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While sacral nerve stimulation (SNS) was reported to have therapeutic potential for colitis, its mechanisms of actions on colonic permeability remained largely unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, colitis was induced by intrarectal administration of TNBS in rats. Five days later, they were treated with SNS or sham\u2010SNS for 10\u00a0days. The effects of SNS on colonic permeability were assessed by measuring the expression of tight\u2010junction proteins involved in regulating permeability and the FITC\u2010dextran test. The mechanism of actions of SNS was investigated by studying the function of the enteric nervous system (ENS) cells and analyzing the autonomic nervous system.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>SNS decreased the disease activity index, microscopic and macroscopic scores, myeloperoxidase activity, and pro\u2010inflammatory cytokines (TNF\u2010\u03b1, IL\u20106). SNS increased the expression of Zonula Occludens\u20101, Occludin, Claudin\u20101, and Junctional adhesion molecule\u2010A in the colon tissue. The FITC\u2010dextran test showed that the colonic permeability was lower with SCS than sham\u2010SNS. SNS increased ChAT, pancreatic polypeptide, and GDNF and reduced norepinephrine NGF, sub\u2010P, and mast cell overactivation in the colon tissue. Concurrently, SNS increased acetylcholine in colon tissues and elevated vagal efferent activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions &amp; Inferences<\/jats:title><jats:p>SNS ameliorates colonic inflammation and enhances colonic barrier function with the proposed mechanisms involving the increase in parasympathetic activity and modulation of the activity of the ENS and immune system, including mast cells.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.13916","type":"journal-article","created":{"date-parts":[[2020,6,15]],"date-time":"2020-06-15T04:15:00Z","timestamp":1592194500000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Sacral nerve stimulation ameliorates colonic barrier functions in a rodent model of colitis"],"prefix":"10.1111","volume":"32","author":[{"given":"Lei","family":"Tu","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology Department of Medicine Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4546-0890","authenticated-orcid":false,"given":"Payam","family":"Gharibani","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Department of Medicine Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieyun","family":"Yin","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Department of Medicine Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0191-5697","authenticated-orcid":false,"given":"Jiande D. 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