Proteinase-activated receptor-1 (PAR1) antagonist plays a protective effect in brain injury. We investigated the potential function and mechanisms of PAR1 antagonist in ICH-induced brain injury. Results showed that PAR1 antagonist protected against neurobehavior deficits, brain edema and BBB integrity in ICH mice via activating JNK/ERK/p38 MAPK signaling pathway at 24h after ICH. In addition, ICH resulted in the increase of FGL2 and TLR4 expression over time, and phosphorylated JNK, ERK and p38 MAPK expression. Suppression of FGL2 and TLR4 alleviated brain injury and decreased the expression of p-JNK, p-ERK, p-p38 MAPK and p-IKKα at 24 h after ICH; while overexpression of them showed the opposite result. Moreover, the protective effect of PAR1 antagonist on ICH-induced brain injury was blocked by FGL2 or TLR4 overexpression, and the levels of p-JNK, p-ERK and p-p38 MAPK were inhibited. Furthermore, PAR1 antagonist combined with TLR4 antagonist markedly alleviated brain injury after ICH at 72h. Overall, PAR1 antagonist protected against short-term brain injury, and the effect of PAR1 antagonist on ICH-induced brain injury was mediated by FGL2 or TLR4.
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