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Published in: Translational Stroke Research 3/2021

01-06-2021 | Subarachnoid Hemorrhage | Review Article

The Role of Thrombin in Brain Injury After Hemorrhagic and Ischemic Stroke

Authors: Fenghui Ye, Hugh J. L. Garton, Ya Hua, Richard F. Keep, Guohua Xi

Published in: Translational Stroke Research | Issue 3/2021

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Abstract

Thrombin 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 thrombosis which takes place in every stroke and subsequent brain injury. The extravascular effects and direct cellular interactions of thrombin are mediated by PARs (PAR-1, PAR-3, and PAR-4) and their downstream signaling in multiple brain cell types. Such effects include inducing blood-brain-barrier disruption, brain edema, neuroinflammation, and neuronal death, although low thrombin concentrations can promote cell survival. Also, thrombin directly links the coagulation system to the immune system by activating interleukin-1α. Such effects of thrombin can result in both short-term brain injury and long-term functional deficits, making extravascular thrombin an understudied therapeutic target for stroke. This review examines the role of thrombin and PARs in brain injury following hemorrhagic and ischemic stroke and the potential treatment strategies which are complicated by their role in both hemostasis and brain.
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Metadata
Title
The Role of Thrombin in Brain Injury After Hemorrhagic and Ischemic Stroke
Authors
Fenghui Ye
Hugh J. L. Garton
Ya Hua
Richard F. Keep
Guohua Xi
Publication date
01-06-2021
Publisher
Springer US
Published in
Translational Stroke Research / Issue 3/2021
Print ISSN: 1868-4483
Electronic ISSN: 1868-601X
DOI
https://doi.org/10.1007/s12975-020-00855-4

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