Perlecan Domain-V Enhances Neurogenic Brain Repair After Stroke in Mice
AbstractThe extracellular matrix fragment perlecan domain V is neuroprotective and functionally restorative following experimental stroke. As neurogenesis is an important component of chronic post-stroke repair, and previous studies have implicated perlecan in developmental neurogenesis, we hypothesized that domain V could have a broad therapeutic window by enhancing neurogenesis after stroke. We demonstrated that domain V is chronically increased in the brains of human stroke patients, suggesting that it is present during post-stroke neurogenic periods. Furthermore, perlecan deficient mice had significantly less neuroblas...
Source: Translational Stroke Research - April 7, 2020 Category: Neurology Source Type: research

A Reproducible New Model of Focal Ischemic Injury in the Marmoset Monkey: MRI and Behavioural Follow-Up
We describe a new method to induce focal brain damage targeting the motor cortex to study damage to the descending motor tracts in the non-human primate. Stereotaxic injection of malonate into the primary motor cortex produced a focal lesion in middle-aged marmosets (Callithrix jacchus). Assessment of sensorimotor function using a neurological scale and testing of forelimb dexterity and strength lasted a minimum of 12  weeks. Lesion evolution was followed by magnetic resonance imaging (MRI) at 24 h, 1 week, 4 and 12 weeks post-injury and before sacrifice for immunohistochemistry. Our model produced consistent les...
Source: Translational Stroke Research - April 6, 2020 Category: Neurology Source Type: research

Elevated miR-9 in Cerebrospinal Fluid Is Associated with Poor Functional Outcome After Subarachnoid Hemorrhage
This study evaluated microRNA (miRNA) changes in cerebrospinal fluid (CSF) and their association with the occurrence of delayed cerebral ischemia (DCI) and poor functional outcome after SAH. Forty-three selected miRNAs were measured in daily CSF samples from a discovery cohort of SAH patients admitted to Rigshospitalet, Copenhagen, Denmark, and compared with neurologically healthy patients. Findings were validated in CSF from a replication cohort of SAH patients admitted to Massachusetts General Hospital, Boston, Massachusetts. The CSF levels of miRNA over time were compared with the occurrence of DCI, and functional outco...
Source: Translational Stroke Research - April 4, 2020 Category: Neurology Source Type: research

Endogenous Regulatory T Cells Promote M2 Macrophage Phenotype in Diabetic Stroke as Visualized by Optical Imaging
AbstractRegulatory T cells (Tregs) play an immunosuppressive role in various diseases, yet their function remains controversial in stroke and obscure in diabetic stroke. In the present study, Tregs were found downregulated in the peripheral blood of type 2 diabetes mellitus (T2DM) stroke models and patients compared with controls. In ischemic stroke mice (both T2DM and wild type), endogenous Tregs boosted by CD28SA increased CD206+ M2 macrophage/microglia cells, decreased infarct volumes, and improved neurological recovery. Our results demonstrated the potential of boosting Tregs for treating T2DM stroke. Furthermore, we u...
Source: Translational Stroke Research - April 2, 2020 Category: Neurology Source Type: research

Knockdown of Arginyl-tRNA Synthetase Attenuates Ischemia-Induced Cerebral Cortex Injury in Rats After Middle Cerebral Artery Occlusion
AbstractSome researchers have previously shown that RNAi knockdown of arginyl-tRNA synthetase (ArgRS) before or after a hypoxic injury can rescue animals from death, based on the model organism,C. elegans. However, there has been no study on the application of arginyl-tRNA synthetase knockdown in treating mammalian ischemic stroke, and its potential mechanism and effect on ischemic brain damage are still unknown. Here, we focused on the Rars gene, which encodes an arginyl-tRNA synthetase, and examined the effects of Rars knockdown in a permanent middle cerebral artery occlusion model in rats. To achieve this aim, adult mal...
Source: Translational Stroke Research - March 27, 2020 Category: Neurology Source Type: research

Cell Death Pathways in Ischemic Stroke and Targeted Pharmacotherapy
AbstractIschemic stroke is one of the significant causes of morbidity and mortality, affecting millions of people across the globe. Cell injury in the infarct region is an inevitable consequence of focal cerebral ischemia. Subsequent reperfusion exacerbates the harmful effect and increases the infarct volume. These cellular injuries follow either a regulated pathway involving tightly structured signaling cascades and molecularly defined effector mechanisms or a non-regulated pathway, also known as accidental cell death, where the process is biologically uncontrolled. Classical cell death pathways are long established and w...
Source: Translational Stroke Research - March 26, 2020 Category: Neurology Source Type: research

