Abstracts

RATIONALE: The relationship between prolonged seizures in infancy and the development of temporal lobe epilepsy has been debated for decades. In the lithium-pilocarpine model of temporal lobe epilepsy, the initial status epilepticus (SE) is able to lead to epilepsy only in adult animals and in some 21-day-old (P21) rats. However, in another subset of P21 rats as well as in P10 rats, the initial SE is not able to lead to spontaneous epilepsy. However, it is not known whether SE triggered in immature rats may sensitize the brain to later insults. Therefore, we induced SE in P10 rats with lithium-pilocarpine and investigated the threshold to convulsive seizures when they were adult.
METHODS: P10 rats were subjected to lithium-pilocarpine SE, and allowed to recover and to grow until adulthood. The experiments were performed on 8 rats subjected to SE and 9 rats receiving saline instead of pilocarpine. At 3 months, they were implanted with cortical electrodes and subjected to various convulsants, either GABA antagonists, picrotoxin (PTX) and pentylenetetrazol (PTZ) or a limbic convulsant, kainate. The latency to and type of clinical seizures as well as the EEG signs were recorded in both groups after various doses of the convulsants.
RESULTS: PTX (2.5 and 4 mg/kg) led to the dose-dependent occurrence of spike-and-waves followed by clonic seizures. PTZ (20 and 25 mg/kg) induced spike-and-wave discharges followed by clonic seizures at the highest dose. All types of seizures lasted for the same time in pilocarpine and saline animals but the latency to spike-and-waves was shorter with PTX in pilocarpine- vs saline-exposed rats. Kainate (5 and 8 mg/kg) induced spike-and-waves followed by staring, wet-dog shakes and stage 4 seizures. There was no difference in either the latency or duration of the seizures between pilocarpine- and saline-treated rats.
CONCLUSIONS: In conclusion, SE triggered by lithium-pilocarpine does not lead to any long-term change in seizure threshold. Conversely febrile seizures decrease the threshold to later seizures. Thus, the nature of the initial insult appears to be a critical factor for the later sensitivity to seizures and possibly for the development of epilepsy.
Support: INSERM U 398 and Fondation pour la Recherche Medicale.