Hyperthermia induces seizures in both humans and rodents, but the unde
rlying mechanism remains unknown. The present study showed that hypert
hermia, causing rapid increase in body temperature, increases the conc
entration of glutamate (Glu) released into a cortical perfusate before
onset of seizures in rats and that this increase in Glu concentration
correlated with a decrease in seizure threshold temperature. These re
sults indicate that increased cortical extracellular Glu induced by hy
perthermia contributes to onset of seizures. The same mechanism may be
involved in clinical seizures induced by fever in patients with febri
le convulsions or epilepsy.