TEMPORAL PROFILE OF THE EFFECTS OF PRETREATMENT WITH BRIEF CEREBRAL-ISCHEMIA ON THE NEURONAL DAMAGE FOLLOWING SECONDARY ISCHEMIC INSULT IN THE GERBIL - CUMULATIVE DAMAGE AND PROTECTIVE EFFECTS

We examined the response of the gerbil brain to secondary ischemic insult following pretreatment with brief ischemia at intervals of 5 min, 1 and 6 h, 1, 2, 4, 7 and 14 days. Two minutes of bilateral carotid artery occlusion produced no histopathological brain damage, whereas 3 min of occlusion caused a moderate to severe reduction in the number of hippocampal CAI pyramidal cells. Two-minute occlusion followed by 3-min occlusion at 5-min, 1- and 6-h intervals resulted in almost complete destruction of CAI neurons. Additional neuronal damage was observed in the striatum at a 1-h interval and in the thalamus and the neocortex at 1- and 6-h intervals. The neuronal damage was most severe at a 1-h interval. Two-minute ischemia followed by 3-min ischemia at intervals of 1, 2, 4 and 7 days, however, caused a marked protective effect, and the hippocampal CAI neurons were preserved. The protective effect was not observed at a 14-day interval and following pretreatment with 1-min ischemia. Thus, pretreatment with brief ischemia leads to complex responses of the brain to secondary ischemic insult; cumulative damage at intervals of 1-6 h and protective effects at intervals of 1-7 days.