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Does Brain Inflammation Mediate Pathological Outcomes in Epilepsy?

  • Karen S. Wilcox
  • Annamaria Vezzani
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 813)

Abstract

Inflammation in the central nervous system (CNS) is associated with epilepsy and is characterized by the increased levels of a complex set of soluble molecules and their receptors in epileptogenic foci with profound neuromodulatory effects. These molecules activate receptor-mediated pathways in glia and neurons that contribute to hyperexcitability in neural networks that underlie seizure generation. As a consequence, exciting new opportunities now exist for novel therapies targeting the various components of the immune system and the associated inflammatory mediators, especially the IL-1β system. This review summarizes recent findings that increased our understanding of the role of inflammation in reducing seizure threshold, contributing to seizure generation, and participating in epileptogenesis. We will discuss preclinical studies supporting the hypothesis that pharmacological inhibition of specific proinflammatory signalings may be useful to treat drug-resistant seizures in human epilepsy, and possibly delay or arrest epileptogenesis.

Keywords

Inflammation IL-1β TNF-α IL-6 Reactive astrogliosis 

Notes

Acknowledgements

A. Vezzani is very grateful to Phil Schwarzkroin for the intense and fruitful collaboration during the 8 years of shared editorial work for Epilepsia. During the time A.V. was serving as associated editor for basic science, she could fully appreciate P.S. extensive and deep scientific knowledge, his patience, constructive criticism, support and commitment. She thanks Phil, in particular, for his willingness to share responsibility and decisions as well as complaints and rewards, and for the very educational and formative time.

K.S. Wilcox would like to acknowledge the kind support Phil Schwartzkroin has demonstrated over the years. While she never had the opportunity to work with him, he was always interested in her work, encouraged her to speak out at meetings, to get involved in the American Epilepsy Society, and provided a welcoming environment for someone entering the field of epilepsy. He is a mentor to all.

Other Acknowledgements

This work was supported by National Institutes of Health Grants NS 078331 (KSW), NS065434 (KSW), and the Margolis Foundation (KSW) and Ministero della salute Grant N. RF-2009-1506142 (AV).

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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  1. 1.Department of Pharmacology and ToxicologyUniversity of UtahSalt Lake CityUSA
  2. 2.Department of NeuroscienceIRCSS-Istituto di Ricerche Farmacologiche “Mario Negri”MilanItaly

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