Status Epilepticus Changes the Ionic Homeostasis of the Amygdala and May Be Related to Sudden Death in Epilepsy

Abstract

Clinical and experimental data have indicated lesions in the amygdaloid nuclei of individuals with epilepsy as indicators of increased risk of sudden death. Among the several factors that are related to this risk, the most worrying is the high refractoriness of the anti-epileptogenic drugs available. These drugs target the inhibitory and excitatory processes of the synaptic circuitry. However, it is known that the full performance of synaptic processes depends on ionic homeostasis, controlled by mechanisms such as: enzymes, sodium/potassium pump, cotransporters, ion exchangers and extra-synaptic channels. In this sense, the present work investigated the expression of mechanisms responsible for ionic homeostasis, such as the cotransporter NKCC1, KCC2 and the Na+/K+ ATPase pump, in the amygdaloid nuclei of rats submitted to the status epilepticus (SE) by pilocarpine injection. The results showed clear lesions in various amygdaloid nuclei and variations in KCC2 and Na+/K+ ATPase expression. The observed changes suggest an imbalance in the control of inhibitory and excitatory processes, which modulate the synchronous activities of the amygdala, such as cardiorespiratory functions, evidencing a possible biomarker of the increase in the risk of sudden death in epilepsy (SUDEP) and revealing possible targets for its prevention.