Abstract

BACKGROUND Spinal cord ischemia/reperfusion (I/R) injury is a severe complication following thoracoabdominal aortic surgeries, often leading to paraplegia. Ferroptosis, an iron-dependent form of regulated cell death, contributes significantly to this pathology. This study investigates the hypothesis that miR-10a-5p attenuates spinal cord I/R injury by targeting TAK1, thereby suppressing ACSL4-mediated ferroptosis and neuroinflammation. METHODS A spinal cord I/R injury model was established in male Sprague-Dawley male rats via transient aortic occlusion. Intrathecal injections of the ferroptosis inhibitor Liproxstatin-1 (Lip-1), siRNA targeting ACSL4 or TAK1, and miR-10a-5p agomir/antagomir were administered prior to ischemia induction. Neurological function was assessed using Tarlov scores. Histopathological changes were evaluated by H&E, Nissl, and immunofluorescence staining. Mitochondrial ultrastructure was examined by transmission electron microscopy (TEM). Expression levels of ferroptosis-related markers (ACSL4, GPX4, COX2, FTH1), inflammatory cytokines (TNF-α, IL-1β), and lipid peroxidation products (MDA, 12-HETE, 15-HETE, LPO) were measured using Western blot, qPCR, and ELISA. The targeting relationship between miR-10a-5p and TAK1 was validated by dual-luciferase reporter assay. RESULTS Spinal cord I/R injury induced significant neurological deficits, ferroptosis (evidenced by increased iron, MDA, ACSL4, and COX2; decreased GPX4 and GSH), lipid peroxidation, and inflammation. Lip-1 treatment ameliorated these changes. Knockdown of ACSL4 or TAK1 similarly inhibited ferroptosis, reduced inflammation, and improved motor function. Spinal cord I/R injury induced significant downregulation of miR-10a-5p. It directly targeted TAK1, as confirmed by luciferase assay.