Abstract
The traditional view of the adult brain as a static organ has changed in the past three decades, with the emergence of evidence that it remains plastic and has some regenerative capacity after injury. In the injured brain, microglia and macrophages clear cellular debris and orchestrate neuronal restorative processes. However, activation of these cells can also hinder CNS repair and expand tissue damage. Polarization of macrophage populations toward different phenotypes at different stages of injury might account for this dual role. This Perspectives article highlights the specific roles of polarized microglial and macrophage populations in CNS repair after acute injury, and argues that therapeutic approaches targeting cerebral inflammation should shift from broad suppression of microglia and macrophages towards subtle adjustment of the balance between their phenotypes. Breakthroughs in the identification of regulatory molecules that control these phenotypic shifts could ultimately accelerate research towards curing brain disorders.
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Acknowledgements
X.H. is supported by the American Heart Association (grant no. 13SDG14570025) and the Ethyl Vincent pilot grant in multiple sclerosis from the Department of Neurology, University of Pittsburgh. R.K.L. is supported by a Commonwealth Universal Research Enhancement (CURE) Award from the Pennsylvania Department of Health, and a Michael J. Fox Foundation Innovation Award. Y.G. is supported by Chinese Natural Science Foundation grants 81171149 and 81371306. J.C. is supported by NIH grants NS45048, NS62157, NS59806 and NS36736, Chinese Natural Science Foundation grant no. 81228008, and a Veterans Administration Merit Review.
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X.H., Y.S., Y.G. and P.Z. researched the data for the article. X.H., R.K.L. and J.C. provided substantial contributions to discussions of the content. X.H. wrote the article. X.H., R.K.L., J.S. and J.C. contributed to review and/or editing of the manuscript before submission.
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Hu, X., Leak, R., Shi, Y. et al. Microglial and macrophage polarization—new prospects for brain repair. Nat Rev Neurol 11, 56–64 (2015). https://doi.org/10.1038/nrneurol.2014.207
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DOI: https://doi.org/10.1038/nrneurol.2014.207
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