Animal models

Epilepsy accounts for a significant portion of the dis-ease burden worldwide. Research in this field is fundamental and mandatory. Animal models have played, and still play, a substantial role in understanding the patho-physiology and treatment of human epilepsies. A large number and variety of approaches are available, and they have been applied to many animals. In this chapter the in vitro and in vivo animal models are discussed,with major emphasis on the in vivo studies. Models have used phylogenetically different animals - from worms to monkeys. Our attention has been dedicated mainly to rodents.In clinical practice, developmental aspects of epilepsy often differ from those in adults. Animal models have often helped to clarify these differences. In this chapter, developmental aspects have been emphasized.Electrical stimulation and chemical-induced models of seizures have been described first, as they represent the oldest and most common models. Among these models, kindling raised great interest, especially for the study of the epileptogenesis. Acquired focal models mimic seizures and occasionally epilepsies secondary to abnormal cortical development, hypoxia, trauma, and hemorrhage.Better knowledge of epileptic syndromes will help to create new animal models. To date, absence epilepsy is one of the most common and (often) benign forms of epilepsy. There are several models, including acute pharmacological models (PTZ, penicillin, THIP, GBL) and chronic models (GAERS, WAG/Rij). Although atypical absence seizures are less benign, thus needing more investigation, only two models are so far available (AY-9944,MAM-AY). Infantile spasms are an early childhood encephalopathy that is usually associated with a poor out-come. The investigation of this syndrome in animal models is recent and fascinating. Different approaches have been used including genetic (Down syndrome,ARX mutation) and acquired (multiple hit, TTX, CRH,betamethasone-NMDA) models.An entire section has been dedicated to genetic models, from the older models obtained with spontaneous mutations (GEPRs) to the new engineered knockout, knocking, and transgenic models. Some of these models have been created based on recently recognized patho-genesis such as benign familial neonatal epilepsy, early infantile encephalopathy with suppression bursts, severe myoclonic epilepsy of infancy, the tuberous sclerosis model, and the progressive myoclonic epilepsy. The contribution of animal models to epilepsy re-search is unquestionable. The development of further strategies is necessary to find novel strategies to cure epileptic patients, and optimistically to allow scientists first and clinicians subsequently to prevent epilepsy and its consequences.