BOTH MILD HYPOTHERMIA AND DOPAMINE D2 AGONIST ARE NEUROPROTECTIVE AGAINST HYPERTHERMIA-INDUCED INJURY IN PC12 CELLS

We exposed rat pheochromocytoma PC12 cells to hyperthermia or high dosage of dopamine and examined the direct effects of mild hypothermia or dopamine D(2) receptor agonist. At a hyperthermia of 42-43 degrees C for 120 min there was approximately 50% loss of cell viability accompanied by dopamine overproduction. The model of cell death due to hyperthermia in PC12 cells belonged to the necrotic and late apoptotic population. At each temperature examined below 37 degrees C, significant decrease in cytotoxicity, the percentage of necrotic and late apoptotic cells, and dopamine overproduction were observed. Cytotoxicity could also be induced by high dosages of dopamine. Both hyperthermia and dopamine induced cytotoxicity in PC12 cells could also be reduced by dopamine D(2) agonists. These results indicate the dopamine is important in hyperthermic situations. The results also indicate that mild hypothermia and dopamine D(2) receptor agonists are neuroprotective against hyperthermia-induced brain injury.