Amantadine modulates novel macrophage phenotypes to enhance neural repair following spinal cord injury

作者：Shijie Yang, Beibei Yu, Qing Zhang, Yongfeng Zhang, Longhui Fu, Bisheng Zhou, Haining Wu, Jianzhong Li, Shouping Gong · 发表于：Journal of Translational Medicine · 年份：2025 · DOI：10.1186/s12967-024-05916-y · 被引用次数：12 · 研究领域：Spinal Cord Injury Research、Neuroinflammation and Neurodegeneration Mechanisms、Nerve injury and regeneration

Spinal cord injury (SCI) triggers a complex inflammatory response that impedes neural repair and functional recovery. The modulation of macrophage phenotypes is thus considered a promising therapeutic strategy to mitigate inflammation and promote regeneration. We employed microarray and single-cell RNA sequencing (scRNA-seq) to investigate gene expression changes and immune cell dynamics in mice following crush injury at 3 and 7 days post-injury (dpi). High-dimensional gene co-expression network analysis (hdWGCNA) and slingshot trajectory analysis were employed to identify key gene modules and macrophage differentiation pathways. Subsequently, immunofluorescence staining, flow cytometry, and western blotting were performed to validate the identified effects of amantadine on macrophage differentiation and inflammation. To elucidate the molecular mechanisms underlying the injury response at the transcriptional level, we performed a microarray analysis followed by gene set enrichment analysis (GSEA). The results revealed that pathways related to phagocytosis and macrophage activation are significantly involved post-injury, shedding light on the regulatory role of macrophages in SCI repair. To further investigate macrophage dynamics within the injured spinal cord, we conducted scRNA-Seq, identifying three distinct macrophage subtypes: border-associated macrophages (BAMs), inflammatory macrophages (IMs), and chemotaxis-inducing macrophages (CIMs). Trajectory analysis suggested a d...