Cerebral ischemic preconditioning induces lasting effects on CA1 neuronal survival, prevents memory impairments but not ischemia-induced hyperactivity

In ischemic preconditioning, prior exposure to a short 3-min global ischemia provides substantial protection against the deleterious effects of a subsequent prolonged ischemic insult in rats. The objective of the present study was to determine if the neuronal protection induced by ischemic preconditioning influence functional recovery following a 6-min ischemic insult in rats. Animals received either sham-operation, a 3-min ischemia, a preconditioning 3-min global ischemia followed 3 days later by a 6-min global ischemia or a single 6-min global ischemia. Open field habituation, memory performance in the 8-arm radial maze and object recognition were assessed at different intervals following ischemia. Our findings revealed that preconditioning reversed ischemia-induced spatial memory deficits in the 8-arm radial maze, as suggested by significant reduction of working memory errors in preconditioned as compared to ischemic animals. Preconditioning also attenuated ischemia-induced object recognition deficits at short-term intervals. Nonetheless, preconditioning failed to alter ischemia-induced hyperactivity as demonstrated by enhanced behavioral activity in the open field in both preconditioned and ischemic animals compared to 3-min ischemic and sham-operated rats. CA1 cell counts revealed significant neuronal sparing in preconditioned animals that was observed 6-month following reperfusion. Together, these findings suggest that neuronal survival in preconditioned rats is associated with significant improvements of hippocampal-dependent memory functions and, further support that ischemia-induced hyperactivity may not solely depend on selective neuronal damage to hippocampal neurons.