Blood DNA Methylation Analysis Reveals a Distinctive Epigenetic Signature of Vasospasm in Aneurysmal Subarachnoid Hemorrhage
AbstractVasospasm is a potentially preventable cause of poor prognosis in patients with aneurysmal subarachnoid hemorrhage (aSAH). Epigenetics might provide insight on its molecular mechanisms. We aimed to analyze the association between differential DNA methylation (DNAm) and development of vasospasm. We conducted an epigenome-wide association study in 282 patients with aSAH admitted to our hospital. DNAm was assessed with the EPIC Illumina chip (> 850 K CpG sites) in whole-blood samples collected at hospital admission. We identified differentially methylated positions (DMPs) at the CpG level using Cox regression m...
Source: Translational Stroke Research - April 23, 2024 Category: Neurology Source Type: research
Haptoglobin Attenuates Cerebrospinal Fluid Hemoglobin-Induced Neurological Deterioration in Sheep
Abstract Secondary brain injury (SBI) occurs with a lag of several days post-bleeding in patients with aneurysmal subarachnoid hemorrhage (aSAH) and is a strong contributor to mortality and long-term morbidity. aSAH-SBI coincides with cell-free hemoglobin (Hb) release into the cerebrospinal fluid. This temporal association and convincing pathophysiological concepts suggest that CSF-Hb could be a targetable trigger of SBI. However, sparse experimental evidence for Hb ’s neurotoxicity in vivo defines a significant research gap for clinical translation. We modeled the CSF-Hb exposure observed in aSAH patients in conscious s...
Source: Translational Stroke Research - April 23, 2024 Category: Neurology Source Type: research
Correction to: Inhibition of USP30 Promotes Mitophagy by Regulating Ubiquitination of MFN2 by Parkin to Attenuate Early Brain Injury After SAH
(Source: Translational Stroke Research)
Source: Translational Stroke Research - April 18, 2024 Category: Neurology Source Type: research
Glymphatic Impairment Associated with Neurocognitive Dysfunction in Moyamoya Disease
AbstractGlymphatic system alterations have been proved to be associated with cognitive dysfunction in neurodegenerative diseases. The glymphatic pathway has not been elucidated in moyamoya disease (MMD), which was recognized as a chronic hypoperfusion model for neurodegenerative disease. Here, we aimed to investigate the glymphatic system activity and its relation with neurocognition, and associated hallmarks in MMD. We prospectively recruited 30 MMD patients and 30 matched healthy controls (HC). Participants underwent MRI and neurocognition evaluation. The glymphatic function was assessed by diffusion tensor image analysi...
Source: Translational Stroke Research - April 17, 2024 Category: Neurology Source Type: research
Depth-Specific Hypoxic Responses to Spreading Depolarizations in Gyrencephalic Swine Cortex Unveiled by Photoacoustic Imaging
AbstractSpreading depolarizations (SDs) are a marker of brain injury and have a causative effect on ischemic lesion progression. The hemodynamic responses elicited by SDs are contingent upon the metabolic integrity of the affected tissue, with vasoconstrictive reactions leading to pronounced hypoxia often indicating poor outcomes. The stratification of hemodynamic responses within different cortical layers remains poorly characterized. This pilot study sought to elucidate the depth-specific hemodynamic changes in response to SDs within the gray matter of the gyrencephalic swine brain. Employing a potassium chloride –indu...
Source: Translational Stroke Research - April 16, 2024 Category: Neurology Source Type: research
Flow-Diverting Devices in the Treatment of Vertebral Artery Aneurysms: Insights into Efficacy and Safety from a Systematic Review and Meta-analysis
The objective of this study is to conduct a systematic review and meta-analysis aimed at evaluating the efficacy and safety of flow-diverting devices (FDs) treatment for intracranial vertebral artery (VA) aneurysms. We searched PubMed, Web of Science, OVID, and Embase for English-language studies up to February 2024 and included clinical studies on FD treatment of intracranial VA aneurysms. Sensitivity analysis evaluated outcome stability. Of 2273 articles, 29 studies involving 541 aneurysms treated with FDs were included. Based on the Methodological Index for Non-Randomized Studies (MINORS), six were high-quality and 23 m...
Source: Translational Stroke Research - April 11, 2024 Category: Neurology Source Type: research
Three Pillars of Recovery After Aneurysmal Subarachnoid Hemorrhage: A Narrative Review
AbstractAneurysmal subarachnoid hemorrhage (aSAH) is a devastating neurologic disease with high mortality and disability. There have been global improvements in survival, which has contributed to the prevalence of patients living with long-term sequelae related to this disease. The focus of active research has traditionally centered on acute treatment to reduce mortality, but now there is a great need to study the course of short- and long-term recovery in these patients. In this narrative review, we aim to describe the core pillars in the preservation of cerebral function, prevention of complications, the recent literatur...
Source: Translational Stroke Research - April 11, 2024 Category: Neurology Source Type: research
Association of Genetic Variants with Postoperative Donor Artery Development in Moyamoya Disease: RNF213 and Other Moyamoya Angiopathy-Related Gene Analysis
AbstractRobust postoperative bypass development is a characteristic of moyamoya disease (MMD); however, genetic factors mediating this phenomenon remain incompletely understood. Therefore, we aimed to elucidate the relationship between postoperative donor artery development and genetic variants. We retrospectively enrolled 63 patients (79 hemispheres) who underwent combined revascularization surgery. Postoperative development of the superficial temporal artery (STA), middle meningeal artery, and deep temporal artery (DTA) was assessed using the caliber-change ratio determined from magnetic resonance angiography measurement...
