Abstract 84: Effects of Edaravone on Brain Apoptotic Gene in CA/CPR Rats

Abstract

Edaravone(3-methyl-1-phenyl-2-pyrazolin-5-one), a strong novel free radical scavenger, is used in clinically as a novel neuroprotective agent for the treatment of patients with acute ischemic stroke. We assessed the hypothesis that the neuroprotective effect of edaravone corresponding with brain apoptosis could improvethe survival outcomes in a rat model of cardiac arrest/cardiopulmonary resuscitation (CA/CPR). Adult male Sprague-Dawley rats were divided into saline, edaravone groupssubjected to sham group (sham surgery, n=10), saline group (CA for 5 min following CPR and intravenous ejection of saline 1.5 ml/kg, n=20), edaravone (CA for 5 min following CPR and intravenous ejection of edaravone 3 mg/kg, n=20)groups. The resuscitated animals were observed for 72 h after the restoration of spontaneous circulation. The rat survival time, survival rate was assessed and the expression of caspase-3, caspase-8, Bax and Bcl-2mRNA at 12, 24, 48 and 72 hours in hippocampus was measured by real time-PCR. Edaravone markedly enhanced the survival time and rate of rats (Kaplan-Meier analysis) after CA/CPR compared to saline group [(70.00±26.69) h, 95% CI (17.67-122.33)] vs[(23.00±3.91) h, 95% CI (15.33-30.67)] and (45% vs. 25%, χ2=4.900, P=0.027). The expression of apoptotic gene mRNA was significant upregulation (except caspase-8 and Bax in edaravone group at 72 h) in both the saline and edaravone groups (P<0.05) compared to sham group. Edaravone significantly decreased the expression of caspase-3, caspase-8 and Bax mRNA (P<0.05) and facilitate Bcl-2 expression (P<0.05) compared to saline group (Tab1-4). This study suggests that (i)CA/CPR results in upregulation of pro-and anti-apoptosis; (ii)edaravone suppresses the up-regulation of the pro-apoptotic gene expression and facilitates the expression of anti-apoptotic gene in the hippocampus, involved in the improvement of the survival outcomes after CPR.