Summary: Epileptogenesis refers to a phenomenon in which the brain undergoes molecular and cellular alterations after a brain-damaging insult, which increase its excitability and eventually lead to the occurrence of recurrent spontaneous seizures. Common epileptogenic factors include traumatic brain injury (TBI), stroke, and cerebral infections. Only a subpopulation of patients with any of these brain insults, however, will develop epilepsy. Thus, there are two great challenges: (1) identifying patients at risk, and (2) preventing and/or modifying the epileptogenic process. Target identification for antiepileptogenic treatments is difficult in humans because patients undergoing epileptogenesis cannot currently be identified. Animal models of epileptogenesis are therefore necessary for scientific progress. Recent advances in the development of experimental models of epileptogenesis have provided tools to investigate the molecular and cellular alterations and their temporal appearance, as well as the epilepsy phenotype after various clinically relevant epileptogenic etiologies, including TBI and stroke. Studying these models will lead to answers to critical questions such as: Do the molecular mechanisms of epileptogenesis depend on the etiology? Is the spectrum of network alterations during epileptogenesis the same after various clinically relevant etiologies? Is the temporal progression of epileptogenesis similar? Work is ongoing, and answers to these questions will facilitate the identification of molecular targets for antiepileptogenic treatments, the design of treatment paradigms, and the determination of whether data from one etiology can be extrapolated to another. Key Words: Endothelin-1-Gene arrayLateral fluid-percussion injury-Magnetic resonance imagingPhotothrombotic stroke-Traumatic brain injury-Video-EEG monitoring.According to the World Health Organization, approximately 0.8% (50 million) of the world population has epilepsy (available from http://www.who.int/ mediacentre/factsheets/fs165/en/). Epilepsies can be divided into three major categories based on etiology: idiopathic, symptomatic, and presumed symptomatic (previously called "cryptogenic") (Engel, 2001). In idiopathic epilepsies, genetic factors causing, for example, channelopathies, are presumed to have a major causative role in the development of seizures. In symptomatic epilepsies, there is an identifiable lesion in the brain that triggers seizures. The lesion can be a genetically programmed cellular alteration like neuronal migration disorder in cortex or an acquired lesion like traumatic brain injury (TBI) or stroke. Presumed symptomatic epilepsies are those most likely to be symptomatic, but the lesions cannot be identified using currently available methods (Engel, 2001).

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Cerebrovascular diseases are one of the most common causes of epilepsy in adults, and the incidence of stroke-induced epileptogenesis is increasing as the population ages. The mechanisms that lead to stroke-induced epileptogenesis in a subpopulation of patients, however, are still poorly understood. Recent advances in inducing epileptogenesis in rodent focal ischemia models have provided tools that can be used to identify the risk factors and neurobiologic changes leading to development of epilepsy after stroke. Here we summarize data from models in which epileptogenesis has been studied after focal ischemia; photothrombosis, middle cerebral artery (MCA) occlusion with filament, and endothelin-1-induced MCA occlusion. Analysis of the data indicates that neurobiologic changes occurring during stroke-induced epileptogenesis share some similarities to those induced by status epilepticus or traumatic brain injury.

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