Modeling post-traumatic epilepsy for therapy development

Epilepsy is the most prevalent serious neurological disorder, afflicting almost 1% of the population worldwide. It is a heterogeneous disorder, comprising numerous syndromes with a wide range of etiologies, that is defined by the manifestation of chronic spontaneous recurrent seizures (CSRSs). An epileptic seizure, in turn, is defined by the International League Against Epilepsy (ILAE) as “transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain”. Post-traumatic epilepsy (PTE) arises after mechanical damage to the brain and is diagnosed when spontaneous seizures are observed at least a week after brain injury. PTE is the most prevalent acquired epilepsy in young adults and accounts for 5% of epilepsies overall. There are currently no cures for PTE and no means to prevent the disorder in those at risk. Available treatments of PTE are symptomatic, and at least 40% of patients have seizures that cannot be controlled with any of the available drugs. This dire situation requires rethinking the development and use of animal models for the development of therapies for PTE. In this chapter we will introduce the problem and discuss several topics crucial for modeling PTE for therapy development.