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COVID-19-Related Stroke
AbstractThe COVID-19 pandemic is associated with neurological symptoms and complications including stroke. There is hypercoagulability associated with COVID-19 that is likely a “sepsis-induced coagulopathy” and may predispose to stroke. The SARS-CoV-2 virus binds to angiotensin-converting enzyme 2 (ACE2) present on brain endothelial and smooth muscle cells. ACE2 is a key part of the renin angiotensin system (RAS) and a counterbalance to angiotensin-converting enzyme 1 (ACE1) and angiotensin II. Angiotensin II is proinflammatory, is vasoconstrictive, and promotes organ damage. Depletion of ACE2 by SARS-CoV-2 may tip the...
Source: Translational Stroke Research - May 6, 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. Decision...
Source: Translational Stroke Research - January 13, 2020 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 17, 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 angiography and histology....
Source: Translational Stroke Research - December 4, 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 7, 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

Enhancing Base Excision Repair of Mitochondrial DNA to Reduce Ischemic Injury Following Reperfusion
AbstractWe hypothesize that enhancing mitochondrial base excision repair (BER) capability in brain will reduce reperfusion-associated ischemic brain injury. Post-stroke reperfusion was modeled in mice via transient filament occlusion of the middle cerebral artery (60  min) (transient MCAO). Administration of a TAT-modified form of a DNA glycosylase (EndoIII) following reperfusion of the brain reduced resultant brain infarct volume. Protection was dose-dependent, BER enzyme specific, and regionally specific (more effective via the jugular vein). EndoIII is compa tible with tissue plasminogen activator (tPA). The time windo...
Source: Translational Stroke Research - December 8, 2018 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

MMP10 Promotes Efficient Thrombolysis After Ischemic Stroke in Mice with Induced Diabetes
AbstractDiabetes is an important risk factor for ischemic stroke (IS). Tissue-type plasminogen activator (tPA) has been associated with less successful revascularization and poor functional outcome in diabetes. We assessed whether a new thrombolytic strategy based on MMP10 was more effective than tPA in a murine IS model of streptozotocin (STZ)-induced diabetes. Wild-type mice were administered a single dose of streptozotocin (STZ) (180  mg/kg) to develop STZ-induced diabetes mellitus. Two weeks later, IS was induced by thrombin injection into the middle cerebral artery and the effect of recombinant MMP10 (6.5 μg/kg), t...
Source: Translational Stroke Research - July 27, 2018 Category: Neurology Source Type: research

Do the Risk Factors Determine the Severity and Outcome of Cerebral Venous Sinus Thrombosis?
We report the burden of risk factors in cerebral venous sinus thrombosis (CVST) and its relationship with the clinical severity, extent of MRI and MRV abnormality, and outcome. One hundred and twenty-eight consecutive patients with CVST were included. Their demographic, presenting symptoms and neurological findings were noted and risk factors of CVST were evaluated. The outcomes were assessed using modified Rankin Scale (mRS). Based on the risk factors, the patients could be categorized as prothrombotic conditions only in 46 (35.9%), prothrombotic with other risk factors in 36 (28.1%), non-prothrombotic risk factors in 20 ...
Source: Translational Stroke Research - January 10, 2018 Category: Neurology Source Type: research

Annexin A2 Plus Low-Dose Tissue Plasminogen Activator Combination Attenuates Cerebrovascular Dysfunction After Focal Embolic Stroke of Rats
The objective of this study was to investigate the effects and mechanisms of the combination in early BBB integrity and cerebrovascular patency in the rat focal embolic stroke model. Ischemic brain infarct volume and hemorrhagic transformation were quantified at 24  h after stroke. At an earlier time point, 16 h after stroke, BBB integrity was evaluated by IgG extravasation, and the involved mechanisms were assessed for tight junction ZO-1 and adhesion junction ve-cadherin protein expression, matrix metalloproteinase activation, extracellular matrix collagen IV and endothelial barrier antigen expression, and activation o...
Source: Translational Stroke Research - June 3, 2017 Category: Neurology Source Type: research

Cytoprotective Drug-Tissue Plasminogen Activator Protease Interaction Assays: Screening of Two Novel Cytoprotective Chromones
In conclusion, the results suggest that high concentrations of both cytoprotectives reduced 4-nitroaniline production in vitro, but the inhibition only occurs with concentrations 104 –1025-fold that of EC50 values in an efficacy assay. Thus, CSMC-19 and CSMC-140 should be further developed and evaluated in embolic stroke models in the absence or presence of a thrombolytic. If necessary, they could be administered once effective tPA thrombolysis has been confirmed to avoid the possibility that the chromone will reduce the efficacy of tPA in patients. Stroke investigator developing new cytoprotective small molecules should...
Source: Translational Stroke Research - April 12, 2017 Category: Neurology Source Type: research

Re-evaluate the Efficacy and Safety of Human Urinary Kallidinogenase (RESK): Protocol for an Open-Label, Single-Arm, Multicenter Phase IV Trial for the Treatment of Acute Ischemic Stroke in Chinese Patients
AbstractAcute ischemic stroke (AIS) is a major medical challenge in China. Thrombolytic drugs recommended for the treatment of AIS usually have a narrow time window. Human urinary kallidinogenase (HUK) was approved by the China Food and Drug Administration (CFDA) in 2005 for the treatment of mild to moderate AIS, and it is thus widely used in China. However, large-scale clinical study data for a more complete understanding of various aspects of its safety and efficacy characteristics are still unavailable. The ongoing Reevaluate the Efficacy and Safety of Human Urinary Kallidinogenase (RESK) trial is designed to reevaluate...
Source: Translational Stroke Research - March 5, 2017 Category: Neurology Source Type: research

Neurogenesis in Stroke Recovery
Abstract Stroke, resulting from limited blood flow to the brain, is one of the most important causes of morbidity and mortality worldwide. Stroke is classified as ischemic, due to lack of blood flow, or hemorrhagic, due to bleeding. Because 87 % of strokes are classified as ischemic, this type will be the predominant focus of this review. Except for thrombolytic therapy, there is no established treatment to reduce the neurological deficits caused by ischemic stroke. Therefore, it is necessary to develop new therapeutic strategies designed to improve neurological functions after ischemic stroke. Recently, therapie...
Source: Translational Stroke Research - March 17, 2016 Category: Neurology Source Type: research

Partial MHC Constructs Treat Thromboembolic Ischemic Stroke Characterized by Early Immune Expansion
Abstract Inflammation and thrombosis are tightly linked, with inflammation contributing to thromboembolism and to stroke outcome. Thromboembolism is a frequent cause of ischemic stroke; yet, the most used occlusion mouse models of experimental stroke do not effectively replicate thromboembolism. Our group recently described a novel thromboembolic mouse model of stroke that successfully occludes the middle cerebral artery with high reproducibility. In the current study, we characterize the peripheral and local immune outcomes as well as the ischemic response to immune therapy in a clinically relevant mouse model of...
Source: Translational Stroke Research - December 1, 2015 Category: Neurology Source Type: research

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