Novel animal models of pediatric epilepsy

Abstract

When mimicking epileptic processes in a laboratory setting, it is important to understand the differences between experimental models of seizures and epilepsy. Because human epilepsy is defined by the appearance of multiple spontaneous recurrent seizures, the induction of a single acute seizure without recurrence does not constitute an adequate epilepsy model. Animal models of epilepsy might be useful for various tasks. They allow for the investigation of pathophysiological mechanisms of the disease, the evaluation, or the development of new antiepileptic treatments, and the study of the consequences of recurrent seizures and neurological and psychiatric comorbidities. Although clinical relevance is always an issue, the development of models of pediatric epilepsies is particularly challenging due to the existence of several key differences in the dynamics of human and rodent brain maturation. Another important consideration in modeling pediatric epilepsy is that "children are not little adults," and therefore a mere application of models of adult epilepsies to the immature specimens is irrelevant. Herein, we review the models of pediatric epilepsy. First, we illustrate the differences between models of pediatric epilepsy and models of the adulthood consequences of a precipitating insult in early life. Next, we focus on new animal models of specific forms of epilepsies that occur in the developing brain. We conclude by emphasizing the deficiencies in the existing animal models and the need for several new models.

Fig. 1

Graph with the main pediatric epilepsy syndromes according to their incidences and consequences. In blue, the epilepsy syndromes with available animal models. In red, the epilepsy syndromes with needed animal models. CAE = childhood absence epilepsy; IGE = idiopathic generalized epilepsies; Sd = syndrome; TSC = tuberous sclerosis complex