ENAGenomicsXijing hospitalhttps://www.ebi.ac.uk/ena/browser/view/PRJNA1312019Mus musculusMicroglia 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 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-toMG2 differentiation, as confirmed through bulk and single-cell RNA sequencing 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. Overall design: Prior to surgery, mice were fasted for 6 hours received anesthesia with a single intraperitoneal injection of 270-330 mg/kg Avertin (Sigma-Aldrich, MO, USA, T48402). The T9 lamina was surgically exposed while preserving the integrity of the dura mater, followed by a 30-second aneurysm clip compression for all injured groups. The muscle and skin were then sutured closed. Following SCI, manual bladder expression was performed 3 times daily until bladder function recovered. For the first 3 days, intrathecal injections were administered: the treatment group received Eupatilin (30 μl, 1.5 mg/mL, Bide, Shanghai, China, BD298186), while the SCI control group received an equivalent volume of saline.ENAfalseEupatilin Ameliorates Spinal Cord Injury by Inhibiting Damage-associated Microglia and Optimizing the Regenerative MicroenvironmentEupatilin Ameliorates Spinal Cord Injury by Inhibiting Damage-associated Microglia and Optimizing the Regenerative Microenvironment2025-09-242025-09-08PRJNA1312019GSE30674510090