Genetic Animal Models of Epilepsy

Abstract

By definition, human epilepsy, or epilepsies, are characterized by chronically recurring, spontaneous clinical seizures. Experimental research on epilepsy and antiepileptic drugs has mostly been done in mice and rats, in which seizures were induced by chemical or electrical means (Purpura et al., 1972; Löscher and Schmidt, 1988). Although these rodent models have proved useful for the development of new antiepileptic drugs, they are obviously not closely related to human epilepsy but represent models of seizure states rather than models of epilepsy. An ideal animal model for epilepsy should show the following characteristics: (1) the development of spontaneously occurring recurrent seizures, (2) a type of seizure similar in its clinical phenomenology to seizures occurring in human epilepsy, (3) the clinical seizures should be associated with epileptic-like activity in the electroencephalogram (EEG), (4) pharmacokinetics of antiepileptic drugs similar to those in man, thus allowing the maintenance of effective drug levels during chronic treatment, and (5) effective plasma concentrations of antiepileptic drugs similar to those required for control of human epilepsies. No model at present meets all these criteria. However, there are several more recent genetic animal models of epilepsy that resemble idiopathic epilepsy in humans more closely than any other experimental model. In these genetic animal models, seizures are either induced by specific sensory stimulation in genetically susceptible animals, such as baboons, gerbils, and DBA/2 mice, or the seizures occur spontaneously, for example, in epileptic dogs and rats. These animal models thus provide a means of investigating genetic, neurochemical, neuropathological, neurophysiological, and neuropharmacological aspects of epilepsy that no artificially produced seizure model can provide. However, despite the specific potential of genetic animal models of epilepsy for the development of new, highly specific antiepileptic drugs, most of them are only rarely used in preclinical evaluation of anticonvulsant drugs to date.