The role of inflammation in epileptogenesis

• Type of Material: Article
• Authors: Annamaria Vezzani, Mario Negri Institute for Pharmacological Research; Alon Friedman, Ben Gurion University of the Negev; Raymond J Dingledine, Emory University
• Language: English
• Date: 2013-06-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Elsevier Ltd. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.neuropharm.2012.04.004
• Title of Journal or Parent Work: Neuropharmacology
• ISSN: 0028-3908
• Volume: 69
• Start Page: 16
• End Page: 24
• Grant/Funding Information: Supported in part by NINDS grants 1 R21 NS074169, 1 U01 NS074509, and by the CounterAct program, Office of the Director, NIH, and NINDS grant number 2 U01 NS058158 (RD), and by Fondazione Cariplo, Fondazione Monzino and Regione Lombardia under Institutional Agreement n. 14501A (to AV).
• Keywords: COX-2; Astrocytes; Pharmacology & Pharmacy; Blood-brain barrier; STATUS EPILEPTICUS; KAINIC ACID; BLOOD-BRAIN-BARRIER; Life Sciences & Biomedicine; Science & Technology; LONG-TERM POTENTIATION; GROWTH-FACTOR-BETA; TEMPORAL-LOBE EPILEPSY; EXPERIMENTAL FEBRILE SEIZURES; Neurosciences & Neurology; Neurosciences; Cell loss; TOLL-LIKE RECEPTOR; Microglia; Cytokines; Seizures; RAT CA1 HIPPOCAMPUS; CENTRAL-NERVOUS-SYSTEM
• Research Categories: Health Sciences, Pharmacology; Biology, Physiology; Biology, Neuroscience

Abstract

One compelling challenge in the therapy of epilepsy is to develop anti-epileptogenic drugs with an impact on the disease progression. The search for novel targets has focused recently on brain inflammation since this phenomenon appears to be an integral part of the diseased hyperexcitable brain tissue from which spontaneous and recurrent seizures originate. Although the contribution of specific proinflammatory pathways to the mechanism of ictogenesis in epileptic tissue has been demonstrated in experimental models, the role of these pathways in epileptogenesis is still under evaluation. We review the evidence conceptually supporting the involvement of brain inflammation and the associated blood-brain barrier damage in epileptogenesis, and describe the available pharmacological evidence where post-injury intervention with anti-inflammatory drugs has been attempted. Our review will focus on three main inflammatory pathways, namely the IL-1 receptor/Toll-like receptor signaling, COX-2 and the TGF-β signaling. The mechanisms underlying neuronal-glia network dysfunctions induced by brain inflammation are also discussed, highlighting novel neuromodulatory effects of classical inflammatory mediators such as cytokines and prostaglandins. The increase in knowledge about a role of inflammation in disease progression, may prompt the use of specific anti-inflammatory drugs for developing disease-modifying treatments. This article is part of the Special Issue entitled 'New Targets and Approaches to the Treatment of Epilepsy'.