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. Therefore, 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 after the model was established. Forty-eight hours later, compared with those administered saline, rabbits receiving
SCH79797 showed markedly decreased neuronal damage as assessed by serum
neuron specific enolase levels and less neurological dysfunction as determined using cerebral performance category scores. Additionally, in the hippocampus, cell apoptosis, polymorphonuclear cell infiltration, and c-Jun levels were decreased, whereas
extracellular signal-regulated kinase phosphorylation 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. These findings suggest that
SCH79797 mitigates
brain injury via anti-inflammatory 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.