00 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract Central nervous system neoplasms with combined features of malignant glioma and primitive neuroectodermal tumor (MG-PNET) are rare, poorly characterized, and pose diagnostic as well as treatment dilemmas. We studied 53 MG-PNETs in patients from ... (Source: Brain Pathology)

Altered Adhesive Structures and Their Relation to RhoGTPase Activation in Merlin-Deficient Schwannoma

Brain Pathology — Fri, 25 Apr 2008 18:17:31 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract Schwannomas are Schwann cell tumors of the nervous system that occur spontaneously and in patients with neurofibromatosis 2 (NF2) and lack the tumor suppressor merlin. Merlin is known to bind paxillin, beta1 integrin and focal adhesion kinase, ... (Source: Brain Pathology)

Transthyretin Accelerates Vascular Aβ Deposition in a Mouse Model of Alzheimer's Disease

Brain Pathology — Tue, 22 Apr 2008 18:10:56 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract Transthyretin (TTR) binds amyloid-β (Aβ) and prevents Aβ fibril formation in vitro. It was reported that the lack of neurodegeneration in a transgenic mouse model of Alzheimer's disease (AD) (Tg2576 mouse) was associated with increased TTR level ... (Source: Brain Pathology)

No Long-Term Effect Two Years after Intrauterine Exposure to Dexamethasone on Dentate Gyrus Volume, Neuronal Proliferation and Differentiation in Common Marmoset Monkeys

Brain Pathology — Fri, 18 Apr 2008 18:13:17 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract Glucocorticoids are prenatally administered to promote the maturation of the lungs. They, however, can affect neuronal proliferation and differentiation. In newborn marmoset monkeys, intrauterine hyperexposure to dexamethasone (DEX) resulted in ... (Source: Brain Pathology)

Immunohistochemical Analysis Supports a Role for INI1/SMARCB1 in Hereditary Forms of Schwannomas, but Not in Solitary, Sporadic Schwannomas

Brain Pathology — Wed, 16 Apr 2008 18:18:46 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract The INI1/SMARCB1 protein product (INI1), a component of a transcription complex, was recently implicated in the pathogenesis of schwannomas in two members of a single family with familial schwannomatosis. Tumors were found to have both ... (Source: Brain Pathology)

Tumor Necrosis Factor α is Reparative via TNFR1 in the Hippocampus and via TNFR2 in the Striatum after Virus-Induced Encephalitis

Brain Pathology — Wed, 16 Apr 2008 01:15:50 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract Differentiating between injurious and reparative factors facilitates appropriate therapeutic intervention. We evaluated the role of tumor necrosis factor α (TNFα) in parenchymal brain pathology resolution following virus-induced encephalitis ... (Source: Brain Pathology)

Heparan Sulfate Accumulation with Aβ Deposits in Alzheimer's Disease and Tg2576 Mice is Contributed by Glial Cells

Brain Pathology — Wed, 16 Apr 2008 01:15:28 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract Amyloid β-peptide (Aβ) plaques, one of the major neuropathological lesions in Alzheimer's disease (AD), can be broadly subdivided into two morphological categories: neuritic and diffuse. Heparan sulfate (HS) and HS proteoglycans (HSPGs) are ... (Source: Brain Pathology)

Adult Onset Leukodystrophy with Neuroaxonal Spheroids: Clinical, Neuroimaging and Neuropathologic Observations

Brain Pathology — Wed, 16 Apr 2008 01:15:15 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract Pigmented orthochromatic leukodystrophy and hereditary diffuse leukoencephalopathy with spheroids are two adult onset leukodystrophies with neuroaxonal spheroids presenting with prominent neurobehavioral, cognitive and motor symptoms. These are ... (Source: Brain Pathology)

Melatonin Attenuates Hypoxia-Induced Ultrastructural Changes and Increased Vascular Permeability in the Developing Hippocampus

Brain Pathology — Wed, 16 Apr 2008 01:14:43 +0100

We examined the hippocampus of ... (Source: Brain Pathology)

Antagonism of the Chemokine Receptors CXCR3 and CXCR4 Reduces the Pathology of Experimental Autoimmune Encephalomyelitis

