Early-life experience alters response of developing brain to seizures

Abstract Prolonged seizures during childhood are associated with behavior problems, memory impairment and school failure. No effective treatment currently exists after seizures to mitigate neuronal injury and long-term neurological sequelae for children with epilepsy. We studied the therapeutic efficacy of early-life environment on seizure-induced behavioral deficits, neuronal injury and the inflammatory reaction using the kainic acid (KA) seizure model. Two rearing conditions, maternal separation for 3 h daily versus maternal care in an enriched environment, were followed by single housing for the former (Deprived) and group housing in an enriched environment for the latter (Enriched). To examine the influence of differential rearing on the behavioral effects of early-life seizures, KA was injected on P21. On P28, marked reduction in exploratory behavior was noted after seizures only in the Deprived group. To investigate seizure-induced hippocampal injury, a separate group of rats were injected with KA on P35 since consistent seizure-induced neuronal injury is observed only in mature rats. Brains of rats sacrificed on P37 displayed a significant reduction in DNA fragmentation and microglial activation in Enriched compared to Deprived animals. Our results suggest that a nurturing early environment can enhance the ability of the developing brain to recover from seizures and provide a buffer against their damaging effects. While the nurturing environment was neuroprotective, the combination of deprived rearing and the insult of early-life seizures resulted in significant behavioral deficits, an increase in neuronal injury and activation of microglia in young rats.