The long-term effects of seizures on the developing brain: clinical and laboratory issues

The long-term effects of seizures on the developing brain is a difficult clinical problem to study since cognitive impairment and behavioral abnormalities may be related to the etiological agent responsible for the seizures, age at time of onset of seizures, the type, frequency, or duration of the seizures, or the antiepileptic drugs used to treat the seizures. Many of these variables can be eliminated by using animal models of epilepsy. Work in our laboratory using the kainic acid (KA) model has demonstrated that status epilepticus in prepubescent and mature rats leads to significant deficits in memory, learning and behavior as adults when compared to control littermates without seizures. These rats also had a high incidence of spontaneous recurrent seizures (SRS) and an increased susceptibility to seizures using kindling and flurothyl. However, younger animals (less than or equal to 20 day old) with KA-induced seizures of similar severity were not associated with later neurological deficits. The immature animals also had a low rate of SRS and did not differ from controls in susceptibility to kindling or flurothyl. Studies using the continuous hippocampal stimulation model of epilepsy have also demonstrated that prolonged seizures in the developing brain are less severe than those in the mature animal. The pathophysiological mechanisms that "protect" the young brain from long-term detrimental effects of prolonged seizures are unknown.