Hyperthermia-induced seizures in rat pups with preexisting ischemic brain injury.

To investigate the mechanism(s) relating perinatal brain injury to increased seizure sensitivity in the developmental age period, we studied hyperthermia-induced seizures in rat pups with a preexisting unilateral ischemic cerebral injury. At 2 days of age, the pups underwent a carotid artery ligation followed by 20 min of anoxia. By light microscopy, there were no pathologic changes in the postischemic cerebral cortex at 5, 10, or 20 days of age. Seizures were induced by hyperthermia at 5, 10, 15, or 20 days of age. Seizure temperature thresholds increased with maturation in both postischemic and control animals. Temperature thresholds for behavioral seizures were significantly lower at 10, 15, and 20 days in postischemic pups, compared with control animals. By EEG criteria, seizure thresholds also were lower at 10 and 15 days in the postischemic pups compared with control animals. Preictal EEG slowing appeared at the same temperature in experimental and control animals at all ages. We conclude that the rat pup is an appropriate model for the study of enhanced epileptogenesis in the presence of a perinatal ischemic encephalopathy.