Study on the Effects of Transcutaneous Auricular Acupuncture Stimulation of the Vagus Nerve on Post-Traumatic Cerebral Oedema.

Abstract

BACKGROUND: Secondary cerebral oedema following traumatic brain injury (TBI) is a major cause of poor prognosis, primarily driven by neuroinflammation. High-mobility group box 1 (HMGB1) is a key damage-associated molecular pattern that initiates a potent inflammatory cascade, yet targeted pharmacological interventions face clinical translation challenges. Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) has shown anti-inflammatory potential, but its efficacy and specific mechanisms in treating traumatic cerebral oedema remain unclear. METHODS: A controlled cortical impact (CCI) model was established in male C57BL/6 mice. The animals were randomly divided into five groups: sham, TBI, TBI + taVNS, TBI + HMGB1 agonist (high glucose), and TBI + HMGB1 antagonist (glycyrrhizic acid). taVNS was administered daily for 7 days. Cerebral oedema volume was quantified via magnetic resonance imaging (MRI) on days 3 and 10 post-injury. Neurological function was assessed using the open field test and modified neurological sign score (mNSS). Molecular mechanisms were investigated through transcriptomic sequencing, enzyme-linked immunosorbent assay (ELISA), western blotting, and immunofluorescence to analyze HMGB1 and downstream inflammatory factors (interleukin-1&#x3b2; (IL-1&#x3b2;), interleukin-6 (IL-6)). RESULTS: Transcriptomic analysis revealed that taVNS reversed TBI-induced dysregulation of genes enriched in HMGB1-related pathways (e.g., Ras-associated protein-1 (), mitogen-activated protein kinase ()). Compared with the TBI group, taVNS significantly accelerated the resolution of cerebral oedema (reduction rate: 74.7 &#xb1; 12.1% vs 53.5 &#xb1; 16.2%,< 0.05) and improved neurological function. Mechanistically, taVNS markedly suppressed the upregulation of HMGB1, IL-1&#x3b2;, and IL-6 in both serum and brain tissue. Crucially, the therapeutic effects of taVNS were abolished by HMGB1 agonism (high glucose), while HMGB1 antagonism (glycyrrhizic acid) alone mimicked the benefits of taVNS. CONCLUSIONS: This study demonstrates that taVNS effectively promotes the resolution of post-traumatic cerebral oedema and facilitates neurological recovery by specifically inhibiting the HMGB1-mediated inflammatory pathway. These findings position taVNS as a promising, non-invasive therapeutic strategy for the early management of secondary brain injury.