8 - Cell death, plasticity, and epilepsy: insights provided by experimental models of hippocampal sclerosis

Summary

Introduction

Many models of epilepsy, or of epileptic foci, take advantage of a genetic predisposition or induce a process(es) either in vivo or in vitro, often in conjunction with the use of convulsant drugs, which results in the most commonly accepted cornerstones of epileptogenicity – neuronal hyperexcitability and synchrony. The mechanisms of this aberrant functioning are then examined for insights they can provide into the genesis of seizures. In one sense seizures are the independent, rather than dependent, variable. The models discussed here, involving selective lesions of hippocampal subfields, are considered relevant for an entirely different reason. Selective cell death in the hippocampus – mesial temporal, or hippocampal, sclerosis (HS) – is observed in the majority of individuals with temporal lobe complex partial seizures and these individuals, as a group, represent the majority of the population with idiopathic, pharmacologically intractable epilepsy. By creating similar patterns of cell loss experimentally and examining the consequences to the functioning of the hippocampal remnants, hyperexcitability and/or synchrony become the dependent variables and the contribution of features of HS to their development can be studied. Three theoretical positions can be taken. One extreme argues that HS is the benign consequence of seizures and is mechanistically unrelated to their cause except perhaps to provide sufficient neuropil for their propagation or expression.