Ischemic tolerance in hippocampal CA1 neurons studied using contralateral controls

We induced ischemic tolerance unilaterally in gerbil hippocampus using the contralateral hippocampus as control. Ischemia for 2min of right common carotid occlusion was reversible but sufficient to cause heat-shock protein 70 production in CA1 neurons. This pretreatment given four days prior to occlusion of both common carotids for 5 min, but not at longer preceding intervals, induced tolerance in right CA1 neurons. Neuroprotection was still evident two months after the 5 min occlusion. Adenosine triphosphate content and immunoreactive microtubule associated protein 2 in the hippocampus showed that the 5 min ischemic insult was essentially equal in both hemispheres. Repetitive pretreatments at two day intervals caused almost complete protection of CA1 neurons against subsequent 5 min ischemia, while a single pretreatment showed 80% protection. However, the increase in heat-shock protein 70 with repealed pretreatments was not significantly more than with one pretreatment. We concluded that true ischemic tolerance was induced by ischemic stress itself, was long-lasting, was not due to mitigation of subsequent ischemia, and was augmented by repetition without further increase of heat-shock protein 70. (C) 1997 IBRO. Published by Elsevier Science Ltd.