NEUROPROTECTIVE EFFECTS OF HYPOTHERMIA AND U-78517F IN CEREBRAL-ISCHEMIA ARE DUE TO REDUCING OXYGEN-BASED FREE-RADICALS - AN ELECTRON-PARAMAGNETIC-RESONANCE STUDY WITH GERBILS

Free radicals are implicated as causative agents in various forms of t issue destruction, Considerable circumstantial evidence suggests that oxygen-based free radicals generated as blood flow returns to formerly ischemic brain areas are mainly responsible for the neurodegeneration that follows periods of cerebral ischemia, In general, oxygen-based f ree radicals are highly reactive and exist for only a brief period of time, This makes the direct measurement of many of these free radicals rather difficult, Much of the current knowledge of free radicals in c erebral ischemia is based on observations of chemical changes brought about by the free radicals rather than on direct observations of the f ree radicals themselves, Low temperature electron paramagnetic resonan ce spectroscopy is one method that allows the direct study of free rad icals, Compared to samples from sham-operated controls, samples of hip pocampus taken from gerbils exposed to 15 min of forebrain ischemia fo llowed by 15 min of reperfusion, frozen in liquid nitrogen less than 2 0 sec after sacrifice, and scanned by low temperature (100 K) electron paramagnetic resonance, show a significant increase in oxygen-based f ree radicals and a decrease in carbon-based ubiquinone-like free radic als, The ischemia-induced increase in oxygen-based free radicals is pr evented by the intraperitoneal injection of the antioxidant drug U-785 17F at the start of reperfusion and by hypothermia, However, neither i ntervention alters the ischemia-induced reduction in the ubiquinone-li ke free radicals, This suggests that the neuroprotective actions of hy pothermia and U-78517F include a direct reduction in the oxygen-based free radical burden of the post-ischemic tissue. (C) 1996 Wiley-Liss, Inc.