Abstract

We examined the effects of the free radical spin trap N-tert-butyl-alpha-phenylnitrone (PBN) on focal cerebral ischemia/reperfusion injury in halothane-anesthetized rats. Ninety minutes after middle cerebral artery occlusion by an intraluminal filament, the artery was reperfused. Intravenous injections of 25 mg/kg PBN 5 min before and 30 min after insertion of the filament significantly attenuated the lesion volume measured 24 h after ischemia. During ischemia and during the first 30 min after reperfusion, cerebral blood volume and blood flow were measured by volume-sensitive and newly developed flow-sensitive magnetic resonance imaging (MRI) techniques and by laser-Doppler flowmetry. In all animals the area of decreased blood flow was larger than the area of decreased volume by a factor of 2.2. The area of the postreperfusion flow deficits matched the final lesion volumes at 24 h measured histologically much better than did the blood volume deficits in both saline and PBN-treated animals. Reperfusion led to a return of blood flow and volume to values close to the contralateral side in the PBN-treated animals, in contrast to the saline-treated control group. We conclude that in focal ischemia/reperfusion PBN provides protection of the vascular endothelium, leading to enhanced postischemic reperfusion. The implication of this is that the vascular endothelium may be a primary target for the damaging action of free radicals given the protection afforded by putative spin traps.