Multimodal investigation of epileptogenesis with emphasis in the implementation of new animal models and new tools

Abstract

Epilepsy affects about 1% to 2% of world population, and the mesial temporal lobe epilepsy (TLE) the most frequent, representing 40% of patients, these are often refractory to medicaI treatment. One of the most used tools to try to understand the pathophysiology of MTLE is induced animal models. Despite several animal models currently available and widely studied, most of these lesions present in the central nervous system and phenotypic events that are not commonly identified in patients with TLE, which is primarily neuronal loss in hippocampal regions and several initial insults such as: ischemia, trauma, and status epilepticus (SE). That said, I propose to work with animal models recently described (Norwood et aI., 2010 and Navarro-Mora G, 2009) whose main advantage to generate a discrete lesion, actually closer to that found in patients with TLE and without the initial insult precipitating the type SE. With these models we propose to use a series of tools to investigate various phenomena and biological pathways that intersect in the determination of epileptogenesis in TLE. This strategy will provide an interdisciplinary approach that goes from structural neuroimaging to molecular biology, through neurophysiology, neurochemistry and bio-informatics. Moreover, as all groups participating in the proposal have extensive experience in research in epilepsy, the results obtained here can be compared with those previously produced in other animal models and those observed in series of patients. We believe our strategy of integration of knowledge proposed here will generate new knowledge, comprehensive and integrated on epileptogenesis in mesial temporal lobe structures and have a chance to make a big impact in the field of applied neuroscience. (AU)