Key result
Preclinical evaluation of antiepileptic drugs using genetic rat models requires careful consideration of EEG recording techniques, study design, and behavioral monitoring to accurately predict clinical efficacy in absence epilepsy.
Why the study?
Genetic rat models such as WAG/Rij and GAERS are used to evaluate antiepileptic treatments, but monitoring animal behavior alongside EEG/ECoG is necessary, warranting an overview of study designs and pitfalls.
This review provides an overview of the design, methodology, and pitfalls of using genetic rat models (WAG/Rij and GAERS) and EEG/ECoG recordings to evaluate antiepileptic drugs for absence epilepsy.
Preclinical AED testing in genetic rat models demands rigorous EEG and behavioral protocols; leaves open reliable clinical efficacy predictions without such standards.
The genetic rat models such as rats of the WAG/Rij strain and GAERS were developed as models for generalized genetic epilepsy and in particular for childhood absence epilepsy. These animal models were described in the eighties of the previous century and both models have, among others, face, construct and predictive validity. Both models were and are currently used as models to predict the action of antiepileptic medication and other experimental treatments, to elucidate neurobiological mechanisms of spike-wave discharges and epileptogenesis. Although the electroencephalagram (EEG)/electrocorticogram (ECoG) is imperative for establishing absence seizures and to quantify the for absence epilepsy typical spike-wave discharges, monitoring the animals behavior is equally necessary. Here an overview is given regarding the design of drug evaluation studies, which animals to use, classical and new EEG variables, the monitoring and quantification of the behavior of the rats, some pitfalls regarding the interpretation of the data, and some developments in EEG technology.
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Luijtelaar et al. (2020) conducted a review in Absence epilepsy (preclinical models). Antiepileptic drugs (preclinical evaluation) was evaluated. Preclinical evaluation of antiepileptic drugs using genetic rat models requires careful consideration of EEG recording techniques, study design, and behavioral monitoring to accurately predict clinical efficacy in absence epilepsy.
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