Are seizures harmful: what can we learn from animal models?

Abstract

Epilepsy is a brain disease that requires distributed neuronal networks for its expression. Several characteristics of epilepsy, including its natural history, the latency between an initial insult and the first manifestation of seizures, the complex interaction of seizures with development as a function of developmental stage, the modulating effect of systemic physiological responses, and the fact that seizures are ultimately defined by a combination of electrical and behavioral criteria all suggest that epilepsy should ideally be studied in an intact whole animal preparation. Such preparations offer the ability to study acute and chronic changes in brain structure and function after single or repeated seizures. Animal models have major limitations, however, including strain specificity, difficulty in isolating potentially confounding variables, a relative lack of accessible higher cortical functions, such as language and abstract processing, and shorter lifespans that may be insufficient to allow the complete expression of seizure-related injury. Information we have learned from animal studies includes a broad understanding of the chemical, molecular and anatomic consequences of seizures, including their temporal and spatial relationships to each other, and information on the consequences of seizures as a function of development. Recent studies have cast light on potential mechanisms of resistance to seizure-induced injury in the developing brain. In the future, we can anticipate that animal models will continue to be useful, especially when whole-animal preparations are used to generate material for detailed in vitro examination.