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Source: Translational Stroke Research

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Total 421 results found since Jan 2013.

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, suggestive of l...
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 of the 1-...
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 immunohist...
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 deficits, and immunoh...
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 vivo...
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 - 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

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

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 were evalu...
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 selection bias....
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

Cardioembolic Ischemic Stroke Gene Expression Fingerprint in Blood: a Systematic Review and Verification Analysis
AbstractAn accurate etiological classification is key to optimize secondary prevention after ischemic stroke, but the cause remains undetermined in one third of patients. Several studies pointed out the usefulness of circulating gene expression markers to discriminate cardioembolic (CE) strokes, mainly due to atrial fibrillation (AF), while only exploring them in small cohorts. A systematic review of studies analyzing high-throughput gene expression in blood samples to discriminate CE strokes was performed. Significantly dysregulated genes were considered as candidates, and a selection of them was validated by RT-qPCR in 1...
Source: Translational Stroke Research - September 2, 2019 Category: Neurology Source Type: research

Experimental Aneurysmal Subarachnoid Hemorrhage: Tiding Over
Source: Translational Stroke Research - September 2, 2019 Category: Neurology Source Type: research

Ischemic Neuroprotectant PKC ε Restores Mitochondrial Glutamate Oxaloacetate Transaminase in the Neuronal NADH Shuttle after Ischemic Injury
AbstractThe preservation of mitochondrial function is a major protective strategy for cerebral ischemic injuries. Previously, our laboratory demonstrated that protein kinase C epsilon (PKC ε) promotes the synthesis of mitochondrial nicotinamide adenine dinucleotide (NAD+). NAD+ along with its reducing equivalent, NADH, is an essential co-factor needed for energy production from glycolysis and oxidative phosphorylation. Yet, NAD+/NADH are impermeable to the inner mitochondrial membrane and their import into the mitochondria requires the activity of specific shuttles. The most important neuronal NAD+/NADH shuttle is the mal...
Source: Translational Stroke Research - August 31, 2019 Category: Neurology Source Type: research

Perfusion Changes of Unexplained Early Neurological Deterioration After Reperfusion Therapy
AbstractEarly neurological deterioration (END) after thrombolysis occurs in 10% acute ischemic stroke (AIS) patients, and its mechanism remains unclear in majority of cases, named as unexplained END. We tested the hypothesis that penumbra/infarct growth beyond the initial penumbra might be the cause of unexplained END. We reviewed the database of AIS patients who received reperfusion therapy. Unexplained END was defined as ≥ 2-point increase of NIHSS from baseline to 24 h, without straightforward causes. For each unexplained END patient, we extracted 2 matched controls based on 4 clinical and radiological characterist...
Source: Translational Stroke Research - August 28, 2019 Category: Neurology Source Type: research

A Brain-Targeted Orally Available ROCK2 Inhibitor Benefits Mild and Aggressive Cavernous Angioma Disease
AbstractCavernous angioma (CA) is a vascular pathology caused by loss of function in one of the 3 CA genes (CCM1,CCM2, andCCM3) that result in rho kinase (ROCK) activation. We investigated a novel ROCK2 selective inhibitor for the ability to reduce brain lesion formation, growth, and maturation. We used genetic methods to explore the use of a ROCK2-selective kinase inhibitor to reduce growth and hemorrhage of CAs. The role of ROCK2 in CA was investigated by crossingRock1 orRock2 hemizygous mice withCcm1 orCcm3 hemizygous mice, and we found reduced lesions in theRock2 hemizygous mice. A ROCK2-selective inhibitor, BA-1049 wa...
Source: Translational Stroke Research - August 24, 2019 Category: Neurology Source Type: research

