Mild intraischemic hypothermia suppresses consumption of endogenous antioxidants after temporary focal ischemia in rats.
Oxidative damage by free radicals has been proposed as a mechanism of cerebral injury due to ischemia and reperfusion. Hypothermia protects against ischemic necrosis; however, its effect on oxidative stress has not been investigated. In this study, the effects of hypothermia on oxidative stress were studied by determining consumption of endogenous antioxidants after temporary focal ischemia in rats. Thirty-two Sprague-Dawley rats anesthetized with 1.5% isoflurane underwent 3 h of middle cerebral artery occlusion under hypothermic (33 degrees C) or normothermic (37 degrees C) conditions followed by 3 h of normothermic reperfusion. In the first study (n = 8 per group), intraischemic hypothermia suppressed the reduction of tissue concentrations of endogenous antioxidants, ascorbate (P < or = 0.05), and glutathione (P < or = 0.05) in ischemic cortex but not in caudoputamen. In a parallel study (n = 8 per group), hypothermia reduced tissue damage in ischemic frontoparietal cortex (P < or = 0.05), but not in caudoputamen. Laser-Doppler estimates of cortical blood flow showed that intraischemic hypothermia significantly attenuated early postischemic hyperperfusion (P < or = 0.01) and delayed postischemic hypoperfusion (P < or = 0.01). These results demonstrate that intraischemic mild hypothermia reduces oxidative stress and cell injury after prolonged focal ischemia followed by reperfusion. The reduction of oxidative stress by hypothermia may be related indirectly to attenuation of postischemic blood flow changes.
Department of Neurological Surgery, School of Medicine, University of California, San Francisco.
H
H
Karibe
S F
SF
Chen
G J
GJ
Zarow
J
J
Gafni
S H
SH
Graham
P H
PH
Chan
P R
PR
Weinstein
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001205:Ascorbic Acid / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D001831:Body Temperature / Q000502:physiology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002536:Cerebral Arteries / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology; D005978:Glutathione / Q000378:metabolism; D007036:Hypothermia, Induced; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion
D000975:Antioxidants; D005978:Glutathione; D001205:Ascorbic Acid