A synergistic role of hyperthermic and pharmacological preconditioning to protect astrocytes against ischemia/reperfusion injury.

Recent studies provide solid evidence for the importance to delineate the co-relationship between preconditioning stimuli and therapeutic efficacy of drugs commonly used in clinic. However, very little is known about this important topic. In the present study, we investigated the effects of hyperthermia on the protective role of ginkgolides on astrocytes against ischemia/reperfusion (I/R) injury and also evaluated the effects of the timing of co-treatment of hyperthermia with ginkgolides on astrocytes against the I/R injury. We demonstrated that there is a synergistic action between hyperthermic and pharmacological preconditioning to protect astrocytes against the I/R injury. Our findings also showed that astrocytes have completely different responses to the treatment with hyperthermia or ginkgolides alone or co-treatment together at different stages of the I/R process. Hyperthermic preconditioning before the I/R can protect astrocytes against the I/R injury. However, if treated in the ischemia and reperfusion stage, hyperthermia exacerbates the cell injury and significantly attenuates the protective effectiveness of ginkgolides. These findings imply that the timing of treatment with hypothermia and/or ginkgolides is one of the key factors to determine their protective effects on the cells against the I/R injury.