Microglia/Macrophage Polarization Dynamics in White Matter after Traumatic Brain Injury
Open accessAbstract
Mononuclear phagocytes are a population of multi-phenotypic cells and have dual roles in brain destruction/reconstruction. The phenotype-specific roles of microglia/macrophages in traumatic brain injury (TBI) are, however, poorly characterized. In the present study, TBI was induced in mice by a controlled cortical impact (CCI) and animals were killed at 1 to 14 days post injury. Real-time polymerase chain reaction (RT–PCR) and immunofluorescence staining for M1 and M2 markers were performed to characterize phenotypic changes of microglia/macrophages in both gray and white matter. We found that the number of M1-like phagocytes increased in cortex, striatum and corpus callosum (CC) during the first week and remained elevated until at least 14 days after TBI. In contrast, M2-like microglia/macrophages peaked at 5 days, but decreased rapidly thereafter. Notably, the severity of white matter injury (WMI), manifested by immunohistochemical staining for neurofilament SMI-32, was strongly correlated with the number of M1-like phagocytes. In vitro experiments using a conditioned medium transfer system confirmed that M1 microglia-conditioned media exacerbated oxygen glucose deprivation–induced oligodendrocyte death. Our results indicate that microglia/macrophages respond dynamically to TBI, experiencing a transient M2 phenotype followed by a shift to the M1 phenotype. The M1 phenotypic shift may propel WMI progression and represents a rational target for TBI treatment.
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In the initial week following injury, the microglia population adopts a balanced distribution between pro- and anti-inflammatory states to promote neurogenesis and enhance the immune response to injury.
“In the initial week following injury, the microglia population adopts a balanced distribution between pro- and anti-inflammatory states to promote neurogenesis and enhance the immune response to injury [89,110,111].”
From Untangling senescent and damage‐associated microglia in the aging and diseased brain (2023) · cites this paper as [111]
In vitro, conditioned media derived from microglia in an induced pro-inflammatory M1-like state reduces survival of oligodendrocytes, whereas conditioned media from microglia in an induced anti-inflammatory M2-like state promotes remyelination.
“In vitro, conditioned media derived from microglia in an induced pro-inflammatory ‘M1-like’ state reduces survival of oligodendrocytes in vitro, whereas conditioned media from microglia in an induced anti-inflammatory ‘M2-like’ state promotes remyelination [111,113].”
From Untangling senescent and damage‐associated microglia in the aging and diseased brain (2023) · cites this paper as [111]
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- Authors
- Wang, G., Zhang, J., Hu, X., Zhang, L., Mao, L., Jiang, X., Liou, A. K.-F., Leak, R. K., Gao, Y., & Chen, J.
- Affiliations
- University of Pittsburgh (US)
- Fudan University (CN)
- Duquesne University (US)
- Corresponding author
- Gao, Yanqin
- Chen, Jun
- ORCID
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 2013-08-14
- Volume
- 33
- Issue
- 12
- Pages
- 1864-1874
- ISSN
- 0271-678X (ISSN-L)
- 1559-7016
- PMC
- PMC3851898
- OpenAlex
- W2041363468
- Cited by
- 473
- References
- 43
- Citations by year
- 2026: 12 · 2025: 26 · 2024: 35 · 2023: 23 · 2022: 40 · 2021: 58 · 2020: 43 · 2019: 45 · 2018: 45 · 2017: 41 · 2016: 44 · 2015: 45 · 2014: 16
- FWCI
- 22.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS 45048, NS43802, R01NS062157, NS 36736, R01NS045048, R01NS043802, R01NS036736)
- Topics
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Keywords
- traumatic brain injury, microglial polarization, macrophage polarization, M1 macrophage phenotype, M2 phenotype, white matter injury, corpus callosum, oligodendrocyte death, oxygen-glucose deprivation, conditioned medium, controlled cortical impact, mononuclear phagocytes
- MeSH terms
- Animals, Brain, Brain Injuries, Cells, Cultured, Glucose, Macrophages, Male, Mice, Inbred C57BL, Oxygen, Phagocytosis, RNA, Messenger, Microglia, Mice
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