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

Zide Wang1, Zhe Meng1, Yaosai Liu1

  • 1Department of Neurosurgery, Beiing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing 102218, China.

Iscience
|October 28, 2025
PubMed

Insights

Damage-associated microglia (DAM) are key in spinal cord injury (SCI). Eupatilin treatment promotes their beneficial transition to homeostatic microglia (MG2), aiding recovery.

Area of Science:

  • Neuroscience
  • Immunology
  • Genetics

Background:

  • Microglia, particularly damage-associated microglia (DAM), are crucial in spinal cord injury (SCI) pathogenesis.
  • Understanding microglial heterogeneity and dynamics is vital for developing effective SCI therapies.

Purpose of the Study:

  • To identify specific DAM subsets in acute SCI and investigate their functional characteristics.
  • To evaluate the therapeutic potential of Eupatilin in modulating microglial responses post-SCI.

Main Methods:

  • Integrated in-silico analysis of single-cell RNA sequencing (scRNA-seq) and microarray data.
  • Validation using a mouse spinal cord contusion model (C57BL/6).
  • Assessment of Eupatilin's effects via bulk and scRNA-seq.

Main Results:

  • Specific DAM subsets in acute SCI were identified, marked by hub genes Fcer1g, Grn, and Gusb.
  • Increased DAM accumulation and a shift towards homeostatic microglia (MG2) were observed post-injury.
  • Eupatilin treatment enhanced DAM-to-MG2 differentiation, supported by gene expression changes.

Conclusions:

  • DAM are functionally distinct populations in acute SCI.
  • Eupatilin facilitates beneficial microglial polarization from DAM to MG2.
  • Targeting DAM-to-MG2 transitions offers a promising therapeutic strategy for SCI recovery.