Prolonged febrile seizures in the immature rat model enhance hippocampal excitability long term

Febrile seizures (FSs) constitute the most prevalent seizure type during ch ildhood. Whether prolonged FSs alter limbic excitability, leading to sponta neous seizures (temporal lobe epilepsy) during adulthood, has been controve rsial. Recent data indicate that, in the immature rat model, prolonged FSs induce transient structural changes of some hippocampal pyramidal neurons a nd long-term functional changes of hippocampal circuitry. However, whether these neuroanatomical and electrophysiological changes promote hippocampal excitability and lead to epilepsy has remained unknown. By using in vivo an d in vitro approaches, we determined that prolonged hyperthermia-induced se izures in immature rats caused long-term enhanced susceptibility to limbic convulsants that lasted to adulthood. Thus, extensive hippocampal electro-e ncephalographic and behavioral monitoring failed to demonstrate spontaneous seizures in adult rats that had experienced hyperthermic seizures during i nfancy. However, 100% of animals developed hippocampal seizures after syste mic administration of a low dose of kainate, and most progressed to status epilepticus. Conversely, a minority of normothermic and hyperthermic contro ls had (brief) seizures, none developing status epilepticus. In vitro, spon taneous epileptiform discharges were not observed in hippocampal-entorhinal cortex slices derived from either control or experimental groups. However, Schaeffer collateral stimulation induced prolonged, self-sustaining, statu s epilepticus-like discharges exclusively in slices from experimental rats. These data indicate that hyperthermic seizures in the immature rat model o f FSs do not cause spontaneous limbic seizures during adulthood, However, t hey reduce thresholds to chemical convulsants in vivo and electrical stimul ation in vitro, indicating persistent enhancement of limbic excitability th at may facilitate the development of epilepsy.