Dynamic development of microglia and macrophages after spinal cord injury

• Published in: Neural regeneration research Vol. 20; no. 12; pp. 3606 - 3619
• Main Authors: Zhou, Hu-Yao, Wang, Xia, Li, Yi, Wang, Duan, Zhou, Xuan-Zi, Xiao, Nong, Li, Guo-Xing, Li, Gang
• Format: Journal Article
• Language: English
• Published: India Wolters Kluwer - Medknow 01.12.2025; Medknow Publications & Media Pvt. Ltd; Department of Rehabilitation,Children's Hospital of Chongqing Medical University,National Clinical Research Center for Child Health and Disorders,Ministry of Education Key Laboratory of Child Development and Disorders,Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders,Chongqing,China%Department of Rehabilitation,Children's Hospital of Chongqing Medical University,National Clinical Research Center for Child Health and Disorders,Ministry of Education Key Laboratory of Child Development and Disorders,Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders,Chongqing,China%Institute of Life Sciences,Chongqing Medical University,Chongqing,China%Institute of Life Sciences,Chongqing Medical University,Chongqing,China; Institute of Life Sciences,Chongqing Medical University,Chongqing,China; Molecular Medicine Diagnostic and Testing Center,Chongqing Medical University,Chongqing,China; Wolters Kluwer Medknow Publications
• Edition: 2
• Subjects: acute inflammation; bioinformatics analysis; fibroblast; integrin β2; ligand–receptor interaction; neuroinflammation; oncostatin m; Research Article; single-cell rna sequencing; spatial transcriptomics; Spinal cord injuries; spinal cord injury; single-cell RNA sequencing; spinal cord injury; acute inflammation; fibroblast; integrin β2; oncostatin M; neuroinflammation; spatial transcriptomics; ligand-receptor interaction; bioinformatics analysis
• ISSN: 1673-5374; 1876-7958
• DOI: 10.4103/NRR.NRR-D-24-00063

Secondary injury following spinal cord injury is primarily characterized by a complex inflammatory response, with resident microglia and infiltrating macrophages playing pivotal roles. While previous studies have grouped these two cell types together based on similarities in structure and function, an increasing number of studies have demonstrated that microglia and macrophages exhibit differences in structure and function and have different effects on disease processes. In this study, we used single-cell RNA sequencing and spatial transcriptomics to identify the distinct evolutionary paths of microglia and macrophages following spinal cord injury. Our results showed that microglia were activated to a pro-inflammatory phenotype immediately after spinal cord injury, gradually transforming to an anti-inflammatory steady state phenotype as the disease progressed. Regarding macrophages, our findings highlighted abundant communication with other cells, including fibroblasts and neurons. Both pro-inflammatory and neuroprotective effects of macrophages were also identified; the pro-inflammatory effect may be related to integrin β2 (Itgb2) and the neuroprotective effect may be related to the oncostatin M pathway. These findings were validated by in vivo experiments. This research underscores differences in the cellular dynamics of microglia and macrophages following spinal cord injury, and may offer new perspectives on inflammatory mechanisms and potential therapeutic targets.