High-Dose Vitamin C Prevents Secondary Brain Damage After Stroke via Epigenetic Reprogramming of Neuroprotective Genes
AbstractVitamin C has recently been identified as an epigenetic regulator by activating ten-eleven translocases (TETs), enzymes involved in generating DNA hydroxymethylcytosine (5hmC). Currently, we investigated whether high-dose vitamin C promotes neuroprotection through epigenetic modulation of 5hmC, if there are sex-specific differences in outcome, and the therapeutic potential of vitamin C in stroke-related comorbidities in adult mice. Post-stroke treatment with ascorbate (reduced form), but not dehydroascorbate (oxidized form), increased TET3 activity and 5hmC levels and reduced infarct following focal ischemia. Hydro...
Source: Translational Stroke Research - March 20, 2022 Category: Neurology Source Type: research
Changes in Cerebral Blood Flow and Diffusion-Weighted Imaging Lesions After Intracerebral Hemorrhage
AbstractIntracerebral hemorrhage (ICH) is a common subtype of stroke and places a great burden on the family and society with a high mortality and disability rate and a poor prognosis. Many findings from imaging and pathologic studies have suggested that cerebral ischemic lesions visualized on diffusion-weighted imaging (DWI) in patients with ICH are not rare and are generally considered to be associated with poor outcome, increased risk of recurrent (ischemic and hemorrhagic) stroke, cognitive impairment, and death. In this review, we describe the changes in cerebral blood flow (CBF) and DWI lesions after ICH and discuss ...
Source: Translational Stroke Research - March 19, 2022 Category: Neurology Source Type: research
Inflammasome-Regulated Pyroptotic Cell Death in Disruption of the Gut-Brain Axis After Stroke
We examined the time course of inflammasome protein expression in brain and intestinal lysate using western blot analysis at 1-, 3-, and 7-days post-injury for caspase-1, interleukin-1β, nod-like receptor protein 3 (NLRP3), and apoptosis speck-like protein containing a caspase-recruiting domain (ASC) and gasderm in-D (GSDMD) cleavage. In a separate group of mice, we processed brain tissue 24 and 72 h after thrombotic stroke for immunohistochemical analysis of neuronal and endothelial cell pyroptosis. We examined intestinal tissue for morphological changes and pyroptosis of macrophages. We performed behavior al tests and...
Source: Translational Stroke Research - March 19, 2022 Category: Neurology Source Type: research
Beneficial Effect of Sodium Nitrite on EEG Ischaemic Markers in Patients with Subarachnoid Haemorrhage
AbstractSubarachnoid haemorrhage (SAH) is associated with long-term disability, serious reduction in quality of life and significant mortality. Early brain injury (EBI) refers to the pathological changes in cerebral metabolism and blood flow that happen in the first few days after ictus and may lead on to delayed cerebral ischaemia (DCI). A disruption of the nitric oxide (NO) pathway is hypothesised as a key mechanism underlying EBI. A decrease in the alpha-delta power ratio (ADR) of the electroencephalogram has been related to cerebral ischaemia. In an experimental medicine study, we tested the hypothesis that intravenous...
Source: Translational Stroke Research - March 14, 2022 Category: Neurology Source Type: research
Delayed rFGF21 Administration Improves Cerebrovascular Remodeling and White Matter Repair After Focal Stroke in Diabetic Mice
This study aims to evaluate the potential effects of rFGF21 on cerebrovascular remodeling after T2DM stroke. Permanent distal middle cerebral artery occlusion was performed in heterozygous non-diabetic db/ + and homozygous diabetic db/db mice. Daily rFGF21 administration was initiated 1 week after stroke induction and maintained for up to 2 weeks thereafter. Multiple markers associated with post-stroke recovery, including angiogenesis, oligodendrogenesis, white matter integrity, and neurogenesi s, were assessed up to 3 weeks after stroke. Our results showed an impairment in post-stroke vascular remodeling under T2D...
Source: Translational Stroke Research - March 14, 2022 Category: Neurology Source Type: research
A Novel Plant-Produced Asialo-rhuEPO Protects Brain from Ischemic Damage Without Erythropoietic Action
AbstractMammalian cell-produced recombinant human erythropoietin (rhuEPOM) has been shown to be a multimodal neuroprotectant targeting an array of key pathological mechanisms in experimental stroke models. However, the rhuEPOM clinical trials were terminated due to increased risk of thrombosis, largely ascribed to its erythropoietic function. We recently took advantage of a plant-based expression system lacking sialylation capacity to produce asialo-rhuEPOP, a rhuEPO derivative without sialic acid residues. In the present study, we proved that asialo-rhuEPOP is non-erythropoietic by repeated intravenous injection (44 μg...
Source: Translational Stroke Research - March 14, 2022 Category: Neurology Source Type: research
Cerebral Microvascular Injury in Patients with Left Ventricular Assist Device: a Neuropathological Study
AbstractStrokes are common among patients with left ventricular devices (LVAD). We hypothesize that there is ongoing cerebral microvascular injury with LVAD support and aim to describe this among LVAD-implanted patients through post-mortem neuropathologic evaluation. We identified and reviewed medical records of LVAD patients who underwent brain autopsy between January 2006 and December 2019 at a tertiary center. Cerebral injury was defined as both gross and microscopic injuries within the intracranial space including cerebral infarct (CI), hypoxic-ischemic brain injury (HIBI), intracranial hemorrhage (ICH), and cerebral m...
