Abstracts

RATIONALE:_Seizures in the neonatal period are often associated with significant neorological impairment. Previous studies have demonstrated that rats subjected to recurrent neonatal seizures have impaired learning, lower seizure thresholds and sprouting of mossy fibers as adults. The goal of this study was to determine the time course of these changes in cognition and brain excitability. METHODS:Male rats at postnatal day (P) 1 were exposed to a convulsant dose of flurothyl five times daily for nine days (total 45 seizures). Content recognition testing by fear conditioning was performed at P18, visual-spatial learning in the water-maze at P20 and P35, and seizure susceptibility to flurothyl at P20 and P40. Rats were sacrificed at P20 and P40 and brains examined for mossy fiber sprouting, cell number and glutamate receptor density. RESULTS:Rats exposed to recurrent neonatal seizures showed significant impairment in the water-maze and reduced seizure threshold as early as P20, and these changes were stable when the water-maze and seizure threshold were repeated at P35 and P40. CONCLUSIONS:_Our studies suggest that the cognitive dysfunction and altered seizure threshold occurs rapidly after neonatal seizures and is not progressive.