Transcutaneous carbon dioxide application with hydrogel prevents muscle atrophy in a rat sciatic nerve crush model

The acceleration of nerve regeneration remains a clinical challenge. We previously demonstrated that transcutaneous CO₂ application using a novel hydrogel increases the oxygen concentration in local tissue via an “artificial Bohr effect” with the potential to prevent muscle atrophy. In this study, we investigated the effect of transcutaneous CO₂ administration on limb function after peripheral nerve injury in a rat sciatic nerve injury model. In total, 73 Sprague-Dawley rats were divided into a sham group, a control group (crush injury to sciatic nerve and no treatment) or a CO₂ group (crush injury with transcutaneous CO₂ application). CO₂ was administered percutaneously for 20 min five times per week. Scores for the sciatic function index and pinprick test were significantly higher in the CO₂ group than control group. The muscle wet weight ratios of the tibialis anterior and soleus muscles were higher in the CO₂ group than control group. Electrophysiological examination showed that the CO₂ group had higher compound motor action potential amplitudes and shorter distal motor latency than the control group. Histological examination of the soleus muscle sections at postoperative week 2 showed shorter fiber diameter in the control group than in the CO₂ group. The mRNA expression of Atrogin-1 and MuRF-1 was lower, mRNA expression of VEGF and myogenin and MyoD was higher in CO₂ group at postoperative week 2 compared to the control group.