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Clinical and Developmental Immunology
Volume 2013 (2013), Article ID 948976, 13 pages
http://dx.doi.org/10.1155/2013/948976
Review Article

The Benefits and Detriments of Macrophages/Microglia in Models of Multiple Sclerosis

1Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada T2N 4N1
2The Departments of Clinical Neurosciences and Oncology, University of Calgary, Calgary, AB, Canada T2N 4N1

Received 26 March 2013; Accepted 16 May 2013

Academic Editor: Wolfgang J. Streit

Copyright © 2013 Khalil S. Rawji and V. Wee Yong. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The central nervous system (CNS) is immune privileged with access to leukocytes being limited. In several neurological diseases, however, infiltration of immune cells from the periphery into the CNS is largely observed and accounts for the increased representation of macrophages within the CNS. In addition to extensive leukocyte infiltration, the activation of microglia is frequently observed. The functions of activated macrophages/microglia within the CNS are complex. In three animal models of multiple sclerosis (MS), namely, experimental autoimmune encephalomyelitis (EAE) and cuprizone- and lysolecithin-induced demyelination, there have been many reported detrimental roles associated with the involvement of macrophages and microglia. Such detriments include toxicity to neurons and oligodendrocyte precursor cells, release of proteases, release of inflammatory cytokines and free radicals, and recruitment and reactivation of T lymphocytes in the CNS. Many studies, however, have also reported beneficial roles of macrophages/microglia, including axon regenerative roles, assistance in promoting remyelination, clearance of inhibitory myelin debris, and the release of neurotrophic factors. This review will discuss the evidence supporting the detrimental and beneficial aspects of macrophages/microglia in models of MS, provide a discussion of the mechanisms underlying the dichotomous roles, and describe a few therapies in clinical use in MS that impinge on the activity of macrophages/microglia.