Prior Antiplatelet Therapy, Excluding Phosphodiesterase Inhibitor Is Associated with Poor Outcome in Patients with Spontaneous Intracerebral Haemorrhage
In this study, ADP-I and COX-1, but not PDE-I, are the most likely contributors to the association of APT with poor outcome with spontaneous ICH patients. These findings suggest that the complexity of the different mechanism of actions of prior APT can alter the outcome in spontaneous ICH.
Source: Translational Stroke Research - August 24, 2019 Category: Neurology Source Type: research

Phase I Safety Trial: Extended Daily Peripheral Sensory Stimulation Using a Wrist-Worn Vibrator in Stroke Survivors
AbstractPeripheral sensory stimulation augments post-stroke upper extremity rehabilitation outcomes. Most sensory stimulations interfere with natural hand tasks and the stimulation duration is limited. We developed TheraBracelet, low-level random-frequency vibration applied via a wristwatch, to enable stimulation during hand tasks and potentially extend stimulation durations. To determine safety of prolonged exposure to TheraBracelet. Single-site double-blind crossover randomized controlled trial. Chronic stroke survivors were instructed to wear a device on the affected wrist for> 8 h/day everyday for 2 months while...
Source: Translational Stroke Research - August 23, 2019 Category: Neurology Source Type: research

Change in CSF Dynamics Responsible for ICP Elevation After Ischemic Stroke in Rats: a New Mechanism for Unexplained END?
AbstractIt has been proposed that intracranial pressure (ICP) elevation and collateral failure are responsible for unexplained early neurological deterioration (END) in stroke. The study ’s aims were to investigate whether cerebral spinal fluid (CSF) dynamics, rather than edema, are responsible for elevation of ICP after ischemic stroke. Permanent middle cerebral artery occlusion (pMCAO) was induced with an intraluminal filament. At 24 h after stroke, baseline ICP was measured an d CSF dynamics were probed via a steady-state infusion method. Diffusion-weighted imaging (DWI) and T2-weighted magnetic resonance imaging wer...
Source: Translational Stroke Research - August 15, 2019 Category: Neurology Source Type: research

Central Noradrenergic Agonists in the Treatment of Ischemic Stroke —an Overview
AbstractIschemic stroke is the leading cause of morbidity and mortality with a significant health burden worldwide and few treatment options. Among the short- and long-term effects of ischemic stroke is the cardiovascular sympathetic autonomic dysfunction, presented in part as the by-product of the ischemic damage to the noradrenergic centers of the brain. Unlike high levels in the plasma, the brain may face suboptimal levels of norepinephrine (NE), with adverse effects on the clinical and functional outcomes of ischemic stroke. The intravenous administration of NE and other sympathomimetic agents, in an attempt to increas...
Source: Translational Stroke Research - July 20, 2019 Category: Neurology Source Type: research

Adult Neurogenesis in the Subventricular Zone and Its Regulation After Ischemic Stroke: Implications for Therapeutic Approaches
AbstractAdult neurogenesis in the subventricular zone is a topic of intense research, since it has vast implications for the fundamental understanding of the neurobiology of the brain and its potential to being harnessed for therapy in various neurological disorders. Investigation of adult neurogenesis has been complicated by the difficulties with characterization of neural stem cells in vivo. However, recent single-cell transcriptomic studies provide more detailed information on marker expression in neural stem cells and their neuronal lineage, which hopefully will result in a more unified discussion. Regulation of the mu...
Source: Translational Stroke Research - July 15, 2019 Category: Neurology Source Type: research

Activation of Sigma-1 Receptor Enhanced Pericyte Survival via the Interplay Between Apoptosis and Autophagy: Implications for Blood –Brain Barrier Integrity in Stroke
This study identified the unique roles for σ-1R in mediating pericyte survival via the regulation of the interplay between apoptosis and autophagy, suggesting that a novel σ-1R agonist may be a promising therapeutic agent for the treatment of stroke patients.
Source: Translational Stroke Research - July 9, 2019 Category: Neurology Source Type: research