Source: Translational Stroke Research - April 9, 2024 Category: Neurology Source Type: research
Correction to: Gas6 Promotes Microglia Efferocytosis and Suppresses Inflammation Through Activating Axl/Rac1 Signaling in Subarachnoid Hemorrhage Mice
(Source: Translational Stroke Research)
Source: Translational Stroke Research - April 8, 2024 Category: Neurology Source Type: research
Evolving Therapeutic Landscape of Intracerebral Hemorrhage: Emerging Cutting-Edge Advancements in Surgical Robots, Regenerative Medicine, and Neurorehabilitation Techniques
AbstractIntracerebral hemorrhage (ICH) is the most serious form of stroke and has limited available therapeutic options. As knowledge on ICH rapidly develops, cutting-edge techniques in the fields of surgical robots, regenerative medicine, and neurorehabilitation may revolutionize ICH treatment. However, these new advances still must be translated into clinical practice. In this review, we examined several emerging therapeutic strategies and their major challenges in managing ICH, with a particular focus on innovative therapies involving robot-assisted minimally invasive surgery, stem cell transplantation, in situ neuronal...
Source: Translational Stroke Research - April 1, 2024 Category: Neurology Source Type: research
Development of a 3D Brain Model to Study Sex-Specific Neuroinflammation After Hemorrhagic Stroke
AbstractSubarachnoid hemorrhage (SAH) accounts for 5% of stroke, with women having a decreased inflammatory response compared to men; however, this mechanism has yet to be identified. One hurdle in SAH research is the lack of human brain models. Studies in murine models are helpful, but human models should be used in conjunction for improved translatability. These observations lead us to develop a 3D system to study the sex-specific microglial and neuroglial function in a novel in vitro human SAH model and compare it to our validated in vivo SAH model. Our lab has developed a 3D, membrane-based in vitro cell culture system...
Source: Translational Stroke Research - April 1, 2024 Category: Neurology Source Type: research
GPR39 Agonist TC-G 1008 Promoted Mitochondrial Biogenesis and Improved Antioxidative Capability via CREB/PGC-1 α Pathway Following Intracerebral Hemorrhage in Mice
AbstractMitochondrial dysfunction and excessive reactive oxygen species production due to impaired mitochondrial biogenesis have been proven to exacerbate secondary brain injury after intracerebral hemorrhage (ICH). The G-protein-coupled receptor 39 (GPR39) agonist TC-G 1008 has been shown to exert anti-oxidative stress effect in acute hypoxic brain injury. Herein, our study aimed to investigate the potential effects of TC-G 1008 on neuronal mitochondrial biogenesis and antioxidative stress in a mouse model of ICH and explore the underlying mechanisms. A total of 335 male C57/BL6 mice were used to establish an autologous b...
Source: Translational Stroke Research - March 15, 2024 Category: Neurology Source Type: research
Experimental Ischemic Stroke Induces Secondary Bihemispheric White Matter Degeneration and Long-Term Cognitive Impairment
In this study, we examined the progression of locomotor and cognitive function up to 4 months after inducing ischemic stroke by middle cerebral artery occlusion in young adult rats. Despite evident ongoing locomotor recovery, long-term cognitive and affective impairments persisted after ischemic stroke, as indicated by Morris water maze, elevated plus maze, and open field performance. At 4 months after stroke, multimodal MRI was conducted to assess white matter degeneration. T2-weighted MRI (T2WI) unveiled bilateral cerebroventricular enlargement after ischemic stroke. Fluid Attenuated Inversion Recovery MRI (FLAIR) reveal...
Source: Translational Stroke Research - March 15, 2024 Category: Neurology Source Type: research
Type I Interferon Signalling and Ischemic Stroke: Mechanisms and Therapeutic Potentials
AbstractType I interferon (IFN-I) signalling is intricately involved in the pathogenesis of multiple infectious diseases, autoimmune diseases, and neurological diseases. Acute ischemic stroke provokes overactivation of IFN-I signalling within the injured brain, particularly in microglia. Following cerebral ischemia, damage-associated molecular patterns (DAMPs) released from injured neural cells elicit marked proinflammatory episodes within minutes. Among these, self-nucleic acids, including nuclear DNA and mitochondrial DNA (mtDNA), have been recognized as a critical alarm signal to fan the flames of neuroinflammation, pre...
Source: Translational Stroke Research - March 11, 2024 Category: Neurology Source Type: research
Cerebral Perfusion Characteristics and Dynamic Brain Structural Changes in Stroke-Prone Renovascular Hypertensive Rats: A Preclinical Model for Cerebral Small Vessel Disease
AbstractHypertension is a leading cause of cerebral small vessel disease (CSVD) and vascular dementia in elderly individuals. We aimed to assess cerebral perfusion and dynamic changes in brain structure in stroke-prone renovascular hypertensive rats (RHRSPs) with different durations of hypertension and to investigate whether they have pathophysiological features similar to those of humans with CSVD. The RHRSP model was established using the two-kidney, two-clip (2k2c) method, and the Morris water maze (MWM) test, MRI, immunohistochemistry, and biochemical analysis were performed at multiple time points for up to six mont...
Source: Translational Stroke Research - March 5, 2024 Category: Neurology Source Type: research
