Anti-apoptotic and neuroprotective effects of edaravone following transient focal ischemia in rats

To investigate the effect of an antioxidant edaravone on the apoptotic process, we examined Bax and Bcl-2 immunohistochemical expression and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) reactivity. Rat focal ischemia models were prepared by 2 h transient middle cerebral artery occlusion. Edaravone or physiological saline was intravenously administered after reperfusion. After 24 h of reperfusion, infarction volume assessments, Bax and Bcl-2 immunohistochemistry and TUNEL staining were performed as well as neurological evaluation. Cortical cerebral blood flow was not statistically different between the treatment-groups. Edaravone-treated animals showed significantly improved neurological outcome. Total and cortical infarct volumes in the edaravone group significantly decreased. In addition, edaravone-treatment provided a significant reduction in the number of TUNEL-positive apoptotic cells, a decrease in Bax immunoreactivity and an increase in Bcl-2 expression within the peri-infarct area. Edaravone shows an excellent neuroprotective effect against ischemia/reperfusion brain injury through a Bax/Bcl-2 dependent anti-apoptotic mechanism.