Cortical dysplasia and epilepsy: animal models.

Abstract

Cortical dysplasia syndromes--those conditions of abnormal brain structure/organization that arise during aberrant brain development--frequently involve epileptic seizures. Neuropathological and neuroradiological analyses have provided descriptions and categorizations based on gross anatomical and cellular histological features (e.g., lissencephaly, heterotopia, giant cells), as well as on the developmental mechanisms likely to be involved in the abnormality (e.g., cell proliferation, migration). Recently, the genes responsible for several cortical dysplastic conditions have been identified and the underlying molecular processes investigated. However, it is still unclear how the various structural abnormalities associated with cortical dysplasia are related to (i.e., "cause") chronic seizures. To elucidate these relationships, a number of animal models of cortical dysplasia have been developed in rats and mice. Some models are based on laboratory manipulations that injure the brain (e.g., freeze, undercut, irradiation, teratogen exposure) of immature animals; others are based on spontaneous genetic mutations or on gene manipulations (knockouts/transgenics) that give rise to abnormal cortical structures. Such models of cortical dysplasia provide a means by which investigators can not only study the developmental mechanisms that give rise to these brain lesions, but also examine the cause-effect relationships between structural abnormalities and epileptogenesis.