Jb. Schulz et al., FACILITATION OF POSTISCHEMIC REPERFUSION WITH ALPHA-PBN - ASSESSMENT USING NMR AND DOPPLER FLOW TECHNIQUES, American journal of physiology. Heart and circulatory physiology, 41(4), 1997, pp. 1986-1995
We examined the effects of the free radical spin trap N-tert-butyl-alp
ha-phenylnitrone (PBN) on focal cerebral ischemia/reperfusion injury i
n halothane-anesthetized rats. Ninety minutes after middle cerebral ar
tery 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 m
easured 24 h after ischemia. During ischemia and during the first 30 m
in after reperfusion, cerebral blood volume and blood flow were measur
ed by volume-sensitive and newly developed flow-sensitive magnetic res
onance 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 f
low deficits matched the final lesion volumes at 24 h measured histolo
gically 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 a
nimals, in contrast to the saline-treated control group. We conclude t
hat in focal ischemia/reperfusion PBN provides protection of the vascu
lar endothelium, leading to enhanced postischemic reperfusion. The imp
lication of this is that the vascular endothelium may be a primary tar
get for the damaging action of free radicals given the protection affo
rded by putative spin traps.