Relation of Retinal Oxygen Measures to Electrophysiology and Survival Indicators after Permanent, Incomplete Ischemia in Rats
AbstractStudies in experimental ischemia models by permanent bilateral common carotid artery occlusion (BCCAO) have reported reduced retinal electrophysiological function, coupled with inner retinal degeneration and gliosis. In the current study, we tested the hypothesis that long-term (up to 14  days) BCCAO impairs oxygen delivery (DO2), which affects oxygen metabolism (MO2) and extraction fraction (OEF), electrophysiological function, morphology, and biochemical pathways. Twenty-one rats underwent BCCAO (N = 12) or sham surgery (N = 9) and were evaluated in separate groups after 3, 7, or ...
Source: Translational Stroke Research - March 24, 2020 Category: Neurology Source Type: research

CD133+Exosome Treatment Improves Cardiac Function after Stroke in Type 2 Diabetic Mice
In this study, we tested whether treatment with exosomes harvested from human umbilical cord blood derived CD133+ cells (CD133+Exo) improves cardiac function in type 2 diabetes mellitus (T2DM) stroke mice. Adult (3 –4 m), male, BKS.Cg-m+/+Leprdb/J (db/db, T2DM) and non-DM (db+) mice were randomized to sham or photothrombotic stroke groups. T2DM-stroke mice were treated with phosphate-buffered saline (PBS) or CD133+Exo (20  μg, i.v.) at 3 days after stroke. T2DM sham and T2DM+CD133+Exo treatment groups were included as controls. Echocardiography was performed, and mice were sacrificed at 28 days...
Source: Translational Stroke Research - March 20, 2020 Category: Neurology Source Type: research

Systematic Review and Meta-analysis of Methodological Quality in In Vivo Animal Studies of Subarachnoid Hemorrhage
AbstractAs a result of increased awareness of wide-spread methodological bias and obvious translational roadblocks in subarachnoid hemorrhage (SAH) research, various checklists and guidelines were developed over the past decades. This systematic review assesses the overall methodological quality of preclinical SAH research. An electronic search for preclinical studies on SAH revealed 3415 potential articles. Of these, 765 original research papers conducted in vivo in mice, rats, rabbits, cats, dogs, pigs, goats, and non-human primates with a focus on brain damage related to delayed cerebral vasospasm and early brain injury...
Source: Translational Stroke Research - March 15, 2020 Category: Neurology Source Type: research

Letter to Quantitative Angiographic Hemodynamic Evaluation After Revascularization Surgery for Moyamoya Disease
(Source: Translational Stroke Research)
Source: Translational Stroke Research - March 14, 2020 Category: Neurology Source Type: research

Lesion Size- and Location-Dependent Recruitment of Contralesional Thalamus and Motor Cortex Facilitates Recovery after Stroke in Mice
This study highlights the importance of in vivo fiber tracking and the role of the contralesional hemisphere during spontaneous functional improvement as a potential novel stroke biomarker and therapeutic targets. (Source: Translational Stroke Research)
Source: Translational Stroke Research - March 12, 2020 Category: Neurology Source Type: research

Proposed Definition of Experimental Secondary Ischemia for Mouse Subarachnoid Hemorrhage
AbstractInconsistency in outcome parameters for delayed cerebral ischemia (DCI) makes it difficult to compare results between mouse studies, in the same way inconsistency in outcome parameters in human studies has for long obstructed adequate comparison. The absence of an established definition may in part be responsible for the failed translational results. The present article proposes a standardized definition for DCI in experimental mouse models, which can be used as outcome measure in future animal studies. We used a consensus-building approach to propose a definition for “experimental secondary ischemia” (...
Source: Translational Stroke Research - March 9, 2020 Category: Neurology Source Type: research