Brain Pathology — Wed, 16 Apr 2008 01:14:28 +0100

In this study, we have investigated the role of CXCR3 and CXCR4 in the activation of T lymphocytes and their migration to the central nervous system (CNS) ... (Source: Brain Pathology)

Cerebral Amyloid Angiopathy and Parenchymal Amyloid Deposition in Transgenic Mice Expressing the Danish Mutant Form of Human BRI2

Brain Pathology — Thu, 10 Apr 2008 18:11:29 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract Familial Danish dementia (FDD) is an autosomal dominant neurodegenerative disease clinically characterized by the presence of cataracts, hearing impairment, cerebellar ataxia and dementia. Neuropathologically, FDD is characterized by the ... (Source: Brain Pathology)

Anti-O6-Methylguanine-Methyltransferase (MGMT) Immunohistochemistry in Glioblastoma Multiforme: Observer Variability and Lack of Association with Patient Survival Impede Its Use as Clinical Biomarker*

Brain Pathology — Wed, 09 Apr 2008 18:29:06 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract Silencing of O6-methylguanine-DNA methyltransferase (MGMT) protein expression because of MGMT gene promoter hypermethylation is considered to be associated with postoperative chemoradiotherapy benefits in glioblastoma multiforme (GBM) patients. ... (Source: Brain Pathology)

Strain-Associated Variations in Abnormal PrP Trafficking of Sheep Scrapie

Brain Pathology — Tue, 08 Apr 2008 23:35:01 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract Prion diseases are associated with the accumulation of an abnormal form of the host-coded prion protein (PrP). It is postulated that different tertiary or quaternary structures of infectious PrP provide the information necessary to code for ... (Source: Brain Pathology)

Genome-Wide Analysis of Subependymomas Shows Underlying Chromosomal Copy Number Changes Involving Chromosomes 6, 7, 8 and 14 in a Proportion of Cases

Brain Pathology — Tue, 08 Apr 2008 18:18:03 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract Subependymomas (SE) are slow-growing brain tumors that tend to occur within the ventricles of middle-aged and elderly adults. The World Health Organization classifies these tumors within the ependymoma group. Previous limited analysis of this ... (Source: Brain Pathology)

Three-Layered Structure Shared Between Lewy Bodies and Lewy Neurites—Three-Dimensional Reconstruction of Triple-Labeled Sections

Brain Pathology — Thu, 03 Apr 2008 18:18:19 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract Lewy bodies (LBs) and Lewy neurites (LNs) are the hallmarks of Parkinson's disease (PD). Although LBs and LNs, frequently coexistent, share some histological properties, their appearances are quite different under conventional two-dimensional ... (Source: Brain Pathology)

Expression of Integrin αvβ3 in Gliomas Correlates with Tumor Grade and Is not Restricted to Tumor Vasculature

Brain Pathology — Thu, 03 Apr 2008 11:26:32 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract In malignant gliomas, the integrin adhesion receptors seem to play a key role for invasive growth and angiogenesis. However, there is still a controversy about the expression and the distribution of αvβ3 integrin caused by malignancy. The aim of ... (Source: Brain Pathology)

Staging of Neurofibrillary Pathology in Alzheimer's Disease: A Study of the BrainNet Europe Consortium

Brain Pathology — Fri, 28 Mar 2008 18:21:00 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract It has been recognized that molecular classifications will form the basis for neuropathological diagnostic work in the future. Consequently, in order to reach a diagnosis of Alzheimer's disease (AD), the presence of hyperphosphorylated tau (HP-... (Source: Brain Pathology)

The Evolution of Our Understanding on Glioma

Brain Pathology — Fri, 28 Mar 2008 04:22:44 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract The description of neuroglia by Virchow in 1848 may be considered the starting point of our understanding of primary brain tumors. At the beginning of the 20th century, surgical removal of primary brain tumors became possible, and therefore, ... (Source: Brain Pathology)

Comprehensive Characterization of Genomic Aberrations in Gangliogliomas by CGH, Array-based CGH and Interphase FISH

