Abstracts

Whereas febrile seizures are the most common seizure type in children, their relationships with mesial temporal lobe epilepsy remain controversial. Febrile seizures have been suggested to modify the functional organization of the hippocampus. However, they may not be sufficient to induce epilepsy by themselves and an additional event appears necessary to develop mesial temporal lobe epilepsy with hippocampal sclerosis. To test this hypothesis, we developed a model of hyperthermic seizures in P10-P11 mice and their consequences on epileptogenesis were examined following intrahippocampal kainic acid injection in adult animals. Hyperthermic seizures were induced by a 30 min rise of body temperature (42 [plusmn]1 [deg]C) of P10-11 mice, as described in the rat pups (Baram et al. Dev. Brain Res. 1997; 98:265-270). Seizures were video recorded and EEG monitored using bipolar hippocampal and cortical electrodes. Control animals were exposed to 30[plusmn]1[deg]C pulsed air for 30 min.
At the age of 3 months, intrahippocampal kainic acid (1 nmol in 50 nl) was injected unilaterally as previously described (Riban et al, Neuroscience 2002; 112:101-111) in mice with hyperthermic seizures and their controls. EEG recordings were then performed 3 times a week for 3 weeks. The time course of epileptogenesis, the duration and occurrence of hippocampal discharges were compared between the 2 groups. Hyperthermic seizures in P10-11 mice were first characterised by nose rubbing, followed by myoclonies preceeding tonico-clonic seizures. Both types of seizures were associated with hippocampal discharges. Animals experiencing hyperthermic seizures developed more rapidly epileptogenesis following intrahippocampal injection of kainate, as compared to controls. In particular, during the first week post kainate, hippocampal discharges occurred earlier in animals with hyperthermic seizures. Once established (20-22 days postkainate), hippocampal seizures had similar duration and occurrence as the controls. Generalized convulsive seizures rarely occurred in both groups. This study shows that hyperthermic seizures associated with hippocampal discharges can be induced in P10-11 mice. Our data suggest that such seizures facilitate initiation of epileptogenesis induced by intrahippocampal kainic acid injection in adult animals. (Supported by Inserm.)