Intracranial Pressure Monitoring-Aided Management Associated with Favorable Outcomes in Patients with Hypertension-Related Spontaneous Intracerebral Hemorrhage
AbstractTo investigate the effect of intracranial pressure (ICP) monitoring on the functional outcome of patients with hypertension-related spontaneous intracerebral hemorrhage (ICH). We included 196 patients with Glasgow Coma Scale (GCS) scores of 3 –12 in this observational study, of which 103 underwent ICP monitors. Binary and ordinal regression analyses were used to estimate the effect of ICP monitoring on the functional outcome. The rate of adverse events, blood pressure control, and length of hospitalization were compared between the two groups. ICP monitoring had a significant impact on the clinical outcome of...
Source: Translational Stroke Research - March 6, 2020 Category: Neurology Source Type: research

Methylprednisolone Reduces Persistent Post-ischemic Inflammation in a Rat Hypoxia-Ischemia Model of Perinatal Stroke
In conclusion, we demonstrated that administration of MPSS during the tertiary phase of perinatal stroke results in attenuation of the chroni c inflammatory response, leading to pathophysiological and functional recovery. This work validates the high clinical impact of MPSS to treat neonatal conditions linked to chronic inflammation. (Source: Translational Stroke Research)
Source: Translational Stroke Research - March 5, 2020 Category: Neurology Source Type: research

Early Progressive Changes in White Matter Integrity Are Associated with Stroke Recovery
AbstractInformation on microstructural white matter integrity has been shown to explain post-stroke recovery beyond clinical measures and focal brain damage. Especially, knowledge about early white matter changes might improve prediction of outcome. We investigated 42 acute reperfused ischemic stroke patients (mean age 66.5  years, 40% female, median admission NIHSS 9.5) with a symptomatic MRI-confirmed unilateral middle cerebral artery territory infarction 24–72 h post-stroke and after 3 months. All patients underwent neurological examination and brain MRI. Fifteen older healthy controls (mean age 57....
Source: Translational Stroke Research - March 4, 2020 Category: Neurology Source Type: research

PSD-93 Interacts with SynGAP and Promotes SynGAP Ubiquitination and Ischemic Brain Injury in Mice
In conclusion, we provide the first evidence that PSD-93 directly interacts with SynGAP and mediates its ubiquitination and degradation to aggravate ischemic brain damage. Tat-SynGAP (670–685aa) may be considered as a candidate for treatment of acute i schemic stroke. (Source: Translational Stroke Research)
Source: Translational Stroke Research - March 4, 2020 Category: Neurology Source Type: research

FTY720 Protects Against Ischemia –Reperfusion Injury by Preventing the Redistribution of Tight Junction Proteins and Decreases Inflammation in the Subacute Phase in an Experimental Stroke Model
AbstractInjury due to brain ischemia followed by reperfusion (I/R) may be an important therapeutic target in the era of thrombectomy. FTY720, a widely known sphingosine-1-phosphate receptor agonist, exerts various neuroprotective effects. The aim of this study was to examine the protective effect of FTY720 with respect to I/R injury, especially focusing on blood –brain barrier (BBB) protection and anti-inflammatory effects. Male rats were subjected to transient ischemia and administered vehicle or 0.5 or 1.5 mg/kg of FTY720 immediately before reperfusion. Positron emission tomography (PET) with [18F]DPA-714 was ...
Source: Translational Stroke Research - February 27, 2020 Category: Neurology Source Type: research

Multinucleated Giant Cells in Experimental Intracerebral Hemorrhage
In conclusion, MGCs represent a macrophage/microglia subtype with strong phagocytosis capacity. MGCs exhibited not only an M2 but also an M1 phenotype and appeared involved in hemoglobin degradation. Anti-CD47 antibody boosted the number of MGCs, which may contribute to enhance hematoma clearance. Understanding the exact roles of MGCs in ICH may reveal novel targets for ICH treatment. (Source: Translational Stroke Research)
Source: Translational Stroke Research - February 23, 2020 Category: Neurology Source Type: research

Modeling Mixed Vascular and Alzheimer ’s Dementia Using Focal Subcortical Ischemic Stroke in Human ApoE4-TR:5XFAD Transgenic Mice
AbstractSubcortical white matter ischemic lesions are increasingly recognized to have pathologic overlap in individuals with Alzheimer ’s disease (AD). The interaction of white matter ischemic lesions with amyloid pathology seen in AD is poorly characterized. We designed a novel mouse model of subcortical white matter ischemic stroke and AD that can inform our understanding of the cellular and molecular mechanisms of mixed vascul ar and AD dementia. Subcortical white matter ischemic stroke underlying forelimb motor cortex was induced by local stereotactic injection of an irreversible eNOS inhibitor. Subcortical white...
Source: Translational Stroke Research - February 21, 2020 Category: Neurology Source Type: research

