A Possible Role of Lipid Peroxidation in Cellular Damages Caused by Cerebral Ischemia and the Protective Effect of a-Tocopherol Administration

Incomplete global cerebral ischemia was induced by clamping the bilateral common carotid arteries of spontaneously hypertensive rats (SHR) and blood reperfusion was allowed by declamping the arteries after indicated times. To investigate the possible role of lipid peroxidation which causes irreversible ischemic cell injury during ischemia and subsequent reperfusion, cerebral energy metabolism, brain edema, neurological signs and cerebral and serum lipid peroxides were examined. The effect of a-tocopherol administration on these parameters was also studied from the standpoint of its action as a free radical scavenger. During ischemia up to 5 hours, cerebral ATP decreased and lactate increased rapidly, and concomitantly neurological signs, such as eye closure and jumping seizures, and slowly progressing brain edema were observed. The level of lipid peroxides in the brain and serum remained practically unchanged during ischemia, although an increasing tendency was noted. When blood reperfusion was allowed 3 hours after ischemia, tissue ATP level was restored only partially (67.4% of normal), but lactate returned to the normal level. The reperfusion resulted in a rapid rise in the lipid peroxide level both in cerebral tissue and serum and also caused a more severe expression of neurologi­ cal signs. Intravenous injection of a-tocopherol (20 mg/kg body weight) 30 minutes prior to ligation of the carotid arteries significantly suppressed the rise in lipid peroxides both in the brain and serum, improved the severely expressed neurological signs, and promoted resynthesis of ATP. These improvements in the param­ eters were observed only after the reperfusion was made following ischemia for 3 hours. The results suggest that a-tocopherol plays a role in protecting ischemic Cellular damages by scavenging free radicals and subsequently lipid peroxides formed by oxygen supply through blood reperfusion. Stroke Vol 14, No 6, 1983