How Do We Make Models That Are Useful in Understanding Partial Epilepsies?

Abstract

The goals of constructing epilepsy models are (1) to develop approachesto prophylaxis of epileptogenesis following cortical injury; (2) todevise selective treatments for established epilepsies based onunderlying pathophysiological mechanisms; and (3) use of a disease(epilepsy) model to explore brain molecular, cellular and circuitproperties. Modeling a particular epilepsy syndrome requires detailedknowledge of key clinical phenomenology and results of human experimentsthat can be addressed in critically designed laboratory protocols.Contributions to understanding mechanisms and treatment of neurologicaldisorders has often come from research not focused on a specificdisease-relevant issue. Much of the foundation for current research inepilepsy falls into this category. Too strict a definition of therelevance of an experimental model to progress in preventing or curingepilepsy may, in the long run, slow progress. Inadequate exploration ofthe experimental target and basic laboratory results in a given modelcan lead to a failed effort and false negative or positive results.Models should be chosen based on the specific issues to be addressedrather than on convenience of use. Multiple variables includingmaturational age, species and strain, lesion type, severity andlocation, latency from injury to experiment and genetic background willaffect results. A number of key issues in clinical and basic research inpartial epilepsies remain to be addressed including the mechanismsactive during the latent period following injury, susceptibility factorsthat predispose to epileptogenesis, injury - induced adaptive versusmaladaptive changes, mechanisms of pharmaco-resistance and strategies todeal with multiple pathophysiological processes occurring in parallel.