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

Plasma Neurofilament Light Chain Is Associated with Poor Functional Outcome and Mortality Rate After Spontaneous Subarachnoid Hemorrhage
AbstractThe initial clinical status after subarachnoid hemorrhage (SAH) is an important outcome predictor, but the mechanisms behind the early brain injury (EBI) remains incompletely understood. Elevated neurofilament levels in the cerebrospinal fluid at protracted stages after SAH are associated with poor outcome, but the potential association between plasma neurofilament (pNfL) levels during EBI, disease severity on admission, and poor outcome remains unaddressed. Plasma NfL (pNfL) was measured by single molecule array in 44 SAH patients on admission and 24  h after ictus, as well as in 44 controls. Disease severity...
Source: Translational Stroke Research - December 5, 2019 Category: Neurology Source Type: research

Occlusion of Animal Model Arteriovenous Malformations Using Vascular Targeting
This study assessed the efficacy of a pro-thrombotic VTA targeting phosphatidylserine (PS) in a radiation-primed AVM animal model. The model AVM was surgically created in rats by anastomosis of the left external jugular vein to the adjacent common carotid artery. After 6  weeks, the AVM was irradiated (20 Gy) using gamma knife surgery (GKS). A PS-targeting VTA was created by conjugation of annexin V with human thrombin and administered intravenously 3 weeks post-GKS or sham. Unconjugated thrombin was used as a non-targeting control. AVM thrombosis and occlusion w as monitored 3 weeks later by angiograph...
Source: Translational Stroke Research - December 5, 2019 Category: Neurology Source Type: research

A Novel Partial MHC Class II Construct, DRmQ, Inhibits Central and Peripheral Inflammatory Responses to Promote Neuroprotection in Experimental Stroke
AbstractRecognizing that the pathologic progression of stroke is closely associated with aberrant immune responses, in particular the activation of peripheral leukocytes, namely T cells, we hypothesized that finding a treatment designed to inhibit neuroantigen-specific T cells and block cytotoxic monocytes and macrophages may render therapeutic effects in stroke. We previously reported that subcutaneous administration of partial MHC class II constructs promote behavioral and histological effects in stroke mice by centrally promoting a protective M2 macrophage/microglia phenotype in the CNS and peripherally reversing stroke...
Source: Translational Stroke Research - December 3, 2019 Category: Neurology Source Type: research

Delayed Administration of Angiotensin II Type 2 Receptor (AT2R) Agonist Compound 21 Prevents the Development of Post-stroke Cognitive Impairment in Diabetes Through the Modulation of Microglia Polarization
AbstractA disabling consequence of stroke is cognitive impairment, occurring in 12% –48% of patients, for which there is no therapy. A critical barrier is the lack of understanding of how post-stroke cognitive impairment (PSCI) develops. While 70% of stroke victims present with comorbid diseases such as diabetes and hypertension, the limited use of comorbid disease models in prec linical research further contributes to this lack of progress. To this end, we used a translational model of diabetes to study the development of PSCI. In addition, we evaluated the application of compound 21 (C21), an angiotensin II Type 2 ...
Source: Translational Stroke Research - December 3, 2019 Category: Neurology Source Type: research

Statin Therapy in Ischemic Stroke Models: A Meta-Analysis
AbstractStatins, drugs known for lipid lowering capabilities and reduction of cardiovascular disease, have demonstrated neuroprotective effects following ischemic stroke in retrospective clinical and animal studies. However, dosing (methods, time, type of statin, and quantity) varies across studies, limiting the clinical applicability of these findings. Furthermore, a comprehensive review of statins in edema and blood-brain barrier (BBB) breakdown is needed to provide insight on diverse, less explored neuroprotective effects. In the present study, we conduct a meta-analysis of publications evaluating statin administration ...
Source: Translational Stroke Research - December 2, 2019 Category: Neurology Source Type: research

From Stroke to Dementia: a Comprehensive Review Exposing Tight Interactions Between Stroke and Amyloid- β Formation
AbstractStroke and Alzheimer ’s disease (AD) are cerebral pathologies with high socioeconomic impact that can occur together and mutually interact. Vascular factors predisposing to cerebrovascular disease have also been specifically associated with development of AD, and acute stroke is known to increase the risk to develop d ementia.Despite the apparent association, it remains unknown how acute cerebrovascular disease and development of AD are precisely linked and act on each other. It has been suggested that this interaction is strongly related to vascular deposition of amyloid- β (Aβ), i.e., cerebral amy...
Source: Translational Stroke Research - November 28, 2019 Category: Neurology Source Type: research

