Animal models of drug-resistant epilepsy

Abstract

Several animal models are discussed in order to outline features of difficult-to-treat or drug-resistant epilepsy. These models can be categorised as those which show a poor response to different antiepileptic drugs and those in which subgroups of drug-resistant animals are selected, based on interindividual differences. Non-responders to antiepileptic drugs have been described in the amygdala kindling model, as well as the chronic phase of post-status epilepticus models. Epileptic dogs which do not respond to standard antiepileptic drugs may serve as a translational model to provide a more clinical environment for drug testing. Drug resistance or a poor response to several antiepileptic drugs has been reported for the 6-Hz model, lamotrigine-pretreated kindled rats, pentylentetrazole-induced seizures in rats pre-exposed to pilocarpine, as well as following intrauterine exposure of rats to methylazoxymethanol. Using models to select non-responders is highly time-consuming and elaborate, limiting their use in routine drug-screening procedures. Current efforts to identify biomarkers of drug resistance may simplify the selection process, e.g. replacing several weeks of seizure monitoring by a single imaging scan. Moreover, further elucidation of mechanisms of resistance may help to design a series of ex vivo or in vitro screening procedures in order to evaluate whether a test compound is affected.