Repetitive trans-spinal magnetic stimulation improves motor function in rats with spinal cord injury and is associated with upregulation of EphA4 signaling pathway proteins

Objective: Spinal cord injury (SCI) is a highly disabling neurological condition that remains a worldwide challenge in healthcare. Our previous studies found that repetitive trans-spinal magnetic stimulation (rTSMS) applied at the L2 spinal segment yielded the most significant improvement in motor function in rats with SCI; however, the underlying mechanism remains unclear. Recent research indicates that disruption of the EphA4 signaling pathway in glutamatergic interneurons within the spinal cord leads to a loss of motor rhythm and a hopping gait in rats. Conversely, activating the locomotor central pattern generator (CPG) located in the L1-2 spinal segments promotes the recovery of motor function. Thus, by examining the effects of rTSMS on proteins associated with the EphA4 signaling pathway, this study provides novel insights for future investigations into its potential mechanisms of action. Methods: A multidimensional approach, including behavioral assessments, immunofluorescence, RT-PCR, and Western blotting, was employed to evaluate the effects of rTSMS on motor function in rats with acute SCI. We also assessed its impact on EphA4 mRNA expression levels and the synthesis of related proteins, including VGluT2, EphA4, EphrinB3, and downstream effector molecules Chn1 and Nck1. Results: The results showed that rTSMS improved the Basso, Beattie, and Bresnahan (BBB) locomotor scores in rats with acute spinal cord injury. It also exerted positive effects on upregulating the expression level of EphA4 mRNA and promoting the synthesis of proteins, including VGluT2, EphA4, EphrinB3, and the downstream effector molecules Chn1 and Nck1. Conclusion: This study suggests that repetitive trans-spinal magnetic stimulation effectively improves motor function after acute spinal cord injury, concomitant with an upregulation of EphA4 pathway-related proteins, thereby providing a new direction for future mechanistic research.