Epileptogenic & Excitotoxic Mechnaisms

This volume is based on an advanced course on epileptogenic and excitotoxic mechanisms with emphasis on development. Information on partial and generalised epileptogenesis, derived from different experimental models, is comprehensively reviewed. Special sections are devoted to anatomical, biochemical and functional aspects of the maturing brain and to their interaction with epileptogenic agents. Several seizure-related factors, for example an intracellular rise of calcium, can lead to excitotoxic cellular damage. Despite some protective mechanisms, this risk is particularly worrying in the immature brain due to the over-expression and facilitation of NMDA receptors, the depolarising effect of GAGA and the immaturity of ionic homoeostasis. Seizures in early developmental stages can thus result in permanent defects and epileptic sequelae. Our present understanding of basic mechanisms of the epilepsies allows pharmacologists to design new drugs with specific pharmacological action targeted on crucial epileptogenic factors. These results, together with those of developmental studies of excitotoxicity, provide a basis for new therapeutic strategies aimed at preventing the development of severe infantile epileptic encephalopathies and at alleviating their dramatic consequences. The authors have combined their personal experience with a comprehensive review of the literature, providing the reader, either scientist or clinician, with an updated and exhaustive account of every topic.