The role of inflammation in epileptogenesis

NEUROPHARMACOLOGY

卷:69

Review

Vezzani, Annamaria¹  Friedman, Alon^2,3,4,5  Dingledine, Raymond J.⁶ 

[1] Mario Negri Inst Pharmacol Res, Dept Neurosci, Lab Expt Neurol, I-20156 Milan, Italy

[2] Ben Gurion Univ Negev, Fac Hlth Sci, Dept Physiol, IL-84105 Beer Sheva, Israel

[3] Ben Gurion Univ Negev, Zlotowski Ctr Neurosci, IL-84105 Beer Sheva, Israel

[4] Ben Gurion Univ Negev, Fac Hlth Sci, Dept Neurobiol, IL-84105 Beer Sheva, Israel

[5] Ben Gurion Univ Negev, Fac Hlth Sci, Dept Biomed Engn, IL-84105 Beer Sheva, Israel

[6] Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA

关键词: Seizures;    Astrocytes;    Microglia;    Cytokines;    COX-2;    Blood-brain barrier;    Cell loss;   

DOI  :  10.1016/j.neuropharm.2012.04.004

来源: Elsevier

【 摘 要 】

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-beta 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'. (C) 2012 Elsevier Ltd. All rights reserved.

【 授权许可】

Free