MiR-425-5p modulation of CREB1 affects inflammatory response and motor recovery after spinal cord injury

This study aimed to investigate whether miR-425-5p contributes to post-spinal cord injury (SCI) inflammation and motor dysfunction by targeting CREB1.

SCI rat models and H₂O₂-treated C8-D1A/C8-B4 cellular models were established. miR-425-5p and CREB1 were manipulated using inhibitors/antagomirs and siRNAs. Expression levels of miR-425-5p, IL-6, IL-1β, TNF-α, CREB1, and caspase-3 were measured using RT-qPCR. Cell apoptosis was evaluated by flow cytometry. Western blot analysis was performed to assess total CREB1 (t-CREB1) and phosphorylated CREB1 (p-CREB1) levels. Bioinformatics predictions were used to determine the targeting relationship between miR-425-5p and CREB1. BBB locomotor rating scale was employed to quantify motor function recovery in rats.

miR-425-5p expression was markedly up-regulated in the H₂O₂-induced cell model, whereas CREB1 was down-regulated. CREB1 is a target of miR-425-5p. Inhibition of miR-425-5p significantly reduced apoptosis, suppressed pro-inflammatory cytokine expression, thereby promoting motor recovery; these effects were partially reversed by CREB1 knockdown. In SCI rats, miR-425-5p antagomir treatment alleviated inflammation and promoted motor function recovery; these beneficial effects were partially suppressed by co-administration of si-CREB1 to knockdown CREB1.

MiR-425-5p upregulation in SCI directly suppresses CREB1 expression, subsequently exacerbating neuroinflammation, which in turn impairs functional recovery.