Microvascular Damage in the Deep Mucosal Lamina Propria Triggers the Onset of Colitis in Dextran Sulfate Sodium-induced Colitis in Mice.

Background/aim: Dextran sulfate sodium (DSS) is employed to induce colitis in mice for studying ulcerative colitis (UC), an inflammatory bowel disease. However, the precise mechanism underlying its action remains unclear. Microcirculatory issues in the colonic mucosa contribute to DSS-induced colitis; however, early structural changes in the local vascular system have not been thoroughly investigated. Therefore, we aimed to explore the circulatory system and mucosal circulation in the mouse colon and identify the early causes of bleeding in DSS-induced colitis.

Materials and methods: A 2% DSS solution was administered to C57BL/6J mice, and on days 3, 4, and 5 of administration, colonic circulation was examined through histological analysis of the mucosa, vascular casting, and differential staining of arteries and veins by sequential infusion of a fluorescent isothiocyanate-labeled gelatin solution and a small amount of a rhodamine isothiocyanate-labeled gelatin solution.

Results: By day 4, we observed increased vascular leakage, with significant changes in the mucosal vascular networks evident on day 5. Differential staining of the superior mesenteric artery and inferior mesenteric artery elucidated the boundary regions of their perfusion areas in the middle colon. DSS primarily caused vascular injury in this border zone, extending to the mid- and distal colon. Further exploration of the mucosal circulation revealed bleeding originating from the deep mucosal arteriolar plexus.

Conclusion: Early vascular impairment, particularly in the deep mucosal arteriolar plexus, precedes DSS-induced colitis in mice. Understanding these vascular disturbances may provide insights into pathogenesis of inflammatory bowel disease and aid in developing early detection and intervention strategies for UC in humans.