Medizinische Universität Graz - Research portal
Selected Publication:
Gasche, N.
Establishment of an animal model of venous thrombosis in inflammatory bowel diseases
Humanmedizin; [ Diplomarbeit ] 5; 2017. pp.
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- Authors Med Uni Graz:
- Advisor:
- Brodmann Marianne
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- Abstract:
- INTRODUCTION: Inflammatory bowel diseases (IBD) represent a group of recurring inflammatory diseases mainly affecting the intestines. Over the past decades, the incidence of Crohn's disease and ulcerative colitis have continued to increase, which therefore poses a serious health problem in Western society. Furthermore, patients suffering from IBD are more frequently affected by venous thrombosis and its potentially lethal thromboembolic complication, which is one of the most common causes of death in these patients. The cause for the increased thrombogenesis in chronic inflammatory diseases remains mostly unknown. In order to further investigate the etiological mechanisms, we investigated the formation and resolution of venous thrombi in mice suffering from intestinal inflammation. Therefore, we combined an established model of colitis with a venous ligation model hypothesizing that the severity of colitis influences the formation or resolution of venous thrombi. METHODS: The conducted pilot study involved the selection of 10 murine animals, namely five interleukin-10 knockout (IL-10 KO) and five wild type (WT) mice. Initially, intestinal inflammation was triggered by the administration of dextran sodium sulfate (DSS) mixed into drinking water. Subsequently, the inferior vena cava (IVC) of the animals was ligated below the renal veins. The reduced blood flow led to the formation of a thrombus before (caudal of) the stenotic region. The thrombus was examined using sonographic imaging at specific time points. Three weeks after the ligation, the mice were sacrificed and the removed organs as well as thrombi were histologically examined. RESULTS: To our surprise, the WT group was affected to a greater extent by the combination of DSS treatment and ligation of the IVC resulting in the premature death of three mice. The weight of the WT animals plunged shortly after the induction period, whereas the IL-10 KO mice showed little symptoms. It cannot be ruled out that a cage phenomenon occurred, which is explained by different sizes of the drinking containers. Nevertheless, despite milder clinical manifestations of colitis in the IL-10 KO, a more severe chronic inflammation of the intestines [disease activity index: 1.8 (IL-10 KO); 1.25 (WT)] as well as larger organized thrombi in the IVC [volume: 0.8 mm3 (IL-10 KO); 0.3 mm3 (WT)] were observed three weeks following the ligation. The sonographic examinations also depicted greater clots over the course of time. Mouse genotyping confirmed the correct allocation of the mice to the two groups. DISCUSSION: The data from this pilot study show that the implementation of IVC ligation in DSS-treated mice is accompanied by a high degree of stress on the animals, but is generally feasible. Due to the severely reduced health in some mice and the relatively high number of deceased animals, experimental adjustments, such as the extension of the recovery time after DSS induction, should be considered in future experiments. Additionally, identical experimental conditions (cages, drinking bottles, etc.) should be achieved in order to avoid potential sources of error. Further studies with a larger number of mice are necessary to confirm these preliminary results. The murine model can be further used to test various pharmacological substances.