Brain Pathology — Fri, 28 Mar 2008 04:22:32 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract Gangliogliomas are generally benign neuroepithelial tumors composed of dysplastic neuronal and neoplastic glial elements. We screened 61 gangliogliomas [World Health Organization (WHO) grade I] for genomic alterations by chromosomal and array-... (Source: Brain Pathology)

Neonatal Rat Hypoxia-Ischemia: Long-Term Rescue of Striatal Neurons and Motor Skills by Combined Antioxidant-Hypothermia Treatment

Brain Pathology — Fri, 28 Mar 2008 04:22:05 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract Perinatal hypoxia-ischemia can cause long-term neurological and behavioral disability. Recent multicenter clinical trials suggest that moderate hypothermia, within 6 h of birth, offers significant yet incomplete protection. We investigated the ... (Source: Brain Pathology)

Myonuclear Degeneration in LMNA Null Mice

Brain Pathology — Fri, 28 Mar 2008 04:21:57 +0100

We examined the myonuclei of LMNA null mice at the myotendinous junctions (MTJ), the site of longitudinal force transmission from contractile ... (Source: Brain Pathology)

Anaplastic Oligodendroglial Tumors: Refining the Correlation among Histopathology, 1p 19q Deletion and Clinical Outcome in Intergroup Radiation Therapy Oncology Group Trial 9402

Brain Pathology — Fri, 28 Mar 2008 04:21:52 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract Intergroup Radiation Therapy Oncology Group Trial 9402 study, a phase III trial of chemotherapy plus radiotherapy (PCV-plus-RT) vs. radiotherapy alone for pure and mixed anaplastic oligodendroglioma confirmed the prognostic significance of 1p ... (Source: Brain Pathology)

Pineocytoma and Pineal Parenchymal Tumors of Intermediate Differentiation Presenting Cytologic Pleomorphism: A Multicenter Study

Brain Pathology — Fri, 28 Mar 2008 04:21:44 +0100

We examined the clinicopathologic features in a ... (Source: Brain Pathology)

Reduced Glioma Growth Following Dexamethasone or Anti-Angiopoietin 2 Treatment

Brain Pathology — Fri, 28 Mar 2008 04:21:32 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract All patients with glioblastoma, the most aggressive and common form of brain cancer, develop cerebral edema. This complication is routinely treated with dexamethasone, a steroidal anti-inflammatory drug whose effects on brain tumors are not ... (Source: Brain Pathology)

Amoeboid Microglia in the Periventricular White Matter Induce Oligodendrocyte Damage through Expression of Proinflammatory Cytokines via MAP Kinase Signaling Pathway in Hypoxic Neonatal Rats

Brain Pathology — Fri, 28 Mar 2008 04:21:14 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract Hypoxic injury in the perinatal period results in periventricular white matter (PWM) lesions with axonal damage and oligodendroglial loss. It also alters macrophage function by perpetuating expression of inflammatory mediators. Relevant to this ... (Source: Brain Pathology)

Phenotypic and Genotypic Characterization of Orthotopic Human Glioma Models and Its Relevance for the Study of Anti-glioma Therapy

Brain Pathology — Fri, 28 Mar 2008 04:21:08 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract Most human gliomas are characterized by diffuse infiltrative growth in the brain parenchyma. Partly because of this characteristic growth pattern, gliomas are notorious for their poor response to current therapies. Many animal models for human ... (Source: Brain Pathology)

Adrenomedullin Expression is Up-regulated by Acute Hypobaric Hypoxia in the Cerebral Cortex of the Adult Rat

Brain Pathology — Fri, 28 Mar 2008 04:21:06 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract Hypobaric hypoxia can produce neuropsychological disorders such as insomnia, dizziness, memory deficiencies, headache and nausea. Here we report the changes in adrenomedullin (AM) expression observed in rats exposed to hypobaric hypoxia and ... (Source: Brain Pathology)

CD133 Expression and Cancer Stem Cells Predict Prognosis in High-grade Oligodendroglial Tumors

