scholarly journals Tissue plasminogen activator prevents white matter damage following stroke

2011 ◽  
Vol 208 (6) ◽  
pp. 1229-1242 ◽  
Author(s):  
Fernando Correa ◽  
Maxime Gauberti ◽  
Jérôme Parcq ◽  
Richard Macrez ◽  
Yannick Hommet ◽  
...  
Keyword(s):  
White Matter ◽  
Plasminogen Activator ◽  
Cell Fate ◽  
Tissue Plasminogen Activator ◽  
Mechanism Of Action ◽  
White Matter Lesions ◽  
Brain Diseases ◽  
Stroke Treatment ◽  
Tissue Plasminogen ◽  
The Impact

Tissue plasminogen activator (tPA) is the only available treatment for acute stroke. In addition to its vascular fibrinolytic action, tPA exerts various effects within the brain, ranging from synaptic plasticity to control of cell fate. To date, the influence of tPA in the ischemic brain has only been investigated on neuronal, microglial, and endothelial fate. We addressed the mechanism of action of tPA on oligodendrocyte (OL) survival and on the extent of white matter lesions in stroke. We also investigated the impact of aging on these processes. We observed that, in parallel to reduced levels of tPA in OLs, white matter gets more susceptible to ischemia in old mice. Interestingly, tPA protects murine and human OLs from apoptosis through an unexpected cytokine-like effect by the virtue of its epidermal growth factor–like domain. When injected into aged animals, tPA, although toxic to the gray matter, rescues white matter from ischemia independently of its proteolytic activity. These studies reveal a novel mechanism of action of tPA and unveil OL as a target cell for cytokine effects of tPA in brain diseases. They show overall that tPA protects white matter from stroke-induced lesions, an effect which may contribute to the global benefit of tPA-based stroke treatment.

scholarly journals The Impact of Loading Dose on Outcome in Stroke Patients Receiving Low-Dose Tissue Plasminogen Activator Thrombolytic Therapy

2020 ◽  
Vol Volume 14 ◽  
pp. 257-263 ◽  
Author(s):  
Yi-Sin Wong ◽  
Sheng-Feng Sung ◽  
Chi-Shun Wu ◽  
Yung-Chu Hsu ◽  
Yu-Hsiang Su ◽  
...  
Keyword(s):  
Thrombolytic Therapy ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Low Dose ◽  
Loading Dose ◽  
Stroke Patients ◽  
Tissue Plasminogen ◽  
The Impact

Abstract WP105: Tissue Plasminogen Activator (tPA) is Essential for Functional Recovery After Stroke by Promoting Axonal Outgrowth

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Shubei Ma
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Functional Recovery ◽  
Stroke Recovery ◽  
White Matter Integrity ◽  
Blue Staining ◽  
Tissue Plasminogen

Objectives: Stroke is the leading cause of long term neurological disability with limited therapeutic options. Human recombinant tissue plasminogen activator (tPA) is currently the only FDA approved drug for the thrombolytic treatment of ischemic stroke. Emerging evidence suggests that the effects of tPA in ischemic brain may extend beyond its thrombolytic activity. In this study, we investigated the role of tPA in long term stroke recovery. Methods: Cortical infarct was induced by distal middle cerebral artery occlusion (dMCAO) in tPA knockout (KO) and wild type (WT) mice. Sensorimotor functions were evaluated at 3-35 days after dMCAO. White matter integrity was assessed by luxol fast blue staining, immunohistochemistry for SMI-32, and diffusion tensor imaging (DTI). The neuronal tracer biotinylated dextran amine (BDA) was used to label the corticorubral tract and the corticospinal tract. For rescue experiment, tPA (2mg/kg) was delivered intranasally to tPA KO mice once a day for 14 days starting 6h after dMCAO. Results: Infarct volume was comparable between tPA KO and WT mice after dMCAO. Sensorimotor deficits after dMCAO were exacerbated in tPA KO mice than WT mice. tPA KO mice also showed more severe demyelination in post-stroke white matter and reduced axonal sprouting at 35 days after dMCAO compared to WT mice. DTI studies revealed deteriorated white matter integrity in tPA KO mice, as manifested by decreased fractional anisotropy. Intranasal delivery of tPA after dMCAO rescued the neurological phenotype shown by tPA KO mice. Conclusion: Endogenous tPA promotes white matter integrity and is essential for functional recovery after ischemic stroke. tPA may be a novel neurorestorative therapy for stroke recovery.

scholarly journals Recent Advances in Tissue plasminogen activator-based nanothrombolysis for ischemic stroke

2019 ◽  
Vol 58 (1) ◽  
pp. 159-170 ◽  
Author(s):  
Dongdong Huang ◽  
Ke Wu ◽  
Ying Zhang ◽  
Zhihui Ni ◽  
Xiaohong Zhu ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Plasminogen Activator ◽  
Drug Delivery System ◽  
Tissue Plasminogen Activator ◽  
Delivery System ◽  
Rapid Development ◽  
Neurological Dysfunction ◽  
Hemorrhagic Complication ◽  
Stroke Treatment ◽  
Tissue Plasminogen

Abstract Stroke is an acute cerebrovascular disorder caused by sudden decrease or interruption of blood flow in brain arteries. Deficiency of timely and effective reperfusion of ischemic brain tissue can lead to irreversible brain injury and neurological dysfunction. Currently, recombinant tissue plasminogen activator (rt-PA) is the only appropriate thrombolytic agent which is approved by FDA for patients with acute ischemic stoke. However, due to the limitation of very narrow therapeutic time window and severe intracranial hemorrhagic complication, the outcome of stroke treatment mediated by rt-PA still remains unsatisfactory. Therefore, it is urgent to find new alternative drugs or develop novel drug delivery system to achieve better outcomes. In recent years, with the rapid development of nanotechonology, nanomaterials as a drug delivery system can provide new strategies and methods to carry t-PA specifically to the occlusion site and provide advanced treatment for stroke. In this review, we briefly introduced the physiopathologic mechanisms of thrombolysis and focused on the comparison of the t-PA mediated thrombolysis and t-PA conjugated nanomaterial mediated thrombolysis.

scholarly journals Fibrinolysis With TPA Alone Is Only One Third As Effective As It Should Be

2020 ◽  
Vol 5 (3) ◽  
pp. 1-3
Author(s):  
Victor Gurewich ◽  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Mechanism Of Action ◽  
Fibrin Clot ◽  
Efficient Mechanism ◽  
Tissue Plasminogen

Therapeutic fibrinolysis has used tissue Plasminogen Activator (tPA) alone since 1987,when tPA was first approved for the treatment of Acute Myocardial Infarction (AMI). The use of Tpa was based on the belief that it was responsible for fibrinolysis. However, this assumption should have been put into question from the outset when tPA was found to have the same efficacy as Streptokinase (SK). This was unexpected, since SK has an indirect, less efficient mechanism of action and SK has no fibrin clot affinity, in contrast to tPA. Nevertheless, the 30-day AMI mortality with tPA and SK were identical in the first two trials.

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