Macrophagic and microglial responses after focal traumatic brain injury in the female rat
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BACKGROUND: After central nervous system injury, inflammatory macrophages (M1) predominate over anti-inflammatory macrophages (M2). The temporal profile of M1/M2 phenotypes in macrophages and microglia after traumatic brain injury (TBI) in rats is unknown. We subjected female rats to severe controlled cortical impact (CCI) and examined the postinjury M1/M2 time course in their brains. METHODS: The motor cortex (2.5 mm left laterally and 1.0 mm anteriorly from the bregma) of anesthetized female Wistar rats (ages 8 to 10 weeks; N = 72) underwent histologically moderate to severe CCI with a 5-mm impactor tip. Separate cohorts of rats had their brains dissociated into cells for flow cytometry, perfusion-fixed for immunohistochemistry (IHC) and ex vivo magnetic resonance imaging or flash-frozen for RNA and protein analysis. For each analytical method used, separate postinjury times were included for 24 hours; 3 or 5 days; or 1, 2, 4 or 8 weeks. RESULTS: By IHC, we found that the macrophagic and microglial responses peaked at 5 to 7 days post-TBI with characteristics of mixed populations of M1 and M2 phenotypes. Upon flow cytometry examination of immunological cells isolated from brain tissue, we observed that peak M2-associated staining occurred at 5 days post-TBI. Chemokine analysis by multiplex assay showed statistically significant increases in macrophage inflammatory protein 1α and keratinocyte chemoattractant/growth-related oncogene on the ipsilateral side within the first 24 hours after injury relative to controls and to the contralateral side. Quantitative RT-PCR analysis demonstrated expression of both M1- and M2-associated markers, which peaked at 5 days post-TBI. CONCLUSIONS: The responses of macrophagic and microglial cells to histologically severe CCI in the female rat are maximal between days 3 and 7 postinjury. The response to injury is a mixture of M1 and M2 phenotypes.
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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 [110]
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- Authors
- Turtzo, L., Lescher, J., Janes, L., Dean, D. D., Budde, M. D., & Frank, J. A.
- Affiliations
- Uniformed Services University of the Health Sciences (US)
- National Institutes of Health (US)
- Corresponding author
- Turtzo, L
- Venue
- Journal of Neuroinflammation
- Published
- 2014
- Volume
- 11
- Issue
- 1
- Pages
- 82
- ISSN
- 1742-2094 (ISSN-L)
- PMC
- PMC4022366
- OpenAlex
- W2157968665
- Cited by
- 167
- References
- 58
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 9 · 2023: 6 · 2022: 8 · 2021: 16 · 2020: 16 · 2019: 20 · 2018: 12 · 2017: 24 · 2016: 16 · 2015: 20 · 2014: 3 · 2013: 1
- FWCI
- 13.69
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Journal of Neuroinflammation (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense
- Henry M. Jackson Foundation
- National Institutes of Health
- U.S. Public Health Service (01-60855)
- Center for Neuroscience and Regenerative Medicine (60855)
- 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, macrophage polarization, M1/M2 macrophages, microglia, controlled cortical impact, female rats, neuroinflammation, chemokines, CCL17, CCL22, motor cortex
- MeSH terms
- Analysis of Variance, Animals, Brain, Brain Injuries, Calcium-Binding Proteins, Disease Models, Animal, Female, Flow Cytometry, Gene Expression Regulation, Macrophages, Magnetic Resonance Imaging, Microfilament Proteins, Microscopy, Fluorescence, Time Factors, Cytokines, Rats, Wistar, Microglia, Rats
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