Association of High Serum Levels of Growth Factors with Good Outcome in Ischemic Stroke: a Multicenter Study
AbstractThe main objective of this research work was to study the association of serum levels of growth factors (GF) and SDF-1 α with the functional outcome and reduction of lesion volume in ischemic stroke patients. In this multicenter study, 552 patients with non-lacunar stroke (male, 62.1%; mean age, 68.2 ± 11.4) were included within 24 h from symptom onset. The main outcome variable was good functional outcome (modifi ed Rankin Scale [mRS] ≤ 2) at 12 months. Secondary outcome variable was infarct volume (in mL) after 6 ± 3 months. Serum levels of VEGF, Ang-1, G-CSF, BDNF, and SDF-1α were me...
Source: Translational Stroke Research - November 25, 2019 Category: Neurology Source Type: research

The Stabilization of Central Sympathetic Nerve Activation by Renal Denervation Prevents Cerebral Vasospasm after Subarachnoid Hemorrhage in Rats
We examined the effect of RD on early brain injury (EBI) and delayed cerebral ischemia (DCI) as a primary endpoint, and also explored the effect on cerebral vasospasm (CVS) as a secondary endpoint. Although RD did not exert significant effects on primary endpoint, RD signi ficantly prevented CVS and reduced SAH-induced increases in the number of phosphorylated extracellular signal-regulated kinase (ERK)-positive endothelial cells, cyclooxygenase-2 expression, and macrophage infiltration in major cerebral arteries. Moreover, RD significantly decreased the areas display ing dopamine β-hydroxylase and glial fibrillary ac...
Source: Translational Stroke Research - November 20, 2019 Category: Neurology Source Type: research

Stroke Severity, and Not Cerebral Infarct Location, Increases the Risk of Infection
AbstractInfection is a leading cause of death in patients with stroke; however, the impact of cerebral infarct size or location on infectious outcome is unclear. To examine the effect of infarct size on post-stroke infection, we utilised the intraluminal middle-cerebral artery occlusion (MCAO) mouse model of ischemic stroke and adjusted the duration of arterial occlusion. At 1  day following stroke onset, the proportion of mice with infection was significantly greater in mice that had larger infarct sizes. Additionally, the presence of lung infection in these mice with severe strokes extended past 2 days, suggest...
Source: Translational Stroke Research - November 10, 2019 Category: Neurology Source Type: research

Predictors of Lesion Cavitation After Recent Small Subcortical Stroke
AbstractMorphologic evolution of recent small subcortical infarcts (RSSI) ranges from lesion disappearance to lacune formation and the reasons for this variability are still poorly understood. We hypothesized that diffusion tensor imaging (DTI) and blood-brain-barrier (BBB) abnormalities early on can predict tissue damage 1  year after an RSSI. We studied prospectively recruited patients with a symptomatic MRI-defined RSSI who underwent baseline and two pre-specified MRI examinations at 1–3-month and 1-year post-stroke. We defined the extent of long-term tissue destruction, termedcavitation index, as the ratio o...
Source: Translational Stroke Research - November 8, 2019 Category: Neurology Source Type: research

Neurovascular Unit as a Source of Ischemic Stroke Biomarkers —Limitations of Experimental Studies and Perspectives for Clinical Application
AbstractCerebral stroke, which is one of the most frequent causes of mortality and leading cause of disability in developed countries, often leads to devastating and irreversible brain damage. Neurological and neuroradiological diagnosis of stroke, especially in its acute phase, is frequently uncertain or inconclusive. This results in difficulties in identification of patients with poor prognosis or being at high risk for complications. It also makes difficult identification of these stroke patients who could benefit from more aggressive therapies. In contrary to the cardiovascular disease, no single biomarker is available...
Source: Translational Stroke Research - November 7, 2019 Category: Neurology Source Type: research

Quantitative Iron Neuroimaging Can Be Used to Assess the Effects of Minocycline in an Intracerebral Hemorrhage Minipig Model
This study was performed to investigate the noninvasive neuroimaging method for quantifying brain iron content using a minipig ICH model and assess the effects of minocycline treatment on ICH-induced iron overload and brain injury. The minipig ICH model was established by injecting 2  ml of autologous blood into the right basal ganglia, which were then subjected to the treatments of minocycline and vehicle. Furthermore, the quantitative susceptibility mapping (QSM) was used to quantify iron content, and diffusion tensor imaging (DTI) was performed to evaluate white matter tract . Additionally, we also performed immuno...
Source: Translational Stroke Research - November 6, 2019 Category: Neurology Source Type: research

