Initial joint bleed volume in a delayed on-demand treatment setup correlates with subsequent synovial changes in hemophilic mice

Animal Models and Experimental Medicine

article

Kåre Kryger Vøls¹  Mads Kjelgaard-Hansen³  Carsten Dan Ley¹  Axel Kornerup Hansen²  Maj Petersen¹ 

[1] Global Drug Discovery, Novo Nordisk A/S;Veterinary and Animal Sciences, University of Copenhagen;Veterinary Clinical Sciences, University of Copenhagen

关键词: Animal models;    arthropathy;    hemarthrosis;    haemophilia A;    in vivo imaging;    micro-CT;   

DOI  :  10.1002/ame2.12118

学科分类：机械工程学

来源: Wiley

【 摘 要 】

caused by recurrent joint bleeds. We investigated if the joint bleed volume, before initiation of treatment, was linked to the subsequent degree of histopathological changes and the development of bone pathology in a mouse model of hemophilic arthropathy. Methods: FVIII knock-out (F8-KO) mice were dosed with a micro-CT blood pool agent prior to induction of hemarthrosis. Eight hours after induction, the bleed volume was quantified with micro computed tomography (micro-CT) and recombinant FVIII treatment initiated. On Day 8, inflammation in the knees was characterized by fluorescence molecular tomography. On Day 14, knee pathology was characterized by micro-CT and histopathology. In a second study, contrast agent was injected into the knee of wild-type (WT) mice, followed by histopathological evaluation on Day 14. Results: The average joint bleed volume before treatment was 3.9 mm3 . The inflammation-related fluorescent intensities in the injured knees were significantly increased on Day 8. The injured knees had significantly increased synovitis scores, vessel counts, and areas of hemosiderin compared to un-injured knees. However, no cartilage- or bone pathology was observed. The bleed volume before initiation of treatment correlated with the degree of synovitis and was associated with high fluorescent intensity on Day 8. In F8-KO and WT mice, persistence of contrast agent in the joint elicited morphological changes. Conclusion: When applying a delayed on-demand treatment regimen to hemophilic mice subjected to an induced knee hemarthrosis, the degree of histopathological changes on Day 14 reflected the bleed volume prior to initiation of treatment.

【 授权许可】

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