Related Experiment Video
Updated: Oct 19, 2025
Controlled Cortical Impact Model for Traumatic Brain Injury
Published on: August 5, 2014
CCR2 deficiency alters activation of microglia subsets in traumatic brain injury
Kerri Somebang1, Joshua Rudolph2, Isabella Imhof1
1Department of Medicine, Division of Rheumatology, University of California, San Francisco (UCSF), San Francisco, CA, USA; San Francisco VA Health Care System, San Francisco, CA, USA.
Abstract:
In traumatic brain injury (TBI), a diversity of brain resident and peripherally derived myeloid cells have the potential to worsen damage and/or to assist in healing. We define the heterogeneity of microglia and macrophage phenotypes during TBI in wild-type (WT) mice and Ccr2-/- mice, which lack macrophage influx following TBI and are resistant to brain damage. We use unbiased single-cell RNA sequencing methods to uncover 25 microglia, monocyte/macrophage, and dendritic cell subsets in acute TBI and normal brains. We find alterations in transcriptional profiles of microglia subsets in Ccr2-/- TBI mice compared to WT TBI mice indicating that infiltrating monocytes/macrophages influence microglia activation to promote a type I IFN response. Preclinical pharmacological blockade of hCCR2 after injury reduces expression of IFN-responsive gene, Irf7, and improves outcomes. These data extend our understanding of myeloid cell diversity and crosstalk in brain trauma and identify therapeutic targets in myeloid subsets.
Insights
In traumatic brain injury (TBI), infiltrating monocytes worsen outcomes by influencing microglia activation. Blocking CCR2 reduces this effect and improves TBI recovery, highlighting myeloid cell targets.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Traumatic brain injury (TBI) involves diverse myeloid cells that can exacerbate or aid healing.
- Understanding microglia and macrophage heterogeneity is crucial for TBI research.
Purpose of the Study:
- To define microglia and macrophage phenotypes in TBI using wild-type and Ccr2-/- mice.
- To investigate the influence of infiltrating macrophages on microglia activation and TBI outcomes.
Main Methods:
- Unbiased single-cell RNA sequencing was employed to identify cell subsets in acute TBI and normal brains.
- Comparison of transcriptional profiles between wild-type TBI and Ccr2-/- TBI mice.
Main Results:
- Twenty-five distinct microglia, monocyte/macrophage, and dendritic cell subsets were identified.
- In Ccr2-/- TBI mice, altered microglia transcriptional profiles indicated that infiltrating monocytes/macrophages promote a type I interferon response.
- Pharmacological blockade of CCR2 post-injury reduced interferon-responsive gene (Irf7) expression and improved outcomes.
Conclusions:
- Infiltrating monocytes/macrophages significantly influence microglia activation in TBI, promoting a type I interferon response.
- CCR2 blockade represents a potential therapeutic strategy for TBI by modulating myeloid cell crosstalk.
- These findings identify specific myeloid cell subsets as therapeutic targets for brain trauma.
