{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:19:01Z","timestamp":1781104741500,"version":"3.54.1"},"reference-count":47,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T00:00:00Z","timestamp":1684713600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and aims<\/jats:title><jats:p>Traumatic brain injury (TBI) is the main cause of death and can lead to a variety of physiological complications, including gastrointestinal dysfunction. The present study aimed to confirm the miR\u201019a\u2010mediated suppression of diarrhea after TBI through the regulation of VIP expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A rat model of TBI induced by controlled cortical injury was used to observe gastrointestinal morphology by opening the abdomen after TBI. After 72\u00a0h of injury, the fecal water content of the rats was measured. The end ileal segments were removed, and HE staining was used to observe the histopathological changes in the intestine. The levels of serum miR\u201019a and VIP mRNA were detected by qRT\u2010PCR. ELISA was performed to detect VIP levels in serum. Immunohistochemistry was used to detect the level of VIP in ileal tissues, and immunofluorescence was used to detect c\u2010kit expression in ileal tissue. CCK\u20108 assay was used to detect the cell viability of interstitial cells of Cajal (ICCs), and TUNEL assay was used to detect apoptosis of ICCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>miR\u201019a and VIP were highly expressed in the serum of TBI rats, and the knockdown of miR\u201019a alleviated TBI\u2010induced diarrhea. In addition, the overexpression of miR\u201019a or VIP inhibited the proliferation of ICCs, promoted apoptosis, and suppressed intracellular Ca<jats:sup>2+<\/jats:sup>levels, whereas miR\u201019a suppression had the opposite effects. A nonselective nitric oxide synthase inhibitor (L\u2010NA), PKG inhibitors (KT\u20105823 and RP\u20108CPT\u2010cGMPS), and a guanylate cyclase inhibitor (ODQ) restored the inhibitory effects of VIP on ICC proliferation, anti\u2010apoptosis effects, and Ca<jats:sup>2+<\/jats:sup>concentrations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Knockdown of miR\u201019a inhibits activation of the VIP\u2013NO\u2013cGMP\u2013PKG pathway through suppression of VIP expression, which in turn inhibits diarrhea after TBI.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.3071","type":"journal-article","created":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T05:45:52Z","timestamp":1684820752000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Knockdown of miR\u201019a suppresses gastrointestinal dysmotility diarrhea after TBI by regulating VIP 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