Subarachnoid hemorrhage (SAH) is a critical neurological emergency and one of the leading causes of stroke. Neuronal demise serves as the primary factor contributing to early brain injury (EBI) following SAH. This study aims to investigate the molecular mechanism underlying Hirudin's impact on EBI after SAH, with a particular focus on pyroptosis. The SAH rat model was established by performing intravascular puncture, followed by the administration of Hirudin and Nod-like receptor protein 3 (NLRP3) agonist Nigericin into the lateral ventricle. The SAH grading, neurological score, brain water content, blood-brain barrier (BBB) permeability, neuronal damage, inflammatory reaction, neuronal death, distribution of microglia marker Iba-1 and expression levels of NLRP3 inflammasomal-related proteins were evaluated at 72 h post-SAH. Hirudin treatment significantly ameliorated neurological scores and attenuated brain edema, BBB permeability, inflammatory response, microglia activation, and pyroptosis in SAH rats. Additionally, Hirudin treatment downregulated the expression levels of NLRP3 inflammasomal- related proteins, such as NLRP3, apoptosis- associated speck-like protein (ASC) and cleaved caspsase-1. However, Nigericin partially counteracted the aforementioned effects of Hirudin, indicating that Hirudin exerted its inhibitory effect on pyroptosis by modulating the NLRP3 inflammasome pathway. The neuroprotective effect of Hirudin on EBI following SAH is attributed its ability to inhibit pyroptosis mediated by NLRP3 inflammasome, suggesting its potential as a promising therapeutic approach for SAH. Keywords: Subarachnoid hemorrhage, Early brain injury, Hirudin, pyroptosis, Nod-like receptor protein 3 (NLRP3) inflammasome.

Zhuang Medicine Classic Ward Guangxi International Zhuang Medicine Hospital Nanning China

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