ATTENUATION OF ISCHEMIA-REPERFUSION INJURY IN THE RAT NEOCORTEX BY THE HYDROXYL RADICAL SCAVENGER NICARAVEN

OBJECTIVE: Oxygen free radicals are considered important contributors to cerebral ischemia-reperfusion injury. The purpose of this study was to examine the effects of the hydroxyl radical scavenger, (+/-)-N,N'- propylenedinicotinamide (nicaraven), on cerebral injury after focal is chemia-reperfusion. METHODS: A total of 58 male Sprague-Dawley rats wa s subjected to transient focal ischemia by occluding both carotid arte ries and one middle cerebral artery for 3 hours. Animals received cont inuous infusions of doses of 20 mg/kg per hour or 60 mg/kg per hour of nicaraven beginning either 10 minutes before (pretreatment) or immedi ately after (posttreatment) ischemia. Infarction volumes were evaluate d by staining coronal brain sections with 2% 2,3,5-triphenyltetrazoliu m chloride (n = 40). In other animals (n = 18), brain edema was evalua ted 1 hour after ischemia. RESULTS: A dose of 20 mg/kg per hour of nic araven elicited small reductions in infarction volume (14.7 and 12.3% for the pre- and posttreatment groups, respectively). Treatment with a dose of 60 mg/kg per hour of nicaraven provided significant reduction s in the volume of infarction (18.6% [P < 0.05] and 20.9% [P < 0.01] r eductions for the pre- and posttreatment groups, respectively). The re ductions in infarction size did not differ significantly between the p re- and posttreatment groups receiving a dose of 60 mg/kg per hour of nicaraven. Posttreatment with either dose of nicaraven significantly r educed brain edema. CONCLUSIONS: This study demonstrates the neuroprot ective effects of a hydroxyl radical scavenger when administered syste mically during the reperfusion phase after transient focal ischemia. T he results provide, to our knowledge, the first evidence that nicarave n is effective against ischemia-reperfusion injury in the brain and de monstrate that oxygen free radicals generated during reperfusion are i mportant triggers of ischemic brain damage. Furthermore, the findings suggest that nicaraven may be a useful agent in limiting brain injury after ischemic stroke.