RAPID PRECONDITIONING PROTECTS RATS AGAINST ISCHEMIC NEURONAL DAMAGE AFTER 3 BUT NOT 7 DAYS OF REPERFUSION FOLLOWING GLOBAL CEREBRAL-ISCHEMIA

Earlier studies indicated that sublethal ischemic insults separated by many hours may ''precondition'' and, thereby, protect tissues from su bsequent insults. In Wistar rats, we examined the hypothesis that isch emic preconditioning (IPC) can improve histopathological outcome even if the ''conditioning'' and ''test'' ischemic insults are separated by only 30 min. Normothermic (36.5-37 degrees C) global cerebral ischemi a was produced by bilateral carotid artery ligation after lowering mea n systemic blood pressure. The conditioning ischemic insult lasted 2 m in and was associated with a time sufficient to provoke ''anoxic depol arization'' (AD) (i.e., the abrupt maximal increase in extracellular p otassium ion activity). After 30 min of reperfusion, 10-min test ische mia was produced, and histopathology was assessed 3 and 7 days later. After 3 days of reperfusion, neuroprotection was most robust in the le ft lateral, middle and medial subsections of the hippocampal CA1 subfi eld and in the cortex, where protection was 91, 76, 70 and 86%, respec tively. TPC also protected the right lateral, middle and medial subsec tions of the hippocampal CA1 region. These data demonstrate that neuro protection against acute neuronal injury can be achieved by conditioni ng insults followed by only short (30 min) periods of reperfusion. How ever, neuroprotection almost disappeared when reperfusion was continue d for 7 days. When test ischemia was decreased to 7 min, a clear trend of neuroprotection by IPC was observed. These data suggest that subse quent rescue of neuronal populations could be achieved with better und erstanding of the neuroprotective mechanisms involved in this rapid IP C model.