Excitatory Transmission in Status Epilepticus

Abstract

Abstract Prolonged, self-sustaining seizures that can cause neuronal injury and respiratory compromise are called status epilepticus (SE). SE is a dynamic condition where drug responsiveness, electroencephalography, active neuronal circuits, and synapses change over time, which has prompted division into early, established, and refractory stages. As SE evolves, the neuronal circuits generating seizures also change dynamically, engaging more structures. We review the role of excitatory transmission in generating and sustaining SE. Organophosphates precipitate SE by enhancing glutamate release from the presynaptic terminals. GABAergic inhibition fails in the early stages of SE, especially in the hippocampus, and then the glutamatergic transmission is potentiated during established SE. AMPA receptor-mediated excitation increases due to the insertion of the GluA1 subunit into synaptic receptors. NMDA receptor-mediated excitation is enhanced, and blocking this receptor can prevent reduced GABAergic inhibition and enhanced glutamatergic transmission. These studies form the basis for clinical trials to treat SE with NMDA receptor antagonist ketamine and AMPA receptor antagonist perampanel.