Transcutaneous auricular vagus nerve stimulation (ta-VNS) is a non-invasive neuromodulation technique with emerging therapeutic potential for various central nervous system diseases. However, its therapeutic effects and mechanisms in spinal cord injury (SCI) remain largely unexplored. In this study, we demonstrated that ta-VNS significantly improved motor function recovery in SCI patients. Diffusion tensor imaging (DTI) further indicated that ta-VNS promoted structural repair of injured axons and myelin sheaths. Using a rodent model of SCI, we found that ta-VNS facilitated remyelination, attenuated tissue damage, and enhanced motor function recovery. Mechanistically, ta-VNS upregulated the expression of the α7 nicotinic acetylcholine receptor (α7nAChR) in oligodendrocyte precursor cells (OPCs), promoting their proliferation and differentiation into mature oligodendrocytes, thereby supporting remyelination. These beneficial effects of ta-VNS were abolished by administration of a selective α7nAChR antagonist. This study identifies the α7nAChR-mediated pro-myelination axis as a novel mechanistic basis for ta-VNS therapy, thereby establishing this non-invasive neuromodulation as a compelling strategy for promoting repair and recovery after SCI.
Keywords: Neuroregeneration; Nicotinic acetylcholine receptor; Non-invasive neuromodulation; Oligodendrocyte precursor cells; Spinal cord injury.
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