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Updated: Aug 7, 2026
Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
Hematopoietic Growth Factors Induce More Extensive Transcriptomic Remodeling in Cerebral Monocytes/Macrophages than
Sushil Gaire1, Robert S Gardner1, Michele Kyle1
1Department of Neurosurgery, State University of New York Upstate Medical University, 750 E. Adams Street, Syracuse, NY, 13210, USA.
Abstract:
Previous studies show that combined treatment with stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) enhances brain repair and functional recovery during the chronic phase of severe traumatic brain injury (TBI), but the underlying mechanisms remain unclear. Here, we investigated whether SCF + G-CSF modulates brain immune cell states during chronic TBI. In a controlled cortical impact mouse model, SCF + G-CSF was administered subcutaneously for 5 consecutive days beginning 8 months post-injury. CD11b⁺ brain immune cells, including microglia and monocytes/macrophages (Mo/Mac), were isolated one day after the final injection and analyzed by single-cell RNA sequencing. Integrated analyses revealed more extensive transcriptomic changes in Mo/Mac than in microglia following SCF + G-CSF treatment. Flow cytometry confirmed a significant increase in the CD11b+/CD45high Mo/Mac population following treatment. In microglia, SCF + G-CSF modestly upregulated genes such as S100a8, S100a9, Mir682, and Rpl37rt. In contrast, Mo/Mac showed robust upregulation of genes including Wfdc17, Ifitm1/2/3, Tspo, Lrg1, and Igfbp6, consistent with transcriptomic signatures associated with antiviral defense, anti-inflammatory regulation, and acquisition of reparative phenotypes. Volcano plot analysis demonstrated more extensive transcriptomic remodeling in infiltrating peripheral immune cells than in resident microglia. Pathway analysis identified interleukin-17 signaling as a candidate pathway associated with SCF + G-CSF treatment, along with enrichment of programs related to protein synthesis, detoxification, and glial development. Together, these findings demonstrate that the transcriptomic response to SCF + G-CSF treatment is more pronounced in cerebral monocyte/macrophage populations than in microglia, providing insight into candidate immunomodulatory mechanisms associated with brain repair in chronic TBI.
