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This review summarizes the in vivo biological mechanisms activated by VNS and their corresponding clinical applications. Furthermore, it outlines the selection of parameters and equipment for VNS implementation. VNS exhibits anti-inflammatory effects, modulates neurotransmitter release, enhances neural plasticity, inhibits apoptosis and autophagy, maintains blood\u2013brain barrier integrity, and promotes angiogenesis. Clinically, VNS has been utilized in the treatment of epilepsy, depression, headache, stroke, and obesity. Its potential applications extend to anti-inflammatory treatment and the management of cardiovascular and cerebrovascular diseases and various brain disorders. However, further experiments are required to definitively establish the efficacy of VNS\u2019s various mechanisms. Additionally, there is a need to explore and identify optimal rehabilitation treatment parameters for different diseases.<\/jats:p>","DOI":"10.3390\/cimb47020122","type":"journal-article","created":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T03:20:52Z","timestamp":1739503252000},"page":"122","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Mechanism and Applications of Vagus Nerve Stimulation"],"prefix":"10.3390","volume":"47","author":[{"given":"Zhen","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, School of Automation (Artificial Intelligence), Hangzhou Dianzi University, Hangzhou 310018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5235-7357","authenticated-orcid":false,"given":"Kezhou","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, School of Automation (Artificial Intelligence), Hangzhou Dianzi University, Hangzhou 310018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1111\/head.12647","article-title":"Vagus Nerve and Vagus Nerve Stimulation, a Comprehensive Review: Part, I","volume":"56","author":"Yuan","year":"2016","journal-title":"Headache"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1111\/nmo.12817","article-title":"Vagal tone: Effects on sensitivity, motility, and inflammation","volume":"28","author":"Bonaz","year":"2016","journal-title":"Neurogastroenterol. 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