Neuroprotective Effect of Electroacupuncture on Rats with Spinal Cord Injury via Ferroptosis Suppression through Xc-/Glutathione Peroxidase 4 Signaling Activation

Background: Spinal cord injury (SCI) is a devastating condition. SCI pathology has been associated with ferroptosis. Traditional Chinese Medicine has shown potential in the treatment of nervous system diseases via ferroptosis inhibition. However, the effect exerted by electroacupuncture (EA) treatment on SCI via ferroptosis pathway inhibition remains poorly investigated. Objective: To investigate the mechanism by which EA regulates the expression of relevant cytokines in the Xc-/Glutathione peroxidase 4 (GPX4) pathway and suppresses ferroptosis in rats with SCI. Materials and Methods: Eighty healthy female Sprague–Dawley rats were randomly divided into SCI model, EA treatment (SCI + EA), and deferoxamine treatment (SCI + DFO) groups after Basso–Beattie–Bresnahan (BBB) scoring. A sham operation group (sham) was also formed. Each group had 20 animals. In the SCI + EA group, Dazhui (GV14) , Yaoyangguan (GV3) , bilateral Ciliao (BL32) , and Zusanli (ST36) were subjected to EA treatment once daily for 20 min per session for 14 sessions. In the DFO group, rats were injected intraperitoneally with DFO on alternate days. Following the completion of treatment and BBB scoring, the rats were euthanized, and their spinal cord tissues were collected for the subsequent detection of relevant targets. Results: Compared to the rats in the sham group, those in the SCI group had lower BBB scores, spinal cord tissue damage, higher tissue iron and reactive oxygen species concentrations, and lower levels of solute carrier family 7, member 11, (SLC7A11, also known as xCT), and GPX4. The treatment improved all indices. EA was more effective than DFO treatment in improving SLC7A11 protein expression. Conclusion: EA can improve neurological function in rats with SCI by upregulating the expression of related cytokines in the Xc-/GPX4 pathway, suppressing ferroptosis, and alleviating the inflammatory response.