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* = Presenting author

P071 Improvement of experimental mouse models in inflammatory bowel diseases using flexible video endoscopic colon evaluation

C. Gay*1, O. Martin Rodriguez2, A. Daoui2, S. Koch1, P. Saas2, S. Valmary Degano3, S. Perruche2, L. Vuitton1

1CHU Jean Minjoz, Gastro-entérologie, besançon, France, 2UMR 1098 INSERM, Besançon, France, 3CHU Jean Minjoz, Anatomopathologie, besançon, France

Background

Some patients with inflammatory bowel diseases (IBD) are still refractory to conventional and biologic therapies. Experimental models are necessary to obtain new insights into pathogenesis and to develop innovative therapeutic approaches. In human IBD, mucosal healing and deep remission have emerged as major therapeutic goals, and endoscopic scores are key tools to assess disease activity. In this work, we aimed to assess the feasibility of flexible high-resolution video endoscopy in the most popular mouse models of IBD; describe mucosal lesions, their onset and evolution; and better characterised the usual experimental models of IBD.

Methods

A superslim flexible video ureteroscope (URF-V2 Olympus®) was used to perform colonoscopies in anesthetised C57Bl/6 and SWISS mice, in chronic dextran sodium sulfate (DSS), TNBS, or T-cell transfer induced colitis. Clinical and endoscopic data were assessed at different time points for each model, and histological analyses were obtained at sacrifice. At each endoscopic evaluation, the murine endoscopic index of colitis severity was calculated, and all mucosal lesions were recorded.

Results

In total, 650 endoscopies were performed on 133 mice. The median time for anaesthesia and colonoscopy for 1 mouse was 4 minutes and 48 seconds. Mortality rate was 2.2% (3/133 deaths) and endoscopies could be repeated daily without affecting the survival (mean: 5 colonoscopies per mouse). In these models, the onset of the colitis was detected earlier by endoscopy than by clinical assessment (a median of 3 days before in chronic DSS colitis;10 days before in T-cell transfer colitis; and 5 days before in TNBS colitis). DSS-induced colitis was characterised by changes of the vascular pattern from the third day and superficial ulcerations with bleedings from the twentieth day. Histological ulcerations and inflammatory cell infiltration were observed. TNBS-induced colitis occurred 1 day after induction with congestive and redness mucosa surrounding deep ulcerations (also observed at histology). In T-cell transfer colitis, progressive changes and disappearance of vascular pattern associated with thickening of the mucosa occurred from day 7; pseudo polyps were observed later. Deep ulcerations and crypt abscesses were present at histology. Mucosal healing was observed after treatment by mesalazine in DSS and T-cell transfer colitis.

Conclusion

High-resolution flexible endoscopy in mice was feasible, safe, and a good way to delay sacrifices and spare mice. Of note, similar to humans, we were able with flexible endoscopy to describe ulcerations, oedema, and pseudo polyps that are not described in the current scores in mice. Mucosal healing could be a therapeutic target for new therapeutic agents in mouse models.