Source: Translational Stroke Research - March 14, 2022 Category: Neurology Source Type: research
A Systematic Review of Inflammatory Cytokine Changes Following Aneurysmal Subarachnoid Hemorrhage in Animal Models and Humans
AbstractAneurysmal subarachnoid hemorrhage (aSAH) is a severe form of stroke that occurs following rupture of a cerebral aneurysm. Acute inflammation and secondary delayed inflammatory responses, both largely controlled by cytokines, work together to create high mortality and morbidity for this group. The trajectory and time course of cytokine change must be better understood in order to effectively manage unregulated inflammation and improve patient outcomes following aSAH. A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Three different se...
Source: Translational Stroke Research - March 9, 2022 Category: Neurology Source Type: research
Complement C3a Receptor (C3aR) Mediates Vascular Dysfunction, Hippocampal Pathology, and Cognitive Impairment in a Mouse Model of VCID
AbstractVascular contributions to cognitive impairment and dementia (VCID) secondary to chronic mild-moderate cerebral ischemia underlie a significant percentage of cases of dementia. We previously reported that either genetic deficiency of the complement C3a receptor (C3aR) or its pharmacological inhibition protects against cerebral ischemia in rodents, while others have implicated C3aR in the pathogenesis seen in rodent transgenic models of Alzheimer ’s disease. In the present study, we evaluated the role of complement C3a-C3aR signaling in the onset and progression of VCID. We utilized the bilateral common carotid art...
Source: Translational Stroke Research - March 8, 2022 Category: Neurology Source Type: research
Subarachnoid Hemorrhage Induces Sub-acute and Early Chronic Impairment in Learning and Memory in Mice
AbstractSubarachnoid hemorrhage (SAH) leads to significant long-term cognitive deficits, so-called the post-SAH syndrome. Existing neurological scales used to assess outcomes of SAH are focused on sensory-motor functions. To better evaluate short-term and chronic consequences of SAH, we explored and validated a battery of neurobehavioral tests to gauge the functional outcomes in mice after the circle of Willis perforation-induced SAH. The 18-point Garcia scale, applied up to 4 days, detected impairment only at 24-h time point and showed no significant difference between the Sham and SAH group. A decrease in locomotion wa...
Source: Translational Stroke Research - March 8, 2022 Category: Neurology Source Type: research
Plasma sICAM-1 as a Biomarker of Carotid Plaque Inflammation in Patients with a Recent Ischemic Stroke
Abstract18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) identifies carotid plaque inflammation and predicts stroke recurrence in patients with atherothrombotic stroke. The aim of the study was to identify plasma inflammatory biomarkers associated with plaque inflammation according to18F-FDG uptake. We conducted a prospective study of consecutive adult patients with a recent (< 7 days) anterior circulation ischemic stroke and at least one atherosclerotic plaque in the ipsilateral internal carotid artery. We included 64 patients, 57.8% of whom showed a carotid stenosis ≥ 50%. All patients under...
Source: Translational Stroke Research - March 2, 2022 Category: Neurology Source Type: research
Recycled Translation: Repurposing Drugs for Stroke
AbstractStroke, which continues to be a leading cause of death and long-term disability worldwide, has often been described as a clinical graveyard. While multiple small molecule therapeutics have undergone clinical trials in stroke, currently only one Food and Drug Administration (FDA)-approved medication exists for the treatment of stroke, the biological, recombinant tissue plasminogen activator (rt-PA). Repurposing of therapeutics which have previously gained FDA approval for alternative indications serves as a prospective option for stroke therapeutic translation. In contrast to de novo drug development, repurposing st...
Source: Translational Stroke Research - February 26, 2022 Category: Neurology Source Type: research
The Mfn1- βIIPKC Interaction Regulates Mitochondrial Dysfunction via Sirt3 Following Experimental Subarachnoid Hemorrhage
AbstractNeuronal injury following subarachnoid hemorrhage (SAH) has been shown to be associated with mitochondrial dysfunction and oxidative stress. βIIPKC, a subtype of protein kinase C (PKC), accumulates on the mitochondrial outer membrane and phosphorylates mitofusin 1 (Mfn1) at serine 86. Here, we investigated the role of Mfn1-βIIPKC interaction in brain damage and neurological function in both in vivo and in vitro experimental SAH models. The expression of βIIPKC protein and the interaction of Mfn1-βIIPKC were found to be increased after OxyHb treatment in primary cultured cortical neurons and were also observed i...
Source: Translational Stroke Research - February 22, 2022 Category: Neurology Source Type: research
Circle of Willis Morphology in Primary Intracerebral Hemorrhage
AbstractWe aimed to study the distribution of Circle of Willis (CoW) morphology and its association with intracerebral hemorrhage (ICH) etiology and cerebral small vessel disease (CSVD) burden. Patients with primary ICH who had brain MRIs were consecutively enrolled between March 2012 and January 2021. CoW morphology, CSVD features and the combined CSVD burden (including global CSVD burden, total hypertensive arteriopathy [HA] burden, and total cerebral amyloid angiopathy [CAA] burden) were assessed. CoW morphology included poor CoW (defined as CoW score 0 –2), incomplete CoW, and complete fetal-variant of the posterior ...
Source: Translational Stroke Research - February 19, 2022 Category: Neurology Source Type: research
Vascular Endothelial Growth Factor Augments the Tolerance Towards Cerebral Stroke by Enhancing Neurovascular Repair Mechanism
We report that the transgenic overexpression of VEGF (GOF) prior to the stroke stabilizes the vasculature and prevents blood–brain barrier disruption in young and aged animals after stroke. Whereas inhibition of signals for endogenous VEGF (LOF) prior to stroke results in bigger infarction with massive brain swelling and enhanced BBB permeability, furthermore, activating or blocking VEGF signaling after ischemic stroke onset had comparable effects on BBB repair an d cerebral edema. VEGF can function as an anti-permeability factor, and a VEGF-based therapy in the context of stroke prevention and recovery has an enormous p...
Source: Translational Stroke Research - February 17, 2022 Category: Neurology Source Type: research
