Neuronal damage in gerbils caused by intermittent forebrain ischemia.

OBJECT: The purpose of this study was to investigate the possibility of preventing cumulative neuronal damage after repetitive severe ischemia. METHODS: The authors monitored ischemic depolarization in the gerbil hippocampus, which has recently been shown to be a good experimental model of the effects of brief ischemia on the brain, and evaluated neuronal damage in the CA1 subregion 7 days after the ischemic insult. In a single-ischemia paradigm, the results indicate that induction of ischemia-induced neuronal damage depended on the duration of ischemic depolarization. Neuronal damage can be detected in the CA1 subregion after a period of depolarization lasting 210 seconds. Using a double-ischemia paradigm in which the animals were subjected to two periods of ischemia, there was apparently no accumulation of neuronal damage from the first ischemic episode to the second, provided the duration of the first period of ischemic depolarization did not exceed 90 seconds. Neuronal damage accumulated when the duration of the first ischemia episode exceeded 90 seconds, regardless of the duration of the reperfusion interval between the two ischemic insults. Finally, when the ischemic insult was spread over four separate episodes, each lasting 90 seconds (with a reperfusion interval of 5 minutes), neuronal damage was not found when the total depolarization period was less than 420 seconds. CONCLUSIONS: The authors conclude that cumulative neuronal damage may be avoided by adopting an intermittent ischemia approach. The implications of these results for human surgery requiring temporary occlusion of the cerebral arteries are discussed.