Texture Features of Magnetic Resonance Images: an Early Marker of Post-stroke Cognitive Impairment
AbstractStroke is frequently associated with delayed, long-term cognitive impairment (CI) and dementia. Recent research has focused on identifying early predictive markers of CI occurrence. We carried out a texture analysis of magnetic resonance (MR) images to identify predictive markers of CI occurrence based on a combination of preclinical and clinical data. Seventy-two-hour post-stroke T1W MR images of 160 consecutive patients were examined, including 75 patients with confirmed CI at the 6-month post-stroke neuropsychological examination. Texture features were measured in the hippocampus and entorhinal cortex and compar...
Source: Translational Stroke Research - November 1, 2019 Category: Neurology Source Type: research

Progression and Classification of Granular Osmiophilic Material (GOM) Deposits in Functionally Characterized Human NOTCH3 Transgenic Mice
AbstractCADASIL is aNOTCH3-associated cerebral small vessel disease. A pathological ultrastructural disease hallmark is the presence of NOTCH3-protein containing deposits called granular osmiophilic material (GOM), in small arteries. How these GOM deposits develop over time and what their role is in disease progression is largely unknown. Here, we studied the progression of GOM deposits in humanized transgenicNOTCH3Arg182Cys mice, compared them to GOM deposits in patient material, and determined whether GOM deposits in mice are associated with a functional CADASIL phenotype. We found that GOM deposits are not static, but r...
Source: Translational Stroke Research - October 30, 2019 Category: Neurology Source Type: research

CD47 Blocking Antibody Accelerates Hematoma Clearance After Intracerebral Hemorrhage in Aged Rats
This study expands those findings by examining the effects on a CD47 blocking antibody in aged rats. First, male Fischer 344 rats (18 months old) received an intracaudate injection of 50 μL auto logous whole blood or saline. Hematoma features of magnetic resonance imaging (MRI) and neurological deficits were evaluated within 3 days. Second, rats had an intracaudate co-injection of 50 μL autologous blood with either CD47 blocking antibody or IgG. MRI was used to quantify hematoma/iron vol ume, hemolysis, brain swelling, and atrophy at different time points, behavioral tests to assess neurological d...
Source: Translational Stroke Research - October 30, 2019 Category: Neurology Source Type: research

From the Lab to Patients: a Systematic Review and Meta-Analysis of Mesenchymal Stem Cell Therapy for Stroke
AbstractThere may be the potential to improve stroke recovery with mesenchymal stem cells (MSCs); however, questions about the efficacy and safety of this treatment remain. To address these issues and inform future studies, we performed a preclinical and clinical systematic review of MSC therapy for subacute and chronic ischemic stroke. MEDLINE, Embase, the Cochrane Register of Controlled Trials, and PubMed were searched. For the clinical review, interventional and observational studies of MSC therapy in ischemic stroke patients were included. For the preclinical review, interventional studies of MSC therapy  usingin ...
Source: Translational Stroke Research - October 25, 2019 Category: Neurology Source Type: research

Moyamoya Disease and Spectrums of RNF213 Vasculopathy
AbstractMoyamoya disease (MMD) is a rare cerebrovascular disease characterized by progressive stenosis of large intracranial arteries and a hazy network of basal collaterals called moyamoya vessels. A polymorphism (R4810K) in theRing Finger Protein 213 (RNF213) gene, at chromosome 17q25.3, is the strongest genetic susceptibility factor for MMD in East Asian populations. MMD was regarded prevalent in childhood and in East Asian populations. However, the so-called MMD could represent only the tip of the iceberg. MMD is increasingly reported in adult patients and in Western populations. Moreover, theRNF213 variant was recentl...
Source: Translational Stroke Research - October 24, 2019 Category: Neurology Source Type: research

Effect of Simvastatin on Permeability in Cerebral Cavernous Malformation Type 1 Patients: Results from a Pilot Small Randomized Controlled Clinical Trial
(Source: Translational Stroke Research)
Source: Translational Stroke Research - October 23, 2019 Category: Neurology Source Type: research

The Dynamics of Microglial Polarization Reveal the Resident Neuroinflammatory Responses After Subarachnoid Hemorrhage
In this study, we investigated the dynamics of microglial reaction in an endovascular perforated SAH model. By using the Cx3cr1GFP/GFP Ccr2RFP/RFP transgenic mice, we found that the reactive immune cells were largely from resident microglia pool rather than infiltrating macrophages. Immunostaining and real-time PCR were employed to analyze the temporal microglial polarization and the resulting inflammatory responses. Our results showed that microglia accumulated immediately after SAH with a centrifugal spreading through the Cortex Adjacent to the Perforated Site (CAPS) to the remote motor cortex. Microglia polarized dynami...
Source: Translational Stroke Research - October 18, 2019 Category: Neurology Source Type: research

