Transcutaneous Auricular Vagus Nerve Stimulation Alleviates Oxidative Stress and Improves Neurological Outcomes After Traumatic Brain Injury in Mice

OBJECTIVE: Traumatic brain injury (TBI) can trigger secondary oxidative stress and exacerbate neurological dysfunction. This study investigated whether transcutaneous auricular vagus nerve stimulation (taVNS) attenuates oxidative stress and improves neurological recovery after TBI in mice. METHODS: The TBI model was established using a controlled cortical impact (CCI) model. Seventy C57BL/6 mice were divided into the sham group, TBI group, taVNS group, MDHB (pathway agonist, administered alone) group, and ML385 (pathway inhibitor, administered 30 min before each taVNS session) group. Outcomes were assessed by Western blotting, ELISA, immunofluorescence, T2-weighted MRI-based volumetric quantification of edema, and behavioral tests. RESULTS: TBI markedly increased oxidative stress and neurological impairment, as reflected by reduced serum glutathione (GSH) and superoxide dismutase (SOD) levels, increased lesion and edema burden on MRI, and worsened behavioral performance. TaVNS significantly alleviated these changes, increasing GSH and SOD levels, reducing edema burden, and improving mNSS and open-field performance. In addition, taVNS was associated with increased expression of antioxidant-related proteins, including Nrf-2 and HO-1, whereas pharmacological inhibition with ML385 attenuated these beneficial effects. CONCLUSION: These findings suggest that taVNS may alleviate oxidative stress and improve neurological outcomes after TBI in mice, with possible involvement of the Nrf-2/HO-1 pathway.