Platelets as drivers of ischemia/reperfusion injury after stroke

Abstract Ischemic stroke is a leading cause of morbidity and mortality worldwide and, despite reperfusion either via thrombolysis or thrombectomy, stroke patients often suffer from lifelong disabilities. These persistent neurological deficits may be improved by treating the ischemia/reperfusion (I/R) injury that occurs following ischemic stroke. There are currently no approved therapies to treat I/R injury, and thus it is imperative to find new targets to decrease the burden of ischemic stroke and related diseases. Platelets, cell fragments from megakaryocytes, are primarily known for their role in hemostasis. More recently, investigators have studied the nonhemostatic role of platelets in inflammatory pathologies, such as I/R injury after ischemic stroke. In this review, we seek to provide an overview of how I/R can lead to platelet activation and how activated platelets, in turn, can exacerbate I/R injury after stroke. We will also discuss potential mechanisms by which platelets may ameliorate I/R injury.

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Prognostic value of plasma HMGB1 in ischemic stroke patients with cerebral ischemia-reperfusion injury after intravenous thrombolysis

Journal of Stroke and Cerebrovascular Diseases ◽

10.1016/j.jstrokecerebrovasdis.2020.105055 ◽

2020 ◽

Vol 29 (9) ◽

pp. 105055 ◽

Cited By ~ 1

Author(s):

Jia Wang ◽

Yu Jiang ◽

Dan Zeng ◽

Wensheng Zhou ◽

Xiuqin Hong

Keyword(s):

Ischemic Stroke ◽

Cerebral Ischemia ◽

Reperfusion Injury ◽

Prognostic Value ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Intravenous Thrombolysis ◽

Stroke Patients ◽

Cerebral Ischemia Reperfusion ◽

Cerebral Ischemia Reperfusion Injury

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MiR-298 Exacerbates Ischemia/Reperfusion Injury Following Ischemic Stroke by Targeting Act1

Cellular Physiology and Biochemistry ◽

10.1159/000491810 ◽

2018 ◽

Vol 48 (2) ◽

pp. 528-539 ◽

Cited By ~ 11

Author(s):

Hongxue Sun ◽

Di Zhong ◽

Cheng Wang ◽

Yilei Sun ◽

Jiaying Zhao ◽

...

Keyword(s):

Ischemic Stroke ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Artery Occlusion ◽

Neurological Deficits ◽

Luciferase Assay ◽

Regulatory Relationship

Background/Aims: This study investigated the role of the microRNA miR-298 and its target Act1 in ischemic stroke. Methods: Cell viability was assessed with the 3-(4,5-dimethythiazol-2- yl)-2,5-diphenyl tetrazolium bromide assay. Apoptotic cells were detected by flow cytometry, and mRNA and protein expression were assessed by quantitative real-time PCR and western blotting, respectively. The regulatory relationship between miR-298 and Act1 was evaluated with the luciferase assay. To clarify the role of Act1 following ischemic stroke, the transcript was knocked down by short interfering RNA. The in vitro findings were validated in a mouse model of middle cerebral artery occlusion by administration of miR-298 mimic. Results: Act1 was upregulated whereas miR-298 was downregulated in ischemic stroke. miR-298 overexpression by transfection of a mimic suppressed Act1 protein levels in vitro and in vivo, and the luciferase assay showed that miR-298 directly binds to the 3’ untranslated region of the Act1 transcript. miR-298 overexpression enhanced cell apoptosis and autophagy and exacerbated ischemic infarction and neurological deficits, effects that were exerted via negative regulation of Act1/c-Jun N-terminal kinase (JNK)/nuclear factor (NF)-κB signaling and downstream autophagy pathways. Conclusions: Upregulation of miR-298 following ischemic stroke promotes brain injury in vitro and vivo by inhibiting the Act1/JNK/NF-κB signaling cascade and the downstream autophagy pathway. Therapeutic strategies that target miR-298 could be beneficial for the treatment of ischemic stroke.

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