Effects of Lifestyle Factors on Cognitive Resilience: Commentary on “What This Sunny, Religious Town in California Teaches Us About Living Longer”
(Source: Translational Stroke Research)
Source: Translational Stroke Research - February 15, 2020 Category: Neurology Source Type: research

Quantitative Angiographic Hemodynamic Evaluation After Revascularization Surgery for Moyamoya Disease
AbstractThe corresponding hemodynamic changes of the internal carotid artery (ICA) after the revascularization surgery for moyamoya disease (MMD) remain unclear. The aim of this study was to analyze the hemodynamic changes of the ipsilateral ICA after the combined direct and indirect extracranial-intracranial (EC-IC) bypass. MMD patients undergoing combined EC-IC bypass were retrospectively reviewed. The mean transit time (MTT) of ICA was evaluated by color-coding angiography before revascularization and at follow-up. The MTT defined as the blood transit time between the end of cervical portion (C1) and the C7 segment of I...
Source: Translational Stroke Research - February 13, 2020 Category: Neurology Source Type: research

Low Hemoglobin Levels at Admission Are Independently Associated with Cognitive Impairment after Ischemic Stroke: a Multicenter, Population-Based Study
AbstractData on the association between hemoglobin (Hb) levels and poststroke cognitive function are limited. We investigated the relationship between Hb concentrations at admission and poststroke cognitive function using a multicenter database. In total, 1081 patients were recruited from seven Chinese medical centers within 6  months after experiencing ischemic stroke. Cognitive status was evaluated with a series of brief neuropsychological tests. A subgroup of 439 patients from a single center was followed up for 4–6 years and was eventually reassessed with a cognitive test. The association between Hb and...
Source: Translational Stroke Research - February 10, 2020 Category: Neurology Source Type: research

FasL-PDPK1 Pathway Promotes the Cytotoxicity of CD8 + T Cells During Ischemic Stroke
AbstractCD8+ T cells are recognized as key players in exacerbation of ischemic stroke; however, the underlying mechanism in modulating the function of CD8+ T cells has not been completely elucidated. Here, we uncovered that FasL enhanced the cytotoxicity of CD8+ T cells to neurons after ischemic stroke. Inactivation of FasL specific on CD8+ T cells protected against brain damage and neuron loss. Proteomic analysis identified that PDPK1 functioned downstream of FasL signaling and inhibition of PDPK1 effectively reduced cytotoxicity of CD8+ T cells and improved ischemic neurological deficits. Taken together, these results hi...
Source: Translational Stroke Research - February 8, 2020 Category: Neurology Source Type: research

Neuroprotective Effects of Selective Inhibition of Histone Deacetylase 3 in Experimental Stroke
AbstractHistone deacetylase 3 (HDAC3) has been implicated as neurotoxic in several neurodegenerative conditions. However, the role of HDAC3 in ischemic stroke has not been thoroughly explored. We tested the hypothesis that selective inhibition of HDAC3 after stroke affords neuroprotection. Adult male Wistar rats (n = 8/group) were subjected to 2 h of middle cerebral artery occlusion (MCAO), and randomly selected animals were treated intraperitoneally twice with either vehicle (1% Tween 80) or a selective HDAC3 inhibitor (RGFP966, 10 mg/kg) at 2 and 24 h after MCAO. Long-term behavioral tests we...
Source: Translational Stroke Research - February 3, 2020 Category: Neurology Source Type: research

Silencing of Long Non-coding RNA GAS5 Suppresses Neuron Cell Apoptosis and Nerve Injury in Ischemic Stroke Through Inhibiting DNMT3B-Dependent MAP4K4 Methylation
AbstractIschemic stroke is associated with various physiological and pathological processes including neuronal apoptosis. Growth-arrest-specific transcript  5 (GAS5), a long non-coding RNA (lncRNA), has been recently reported to affect ischemic stroke-induced neuron apoptosis, while its mechanisms remain largely undefined. Through in silico analysis, GAS5 was predicted to interact with the promoter of MAP4K4. The aim of the present study was therefore to investigate the possible role of GAS5 in the progression of ischemic stroke via regulation of mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) methyla...
Source: Translational Stroke Research - January 29, 2020 Category: Neurology Source Type: research

