Excitotoxic preconditioning elicited by both glutamate and hypoxia and abolished by lactate transport inhibition in rat hippocampal slices

Ischemic preconditioning (PC) of heart and brain is a well-documented pheno menon. However, the mechanism underlying the increased resistance to severe ischemia by a preceding mild ischemic exposure remains unclear. Over a dec ade ago, we demonstrated the existence of hypoxic PC in the hippocampal sli ce preparation. Here we report the ability of a short exposure to toxic lev els of glutamate to heighten the tolerance of hippocampal slices to a subse quent, longer exposure to the excitotoxin. Glutamate PC could also be induc ed by a short hypoxic exposure, suggesting a common mechanistic pathway for all PC stimuli. Since glutamate receptor activation and hypoxia increase t issue lactate production, a-cyano-4-hydroxycinnamate was applied during the PC period to completely abolished PC. These results indicate that excitoto xic PC and hypoxic PC share similar mechanisms that possibly involve lactat e production and its neuronal utilization. (C) 2001 Published by Elsevier S cience Ireland Ltd.