Early-life seizures in rats increase susceptibility to seizure-induced brain injury in adulthood

Background: Early childhood convulsions have been correlated with the findi ng of subsequent hippocampal neuronal loss and memory impairment in patient s with intractable temporal lobe epilepsy. There is little direct evidence, however, that links early seizures with the later development of epilepsy and selective hippocampal neuronal loss. Objective: To study the long-term effect of early seizures on later seizure-induced neuronal damage and behav ior. Methods: We used a "two hit" rat seizure made in which systemic kainat e was used to induce seizures during the second week of life (P15) and agai n in adulthood (P45). Memory was subsequently tested using a Morris water m aze, and brains were examined for histologic evidence of injury. Results: A lthough the first kainate-induced seizure is not associated with detectable injury or cell death, it predisposes animals to more extensive neuronal in jury after kainate-induced seizures in adulthood. Moreover, although early- life kainate-induced seizures cause no impairment of spatial learning, anim als that have early-life and adult kainate-induced seizures perform signifi cantly worse than those that have seizures only as adults. Conclusions: We concluded that early-life seizures, without causing overt cellular injury, predispose the brain to the damaging effect of seizures later in life.