A protease-activated receptor 1 antagonist protects against global cerebral ischemia/reperfusion injury atfer asphyxial cardiac arrest in rabbits

Cerebral ischemia/reperfusion injury is partially mediated by thrombin, which causes brain damage through protease-activated receptor 1 (PAR1). However, the role and mechanisms underlying the effects of PAR1 activation require further elucidation. hTerefore, the present study investigated the effects of the PAR1 antagonist SCH79797 in a rabbit model of global cerebral ischemia induced by cardiac arrest. SCH79797 was intravenously administered 10 minutes atfer the model was established. Forty-eight hours later, compared with those ad-ministered saline, rabbits receiving SCH79797 showed markedly decreased neuronal damage as assessed by serum neuron speciifc enolase levels and less neurological dysfunction as determined using cerebral performance category scores. Additionally, in the hippocampus, cell apoptosis, polymorphonuclear cell inifltration, and c-Jun levels were decreased, whereas extracellular signal-regulated kinase phosphor-ylation levels were increased. All of these changes were inhibited by the intravenous administration of the phosphoinositide 3-kinase/Akt pathway inhibitor LY29004 (3 mg/kg) 10 minutes before the SCH79797 intervention. hTese ifndings suggest that SCH79797 mitigates brain injury via anti-inlfammatory and anti-apoptotic effects, possibly by modulating the extracellular signal-regulated kinase, c-Jun N-terminal kinase/c-Jun and phosphoinositide 3-kinase/Akt pathways.