Analyzing the Role of the P2X7 Receptor in Epilepsy.

Abstract

Purinergic signaling is increasingly recognized to play a role during the generation of hyperexcitable networks in the brain. Among the purinergic receptors, the ionotropic ATP-gated P2X7 receptor has attracted particular attention as a possible drug target for epilepsy. P2X7 receptor expression is increased in the brain of experimental models of epilepsy and in patients and, P2X7 receptor antagonism modulates seizure severity and epilepsy development. To date, studies analyzing the role of the P2X7 receptor during epilepsy have mainly focused on temporal lobe epilepsy, the most common form of acquired epilepsy in adults which is particularly prone to drug refractoriness.Animal models of seizures and epilepsy are an essential tool in the identification of novel anticonvulsive and antiepileptogenic drug targets and much data demonstrating a role for the P2X7 receptor during epilepsy have been obtained by using these models. The aim of the present book chapter is to provide a detailed description of two commonly used mouse models of temporal lobe epilepsy, which are the intra-amygdala kainic acid model of status epilepticus and the controlled cortical impact model of traumatic brain injury. This chapter concludes with a brief description of how these models can be used to investigate the impact of targeting the P2X7 receptor on acute seizures, epilepsy development and established epilepsy .