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Pathological Mechanisms and Future Therapeutic Directions of Thrombin in Intracerebral Hemorrhage: a Systematic Review

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Journal Front Pharmacol
Date 2024 May 3
PMID 38698822
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Abstract

Intracerebral hemorrhage (ICH), a common subtype of hemorrhagic stroke, often causes severe disability or death. ICH induces adverse events that might lead to secondary brain injury (SBI), and there is currently a lack of specific effective treatment strategies. To provide a new direction for SBI treatment post-ICH, the systematic review discussed how thrombin impacts secondary injury after ICH through several potentially deleterious or protective mechanisms. We included 39 studies and evaluated them using SYRCLE's ROB tool. Subsequently, we explored the potential molecular mechanisms of thrombin-mediated effects on SBI post-ICH in terms of inflammation, iron deposition, autophagy, and angiogenesis. Furthermore, we described the effects of thrombin in endothelial cells, astrocytes, pericytes, microglia, and neurons, as well as the harmful and beneficial effects of high and low thrombin concentrations on ICH. Finally, we concluded the current research status of thrombin therapy for ICH, which will provide a basis for the future clinical application of thrombin in the treatment of ICH.

References
1.
Alberelli M, De Candia E . Functional role of protease activated receptors in vascular biology. Vascul Pharmacol. 2014; 62(2):72-81. DOI: 10.1016/j.vph.2014.06.001. View

2.
Zhang Z, Qi J, Zhu H, Song Y, Wu H, Jia Y . Expression of thrombin and its associated protein in cerebellum of human and rat after intracerebral hemorrhage. Chin Med J (Engl). 2010; 123(15):2077-81. View

3.
Wu H, Zhang Z, Li Y, Zhao R, Li H, Song Y . Time course of upregulation of inflammatory mediators in the hemorrhagic brain in rats: correlation with brain edema. Neurochem Int. 2010; 57(3):248-53. PMC: 2910823. DOI: 10.1016/j.neuint.2010.06.002. View

4.
Donovan F, Pike C, Cotman C, Cunningham D . Thrombin induces apoptosis in cultured neurons and astrocytes via a pathway requiring tyrosine kinase and RhoA activities. J Neurosci. 1997; 17(14):5316-26. PMC: 6793831. View

5.
Zhu H, Wang Z, Yu J, Yang X, He F, Liu Z . Role and mechanisms of cytokines in the secondary brain injury after intracerebral hemorrhage. Prog Neurobiol. 2019; 178:101610. DOI: 10.1016/j.pneurobio.2019.03.003. View