Non-invasive transcutaneous spinal direct current stimulation enhances diaphragm activation during acute hypoxia in rats with high-cervical spinal cord injury (SCI)

SCIs often result in respiratory compromise contributing to mortality and morbidity. There is an urgent need to develop therapeutic interventions to reinstate the complete spectrum of breathing functionality following SCI (e.g., eupnea, hyperpnea, coughing, sighing). Most SCIs are incomplete, and in such cases, an extant substrate exists for using neuromodulatory therapies to enable descending synaptic inputs to activate sub-threshold spinal networks and motor neurons. Transcutaneous spinal direct current stimulation (tsDCS) is a non-invasive method in which a constant, low-intensity current is delivered via surface (skin) electrodes. tsDCS enables excitatory neurotransmitter release which can increase spinal neuron excitability. A prior study demonstrated that tsDCS can increase ventilation and diaphragm motor evoked potentials in spinal intact humans (PMID: 25339753). We recently developed a rodent model of tsDCS and are the first to show that cervical tsDCS can enhance diaphragm activation after high cervical SCI. The goal of the current work was to explore whether tsDCS can be used as an adjunct therapy to other neuromodulatory stimuli. We hypothesized that cathodal tsDCS (3mA, 20 min) when used in conjunction with a brief hypoxic stimulus (10% O 2 , 5 min) would elicit a larger diaphragm EMG response compared to the hypoxic stimulus alone. Adult male rats (n=7, 12 weeks old) were implanted with indwelling diaphragm EMG electrodes and received a C2 hemisection injury. At 8 weeks post-injury, bilateral diaphragm EMG activity was recorded during spontaneous breathing under 1.5% isofluorane. We found that peak diaphragm EMG bursting, recorded ipsilateral to SCI, was greater during simultaneous tsDCS and hypoxia (234±146 % of baseline) when compared to activation during hypoxia alone (164±97 % of baseline, p=0.029). There was no difference in peak contralateral EMG across the two different protocols (p=0.47). Respiratory rate tended to be higher in the tsDCS+Hypoxia group (p=0.076) immediately following the exposure as compared to the hypoxia alone group, whereas EMG activity was back to baseline (p=0.21). We conclude that non-invasive cathodal tsDCS delivered at the mid-cervical region can increase the impact of a hypoxic stimulus on diaphragm muscle output after cervical SCI. Given the evidence that rehabilitation paradigms utilizing brief hypoxia exposures can improve motor recovery after SCI (PMID: 34637802), the pairing of tsDCS and hypoxia merits further study in the context of respiratory rehabilitation. Future work will refine various rehabilitation protocols that can be used in conjunction with tsDCS to promote respiratory recovery following SCI or other diseases presenting with respiratory compromise. 1K99NS133388-01A1 (SR), Parker B Francis Foundation Fellowship (SR), 1 R01 HL153140-01 (DDF) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.