Brain Pathology — Fri, 28 Mar 2008 04:21:04 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract High-grade oligodendroglial tumors, that is, anaplastic oligodendroglial tumors and glioblastomas with oligodendroglial component, differ significantly in terms of prognosis and response to chemotherapy. Differentiation might be difficult ... (Source: Brain Pathology)

WT1 Expression Distinguishes Astrocytic Tumor Cells from Normal and Reactive Astrocytes

Brain Pathology — Fri, 28 Mar 2008 04:20:49 +0100

Brain Pathology, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Abstract Particularly in small brain biopsies, it might be difficult to distinguish reactive astrogliosis from low-grade or infiltration zones of high-grade astrocytomas. So far no immunohistochemical marker allows a reliable distinction. Recently, the ... (Source: Brain Pathology)

A 72-year-old woman with right frontal extra-axial mass

Brain Pathology — Wed, 19 Mar 2008 17:37:24 +0100

Brain Pathology, Volume 18, Issue 2, Page 279-282, April 2008. (Source: Brain Pathology)

Aβ-Degrading Enzymes in Alzheimer's Disease

Brain Pathology — Wed, 19 Mar 2008 17:36:05 +0100

Brain Pathology, Volume 18, Issue 2, Page 240-252, April 2008. Abstract In Alzheimer's disease (AD) Aβ accumulates because of imbalance between the production of Aβ and its removal from the brain. There is increasing evidence that in most sporadic forms of AD, the accumulation of Aβ is partly, if not in some cases ... (Source: Brain Pathology)

Perivascular Drainage of Amyloid-β Peptides from the Brain and Its Failure in Cerebral Amyloid Angiopathy and Alzheimer's Disease

Brain Pathology — Wed, 19 Mar 2008 17:35:22 +0100

Brain Pathology, Volume 18, Issue 2, Page 253-266, April 2008. Abstract Alzheimer's disease is the commonest dementia. One major characteristic of its pathology is accumulation of amyloid-β (Aβ) as insoluble deposits in brain parenchyma and in blood vessel walls [cerebral amyloid angiopathy (CAA)]. The distribution ... (Source: Brain Pathology)

51-year-old woman with double vision

Brain Pathology — Wed, 19 Mar 2008 17:34:40 +0100

Brain Pathology, Volume 18, Issue 2, Page 295-299, April 2008. (Source: Brain Pathology)

53-year-old man with rapid cognitive decline

Brain Pathology — Wed, 19 Mar 2008 17:34:40 +0100

Brain Pathology, Volume 18, Issue 2, Page 292-294, April 2008. (Source: Brain Pathology)

Society news

Brain Pathology — Wed, 19 Mar 2008 17:34:39 +0100

Brain Pathology, Volume 18, Issue 2, Page 303-306, April 2008. (Source: Brain Pathology)

A 61-year-old man with hyponatremia

Brain Pathology — Wed, 19 Mar 2008 17:34:38 +0100

Brain Pathology, Volume 18, Issue 2, Page 283-287, April 2008. (Source: Brain Pathology)

Foreword

Brain Pathology — Wed, 19 Mar 2008 17:34:22 +0100

Brain Pathology, Volume 18, Issue 2, Page 239, April 2008. (Source: Brain Pathology)

Dear reader

Brain Pathology — Wed, 19 Mar 2008 17:34:22 +0100

Brain Pathology, Volume 18, Issue 2, Page iii-iv, April 2008. (Source: Brain Pathology)

The Role of the Immune System in Clearance of Aβ from the Brain

Brain Pathology — Wed, 19 Mar 2008 17:33:31 +0100

Brain Pathology, Volume 18, Issue 2, Page 267-278, April 2008. Abstract In Alzheimer's disease (AD), there is abnormal accumulation of Aβ and tau proteins in the brain. There is an associated immunological response, but it is still unclear whether this is beneficial or harmful. Inflammation in AD, specifically in ... (Source: Brain Pathology)

56-year-old male with left-sided weakness

Brain Pathology — Wed, 19 Mar 2008 17:33:30 +0100

Brain Pathology, Volume 18, Issue 2, Page 300-302, April 2008. (Source: Brain Pathology)