title: A protease-activated receptor 1 antagonist protects against global cerebral ischemia/reperfusion injury after asphyxial cardiac arrest in rabbits.
abstract: 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 injuryviaanti-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.
authors.affiliation: Department of Emergency Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei Province, China; Department of Immunology, Hubei University of Medicine, Shiyan, Hubei Province, China.
authors.forename: Jing-Ning
authors.initials: JN
authors.lastname: Yang
authors.affiliation: Department of Immunology, Hubei University of Medicine, Shiyan, Hubei Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Emergency Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei Province, China.
authors.forename: Min
authors.identifier: 0000-0002-9439-4308
authors.initials: M
authors.lastname: Xiao
keywords: SCH79797; apoptosis; cardiac arrest; global cerebral ischemia/reperfusion; hippocampus; inflammation; nerve regeneration; neural regeneration; neuron specific enolase; neuroprotection; protease-activated receptor 1