The role of the inherited genetic background on the consequences of lithium-pilocarpine status epilepticus: Study in Genetic Absence Epilepsy Rats from Strasbourg and Wistar audiogenic rats

The susceptibility of rats with genetically inherited epilepsy to the genesis and consequences of secondary temporal lobe epilepsy is unknown. Here, we induced lithium-pilocarpine status epilepticus (SE) in Genetic Absence Epilepsy Rats from Strasbourg (GAERS) or in Wistar audiogenic sensitive (AS) rats. Wistar AS needed less pilocarpine than GAERS and Non-Epileptic Rats (NERs) to develop SE. Sixty six, 40 and 5% of Wistar AS, GAERS and NERs, respectively, died within 24 h after SE. In GAERS, SE prevented the occurrence of absence seizures for 5 days. Thereafter a limited number of absence seizures with low amplitude and short duration were recorded. Wistar AS developed limbic epilepsy within 9 days after SE while GAERS and NERs needed 36-39 days to develop spontaneous motor seizures. Neuronal loss consecutive to SE was similar in the three strains and particularly marked in limbic forebrain and parahippocampal cortices. In conclusion, the development of focal limbic epilepsy in GAERS largely impairs the expression of absence seizures. The genetic background underlying the expression of audiogenic seizures sensitizes strongly the rats to a further insult and compromises their survival.