Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6261979 | Brain Research Bulletin | 2011 | 4 Pages |
The present study investigated the role of thrombin in the expression of protease-activated receptor-1 (PAR-1), and the effect of argatroban (Arg) a direct thrombin inhibitor, on PAR-1 expression in perihematomal tissue with intracerebral hemorrhage (ICH). For these experiments 90 rats were divided into 5 groups: sham, ICH, argatroban-treated ICH (ICHÂ +Â Arg), thrombin (TM) and argatroban-treated thrombin (TMÂ +Â Arg). The ICH model or thrombin injection models were established by injecting autologous blood or thrombin, respectively. Rats in TMÂ +Â Arg and ICHÂ +Â Arg groups were administered argatroban (0.9Â mg/kg) after models were established for 3Â h and 12Â h, intraperitoneally. All rats were killed to harvest brains after models were established for 24Â h. The levels of PAR-1 protein and PAR-1 mRNA expression were detected by Western blot and RT-PCR, respectively. Brain water content was also measured. Our results showed that the levels of PAR-1 protein or PAR-1 mRNA in ICH and TM groups were up-regulated compared to that observed for the sham group; while the levels observed in ICHÂ +Â Arg group and TMÂ +Â Arg group were significantly lower than that observed for the ICH group and TM group (PÂ <Â 0.01 or PÂ <Â 0.05). The intraperitoneal administration argatroban also significantly reduced edema in ICH or TM group (PÂ <Â 0.05). Our observations suggested that the production of thrombin following ICH play a key role in the up-regulation of PAR-1 and anti-PAR-1 by systemic administration of argatroban, and may be a potential strategy for ICH therapy.
⺠Expression of PAR-1 in perihematomal tissue was related to thrombin with intracerebral hemorrhage (ICH). ⺠Systemic administration of argatroban (a new direct thrombin inhibitor) could inhibit the expression of PAR-1 in ICH. ⺠Blocking PAR-1 expression after ICH may be a potential treatment for ICH.