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Kumar A, Alvarez-Croda DM, Stoica BA, et al. Microglial/Macrophage Polarization Dynamics following Traumatic Brain Injury. J Neurotrauma. 2015;33(19):1732-1750doi: 10.1089/neu.2015.4268.
Kumar, A., Alvarez-Croda, D. M., Stoica, B. A., Faden, A. I., & Loane, D. J. (2016). Microglial/Macrophage Polarization Dynamics following Traumatic Brain Injury. Journal of neurotrauma, 33(19), 1732-1750. https://doi.org/10.1089/neu.2015.4268
Kumar, Alok, et al. "Microglial/Macrophage Polarization Dynamics following Traumatic Brain Injury." Journal of neurotrauma vol. 33,19 (2016): 1732-1750. doi: https://doi.org/10.1089/neu.2015.4268
Kumar A, Alvarez-Croda DM, Stoica BA, Faden AI, Loane DJ. Microglial/Macrophage Polarization Dynamics following Traumatic Brain Injury. J Neurotrauma. 2016 Oct 01;33(19):1732-1750. doi: 10.1089/neu.2015.4268. Epub 2015 Dec 29. PMID: 26486881; PMCID: PMC5065034.
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J Neurotrauma. 2016 Oct 01;33(19):1732-1750. doi: 10.1089/neu.2015.4268. Epub 2015 Dec 29.

Microglial/Macrophage Polarization Dynamics following Traumatic Brain Injury.

Journal of neurotrauma

Alok Kumar, Dulce-Mariely Alvarez-Croda, Bogdan A Stoica, Alan I Faden, David J Loane

Affiliations

  1. 1 Department of Anesthesiology and Shock, Trauma and Anesthesiology Research (STAR) Center, University of Maryland School of Medicine , Baltimore, Maryland.
  2. 2 Posgrado en Neuroetologia, Universidad Veracruzana , Xalapa, Mexico .

PMID: 26486881 PMCID: PMC5065034 DOI: 10.1089/neu.2015.4268

Abstract

Activated microglia and macrophages exert dual beneficial and detrimental roles after central nervous system injury, which are thought to be due to their polarization along a continuum from a classical pro-inflammatory M1-like state to an alternative anti-inflammatory M2-like state. The goal of the present study was to analyze the temporal dynamics of microglia/macrophage polarization within the lesion micro-environment following traumatic brain injury (TBI) using a moderate-level controlled cortical impact (CCI) model in mice. We performed a detailed phenotypic analysis of M1- and M2-like polarized microglia/macrophages, as well as nicotinamide adenine dinucleotide phosphate oxidase (NOX2) expression, through 7 days post-injury using real-time polymerase chain reaction (qPCR), flow cytometry and image analyses. We demonstrated that microglia/macrophages express both M1- and M2-like phenotypic markers early after TBI, but the transient up-regulation of the M2-like phenotype was replaced by a predominant M1- or mixed transitional (Mtran) phenotype that expressed high levels of NOX2 at 7 days post-injury. The shift towards the M1-like and Mtran phenotype was associated with increased cortical and hippocampal neurodegeneration. In a follow up study, we administered a selective NOX2 inhibitor, gp91ds-tat, to CCI mice starting at 24 h post-injury to investigate the relationship between NOX2 and M1-like/Mtran phenotypes. Delayed gp91ds-tat treatment altered M1-/M2-like balance in favor of the anti-inflammatory M2-like phenotype, and significantly reduced oxidative damage in neurons at 7 days post-injury. Therefore, our data suggest that despite M1-like and M2-like polarized microglia/macrophages being activated after TBI, the early M2-like response becomes dysfunctional over time, resulting in development of pathological M1-like and Mtran phenotypes driven by increased NOX2 activity.

Keywords: M1-like; M2-like; NOX2, polarization; microglia/macrophage; traumatic brain injury

Conflict of interest statement

Author Disclosure Statement No competing financial interests exist.

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