Immune mechanisms in epileptogenesis
- 1Department of Microbiology-Immunology and Interdepartmental Immunobiology, Feinberg School of Medicine, Northwestern University, Chicago IL, USA
- 2Department of Pediatrics, Division of Neurobiology, Children’s Research Center, Lurie Children’s Hospital of Chicago, Chicago IL, USA
- 3Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago IL, USA
Epilepsy is a chronic brain disorder that affects 1% of the human population worldwide. Immune responses are implicated in seizure induction and the development of epilepsy. Pre-clinical and clinical evidence have accumulated to suggest a positive feedback cycle between brain inflammation and epileptogenesis. Prolonged or recurrent seizures and brain injuries lead to upregulation of proinflammatory cytokines and activated immune responses to further increase seizure susceptibility, promote neuronal excitability, and induce blood–brain barrier breakdown. This review focuses on the potential role of innate and adaptive immune responses in the pathogenesis of epilepsy. Both human studies and animal models that help delineate the contributions of brain inflammation in epileptogenesis will be discussed. We highlight the critical role of brain-resident immune mediators and emphasize the contribution of brain-infiltrating peripheral leukocytes. Additionally, we propose possible immune mechanisms that underlie epileptogenesis. Several proinflammatory pathways are discussed, including the interleukin-1 receptor/toll-like receptor signaling cascade, the pathways activated by damage-associated molecular patterns, and the cyclooxygenase-2/prostaglandin pathway. Finally, development of better therapies that target the key constituents and processes identified in these mechanisms are considered, for instance, engineering antagonizing agents that effectively block these pathways in an antigen-specific manner.
Keywords: seizure, epilepsy, epileptogenesis, immune response, inflammation, microglia, astrocytes, T lymphocytes
Citation: Xu D, Miller SD and Koh S (2013) Immune mechanisms in epileptogenesis. Front. Cell. Neurosci. 7:195. doi: 10.3389/fncel.2013.00195
Received: 11 June 2013; Accepted: 08 October 2013;
Published online: 08 November 2013.
Edited by:Roberto Di Maio, University of Pittsburgh, USA
Reviewed by:Michela Matteoli, University of Milano, Italy
Roberto Di Maio, University of Pittsburgh, USA
Copyright © 2013 Xu, Miller and Koh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Sookyong Koh, Department of Pediatrics, Division of Neurobiology, Children’s Research Center, Lurie Children’s Hospital of Chicago, 225 E. Chicago Avenue, Epilepsy Box 29, Chicago, IL 60611, USA e-mail: firstname.lastname@example.org;
Stephen D. Miller, Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Avenue, Chicago, IL 60611, USA e-mail: email@example.com