The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
Microglial/Macrophage Polarization Dynamics following Traumatic Brain Injury
Open accessAbstract
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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“Of recent interest is how post-injury microglia promote increased oxidative damage leading to neurodegeneration through a NOX2-dependent mechanism [100,117,118].”
From Untangling senescent and damage‐associated microglia in the aging and diseased brain (2023) · cites this paper as [117]
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Cites
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Repertoire of microglial and macrophage responses after spinal cord injury
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Microglial Activation and Chronic Neurodegeneration
Lull, M. E., & Block, M. L. (2010) · Neurotherapeutics · doi:10.1016/j.nurt.2010.05.014 · Cited by 1,047 · cited 1×
“NOX2 is a common and essential mechanism of microglial-mediated neurotoxicity in neurodegenerative disease.(35) Activation of NOX2 in microglia is neurotoxic, both through the production of extracellular ROS that damage neighboring neurons(36) and through initiation of redox signaling in microglia that amplifies the p…”
BackgroundInflammation and white matter degeneration persist for years after a single traumatic brain injury
Johnson, V. E., Stewart, J. E., Begbie, F. D., Trojanowski, J. Q., Smith, D. H., & Stewart, W. (2013) · Brain · doi:10.1093/brain/aws322 · Cited by 1,045
Inflammation after trauma: Microglial activation and traumatic brain injury
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Heterogeneity of Microglial Activation in the Innate Immune Response in the Brain
Colton, C. A. (2009) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-009-9164-4 · Cited by 916
Macrophage activation and its role in repair and pathology after spinal cord injury
Gensel, J. C., & Zhang, B. (2015) · Brain Research · doi:10.1016/j.brainres.2014.12.045 · Cited by 792
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Neuroinflammation: The Devil Is in the Details
DiSabato, D. J., Quan, N., & Godbout, J. P. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13607 · Cited by 1,640
Modulators of microglial activation and polarization after intracerebral haemorrhage
Lan, X., Han, X., Li, Q., Yang, Q.-W., & Wang, J. (2017) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.69 · Cited by 915
Neuroimmunology of Traumatic Brain Injury: Time for a Paradigm Shift
Jassam, Y. N., Izzy, S., Whalen, M., McGavern, D. B., & El Khoury, J. (2017) · Neuron · doi:10.1016/j.neuron.2017.07.010 · Cited by 799
Blennow, K., Brody, D. L., Kochanek, P. M., Levin, H. S., McKee, A. C., Ribbers, G. M., Yaffe, K. S., & Zetterberg, H. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.84 · Cited by 693
Microglial Activation in Traumatic Brain Injury
Donat, C. K., Scott, G., Gentleman, S., & Sastre, M. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00208 · Cited by 512
Metadata
- 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.
- Venue
- Journal of Neurotrauma
- Publisher
- SAGE Publications
- Published
- 2016-10
- Volume
- 33
- Issue
- 19
- Pages
- 1732-1750
- ISSN
- 0897-7151 (ISSN-L)
- 1557-9042
- 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
- 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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