Impaired Collateral Flow in Pial Arterioles of Aged Rats During Ischemic Stroke
AbstractCerebral collateral circulation and age are critical factors in determining outcome from acute ischemic stroke. Aging may lead to rarefaction of cerebral collaterals, and thereby accelerate ischemic injury by reducing penumbral blood flow. Dynamic changes in pial collaterals after onset of cerebral ischemia may vary with age but have not been extensively studied. Here, laser speckle contrast imaging (LSCI) and two-photon laser scanning microscopy (TPLSM) were combined to monitor cerebral pial collaterals between the anterior cerebral artery (ACA) and the middle cerebral artery (MCA) in young adult and aged male Spr...
Source: Translational Stroke Research - June 15, 2019 Category: Neurology Source Type: research

Therapeutic Role of a Cysteine Precursor, OTC, in Ischemic Stroke Is Mediated by Improved Proteostasis in Mice
AbstractOxidative stress aggravates brain injury following ischemia/reperfusion (I/R). We previously showed that ubiquilin-1 (Ubqln1), a ubiquitin-like protein, improves proteostasis and protects brains against oxidative stress and I/R-induced brain injury. Here, we demonstrate that a small molecule compound, L-2-oxothiazolidine-4-carboxylic acid (OTC) that functions as a precursor of cysteine, upregulated Ubqln1 and protected cells against oxygen-glucose deprivation –induced cell death in neuronal cultures. Further, the administration of OTC either at 1 h prior to ischemia or 3 h after the reperfusion significantly re...
Source: Translational Stroke Research - May 2, 2019 Category: Neurology Source Type: research

Obesity Paradox in Ischemic Stroke: Clinical and Molecular Insights
AbstractIt has recently emerged the concept of “obesity paradox,” a term used to describe the unexpected improved prognosis and lower mortality rates found in several diseases in patients with higher body weight. Concerning stroke, few clinical studies have assessed this obesity paradox showing contradictory results. Therefore, our aim was t o compare clinical evolution and inflammatory balance of obese and non-obese patients after ischemic stroke. We designed a prospective case-control study in patients with acute ischemic stroke categorized into obese (body mass index, BMI ≥ 30 kg/m2) and non-obese (BMI  <...
Source: Translational Stroke Research - April 13, 2019 Category: Neurology Source Type: research

Impact of Leukoaraiosis Severity on the Association of Time to Successful Reperfusion with 90-Day Functional Outcome After Large Vessel Occlusion Stroke
AbstractThe chance for a favorable outcome after mechanical thrombectomy (MT) for large vessel occlusion stroke decreases with the symptom onset-to-reperfusion time (OTR). Patients with severe leukoaraiosis are at increased risk for a poor outcome after MT. However, whether leukoaraiosis modulates to the association between OTR and 90-day functional outcome is uncertain. We retrospectively analyzed 144 consecutive patients with successful (TICI ≥ 2b/3) MT for anterior circulation large vessel occlusion within 24 h form OTR between January 2012 to November 2016. Leukoaraiosis was dichotomized to absent-to-mild (van Swi...
Source: Translational Stroke Research - April 12, 2019 Category: Neurology Source Type: research

Neurophysiological and Biomechanical Evaluation of the Mechanisms Which Impair Safety of Swallow in Chronic Post-stroke Patients
AbstractOropharyngeal dysphagia (OD) is a common post-stroke complication and is associated with respiratory infections. The aim was to assess the biomechanical impairments in swallow function and the afferent and efferent swallowing pathways impairing swallow safety in chronic post-stroke patients. We studied 30 patients with unilateral stroke and chronic OD (>  3 months from stroke onset) with impaired safety of swallow (Penetration–Aspiration Scale [PAS] ≥ 2). We evaluated the efficacy, safety, and kinematics of the swallow response (residue, PAS, laryngeal vestibule closure time [LVCT]) with videofluoroscop...
Source: Translational Stroke Research - April 2, 2019 Category: Neurology Source Type: research

