Inflammation: Modulation of Neuronal Excitability: Vascular Changes and Inflammation

Perturbations of neurovascular integrity and breakdown of the blood-brain barrier may lead to neuronal hypersynchronization and epileptiform activity. However, the mechanisms underlying these processes are still unclear. Furthermore, inflammatory processes related to the activation of brain vessel endothelia and/or BBB leakage have been reported in epilepsy, but no explanations have yet been provided for the relevant mechanisms of action. Our main goal is to adopt an integrated and multidisciplinary approach to this issue, taking into account different factors in the in vivo study of alterations of the 'whole brain' in epilepsy. Toward that end, we combine electrophysiological, neuropathological, and neuroimmunological data, in order to consider the multiple players involved in vivo in the pathogenesis of epilepsy. We report that vascular alterations and BBB leakage induced by protracted seizures are not merely epiphenomena detected in animal models of chemically induced epilepsy, but may represent crucial steps of a cascade of events responsible for epileptogenic mechanisms. Furthermore, we suggest that such events can implicate leukocyte recruitment and cytokine and chemokine release.