CONDITIONING HEAT-STRESS REDUCES EXCITOTOXIC AND APOPTOTIC COMPONENTSOF OXYGEN-GLUCOSE DEPRIVATION-INDUCED NEURONAL DEATH IN-VITRO

We investigated the effects of sublethal heat stress in murine cortica l cell cultures exposed to combined oxygen and glucose deprivation. Pr etreatment with sublethal heat stress mildly attenuated the widespread neuronal death induced a day later by 30-60 min of oxygen-glucose dep rivation. Heat stress also blunted the increase in extracellular gluta mate concentrations induced by the oxygen-glucose deprivation, as well as the neuronal death and Ca-45(2+) uptake induced by exogenous addit ion of NMDA, although no reduction was seen in neuronal death caused b y exogenous kainate or in NMDA-induced whole-cell currents. However, a rguing against the idea that the neuroprotective effect of heat stress against neuronal death was exclusively due to reduction of excitotoxi city was the finding that heat stress also reduced the neuronal apopto sis induced by oxygen-glucose deprivation in the presence of glutamate antagonists. This antiapoptotic effect was specific in that heat stre ss did not reduce neuronal vulnerability to staurosporine-induced apop tosis. Whereas heat stress transiently suppressed protein synthesis, a chieving comparable protein synthesis inhibition with cycloheximide di d not reproduce the neuroprotective effects of heat stress. These stud ies suggest that a conditioning heat stress is able to attenuate both the excitotoxic and the apoptotic components of oxygen-glucose depriva tion-induced neuronal death in vitro, by mechanisms independent of pro tein synthesis reduction.