Prognostic Value of Circulating Microvesicle Subpopulations in Ischemic Stroke and TIA
AbstractPlatelet microvesicles (PMV) have previously been found elevated in acute ischemic stroke (IS) and could be biomarkers for risk of recurrence. PMV surface antigens such as P-selectin and phosphatidylserine (PS) reflect platelet activation and procoagulance. Tissue factor-positive microvesicles (TF+MV) are considered procoagulant, in particular if co-expressing PS. We enumerated MV subpopulations with these surface antigens in a cohort of 211 patients with primarily non-cardioembolic IS or transient ischemic attack (TIA) and investigated their association with long-term outcome. MV concentrations were determined by ...
Source: Translational Stroke Research - January 25, 2020 Category: Neurology Source Type: research

ACOX3 Dysfunction as a Potential Cause of Recurrent Spontaneous Vasospasm of Internal Carotid Artery
AbstractRecurrent spontaneous vasospasm of the extracranial internal carotid artery (RSV-eICA) is a rarely recognized cause of ischemic stroke in young adults. However, its pathophysiology remains largely unknown. Through whole-exome sequencing of the ACOX3 gene of two dizygotic Korean twin brothers affected by RSV-eICA, we identified two compound heterozygous missense variants c.235  T >  G (p.F79 V) and c.665G >  A (p.G222E). In silico analysis indicated that both variants were classified as pathogenic. In vitro ACOX3 enzyme assay indicated practically no enzyme activity in bot...
Source: Translational Stroke Research - January 23, 2020 Category: Neurology Source Type: research

The Association Between Serum Apelin-13 and the Prognosis of Acute Ischemic Stroke
AbstractWhile a number of studies have reported an association between apelin-13 and ischemic stroke, few have verified its clinical effect. We investigated the prognostic value of serum apelin-13 levels in patients with acute ischemic stroke (AIS). We prospectively recruited 244 AIS patients within 24  h after stroke onset, and 167 healthy controls. We assessed the serum apelin-13 levels using ELISA, and the severity of AIS using the National Institutes of Health Stroke Scale (NIHSS). The primary outcomes included death or major disability (modified Rankin Scale score, 3–6) and major disabilit y (modified Ranki...
Source: Translational Stroke Research - January 22, 2020 Category: Neurology Source Type: research

The Involvement of Canonical Wnt Signaling in Memory Impairment Induced by Chronic Cerebral Hypoperfusion in Mice
AbstractChronic cerebral hypoperfusion (CCH) has been proposed to contribute to the progression of memory loss, which is the main symptom of vascular cognitive impairment (VCI). Accumulating evidence indicates that underlying pathophysiology, such as neurodegeneration, may lead to memory loss. However, the underlying molecular basis of memory loss in CCH remains unclear. Here, we investigated the roles of canonical Wnt signaling, which modulates hippocampal function, in a CCH model. CCH was induced by unilateral common carotid artery occlusion (UCCAO). Mice were randomly divided into a sham-operated group or one of three U...
Source: Translational Stroke Research - January 20, 2020 Category: Neurology Source Type: research

Wall Enhancement, Hemodynamics, and Morphology in Unruptured Intracranial Aneurysms with High Rupture Risk
AbstractThe purpose of this study is to investigate the relationship between morphology, hemodynamics, and aneurysm wall enhancement (AWE) on vessel wall MRI and their potential role in rupture of intracranial aneurysms. Fifty-seven patients (22 males and 35 females; mean age of 58.4) harboring 65 unruptured intracranial aneurysms were retrospectively recruited. Vessel wall MRI images were reviewed and differentiated as no (NAWE), partial (PAWE), and circumferential (CAWE) wall enhancement. Computational geometry and computational fluid dynamics were used to calculate morphological and hemodynamic parameters. The PHASES sc...
Source: Translational Stroke Research - January 20, 2020 Category: Neurology Source Type: research

Clot Analog Attenuation in Non-contrast CT Predicts Histology: an Experimental Study Using Machine Learning
AbstractExact histological clot composition remains unknown. The purpose of this study was to identify the best imaging variables to be extrapolated on clot composition and clarify variability in the imaging of thrombi by non-contrast CT. Using a CT-phantom and covering a wide range of histologies, we analyzed 80 clot analogs with respect to X-ray attenuation at 24 and 48  h after production. The mean, maximum, and minimum HU values for the axial and coronal reconstructions were recorded. Each thrombus underwent a corresponding histological analysis, together with a laboratory analysis of water and iron contents. Deci...
Source: Translational Stroke Research - January 14, 2020 Category: Neurology Source Type: research

