Transneuronal Induction of Tolerance in Cerebral Ischemia

Abstract

Development of enhanced tolerance to ischemic injury has been demonstrated when lethal ischemia is preceded by sublethal ischemic exposure. This study demonstrates a transneuronal induction of tolerance in distant areas, unaffected by primary ischemia, but connected by neuronal circuitry. In Model I, the induction of spreading depression in the cerebral cortex of the rat preceded 10-min cardiac arrest cerebral ischemia by 3 days. In Model II, the middle cerebral artery (MCA) occlusion for 2h in rats was followed 3 days later by 10-min clamping of both common carotid arteries, with simultaneous lowering of mean arterial blood pressure to 50 mm Hg. In Model III, 5-min bilateral occlusion of common carotid arteries in gerbils was preceded 3 days earlier by 35-min occlusion of the left common carotid artery in ischemiasensitive animals. Our observations in Models I and II revealed a marked bilateral preservation of CA1 pyramidal neurons. Gerbils in Model III showed, on the side of the 35-min occlusion, numerous infarcted regions, including hippocampus, whereas the contralateral hippocampus revealed a marked preservation of CA1 neurons. It is assumed that CA1 pyramidal cell protection is transneuronally transmitted via the entorhinal cortex and is associated with early activation of c-fos expression in both hippocampi.