Cited by 339Traumatic Brain Injury and Neurovascular DisturbancesNeuroinflammation and Neurodegeneration MechanismsTraumatic Brain Injury Research

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Microglial/Macrophage Polarization Dynamics following Traumatic Brain Injury

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Kumar, Alok, Alvarez-Croda, Dulce-Mariely, Stoica, Bogdan A., Faden, Alan I., Loane, David J.·2016·Journal of Neurotrauma

DOI 10.1089/neu.2015.4268PMC PMC5065034

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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.

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Additional file 2 of Mer regulates microglial/macrophage M1/M2 polarization and alleviates neuroinflammation following traumatic brain injury
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Additional file 1 of Genetic deletion of Krüppel-like factor 11 aggravates traumatic brain injury
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Additional file of The effect of dipeptidyl peptidase IV on disease-associated microglia phenotypic transformation in epilepsy
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Additional file 5 of Mer regulates microglial/macrophage M1/M2 polarization and alleviates neuroinflammation following traumatic brain injury
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Additional file 6 of Mer regulates microglial/macrophage M1/M2 polarization and alleviates neuroinflammation following traumatic brain injury
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Additional file 4 of Acute colitis during chronic experimental traumatic brain injury in mice induces dysautonomia and persistent extraintestinal, systemic, and CNS inflammation with exacerbated neurological deficits
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Self-citation
Additional file 4 of Mer regulates microglial/macrophage M1/M2 polarization and alleviates neuroinflammation following traumatic brain injury
Wu, H., Zheng, J., Xu, S., Fang, Y., Wu, Y., Zeng, J., Shao, A., Shi, L., Lü, J., Mei, S., et al. (2021) · Figshare · doi:10.6084/m9.figshare.13525175
Additional file 6 of Acute colitis during chronic experimental traumatic brain injury in mice induces dysautonomia and persistent extraintestinal, systemic, and CNS inflammation with exacerbated neurological deficits
Hanscom, M., Loane, D. J., Aubretch, T., Leser, J. M., Molesworth, K., Hedgekar, N., Ritzel, R. M., Abulwerdi, G., Shea‐Donohue, T., & Faden, A. I. (2021) · Figshare · doi:10.6084/m9.figshare.13605625
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Additional file 3 of Genetic deletion of Krüppel-like factor 11 aggravates traumatic brain injury
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Additional file 1 of Mer regulates microglial/macrophage M1/M2 polarization and alleviates neuroinflammation following traumatic brain injury
Wu, H., Zheng, J., Xu, S., Fang, Y., Wu, Y., Zeng, J., Shao, A., Shi, L., Lü, J., Mei, S., et al. (2021) · Figshare · doi:10.6084/m9.figshare.13525163
Additional file 3 of Mer regulates microglial/macrophage M1/M2 polarization and alleviates neuroinflammation following traumatic brain injury
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Additional file 2 of Genetic deletion of Krüppel-like factor 11 aggravates traumatic brain injury
Zhou, C., Sun, P., Hamblin, M. H., & Yin, K.-J. (2022) · Figshare · doi:10.6084/m9.figshare.21601983
Additional file 5 of Acute colitis during chronic experimental traumatic brain injury in mice induces dysautonomia and persistent extraintestinal, systemic, and CNS inflammation with exacerbated neurological deficits
Hanscom, M., Loane, D. J., Aubretch, T., Leser, J. M., Molesworth, K., Hedgekar, N., Ritzel, R. M., Abulwerdi, G., Shea‐Donohue, T., & Faden, A. I. (2021) · Figshare · doi:10.6084/m9.figshare.13605622
Self-citation
Additional file 5 of The effect of dipeptidyl peptidase IV on disease-associated microglia phenotypic transformation in epilepsy
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Additional file 3 of The effect of dipeptidyl peptidase IV on disease-associated microglia phenotypic transformation in epilepsy
Zheng, Z., Liang, P., Hou, B., Lu, X., Ma, Q., Yu, X., Han, S., Peng, B., 陈桃香, Liu, W., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14576573
Additional file 1 of Acute colitis during chronic experimental traumatic brain injury in mice induces dysautonomia and persistent extraintestinal, systemic, and CNS inflammation with exacerbated neurological deficits
Hanscom, M., Loane, D. J., Aubretch, T., Leser, J. M., Molesworth, K., Hedgekar, N., Ritzel, R. M., Abulwerdi, G., Shea‐Donohue, T., & Faden, A. I. (2021) · Figshare · doi:10.6084/m9.figshare.13605610
Self-citation
Additional file 3 of Acute colitis during chronic experimental traumatic brain injury in mice induces dysautonomia and persistent extraintestinal, systemic, and CNS inflammation with exacerbated neurological deficits
Hanscom, M., Loane, D. J., Aubretch, T., Leser, J. M., Molesworth, K., Hedgekar, N., Ritzel, R. M., Abulwerdi, G., Shea‐Donohue, T., & Faden, A. I. (2021) · Figshare · doi:10.6084/m9.figshare.13605616
Self-citation
Additional file 2 of Acute colitis during chronic experimental traumatic brain injury in mice induces dysautonomia and persistent extraintestinal, systemic, and CNS inflammation with exacerbated neurological deficits
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Authors: Kumar, A., Alvarez-Croda, D.-M., Stoica, B. A., Faden, A. I., & Loane, D. J.
Affiliations: University of Maryland, Baltimore (US)
Department of Anesthesiology and Shock, Trauma and Anesthesiology Research (STAR) Center, University of Maryland School of Medicine, Baltimore, Maryland.
Corresponding author: Loane, David J.
ORCID: Kumar, Alok
Stoica, Bogdan A.
Faden, Alan I.
Loane, David J.
Venue: Journal of Neurotrauma
Publisher: SAGE Publications
Published: 2016-10
Volume: 33
Issue: 19
Pages: 1732-1750
ISSN: 0897-7151 (ISSN-L)
1557-9042
DOI: 10.1089/neu.2015.4268
PMC: PMC5065034
OpenAlex: W2209119157
Cited by: 339
References: 52
Citations by year: 2026: 14 · 2025: 26 · 2024: 27 · 2023: 30 · 2022: 41 · 2021: 55 · 2020: 39 · 2019: 31 · 2018: 27 · 2017: 24 · 2016: 23
FWCI: 17.56
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.liebertpub.com/nv/resources-tools/text-and-data-mining-policy/121/ (tdm)
Locations: Journal of Neurotrauma (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (AG028747)
National Institute on Aging (AG028747, P30AG028747)
National Institute of Neurological Disorders and Stroke (R01NS037313, R01NS082308)
Topics: Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
Keywords: microglial polarization, macrophage polarization, traumatic brain injury, M1/M2 phenotype, NOX2, controlled cortical impact, neuroinflammation, neurodegeneration, oxidative damage, hippocampus, cortical injury, temporal dynamics

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Microglial/Macrophage Polarization Dynamics following Traumatic Brain Injury

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