Positron Emission Tomography After Ischemic Brain Injury: Current Challenges and Future Developments
AbstractPositron emission tomography (PET) is widely used in clinical and animal studies, along with the development of diverse tracers. The biochemical characteristics of PET tracers may help uncover the pathophysiological consequences of cardiac arrest (CA) and ischemic stroke, which include cerebral ischemia and reperfusion, depletion of oxygen and glucose, and neuroinflammation. PubMed was searched for studies of the application of PET for “cardiac arrest,” “ischemic stroke,” and “targeted temperature management.” Available studies were included and classified according to the bioche...
Source: Translational Stroke Research - January 14, 2020 Category: Neurology Source Type: research

Recruiting Control Participants into Stroke Biomarker Studies
AbstractThe number of scientists using –omics technologies to investigate biomarkers with the potential to gauge risk and aid in the diagnosis, treatment, and prognosis of stroke continues to rise, yet there are few resources to aid investigators in recruiting control participants. In this review, we describe two major strategies to ma tch control participants to a stroke cohort-propensity score matching and one-to-one matching—including statistical approaches to gauge the balance between groups. We then explore the advantages and disadvantages of traditional recruitment methods including approaching spouses of...
Source: Translational Stroke Research - January 8, 2020 Category: Neurology Source Type: research

Correction to: Field Assessment of Critical Stroke by Emergency Services for Acute Delivery to a Comprehensive Stroke Center: FACE 2 AD
The original version of this article unfortunately contained mistakes. (Source: Translational Stroke Research)
Source: Translational Stroke Research - January 8, 2020 Category: Neurology Source Type: research

Mfsd2a Attenuates Blood-Brain Barrier Disruption After Sub-arachnoid Hemorrhage by Inhibiting Caveolae-Mediated Transcellular Transport in Rats
In this study, a prechiasmatic cistern single-injection model was used to produce experimental SAH in Sprague-Dawley rats. Specific small-interfering RNA and plasmids were used to downregulate and upregulate the expression of Mfsd2a prior to assessments in our SAH model. Omega-3 fatty acid deficiency diet was used to reduce DHA in rat brain. The expression level of Mfsd2a decreased significantly after SAH and reached its lowest level at 72  h post-SAH, which then gradually recovered. At 72 h after SAH, BBB function was disrupted; upregulation of Mfsd2a reversed this damage, whereas downregulation of Mfsd2a exacer...
Source: Translational Stroke Research - January 6, 2020 Category: Neurology Source Type: research

Recombinant Adiponectin Peptide Ameliorates Brain Injury Following Intracerebral Hemorrhage by Suppressing Astrocyte-Derived Inflammation via the Inhibition of Drp1-Mediated Mitochondrial Fission
In conclusion, we propose APNp as a potential therapeutic agent for ICH. We provide the first mechanistic evidence that APNp can modulate Drp1-mediated mitochondrial fission, which then contributes to alleviating astrocyte-derived inflammation. (Source: Translational Stroke Research)
Source: Translational Stroke Research - January 4, 2020 Category: Neurology Source Type: research

Activation of the Hedgehog Pathway Promotes Recovery of Neurological Function After Traumatic Brain Injury by Protecting the Neurovascular Unit
In this study, the controlled cortical impact (CCI) was used to establish a moderate TBI model in adult male Sprague-Dawley rats (250 –300 g), and the NVU was reconstructed in vitro from the blood-brain barrier (BBB) and neurons to investigate the effects of exogenous Shh protein on TBI. The modified neurological severity scores (mNSS) and Morris water maze tests were used to evaluate the effect of Shh on neurological function after TBI. The effect of Shh on the NVU in vivo was evaluated by detecting the degrees of cerebral edema and neuronal apoptosis. The integrity and permeability of the BBB, the level of inf...
Source: Translational Stroke Research - January 2, 2020 Category: Neurology Source Type: research

Human Milk Oligosaccharide 2 ′-Fucosyllactose Reduces Neurodegeneration in Stroke Brain
In conclusion, our data suggest that 2’-FL has neuroprotective action through inhibition of Ca++i, inflammation, and apoptosis. Posttreatment with 2 ’-FL facilitates neural repair in stroke brain. (Source: Translational Stroke Research)
Source: Translational Stroke Research - January 2, 2020 Category: Neurology Source Type: research

