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Source: Translational Stroke Research
Condition: Thrombosis

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Total 33 results found since Jan 2013.

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

Efficacy and Safety of Recombinant Human Prourokinase in Acute Ischemic Stroke: A Phase IIa Randomized Clinical Trial
AbstractRecombinant human prourokinase (rhPro-UK) is a novel thrombolytic that has been approved to treat patients with acute myocardial infarction. However, the safety and efficacy of intravenous rhPro-UK in patients with acute ischemic stroke (AIS) has not been well established. We aimed to investigate the safety and preliminary efficacy of rhPro-UK in patients with AIS in a multi-center phase IIa trial setting. One hundred nineteen patients within 4.5  h of AIS onset were enrolled in this randomized, open-label, 23-center phase IIa clinical trial. Patients were randomly assigned to 35 mg (n = 40) or 50 mg (n =â...
Source: Translational Stroke Research - May 3, 2022 Category: Neurology Source Type: research

A Novel Plant-Produced Asialo-rhuEPO Protects Brain from Ischemic Damage Without Erythropoietic Action
AbstractMammalian cell-produced recombinant human erythropoietin (rhuEPOM) has been shown to be a multimodal neuroprotectant targeting an array of key pathological mechanisms in experimental stroke models. However, the rhuEPOM clinical trials were terminated due to increased risk of thrombosis, largely ascribed to its erythropoietic function. We recently took advantage of a plant-based expression system lacking sialylation capacity to produce asialo-rhuEPOP, a rhuEPO derivative without sialic acid residues. In the present study, we proved that asialo-rhuEPOP is non-erythropoietic by repeated intravenous injection (44  μg...
Source: Translational Stroke Research - March 14, 2022 Category: Neurology Source Type: research

Compartmentalized Actions of the Plasminogen Activator Inhibitors, PAI-1 and Nsp, in Ischemic Stroke
In this study, we compare the effects of PAI-1 and Nsp deficiency in a mouse model of ischemic stroke and show that tPA has both beneficial and harmful effects that are differentially regulated by PAI-1 and Nsp. F ollowing ischemic stroke Nsp deficiency in mice leads to larger strokes, increased BBB permeability, and increased spontaneous intracerebral hemorrhage. In contrast, PAI-1 deficiency results in smaller infarcts and increased cerebral blood flow recovery. Mechanistically, our data suggests that these differences are largely due to the compartmentalized action of PAI-1 and Nsp, with Nsp deficiency enhancing tPA act...
Source: Translational Stroke Research - February 4, 2022 Category: Neurology Source Type: research

Carboxypeptidase U (TAFIa) Is Rapidly Activated and Deactivated Following Thrombolysis and Thrombectomy in Stroke Patients
AbstractThe antifibrinolytic enzyme carboxypeptidase U (CPU, TAFIa, CPB2) is an appealing target for the treatment of acute ischemic stroke (AIS). Increased insights in CPU activation and inactivation during thrombolysis (rtPA) with or without endovascular thrombectomy (EVT) are required to develop CPU inhibitors as profibrinolytic agents with optimal benefits/risks. Therefore, CPU kinetics during ischemic stroke treatment were evaluated. AIS patients with documented cerebral artery occlusion receiving rtPA (N = 20) or rtPA + EVT (N = 16) were included. CPU activation during thrombolysis was measured by an ultr...
Source: Translational Stroke Research - November 19, 2021 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

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

Acute T2*-Weighted Magnetic Resonance Imaging Detectable Cerebral Thrombosis in a Rat Model of Subarachnoid Hemorrhage
AbstractSubarachnoid hemorrhage (SAH) is associated with a high incidence of morbidity and mortality, particularly within the first 72  h after aneurysm rupture. We recently found ultra-early cerebral thrombosis, detectable on T2* magnetic resonance imaging (MRI), in a mouse SAH model at 4 h after onset. The current study examined whether such changes also occur in rat at 24 h after SAH, the vessels involved, whether the degree of thrombosis varied with SAH severity and brain injury, and if it differed between male and female rats. Adult Sprague Dawley rats were subjected to an endovascular perforation SAH model or sham...
Source: Translational Stroke Research - June 2, 2021 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

Delayed Recanalization —How Late Is Not Too Late?
AbstractStroke has become the second most prevalent cause of mortality in the world. Currently, the treatment of ischemic stroke is based on thrombolytic and thrombectomy therapy shortly after the ischemic event ( ≤ 4.5 h for thrombolytic strategies; ≤ 6 h for thrombectomy strategies). However, the majority of patients are unable to receive prompt treatment, particularly in undeveloped countries. Alternative solutions are lacking for those patients that miss the optimal window of opportunity for tre atment. Recently, new developments in imaging techniques and intravascular interventional devices enable the expans...
Source: Translational Stroke Research - April 20, 2021 Category: Neurology Source Type: research

A Novel Mouse Model for Cerebral Venous Sinus Thrombosis
This study is aimed at developing a novel murine model suitable and relevant for evaluating injury patterns during CVST and studying its clinical aspects. CVST was achieved in C57BL/6J mice by autologous clot injection into the superior sagittal sinus (SSS) combined with bilateral ligation of external jugular veins. Clot was preparedex vivo using thrombin before injection. On days 1 and 7 after CVST, SSS occlusion and associated-parenchymal lesions were monitored using different modalities:in vivo real-time intravital microscopy, magnetic resonance imaging (MRI), and immuno-histology. In addition, mice were subjected to a ...
Source: Translational Stroke Research - March 5, 2021 Category: Neurology Source Type: research

Analysis of Treatment Outcome After Endovascular Treatment in Different Pathological Subtypes of Basilar Artery Occlusion: a Single Center Experience
AbstractThe current study aimed to evaluate whether patients with different pathologic subtypes of basilar artery occlusion (BAO) stroke could affect the clinical outcome after receiving endovascular treatment(EVT). A total of 187 consecutive patients with acute BAO receiving endovascular treatment (EVT) from January 2012 to July 2018 at the Beijing Tiantan Hospital were recruited in this study. The patients were categorized into three groups: embolism without vertebral artery (VA) steno-occlusion (group 1), in situ atherosclerotic thrombosis (group 2), and embolism from tandem VA steno-occlusion (group 3). Among the 187 p...
Source: Translational Stroke Research - March 3, 2021 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

Iodinated Contrast Agents Reduce the Efficacy of Intravenous Recombinant Tissue-Type Plasminogen Activator in Acute Ischemic Stroke Patients: a Multicenter Cohort Study
This study aimed to investigate whether the application of iodinated contrast agents before intravenous (IV) recombinant tissue plasminogen activator (rt-PA) reduces the efficacy in acute ischemic stroke (AIS) patients. To determine whether the application of iodinated contrast agents before intravenous rt-PA reduces the efficacy in AIS patients. We analyzed our prospectively collected data of consecutive AIS patients receiving IV rt-PA treatment in the MISSION CHINA study. Clinical outcome at 3  months was assessed with modified Rankin Scale (mRS) score and dichotomized into good outcome (0–2) and poor outcome (3–6)....
Source: Translational Stroke Research - September 7, 2020 Category: Neurology Source Type: research