Transient hyperthermia protects against subsequent seizures and epilepsy-induced cell damage in the rat

Many mild preconditioning stress conditions, including physical and metabolic injuries, increase the resistance of neurons to subsequent more severe stresses of the same or different type. This “tolerance phenomenon” lasts one to several weeks, providing a unique opportunity to investigate endogenous neuroprotective mechanisms. The aim of this study was to find a physiological and easily applicable preconditioning stimulus able to confer protection against convulsant-induced neuronal damage and seizures. We found that moderate transient hyperthermic preconditioning markedly reduced kainic-acid-induced neuronal cell loss and attenuated susceptibility to bicuculline-induced seizures. Prevention of cell damage (∼50%) was efficient both in vitro in organotypic hippocampal slice cultures and in vivo in adult rats. This protection lasted about 1 week and peaked 3 to 5 days after pretreatment. Unraveling the mechanisms of heat shock preconditioning-induced protection against epilepsy should lead to the development of new therapeutic strategies.