Cerebral Organoids Repair Ischemic Stroke Brain Injury
AbstractStroke is the second leading cause of death and main cause of disability worldwide, but with few effective therapies. Although stem cell-based therapy has been proposed as an exciting regenerative medicine strategy for brain injury, there are limitations. The developed cerebral organoids (COs) represent a promising transplantation source for stroke that remains to be answered. Here, we transplanted COs at 55  days and explored the feasibility in the rat middle cerebral artery occlusion (MCAO) model of stroke. COs transplantation at 6 h or even 24 h after MCAO significantly reduces brain infarct volum...
Source: Translational Stroke Research - December 30, 2019 Category: Neurology Source Type: research

Glycyrrhizin Prevents Hemorrhagic Transformation and Improves Neurological Outcome in Ischemic Stroke with Delayed Thrombolysis Through Targeting Peroxynitrite-Mediated HMGB1 Signaling
In conclusion, peroxynitrite-mediated HMGB1/TLR2 signaling contributes to hemorrhagic transformation, and glycyrrhizin could be a potential adjuvant therapy to attenuate hemorrhagic transformation, possibly through inhibiting the ONOO−/HMGB1/TLR2 signaling cascades. (Source: Translational Stroke Research)
Source: Translational Stroke Research - December 24, 2019 Category: Neurology Source Type: research

Stroke Induces Prolonged Changes in Lipid Metabolism, the Liver and Body Composition in Mice
AbstractDuring recovery, stroke patients are at risk of developing long-term complications that impact quality of life, including changes in body weight and composition, depression and anxiety, as well as an increased risk of subsequent vascular events. The aetiologies and time-course of these post-stroke complications have not been extensively studied and are poorly understood. Therefore, we assessed long-term changes in body composition, metabolic markers and behaviour after middle cerebral artery occlusion in mice. These outcomes were also studied in the context of obesity, a common stroke co-morbidity proposed to prote...
Source: Translational Stroke Research - December 21, 2019 Category: Neurology Source Type: research

Short-Term Acute Exercise Preconditioning Reduces Neurovascular Injury After Stroke Through Induced eNOS Activation
AbstractPhysical exercise is known to reduce cardiovascular risk but its role in ischemic stroke is not clear. It was previously shown that an acute single bout of exercise reduced increased eNOS activation in the heart and reduced myocardial infarction. However, the impact of a single bout or short-term exercise on eNOS-induced neuroprotection after stroke was not previously studied. Accordingly, this study was designed to test the hypothesis that short-term acute exercise can provide “immediate neuroprotection” and improve stroke outcomes through induced eNOS activation. Male Wistar rats (300 g) were sub...
Source: Translational Stroke Research - December 20, 2019 Category: Neurology Source Type: research

Immune Characterization in Aneurysmal Subarachnoid Hemorrhage Reveals Distinct Monocytic Activation and Chemokine Patterns
AbstractThe pathophysiology of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) is incompletely understood. Intrathecal activation of inflammatory immune cells is suspected to play a major role for the induction of DCI. The aim of this study is to identify immune cell subsets and mediators involved in the pathogenesis of DCI. We prospectively collected blood and CSF from 25 patients with aSAH at early and late time points. We performed multicolor flow cytometry of peripheral blood and CSF, analyzing immune cell activation and pro-inflammatory cyto- and chemokines. In addition to the primary i...
Source: Translational Stroke Research - December 19, 2019 Category: Neurology Source Type: research

Biomarker Application for Precision Medicine in Stroke
AbstractStroke remains one of the leading causes of long-term disability and mortality despite recent advances in acute thrombolytic therapies. In fact, the global lifetime risk of stroke in adults over the age of 25 is approximately 25%, with 24.9 million cases of ischemic stroke and 18.7 million cases of hemorrhagic stroke reported in 2015. One of the main challenges in developing effective new acute therapeutics and enhanced long-term interventions for stroke recovery is the heterogeneity of stroke, including etiology, comorbidities, and lifestyle factors that uniquely affect each individual stroke survivor. In this com...
Source: Translational Stroke Research - December 18, 2019 Category: Neurology Source Type: research

