Epilepsy

Abstract

Epilepsy is a chronic disorder defined by recurrent and unprovoked seizures and is one of the commonest disorders of the brain. Despite the burgeoning of new antiepileptic drugs, the burden of medically intractable epilepsy has not reduced significantly. One-third of patients with epilepsy continue to have unprovoked seizures despite advances in treatment. Cell death in seizures has been observed in in vitro and in vivo models of epilepsy and is the hallmark of hippocampal sclerosis, the commonest pathology associated with drug-resistant epilepsy. Neuroprotection in epilepsy has a long tradition and with the discovery of new pathways involved in seizure induced cell death, strategies have been refined accordingly. In this chapter we will provide a comprehensive overview on the proposed mechanisms underlying cell death in epilepsy and how these can be targeted by exogenous and endogenous neuroprotectants. We will focus on the NMDA receptor and its downstream signalling cascades and their role in seizure induced cell death and potential drug targets arising from this central position within the cascade of cell death. We will summarize evidence supporting the involvement of AMPA receptors in seizure induced cell death. In the last part the focus will be on mitochondria and ROS as pivotal players in seizure induced cell death and how these are linked to NMDA receptor dysfunction. We will outline strategies targeting these downstream signalling cascades.