Cervical Repetitive Magnetic Stimulation Enhances Respiratory Recovery by Modulating Neuronal Plasticity After Cervical Spinal Cord Injury

Abstract

Cervical spinal cord injury (SCI) frequently leads to life-threatening respiratory insufficiency by disrupting descending phrenic pathways. There is growing interest in non-invasive neuromodulatory approaches to enhance plasticity of spared respiratory circuits. We investigated whether cervical repetitive magnetic stimulation (rMS) applied to the injured cervical spinal cord promotes ventilatory recovery in a preclinical mouse model. Adult mice received a unilateral C3 hemicontusion followed by either rMS or sham stimulation. We found that rMS-treated mice significantly improved recovery of tidal volume and minute ventilation at 21 days post injury(dpi) compared to sham controls under various breathing conditions (isoflurane anesthesia, poikilocapnic phase and hypercapnic challenge). Correspondingly, diaphragm EMG enhanced ipsilateral hemidiaphragm activity in ventral and medial regions, and even contralateral hemidiaphragm activity in its ventral part. This was associated with a marked attenuation of the inflammatory response at the cervical spinal cord level. Indeed, rMS lowered astroglial, fibrotic scarring, pro-inflammatory CD68-, Iba1- microglial/macrophage markers. Moreover, perineuronal net expression (WFA positive staining) is globally reduced in the ventral spinal horn, whereas at the lesion site it is markedly increased and tightly wrapped around motoneurons. Together, these findings demonstrate that rMS promotes functional respiratory recovery after cervical SCI through combined enhancement of diaphragmatic motor output and modulation of the inflammatory and extracellular environment. Together, these functional and cellular findings indicate that spinal rMS promotes a permissive, pro-regenerative environment supporting respiratory circuit plasticity. We conclude that rMS significantly enhances ventilatory recovery via reduced inflammatory response and improved intraspinal rewiring after high cervical SCI, suggesting it is a promising non-invasive strategy. The ability of rMS to engage spared respiratory networks and support neuroplasticity highlights its promise as a safe, non-invasive therapeutic strategy with translational potential for rehabilitation of breathing function after SCI. One Sentence SummaryNoninvasive cervical magnetic stimulation improves breathing after spinal cord injury by boosting diaphragm activity and reducing inflammation.