Cited by 216Traumatic Brain Injury and Neurovascular DisturbancesNeuroinflammation and Neurodegeneration MechanismsTraumatic Brain Injury Research

Temporal Changes in Cell Marker Expression and Cellular Infiltration in a Controlled Cortical Impact Model in Adult Male C57BL/6 Mice

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Jin, Xuemei, Ishii, Hiroshi, Bai, Zhongbin, Itokazu, Takahide, Yamashita, Toshihide·2012·PLoS ONE

Abstract

BACKGROUND: Traumatic injury to the central nervous system (CNS) triggers a robust inflammatory response that leads to axonal damage and secondary degeneration of spared tissue. In contrast, some immune responses have neuroprotective effects. However, detailed information regarding the dynamics of immune responses after traumatic CNS injury is still unavailable. METHODS: In the present study, changes in the immune cells present in the injured brain, spleen, and cervical lymph nodes (CLNs), which are draining lymphatic organs from the CNS, were analyzed after controlled cortical impact (CCI) by flow cytometry and immunohistochemistry. RESULTS: The number of neutrophils and macrophages that infiltrated the injured brain immediately increased 1 d post-injury and declined rapidly thereafter. In the injured brain, resident microglia showed a bimodal increase during the first week and in the chronic phase (≥3 weeks) after injury. Increase in the Iba-1(+) microglia/macrophages was observed around the injured site. Morphologic analysis showed that Iba-1(+) cells were round at 1 week, whereas those at 3 weeks were more ramified. Furthermore, CD86(+)/CD11b(+) M1-like microglia increased at 4 weeks after CCI, whereas CD206(+)/CD11b(+) M2-like microglia increased at 1 week. These results suggest that different subsets of microglia increased in the acute and chronic phases after CCI. Dendritic cells and T cells increased transiently within 1 week in the injured brain. In the CLNs and the spleen, T cells showed dynamic changes after CCI. In particular, the alteration in the number of T cells in the CLNs showed a similar pattern, with a 1-week delay, to that of microglia in the injured brain. CONCLUSION: The data from this study provide useful information on the dynamics of immune cells in CNS injuries.

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  • Microglia associated with the long-term inflammatory phenotype following TBI are commonly defined as MHC-II/CD86/Cd11b positive, with upregulated expression of NOX24, Tlr4, Trem2, CD68, Clec7a, and Stat1, and higher expression of interferon- and immune-associated signaling genes.

    “Microglia associated with the long-term inflammatory phenotype following TBI are commonly defined as MHC-II/CD86/Cd11b positive, with upregulated expression of NOX24, Tlr4, Trem2, CD68, Clec7a, and Stat1, and higher expression of interferon- and immune-associated signaling genes [100,112,115,116].”

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Authors
Jin, X., Ishii, H., Bai, Z., Itokazu, T., & Yamashita, T.
Affiliations
  • Japan Science and Technology Agency (JP)
  • Yunnan Agricultural University (CN)
Corresponding author
Yamashita, Toshihide
Venue
PLoS ONE
Published
2012-07-24
Volume
7
Issue
7
Pages
e41892
ISSN
1932-6203 (ISSN-L)
OpenAlex
W2025828188
Cited by
211
References
48
Citations by year
2026: 7 · 2025: 9 · 2024: 13 · 2023: 13 · 2022: 20 · 2021: 22 · 2020: 23 · 2019: 20 · 2018: 13 · 2017: 19 · 2016: 9 · 2015: 17 · 2014: 10 · 2013: 14 · 2012: 1
FWCI
8.78
Type
journal article
Language
en
Open access
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Japan Science and Technology Agency (CREST)
  • Core Research for Evolutional Science and Technology
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
controlled cortical impact, traumatic brain injury, microglia, macrophages, M1/M2 microglial polarization, dendritic cells, T cells, neutrophils, cervical lymph nodes, spleen, immune cell infiltration, neuroinflammation, Iba1, CD86, CD206
MeSH terms
Aging, Animals, Calcium-Binding Proteins, Cerebral Cortex, Dendritic Cells, Disease Models, Animal, Immunohistochemistry, Lymph Nodes, Macrophages, Male, Mice, Inbred C57BL, Microfilament Proteins, Neutrophils, Spleen, T-Lymphocytes, Time Factors, Biomarkers, Microglia, Mice

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