Functional Dynamics of Neutrophils After Ischemic Stroke
AbstractNeutrophils are forerunners to brain lesions after ischemic stroke and exert elaborate functions. However, temporal alterations of cell count, polarity, extracellular trap formation, and clearance of neutrophils remain poorly understood. The current study was aimed at providing basic information of neutrophil function throughout a time course following stroke onset in patients and animal subjects. We found that neutrophil constitution in peripheral blood increased soon after stroke onset of patients, and higher neutrophil count indicated detrimental stroke outcomes. Comparably, neutrophil count in peripheral blood ...
Source: Translational Stroke Research - March 7, 2019 Category: Neurology Source Type: research

Transplantation of Directly Reprogrammed Human Neural Precursor Cells Following Stroke Promotes Synaptogenesis and Functional Recovery
AbstractStroke is one of the leading causes of long-term disability. Cell transplantation is a promising strategy to treat stroke. We explored the efficacy of directly reprogrammed human neural precursor cell (drNPC) transplants to promote functional recovery in a model of focal ischemic stroke in the mouse sensorimotor cortex. We show that drNPCs express neural precursor cell markers and are neurally committed at the time of transplantation. Mice that received drNPC transplants recovered motor function, irrespective of transplant vehicle or recipient sex, and with no correlation to lesion volume or glial scarring. The maj...
Source: Translational Stroke Research - February 12, 2019 Category: Neurology Source Type: research

White Matter Integrity and Early Outcomes After Acute Ischemic Stroke
AbstractChronic white matter structural injury is a risk factor for poor long-term outcomes after acute ischemic stroke (AIS). However, it is unclear how white matter structural injury predisposes to poor outcomes after AIS. To explore this question, in 42 AIS patients with moderate to severe white matter hyperintensity (WMH) burden, we characterized WMH and normal-appearing white matter (NAWM) diffusivity anisotropy metrics in the hemisphere contralateral to acute ischemia in relation to ischemic tissue and early functional outcomes. All patients underwent brain MRI with dynamic susceptibility contrast perfusion and diffu...
Source: Translational Stroke Research - January 28, 2019 Category: Neurology Source Type: research

Dynamic Detection of Thrombolysis in Embolic Stroke Rats by Synchrotron Radiation Angiography
AbstractA rodent model of embolic middle cerebral artery occlusion is used to mimic cerebral embolism in clinical patients. Thrombolytic therapy is the effective treatment for this ischemic injury. However, it is difficult to detect thrombolysis dynamically in living animals. Synchrotron radiation angiography may provide a novel approach to directly monitor the thrombolytic process and assess collateral circulation after embolic stroke. Thirty-six adult Sprague-Dawley rats underwent the embolic stroke model procedure and were then treated with tissue plasminogen activator. The angiographic images were obtained in vivo by s...
Source: Translational Stroke Research - January 24, 2019 Category: Neurology Source Type: research

Altered Extracellular Vesicle MicroRNA Expression in Ischemic Stroke and Small Vessel Disease
AbstractActive transport of microRNAs (miRNA) in extracellular vesicles (EV) occurs in disease. Circulating EV-packaged miRNAs in the serum of stroke patients were compared to stroke mimics with matched cardio- and cerebrovascular risk factors, with corroboration of results in a pre-clinical model. An unbiased miRNA microarray was performed in stroke vs. stroke mimic patients (n = 39). Results were validated (n = 173 patients) by real-time quantitative polymerase chain reaction. miRNA expression was quantified in total serum/EV (n = 5–7) of naïve adult spontaneously hypertensive stroke-prone rats (SHRSP), th...
Source: Translational Stroke Research - January 7, 2019 Category: Neurology Source Type: research

