About this item:

179 Views | 105 Downloads

Author Notes:

Annamaria Vezzani, Laboratory Experimental Neurology, Deptartment of Neuroscience, Mario Negri Institute for Pharmacological Research, Via G. La Masa 19, 20156 Milano, Italy, Tel +39-02-39014410, Fax +39-02-3546277, Email: vezzani@marionegri.it.

Subjects:

Research Funding:

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:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Pharmacology & Pharmacy
  • Neurosciences & Neurology
  • Seizures
  • Astrocytes
  • Microglia
  • Cytokines
  • COX-2
  • Blood-brain barrier
  • Cell loss
  • BLOOD-BRAIN-BARRIER
  • TEMPORAL-LOBE EPILEPSY
  • GROWTH-FACTOR-BETA
  • CENTRAL-NERVOUS-SYSTEM
  • EXPERIMENTAL FEBRILE SEIZURES
  • LONG-TERM POTENTIATION
  • RAT CA1 HIPPOCAMPUS
  • TOLL-LIKE RECEPTOR
  • STATUS EPILEPTICUS
  • KAINIC ACID

The role of inflammation in epileptogenesis

Tools:

Journal Title:

Neuropharmacology

Volume:

Volume 69

Publisher:

, Pages 16-24

Type of Work:

Article | Post-print: After Peer Review

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'.

Copyright information:

© 2012 Elsevier Ltd. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Creative Commons License

Export to EndNote