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. 2024 Apr 18:15:1293428.
doi: 10.3389/fphar.2024.1293428. eCollection 2024.

Pathological mechanisms and future therapeutic directions of thrombin in intracerebral hemorrhage: a systematic review

Chenxi Tao #  1   2 , Yuanyuan Li #  1   2 , Na An  1 , Haoqi Liu  1 , Zhenhong Liu  1   2 , Yikun Sun  1 , Ying Qian  1 , Na Li  1 , Yanwei Xing  3 , Yonghong Gao  1   2
Affiliations

Pathological mechanisms and future therapeutic directions of thrombin in intracerebral hemorrhage: a systematic review

Chenxi Tao et al. Front Pharmacol. .

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.

Keywords: blood-brain barrier; inflammation; intracerebral hemorrhage; neuronal damage; secondary brain injury; systematic review; thrombin.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
PRISMA flowchart outlining the process of retrieving and filtering articles, with n indicating the number of articles selected.
FIGURE 2
FIGURE 2
Risk of bias assessment of included animal studies.
FIGURE 3
FIGURE 3
The molecular mechanism of thrombin involved in brain injury and repair after ICH. (BBB: blood-brain-barrier; MAC: membrane attack complex; AV: autophagic vacuoles; tPA: tissue plasminogen activator.) Created with BioRender.com.
FIGURE 4
FIGURE 4
Mechanisms by which thrombin affects endothelial cells, astrocytes, pericytes, microglia, and neurons after ICH. (BBB: blood-brain barrier; PAR: protease-activated receptor; VEGF: vascular endothelial growth factor; ROS: reactive oxygen species; ERK: signal-regulated kinase; JNK: c-Jun N-terminal kinase.) Created with BioRender.com.
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