Very Low Frequency Heart Rate Variability Predicts the Development of Post-Stroke Infections
AbstractStroke-induced immunodepression is a major risk factor for severe infectious complications in the immediate post-stroke period. We investigated the predictive value of heart rate variability (HRV) to identify patients at risk of post-stroke infection, systemic inflammatory response syndrome, or severe sepsis during the post-acute interval from days 3 to 5 after stroke onset. A prospective, observational monocentric cohort study was conducted in a university hospital stroke unit of patients with ischemic infarction in the territory of the middle cerebral artery without an ongoing infection at admission. Standard HRV...
Source: Translational Stroke Research - January 7, 2019 Category: Neurology Source Type: research

Preclinical Validation of the Therapeutic Potential of Glasgow Oxygen Level Dependent (GOLD) Technology: a Theranostic for Acute Stroke
AbstractIn acute stroke patients, penumbral tissue is non-functioning but potentially salvageable within a time window of variable duration and represents target tissue for rescue. Reperfusion by thrombolysis and/or thrombectomy can rescue penumbra and improve stroke outcomes, but these treatments are currently available to a minority of patients. In addition to the utility of Glasgow Oxygen Level Dependent (GOLD) as an MRI contrast capable of detecting penumbra, its constituent perfluorocarbon (PFC) oxygen carrier, combined with normobaric hyperoxia, also represents a potential acute stroke treatment through improved oxyg...
Source: Translational Stroke Research - November 30, 2018 Category: Neurology Source Type: research

From Analysis of Ischemic Mouse Brain Proteome to Identification of Human Serum Clusterin as a Potential Biomarker for Severity of Acute Ischemic Stroke
In this study, quantitative proteomic analysis of ischemic mouse brain detected the increase in expression levels of clusterin (CLU) and cystatin C (CST3). Since CLU is a secretary protein, serum samples (n = 70) were obtained from acute ischemic stroke (AIS) patients within 24 h of stroke onset and together with 70 matched health controls. Analysis of CLU levels indicated significantly higher levels in AIS patients than healthy controls (14.91 ± 4.03 vs. 12.79 ± 2.22 ng/L;P = 0.0004). Analysis of serum CST3 also showed significant increase in AIS patients as compared with healthy controls (0.90 ± ...
Source: Translational Stroke Research - November 21, 2018 Category: Neurology Source Type: research

Retinal Vasculature Reactivity During Flicker Light Provocation, Cardiac Stress and Stroke Risk in Africans: The SABPA Study
AbstractStructural and functional similarities exist between the retinal, cerebral and, as previously suggested, the coronary microvasculature. Retinal microvascular structure and functionality (in response to flicker-light-induced-provocation (FLIP)) may relate to coronary artery disease risk and possible stroke risk. We investigated associations between retinal vessel structure, functionality and cardiac stress markers (cardiac troponin T [cTnT], amino-terminal B-type natriuretic peptide [NT-proBNP]) to translate these retina –heart relationships to stroke risk. We included 317 African and Caucasian teachers’ (aged 2...
Source: Translational Stroke Research - November 9, 2018 Category: Neurology Source Type: research

Application of Mesenchymal Stem Cell-Derived Extracellular Vesicles for Stroke: Biodistribution and MicroRNA Study
In this study, we investigated the biodistribution, therapeutic efficacy, and mode of action of MSC-EVs in a rat stroke model. MSC-EVs successfully stimulated neurogenesis and angiogenesis in vivo. When compared to the MSC-treated group, rats treated with MSC-EVs exhibited greater behavioral improvements than the control group (p <  0.05). Our biodistribution study using fluorescence-labeled MSC-EVs and MSCs demonstrated that the amounts of MSC-EVs in the infarcted hemisphere increased in a dose-dependent manner, and were rarely found in the lung and liver. In addition, MSC-EVs were highly inclusive of various prote...
Source: Translational Stroke Research - October 19, 2018 Category: Neurology Source Type: research

