{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T19:09:26Z","timestamp":1790276966332,"version":"4.1.0"},"reference-count":24,"publisher":"IMR Press","issue":"3","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Anhui University Scientific Research Project","award":["AH2023AH040076"],"award-info":[{"award-number":["AH2023AH040076"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Integr. Neurosci."],"abstract":"<jats:p>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\u03b2 (IL-1\u03b2), 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 (Rap1), mitogen-activated protein kinase (MAPK)). Compared with the TBI group, taVNS significantly accelerated the resolution of cerebral oedema (reduction rate: 74.7 \u00b1 12.1% vs 53.5 \u00b1 16.2%, p &lt; 0.05) and improved neurological function. Mechanistically, taVNS markedly suppressed the upregulation of HMGB1, IL-1\u03b2, 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.<\/jats:p>","DOI":"10.31083\/jin47066","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T09:35:19Z","timestamp":1774949719000},"source":"Crossref","is-referenced-by-count":1,"title":["Study on the Effects of Transcutaneous Auricular Acupuncture Stimulation of the Vagus Nerve on Post-Traumatic Cerebral Oedema"],"prefix":"10.31083","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0276-8737","authenticated-orcid":true,"given":"Yifan","family":"Fu","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Anhui Medical University, 230001 Hefei, Anhui, China"},{"name":"Department of Neurosurgery, Anhui Public Health Clinical Center, 230001 Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9792-8844","authenticated-orcid":true,"given":"Xiaoxuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Anhui Medical University, 230001 Hefei, Anhui, China"},{"name":"Department of Neurosurgery, Anhui Public Health Clinical Center, 230001 Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3215-214X","authenticated-orcid":true,"given":"Yuanyuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Anhui Medical University, 230001 Hefei, Anhui, China"},{"name":"Department of Neurosurgery, Anhui Public Health Clinical Center, 230001 Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5084-2991","authenticated-orcid":true,"given":"Minghao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Anhui Medical University, 230001 Hefei, Anhui, China"},{"name":"Department of Neurosurgery, Anhui Public Health Clinical Center, 230001 Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2771-1203","authenticated-orcid":true,"given":"Shilin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Anhui Medical University, 230001 Hefei, Anhui, China"},{"name":"Department of Neurosurgery, Anhui Public Health Clinical Center, 230001 Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3972-7973","authenticated-orcid":true,"given":"Xinyu","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Anhui Medical University, 230001 Hefei, Anhui, China"},{"name":"Department of Neurosurgery, Anhui Public Health Clinical Center, 230001 Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3437-3881","authenticated-orcid":true,"given":"Jiuyu","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Anhui Medical University, 230001 Hefei, Anhui, China"},{"name":"Department of Neurosurgery, Anhui Public Health Clinical Center, 230001 Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuandong","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of University of Science and Technology of China, 230001 Hefei, Anhui, China"},{"name":"Division of Life Sciences and Medicine, University of Science and Technology of China, 230001 Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Anhui Medical University, 230001 Hefei, Anhui, China"},{"name":"Department of Neurosurgery, Anhui Public Health Clinical Center, 230001 Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Fern\u00e1ndez-Gajardo R, Matamala JM, Carrasco R, Guti\u00e9rrez R, Melo R, Rodrigo R. 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