Abstracts

The lithium-pilocarpine (Li-pilo) model in rats reproduces the main clinical, neuropathological, and developmental of human mesial temporal lobe epilepsy (MTLE). This model is characterized by an acute status epilepticus (SE) followed by a latent seizure free period and spontaneous recurrent seizures (SRS). Damage is present in hippocampus, thalamus, amygdala and ventral cortices. However, there is no indication on how an epileptic genetically inherited background could interfere with this model of MTLE. Therefore we induced Li-pilo SE in two strains of genetic epileptic rats, GAERS (Genetically Absence Epilepsy Rats from Strasbourg) which show non-convulsive absence epilepsy with spike-and-wave discharges (SWD) on the cortical EEG, and Wistar AS (AS) which display audiogenic convulsive seizures without paroxysmal activity on the EEG. Adult male, 4-5 month-old, GAERS, AS, and genetically non-epileptic rats (NE) as controls were subjected to Li-pilo SE induced by LiCl (3 meq/kg) 18 h before pilocarpine (20, 18, and 12.5 mg/kg in NE, GAERS, and AS, respectively). SE-induced mortality was recorded and the number of neurons in regions of interest was counted six weeks after the first spontaneous seizure. 13/24 NE rats (54%), 32/40 GAERS (80%) and 34/41 AS (83%) died during SE. AS experienced severe generalized seizures with a tonic component. The latency to the first SRS was 39 [plusmn] 13 days in NE, 36 [plusmn] 11 days in GAERS and 9 [plusmn] 4 days in AS. In control conditions, the number of neurons was reduced in CA1 in GAERS and substantia nigra in AS, and increased in the hilus of GAERS and ventroposteromedian thalamus of GAERS and AS, compared to NE rats. Li-pilo SE led to damage which was most often similar in the three strains. Neuronal loss was severe in piriform cortex (90-99%) in the three strains, severe in thalamus (70-96%) of NE and GAERS and less marked in AS (53-81%), severe in the hilus of the dentate gyrus (41-55%) in the three strains, moderate in CA1 (47%) of NE and AS and less marked in GAERS (32%) and in entorhinal cortex and amygdala (17-36%) of the three strains. These results show the high vulnerability of AS to the consequences of limbic SE with a very fast transfer of activation to the sensitive brainstem of this strain leading to lethal tonic seizures during SE and a rapid appearance of SRS. The extent and location of neuronal damage does not seem to depend much on the strain. In GAERS, the expression of SWD does not seem to be impaired by recurrent seizures but the final analysis of their duration and characteristics is still ongoing. (Supported by INSERM U405)