Gasdermin Family: a Promising Therapeutic Target for Stroke
AbstractStroke is one of the leading causes of death worldwide and therapies are limited. According to the mechanisms underlying stroke, direct cell demise, destruction of organelles, blood-brain barrier disruption, neuroinflammation are potential therapeutic targets. Gasdermin (GSDM) family is a series of recently discovered proteins, which acts as the executor of pyroptosis and protagonist of membrane pore formation. It can be cleaved by inflammatory caspases that are activated by multi-protein complexes, named as inflammasomes, and divided into two domains. The N-terminal domain interacts with lipid localized in the pla...
Source: Translational Stroke Research - October 3, 2018 Category: Neurology Source Type: research

Influence of Thrombolysis on the Safety and Efficacy of Blocking Platelet Adhesion or Secretory Activity in Acute Ischemic Stroke in Mice
AbstractIn acute ischemic stroke (AIS), there is an alarming discrepancy between recanalization rates of up to 70% by combined recombinant tissue-type plasminogen activator (rt-PA) therapy and mechanical thrombectomy, and no clinical benefit in at least every second stroke patient. This is partly due to ischemia/reperfusion (I/R) injury. In a translational approach, we used mice lacking dense- (Unc13d−/−) or α-granules (Nbeal2−/−) and mice after blocking of platelet glycoprotein receptor (GP) Ib conferring protection from I/R injury. These mice underwent transient middle cerebral artery occlusion (tMCAO) and, as i...
Source: Translational Stroke Research - October 1, 2018 Category: Neurology Source Type: research

Ras-Related C3 Botulinum Toxin Substrate 1 Promotes Axonal Regeneration after Stroke in Mice
In conclusion, Rac1 signaling enhances axonal regeneration and improve post-stroke functional recovery in experimental models of stroke.
Source: Translational Stroke Research - October 1, 2018 Category: Neurology Source Type: research

Effect of TTC Treatment on Immunohistochemical Quantification of Collagen IV in Rat Brains after Stroke
AbstractAlthough used extensively in stroke research, there is limited knowledge of how 2, 3, 5-triphenyltetrazolium chloride (TTC)-treated rat brain sections are altered and if they can be used for immunohistochemical quantification after staining with TTC. In the present study, we hypothesized that TTC treatment (TTC+) would not interfere with collagen IV immunohistochemical staining compared with non-TTC-treated (TTC −) brain slices. We further hypothesized that there would be no difference in autofluorescence or nonspecific secondary antibody fluorescence between TTC+ and TTC− brain slices. Coronal brain sections o...
Source: Translational Stroke Research - October 1, 2018 Category: Neurology Source Type: research

Baicalin Attenuates Blood-Brain Barrier Disruption and Hemorrhagic Transformation and Improves Neurological Outcome in Ischemic Stroke Rats with Delayed t-PA Treatment: Involvement of ONOO − -MMP-9 Pathway
AbstractTissue plasminogen activator (t-PA) has a restrictive therapeutic window within 4.5  h after ischemic stroke with the risk of hemorrhagic transformation (HT) and neurotoxicity when it is used beyond the time window. In the present study, we tested the hypothesis that baicalin, an active compound of medicinal plant, could attenuate HT in cerebral ischemia stroke with delayed t-PA t reatment. Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 4.5 h and then continuously received t-PA infusion (10 mg/kg) for 0.5 h and followed by 19-h reperfusion. Baicalin (50, 100, 150 mg/kg) ...
Source: Translational Stroke Research - October 1, 2018 Category: Neurology Source Type: research

Photothrombotic Stroke as a Model of Ischemic Stroke
AbstractThe search of effective anti-stroke neuroprotectors requires various stroke models adequate for different aspects of the ischemic processes. The photothrombotic stroke model is particularly suitable for the study of cellular and molecular mechanisms underlying neurodegeneration, neuroprotection, and neuroregeneration. It is a model of occlusion of small cerebral vessels, which provides detailed study of molecular mechanisms of ischemic cell death and useful for search of potential anti-stroke agents. Its advantages include well-defined location and size of ischemic lesion that are determined by the aiming of the la...
Source: Translational Stroke Research - October 1, 2018 Category: Neurology Source Type: research