Predicting and monitoring colitis development in mice by micro-computed tomography

被引:14
作者
Fredin, Maria Fritsch [1 ,3 ]
Hultin, Leif [1 ]
Hyberg, Gina [1 ]
Rehnstrom, Erika [2 ]
Hornquist, Elisabeth Hultgren [3 ]
Melgar, Silvia [1 ]
Jansson, Liselotte [1 ]
机构
[1] AstraZeneca R&D, Dept Integrat Pharmacol, GI Biol, S-43183 Molndal, Sweden
[2] AstraZeneca R&D, Dept Mol Pharmacol, S-43183 Molndal, Sweden
[3] Univ Gothenburg, Dept Microbiol & Immunol, Inst Biomed, Sahlgrenska Acad, Gothenburg, Sweden
关键词
DSS; micro-CT; IBD; colitis; mouse; colon wall thickness;
D O I
10.1002/ibd.20343
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background: Computed tomography (CT) has been developed as a tool for monitoring human inflammatory bowel disease (1131)). The aim of this study was to evaluate colon wall thickness as a noninvasive marker in the dextran sodium sulfate (DSS) mouse model of colitis using micro-CT. Methods: Mice were. examined by micro-CT 1, 2, or 4 times between day 0 (d0) and d26 after induction of colitis to document the kinetics of changes in colon wall thickness and its relation to colitis development. Results: DSS-treated mice displayed a significantly thicker colon wall at all timepoints (days 5, 8, 12, 19, and 26) investigated compared to healthy controls. Colon wall thickness showed a good correlation to the macroscopic grading of colitis (r = 0.81). The increase in colon wall thickness occurred mainly during the acute phase of colitis (between days 5 and 12) and did not progress much further in the chronic phase of colitis (d26). Colon wall thickness at d26 was thereby predicted by measurements at d12. All mice did not respond equally to DSS and this difference was manifest during the first 2 weeks of colitis, providing an important tool in stratifying responders from nonresponders. Conclusions: While the potential impact of handling and anesthesia should be considered on repeated micro-CT, irradiation exposure during repeated micro-CT did not affect the development of colitis. Thus, the results suggest that micro-CT can be used for monitoring and prediction of the inflammatory response in mouse colitis in future therapeutic studies.
引用
收藏
页码:491 / 499
页数:9
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