EPILEPTOGENESIS INDUCED BY RAPIDLY RECURRING SEIZURES IN GENETICALLY FAST-KINDLING BUT NOT SLOW-KINDLING RATS

A brief period of rapidly recurring hippocampal seizures can lead to t he progressive development of a permanent increase of seizure suscepti bility over several weeks, so-called 'delayed kindling'. We have analy zed seizure parameters critical for the induction of delayed kindling in two strains of rats characterized by fast and slow rates of traditi onal kindling, respectively. Forty seizures were produced during about 3 h by electrical kindling stimulations every 5 min in the ventral hi ppocampus. The fast rats displayed several generalized convulsions and had long periods of epileptiform activity, whereas the slow animals o nly exhibited brief, focal seizures. Changes in excitability were dete rmined after 4 weeks using five test stimulations, and 2 weeks later b y subjecting all animals to traditional hippocampal kindling. The fast rats showed clearly enhanced responsiveness at these time points, whe reas no evidence of permanently increased seizure susceptibility was o btained in the slow rats. Our data indicate that the long-lasting stim ulus-evoked seizures are mainly responsible for inducing delayed kindl ing, whereas the number of seizure events or generalized convulsions, and the total duration of epileptiform activity are less important. We hypothesize that long seizure episodes may be necessary to trigger th e cascade of gene changes regulating the development of epilepsy. (C) 1998 Elsevier Science B.V.