This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Remington, L. T. Articles by Owens, T. Search for Related Content PubMed PubMed Citation Articles by Remington, L. T. Articles by Owens, T.

(American Journal of Pathology. 2007;170:1713-1724.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.060783

Microglial Recruitment, Activation, and Proliferation in Response to Primary Demyelination

Leah T. Remington^*, Alicia A. Babcock^*, Simone P. Zehntner^* and Trevor Owens^*

From the Neuroimmunology Unit,^* Montreal Neurological Institute, McGill University, Montreal, Canada; and the Medical Biotechnology Center, University of Southern Denmark, Odense, Denmark

We have characterized the cellular response to demyelination/remyelination in the central nervous system using the toxin cuprizone, which causes reproducible demyelination in the corpus callosum. Microglia were distinguished from macrophages by relative CD45 expression (CD45^dim) using flow cytometry. Their expansion occurred rapidly and substantially outnumbered infiltrating macrophages and T cells throughout the course of cuprizone treatment. We used bromodeoxyuridine incorporation and bone marrow chimeras to show that both proliferation and immigration from blood accounted for increased microglial numbers. Microglia adopted an activated phenotype during demyelination, up-regulating major histocompatibility class I and B7.2/CD86. A subpopulation of CD45^dim-high microglia that expressed reduced levels of CD11b emerged during demyelination. These microglia expressed CD11c and were potent antigen-presenting cells in vitro. T cells were recruited to the demyelinated corpus callosum but did not appear to be activated. Our study highlights the role of microglia as a heterogeneous population of cells in primary demyelination, with the capacity to present antigen, proliferate, and migrate into demyelinated areas.

This article has been cited by other articles:

				V. E. Miron, S. P. Zehntner, T. Kuhlmann, S. K. Ludwin, T. Owens, T. E. Kennedy, B. J. Bedell, and J. P. Antel Statin Therapy Inhibits Remyelination in the Central Nervous System Am. J. Pathol., May 1, 2009; 174(5): 1880 - 1890. [Abstract] [Full Text] [PDF]

				R. Khorooshi, A. A. Babcock, and T. Owens NF-{kappa}B-Driven STAT2 and CCL2 Expression in Astrocytes in Response to Brain Injury J. Immunol., November 15, 2008; 181(10): 7284 - 7291. [Abstract] [Full Text] [PDF]

				A. A. Babcock, H. Toft-Hansen, and T. Owens Signaling through MyD88 Regulates Leukocyte Recruitment after Brain Injury J. Immunol., November 1, 2008; 181(9): 6481 - 6490. [Abstract] [Full Text] [PDF]

				J. Audoy-Remus, J.-F. Richard, D. Soulet, H. Zhou, P. Kubes, and L. Vallieres Rod-Shaped Monocytes Patrol the Brain Vasculature and Give Rise to Perivascular Macrophages under the Influence of Proinflammatory Cytokines and Angiopoietin-2 J. Neurosci., October 8, 2008; 28(41): 10187 - 10199. [Abstract] [Full Text] [PDF]

				W. Stenzel, S. Soltek, M. Sanchez-Ruiz, S. Akira, H. Miletic, D. Schluter, and M. Deckert Both TLR2 and TLR4 Are Required for the Effective Immune Response in Staphylococcus aureus-Induced Experimental Murine Brain Abscess Am. J. Pathol., January 1, 2008; 172(1): 132 - 145. [Abstract] [Full Text] [PDF]