Ischemic Tolerance in the Maturation of Disseminated Selective Neuronal Necrosis and Cerebral Infarction After Repetitive Ischemia

Summary

We examined whether a brief non-lethal ischemia could induce ischemic tolerance to subsequent ischemia as well as reduce infarct size in gerbils subjected to repeated transient cerebral ischemia. Gerbils subjected to a repeated occlusion of the left common carotid artery (two occlusions separated by a 5-h interval) developed infarction (infarct size 2.28±0.75% of the hemisphere, mean ± SEM) in the frontal cortex. A total of 8 min of unilateral carotid-artery occlusion, experienced 48–72 h prior to the repeated ischemia, reduced the infarct size (0.11±0.04% in the 60-h group, P<0.05). Reduction of succinic dehydrogenase activity examined 48 h after the repeated ischemic insults was significantly milder in the preconditioned animal. Thus, preconditioning by a brief non-lethal ischemia experienced 48 h or more, prior to repeated ischemia, induced tolerance and significantly reduced infarct size. Impairment of mitochondrial function in a non-neuronal cell is probably important in the observed ischemic tolerance.