2. Academic Validation
  3. Eupatilin ameliorates spinal cord injury by inhibiting damage-associated microglia and optimizing the regenerative microenvironment

Eupatilin ameliorates spinal cord injury by inhibiting damage-associated microglia and optimizing the regenerative microenvironment

  • iScience. 2025 Oct 1;28(11):113687. doi: 10.1016/j.isci.2025.113687.
Zide Wang 1,  Zhe Meng 1,  Yaosai Liu 1,  Boyan Su 1,  Guoxi Luan 1,  Peihai Zhang 1,  Jia Yang 2,  Kaiyuan Yang 1,  Guihuai Wang 1,  Xiumei Wang 2,  Beibei Yu 3,  Weitao Man 1
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Beiing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing 102218, China.
  • 2 State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China.
  • 3 Department of Neurosurgery, The Second Affiliated Hospital of Xi'an Jiao Tong University, Xi'an 710032, China.
PMID: 41146716 DOI: 10.1016/j.isci.2025.113687
Abstract

Microglia represent critical therapeutic targets in spinal cord injury (SCI), with damage-associated microglia (DAM) playing key roles in neuroinflammation and tissue repair. Through integrated in-silico analysis of single-cell RNA Sequencing (scRNA-seq) and microarray datasets, we identified DAM subsets specific to acute SCI characterized by hub genes Fcer1g, Grn, and Gusb. Using a C57BL/6 mouse spinal cord contusion model, we validated increased DAM accumulation post-injury and demonstrated their propensity to transition toward homeostatic microglia (MG2). Eupatilin treatment promoted DAM-to-MG2 differentiation, as confirmed through bulk and scRNA-seq analyses, revealing supportive gene expression changes. These findings establish DAM as functionally distinct microglial populations in acute SCI and identify Eupatilin as a therapeutic agent that facilitates beneficial microglial polarization. This work provides mechanistic insights into microglial dynamics during SCI and suggests targeted modulation of DAM-to-MG2 transitions as a promising therapeutic strategy for promoting inflammation resolution and functional recovery.

Keywords

Immunology; Neuroscience.

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