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 ischemia-reperfusion.


METHODS
A total of 58 male Sprague-Dawley rats was subjected to transient focal ischemia by occluding both carotid arteries and one middle cerebral artery for 3 hours. Animals received continuous infusions of doses of 20 mg/kg per hour or 60 mg/kg per hour of nicaraven beginning either 10 minutes before (pretreatment) or immediately after (posttreatment) ischemia. Infarction volumes were evaluated by staining coronal brain sections with 2% 2,3,5-triphenyltetrazolium chloride (n = 40). In other animals (n = 18), brain edema was evaluated 1 hour after ischemia.


RESULTS
A dose of 20 mg/kg per hour of nicaraven 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 reductions in the volume of infarction (18.6% [P < 0.05] and 20.9% [P < 0.01] reductions for the pre- and posttreatment groups, respectively). The reductions in infarction size did not differ significantly between the pre- and posttreatment groups receiving a dose of 60 mg/kg per hour of nicaraven. Posttreatment with either dose of nicaraven significantly reduced brain edema.


CONCLUSIONS
This study demonstrates the neuroprotective effects of a hydroxyl radical scavenger when administered systemically during the reperfusion phase after transient focal ischemia. The results provide, to our knowledge, the first evidence that nicaraven is effective against ischemia-reperfusion injury in the brain and demonstrate that oxygen free radicals generated during reperfusion are important triggers of ischemic brain damage. Furthermore, the findings suggest that nicaraven may be a useful agent in limiting brain injury after ischemic stroke.
Toyoda
T
T
Department of Neurological Surgery, Virginia Neurological Institute, University of Virginia, Charlottesville, USA.
Kassell
N F
NF
Lee
K S
KS
D000818:Animals; D002545:Brain Ischemia / Q000473:pathology*; D002540:Cerebral Cortex / Q000098:blood supply* / Q000473:pathology; D002544:Cerebral Infarction / Q000473:pathology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D017665:Hydroxyl Radical / Q000378:metabolism*; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology*
D016166:Free Radical Scavengers; D009536:Niacinamide; D017665:Hydroxyl Radical; C042625:nicaraven