Treadmill Exercise Suppresses Cognitive Decline and Increases White Matter Oligodendrocyte Precursor Cells in a Mouse Model of Prolonged Cerebral Hypoperfusion
AbstractClinical evidence suggests that patients with subcortical ischemic vascular dementia (SIVD) perform better at cognitive tests after exercise. However, the underlying mechanism for this effect is largely unknown. Here, we examined how treadmill exercise changes the cognitive function and white matter cellular pathology in a mouse model of SIVD. Prolonged cerebral hypoperfusion was induced in 2-month-old male C57BL/6J mice by bilateral common carotid artery stenosis. A week later, the mice were randomly divided into a group that received 6-week treadmill exercise and a sedentary group for observation. In multiple beh...
Source: Translational Stroke Research - October 12, 2019 Category: Neurology Source Type: research

Immune Responses and Anti-inflammatory Strategies in a Clinically Relevant Model of Thromboembolic Ischemic Stroke with Reperfusion
AbstractThe poor clinical relevance of experimental models of stroke contributes to the translational failure between preclinical and clinical studies testing anti-inflammatory molecules for ischemic stroke. Here, we (i) describe the time course of inflammatory responses triggered by a thromboembolic model of ischemic stroke and (ii) we examine the efficacy of two clinically tested anti-inflammatory drugs: Minocycline or anti-CD49d antibodies (tested in stroke patients as Natalizumab) administered early (1  h) or late (48 h) after stroke onset. Radiological (lesion volume) and neurological (grip test) outcomes we...
Source: Translational Stroke Research - September 14, 2019 Category: Neurology Source Type: research

Complex Clearance Mechanisms After Intraventricular Hemorrhage and rt-PA Treatment —a Review on Clinical Trials
AbstractIntracerebral hemorrhage in combination with intraventricular hemorrhage (IVH) is a severe type of stroke frequently leading to prolonged clinical care, continuous disability, shunt dependency, and high mortality. The molecular mechanisms induced by IVH are complex and not fully understood. Moreover, the treatment options for IVH are limited. Intraventricular recombinant tissue plasminogen activator (rt-PA) dissolves the blood clot in the ventricular system; however, whether the clinical outcome is thereby positively affected is still being debated. The mechanistic cascade induced by intraventricular rt-PA therapy ...
Source: Translational Stroke Research - September 14, 2019 Category: Neurology Source Type: research

Beneficial Effects of Theta-Burst Transcranial Magnetic Stimulation on Stroke Injury via Improving Neuronal Microenvironment and Mitochondrial Integrity
We report that rTMS significantly attenuated behavioral deficits and infarct volume after PT stroke. Fur ther investigation demonstrated that rTMS remarkably reduced synaptic loss and neuronal degeneration in the peri-infarct cortical region. Mechanistic studies displayed that beneficial effects of rTMS were associated with robust suppression of reactive micro/astrogliosis and the overproduction of pro -inflammatory cytokines, as well as oxidative stress and oxidative neuronal damage especially at the late stage following PT stroke. Intriguingly, rTMS could effectively induce a shift in microglial M1/M2 phenotype activatio...
Source: Translational Stroke Research - September 12, 2019 Category: Neurology Source Type: research

Stroke Center Care and Outcome: Results from the CSPPC Stroke Program
AbstractThe aim of this study was to assess the association between admission to stroke centers for acute ischemic stroke and complications and mortality during hospitalization in a Chinese population by means of an observational study using data from the China Stroke Center Data-Sharing Platform. We compared in-hospital complications and mortality for patients admitted with acute ischemic stroke (N = 13,236) between November 1, 2018 and December 31, 2018 at stroke center (SH) and non-stroke center (CH) hospitals using distance to hospitals as an instrumental variable to adjust for potential prehospital selec...
Source: Translational Stroke Research - September 8, 2019 Category: Neurology Source Type: research

Infarct Evolution in a Large Animal Model of Middle Cerebral Artery Occlusion
AbstractMechanical thrombectomy for the treatment of ischemic stroke shows high rates of recanalization; however, some patients still have a poor clinical outcome. A proposed reason for this relates to the fact that the ischemic infarct growth differs significantly between patients. While some patients demonstrate rapid evolution of their infarct core (fast evolvers), others have substantial potentially salvageable penumbral tissue even hours after initial vessel occlusion (slow evolvers). We show that the dog middle cerebral artery occlusion model recapitulates this key aspect of human stroke rendering it a highly desirab...
Source: Translational Stroke Research - September 3, 2019 Category: Neurology Source Type: research