Corticosterone-aggravated ischemic neuronal damage in vitro is relieved by vanadate

Preischemic hyperglycemia-aggravated neuronal damage has been postulated to occur via enhanced lactic acidosis. We have hypothesized that preischemic glucose loading induces a short-lived elevation in glucocorticoid release which, when combined with ischemia, aggravates the postischemic outcome. This study tested this hypothesis in rat hippocampal slices exposed to 4 min in vitro ischemia of which 58% exhibited recovery of neuronal function. However, when corticosterone (CT) was present during ischemia, the recovery of neuronal function decreased in a concentration-dependent manner. At 5 microM, CT reduced the recovery rate to 40% while only 10% of slices recovered when exposed to 20 microM CT. Insulin could not block the effect of CT; however, vanadate improved the postischemic recovery of CT-treated (20 microM) slices to 43%. These results indicate that acute, short exposure to CT can significantly exacerbate postischemic outcome and that vanadate can antagonize CT action.