Abstracts

Rationale: Temporal lobe epilepsy (TLE) is the most common form of epilepsy and is often associated with hippocampal sclerosis. The disease usually evolves in three different stages: 1) the acute phase, associated with an initial insult (brain trauma, status epilepticus, infection); 2) the latent period where the person shows no sign of epilepsy; and 3) the chronic phase, characterised by the apparition of recurrent spontaneous seizures. Rats reproduce the evolutionary pattern of TLE after the induction of a prolonged seizure (status epilepticus), making them a good model for the disease. Hippocampal sclerosis (HS) is associated with intractable TLE. Our lab recently showed that hippocampal cell death, induced by a status epilepticus (SE) using kainate acid (KA), is strain dependant (Martin et al. AES 2011). Following SE, Dahl SS strain showed severe neuronal loss (75-100%) in at least one region of the hippocampus in 100% of the cases as compare to 0% for the Lewis strain. It was yet unknown if this sensitivity to excitotoxicity was drug dependant or seizure dependant. Our goal was to determine, for both strains, the sensitivity to seizure using kindling and to measure the induced cell death following a SE using intra hippocampal electrical stimulation (IHES).Methods: Male rats (n=10/strain) were submitted, at 60 days old, to the rapid kindling protocol (Lothman and Williamson 1993). In summary, all rats received 12 stimulations each day until they were fully kindled. Rats were considered fully kindled when one low-intensity stimulation could trigger a stage 5 seizure according to the Racine s scale (Racine, 1972). Animal were euthanized 30 days later for histological analysis. Another group of rats (n=5/strain) received a continuous high intensity IHES (Lothman et al. 1989) to achieve SE comparable to what was seen with KA. Results: There was no significant difference in the number of stimulations necessary for rats to be fully kindled between both strains (p=0,92). No neuronal loss was observed in both strains following kindling suggesting that short seizures are not sufficient to cause excitotoxicity. Following SE induced by IHES, severe neuronal loss was observed in Dahl rats (100%) but not in the Lewis rats (0%). No differences were observed in the duration and intensity of the SE between both strains.Conclusions: Our results confirm that Dahl and Lewis rats are good genetic models of TLE with HS. They both exhibit the same sensitivity to seizures as showed by the kindling experiment. Sensitivity to neuronal loss following SE is also consistent with what was observed in the KA protocol. Dahl SS are considered HS-sensitive and Lewis HS-resistant. This new model will help us understand the molecular mechanisms underlying the development of epilepsy and therefore, help us find new therapeutic targets to stop the epileptogenesis related to the hippocampus sclerosis.