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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

Critical Early Thrombolytic and Endovascular Reperfusion Therapy for Acute Ischemic Stroke Victims: a Call for Adjunct Neuroprotection
This article has 3 main goals: (1) first to emphasize the utility and cost-effectiveness of rt-PA to treat stroke; (2) second to review the recent endovascular trials with respect to efficacy, safety, and cost-effectiveness as a stroke treatment; and (3) to further consider and evaluate strategies to develop novel neuroprotective drugs. A thesis will be put forth so that future stroke trials and therapy development can optimally promote recovery so that stroke victims can return to “normal” life.
Source: Translational Stroke Research - August 29, 2015 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

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

Four Decades of Ischemic Penumbra and Its Implication for Ischemic Stroke
AbstractThe ischemic penumbra defined four decades ago has been the main battleground of ischemic stroke. The evolving ischemic penumbra concept has been providing insight for the development of vascular and cellular approaches as well as diagnostic tools for the treatment of ischemic stroke. rt-PA thrombolytic therapy to prevent the transition of ischemic penumbra to core has been approved for acute ischemic stroke within 3  h and was later recommended to extend to 4.5 h after symptom onset. Mechanical thrombectomy was introduced for the treatment of acute ischemic stroke with a therapeutic window of up to 24 h after s...
Source: Translational Stroke Research - July 5, 2021 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

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

Effects of the New Thrombolytic Compound LT3001 on Acute Brain Tissue Damage After Focal Embolic Stroke in Rats
In this study, we tested the effects of LT3001 as a potential alternative thrombolytic in focal embolic ischemic stroke rat model. Stroked rats received intravenous injection of 10  mg/kg LT3001 or tPA at 1.5, 3, or 4.5 h after stroke, respectively, and the outcomes were measured at different time points after stroke by performing multi-parametric MRI, 2,3,5-triphenyltetrazolium chloride (TTC) staining, and modified neurological severity score. Lastly, we assessed the effect of LT3001 on the tPA activity in vitro, the international normalized ratio (INR), and the serum levels of active tPA and plasminogen activator inhib...
Source: Translational Stroke Research - November 29, 2022 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

The Role of Thrombin in Brain Injury After Hemorrhagic and Ischemic Stroke
AbstractThrombin is increased in the brain after hemorrhagic and ischemic stroke primarily due to the prothrombin entry from blood either with a hemorrhage or following blood-brain barrier disruption. Increasing evidence indicates that thrombin and its receptors (protease-activated receptors (PARs)) play a major role in brain pathology following ischemic and hemorrhagic stroke (including intracerebral, intraventricular, and subarachnoid hemorrhage). Thrombin and PARs affect brain injury via multiple mechanisms that can be detrimental or protective. The cleavage of prothrombin into thrombin is the key step of hemostasis and...
Source: Translational Stroke Research - April 20, 2021 Category: Neurology Source Type: research

Diabetes Mellitus/Poststroke Hyperglycemia: a Detrimental Factor for tPA Thrombolytic Stroke Therapy
AbstractIntravenous administration of tissue-type plasminogen activator (IV tPA) therapy has long been considered a mainstay in ischemic stroke management. However, patients respond to IV tPA therapy unequally with some subsets of patients having worsened outcomes after treatment. In particular, diabetes mellitus (DM) is recognized as a clinically important vascular comorbidity that leads to lower recanalization rates and increased risks of hemorrhagic transformation (HT). In this short-review, we summarize the recent advances in understanding of the underlying mechanisms involved in post-IV tPA worsening of outcome in dia...
Source: Translational Stroke Research - April 20, 2021 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

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

Combination of Polyethylene Glycol-Conjugated Urokinase Nanogels and Urokinase for Acute Ischemic Stroke Therapeutic Implications
AbstractTissue reperfusion is a serious therapeutic strategy of ischemic stroke in addition to recanalization. In this work, we aimed to establish new urokinase-based therapeutics in order to dissolve large vessel thrombus together with microthrombi for stroke implications. Formulations consisted of free urokinase (UK), polyethylene glycol –crosslinked urokinase nanogel (PEG-UK), and a 1:1 mixture of UK and PEG-UK (PEG-UK+UK) were tested both in vitro and in vivo. In vitro experiments confirmed the pH-dependent release of PEG-UK in the PEG-UK+UK formulation. It was activated at pH 6.50, an environmental pH in the infarc...
Source: Translational Stroke Research - October 16, 2020 Category: Neurology Source Type: research

Plasma Kallikrein Contributes to Intracerebral Hemorrhage and Hypertension in Stroke-Prone Spontaneously Hypertensive Rats
This report investigates the role of PKa on hemorrhage and hypertension in stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP were fed with a high salt –containing stroke-prone diet to increase blood pressure and induce intracerebral hemorrhage. The roles of PKa on blood pressure, hemorrhage, and survival in SHRSP were examined in rats receiving a PKa inhibitor or plasma prekallikrein antisense oligonucleotide (PK ASO) compared with rats receivin g control ASO. Effects on PKa on the proteolytic cleavage of atrial natriuretic peptide (ANP) were analyzed by tandem mass spectrometry. We show that SHRSP on high-salt...
Source: Translational Stroke Research - July 9, 2021 Category: Neurology Source Type: research

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