Facilitation of postischemic reperfusion with alpha-PBN: assessment using NMR and Doppler flow techniques.
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.
Schulz
J B
JB
Neurochemistry Laboratory and Neurology Service, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
Panahian
N
N
Chen
Y I
YI
Beal
M F
MF
Moskowitz
M A
MA
Rosen
B R
BR
Jenkins
B G
BG
D000818:Animals; D001794:Blood Pressure; D001921:Brain / Q000098:blood supply* / Q000503:physiopathology; D001931:Brain Mapping; D002245:Carbon Dioxide / Q000097:blood; D002560:Cerebrovascular Circulation; D003497:Cyclic N-Oxides; D006339:Heart Rate; D006439:Hemodynamics; D002546:Ischemic Attack, Transient / Q000000981:diagnostic imaging / Q000503:physiopathology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009589:Nitrogen Oxides; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D015427:Reperfusion Injury / Q000000981:diagnostic imaging / Q000503:physiopathology*; D013113:Spin Labels; D013997:Time Factors; D018608:Ultrasonography, Doppler
D003497:Cyclic N-Oxides; D009589:Nitrogen Oxides; D013113:Spin Labels; D002245:Carbon Dioxide; C029217:phenyl-N-tert-butylnitrone; D010100:Oxygen