The Role or NMDA Receptors in Epileptogenesis

Epilepsy is characterized by repeated sudden-onset epileptic seizures. Around 30% of cases of epilepsy show drug resistance, with the result that the disease can progress and lead to degradation of cognitive capacities and the onset of concomitant psychoneurological diseases. Early therapeutic interventions can reduce disease severity, while suppression of epileptogenesis is regarded as the most promising strategy for preventing the development of epilepsy after disease-provoking events. NMDA receptors are regarded as a potential target for suppressing epileptogenesis. Impairment to NMDA receptor function occurs at all stages of the development of epilepsy. Changes in their expression are seen in the fi rst hours after acute seizures, while NMDA receptors themselves are actively involved in generating epileptic activity. In addition, NMDA receptor antagonists effectively suppress epileptiform activity in a variety of models of convulsive states and status epilepticus. This review considers existing data on the role played by NMDA receptors in the development of epilepsy and how their expression changes at different periods of epileptogenesis, and the potential use of NMDA receptor antagonists and modulators in preventing epileptogenesis is discussed.