PRIMARY AND SECONDARY MECHANISMS OF EPILEPTOGENESIS IN THE TEMPORAL LOBE: THERE IS A BEFORE AND AN AFTER

Extensive data involving several animal models of temporal lobe epilepsy highlight synaptic alterations that likely act synergistically during acquired epileptogenesis. Most of this research has utilized experimental models in which intense electrical activity in adult animals, primarily involving status epilepticus, causes variable neuronal death in the hippocampus and other temporal lobe structures. Neuronal death, including principal cells and specific interneurons, likely has several roles in epileptogenesis after brain injury. Both reduction of GABA-mediated inhibition from selective interneuron loss and the progressive formation of new recurrent excitatory circuits after death of principal neurons enhance excitability and promote seizures during the development of epilepsy. These epileptogenic circuits hypothetically continue to undergo secondary epileptogenesis, which involves further modifications that contribute to a progressive, albeit variable, increase in the frequency and severity of spontaneous recurrent seizures.