Reproductive Senescence and Ischemic Stroke Remodel the Gut Microbiome and Modulate the Effects of Estrogen Treatment in Female Rats
AbstractOur previous work has shown that reproductively senescent (or middle-aged; 10 –12-month-old) Sprague–Dawley female rats, that are naturally estrogen-deficient, have worse stroke outcomes as compared to normally estrous-cycling adult (5–6-month-old) females. Paradoxically, estrogen replacement to this middle-aged group exacerbates stroke outcomes, while it is neuroprotec tive in adult females. Recent studies reveal an important role for the gut microbiome and gut metabolites in cardiovascular health, including stroke outcomes. To determine whether gut dysbiosis underlies stroke severity in reproduc...
Source: Translational Stroke Research - December 16, 2019 Category: Neurology Source Type: research

Automated Assessment of Hematoma Volume of Rodents Subjected to Experimental Intracerebral Hemorrhagic Stroke by Bayes Segmentation Approach
The objective of this study is to develop an automated method that can accurately and efficiently obtain unbiased cerebral hematoma volume. We developed an application (MATLAB program) that can delineate the brain slice from the background and use theHue information in the Hue/Saturation/Value (HSV) color space to segment the hematoma region. The segmentation threshold of Hue is calculated based on the Bayes classifier theorem so that the minimum error is mathematically ensured and automated processing is enabled. To validate the developed method, we compared the outcomes from the developed method with the hemoglobin conte...
Source: Translational Stroke Research - December 14, 2019 Category: Neurology Source Type: research

Field Assessment of Critical Stroke by Emergency Services for Acute Delivery to a Comprehensive Stroke Center: FACE 2 AD
AbstractPatients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) should be triaged to an endovascular-capable hospital by the emergency medical service (EMS). We designed a prehospital LVO prediction scale based on EMS assessments. In the derivation cohort, 1157 patients transferred to our hospital by the EMS because of suspected stroke within 24 h of onset were retrospectively examined. Factors associated with AIS due to LVO were identified based on the EMS assessment, and a prehospital scale identifying LVO was developed. The accuracy of this scale was validated in 502 consecutive patients who were t...
Source: Translational Stroke Research - December 12, 2019 Category: Neurology Source Type: research

Selective mGluR1 Negative Allosteric Modulator Reduces Blood –Brain Barrier Permeability and Cerebral Edema After Experimental Subarachnoid Hemorrhage
AbstractThe blood –brain barrier (BBB) disruption leads to the vasogenic brain edema and contributes to the early brain injury (EBI) after subarachnoid hemorrhage (SAH). However, the mechanisms underlying the BBB damage following SAH are poorly understood. Here we reported that the neurotransmitter glutamate of cer ebrospinal fluid (CSF) was dramatically increased in SAH patients with symptoms of cerebral edema. Using the rat SAH model, we found that SAH caused the increase of CSF glutamate level and BBB permeability in EBI, intracerebroventricular injection of exogenous glutamate deteriorated BBB damage and c erebra...
Source: Translational Stroke Research - December 12, 2019 Category: Neurology Source Type: research

Complement C5 Contributes to Brain Injury After Subarachnoid Hemorrhage
AbstractPrevious studies showed that complement activation is associated with poor functional outcome after aneurysmal subarachnoid hemorrhage (SAH). We investigated whether complement activation is underlying brain injury after aneurysmal SAH (n = 7) and if it is an appropriate treatment target. We investigated complement expression in brain tissue of aneurysmal SAH patients (n = 930) and studied the role of common genetic variants in C3 and C5 genes in outcome. We analyzed plasma levels (n = 229) to identify the functionality of a single nucleotide polymorphism (SNP) associated with ...
Source: Translational Stroke Research - December 6, 2019 Category: Neurology Source Type: research

Neural Stem Cell Extracellular Vesicles Disrupt Midline Shift Predictive Outcomes in Porcine Ischemic Stroke Model
This study investigated the utility of MRI as a predictive measure of clinical and functional outcomes when a stroke intervention is withheld or provided, in order to identify biomarkers for stroke functional outcome under these conditions. Fifteen MRI and ninety functional parameters were measured in a middle cerebral artery occlusion (MCAO) porcine ischemic stroke model. Multiparametric analysis of correlations between MRI measurements and functional outcome was conducted. Acute axial and coronal midline shift (MLS) at 24 h post-stroke were associated with decreased survival and recovery measured by modified Rankin scale...
Source: Translational Stroke Research - December 6, 2019 Category: Neurology Source Type: research