Abstract
BackgroundIn multiple sclerosis, coagulation factors have been shown to modulate inflammation. In this translational study, we investigated whether long-term anticoagulation with warfarin or rivaroxaban has beneficial effects on the course of autoimmune experimental encephalomyelitis (EAE).MethodsFemale SJL/J mice treated with anticoagulants namely warfarin or rivaroxaban were immunized with PLP139–151. Stable anticoagulation was maintained throughout the entire experiment. Mice without anticoagulation treated with the vehicle only were used as controls. The neurological deficit was recorded during the course of EAE, and histopathological analyses of inflammatory lesions were performed.ResultsIn preventive settings, both treatment with warfarin and rivaroxaban reduced the maximum EAE score as compared to the control group and led to a reduction of inflammatory lesions in the spinal cord. In contrast, therapeutic treatment with warfarin had no beneficial effects on the clinical course of EAE. Signs of intraparenchymal hemorrhage at the site of the inflammatory lesions were not observed.ConclusionWe developed long-term anticoagulation models that allowed exploring the course of EAE under warfarin and rivaroxaban treatment. We found a mild preventive effect of both warfarin and rivaroxaban on neurological deficits and local inflammation, indicating a modulation of the disease induction by anticoagulation.
Highlights
In multiple sclerosis, coagulation factors have been shown to modulate inflammation
In the mice subjected to EAE, water consumption dropped to 1.5 ml per day at day 12 after immunization (Additional file 1: Figure S1a), making a drinking waterbased application of warfarin impracticable
For oral anticoagulation with warfarin, the water consumption of healthy SJL/J mice was measured at least every other day
Summary
Coagulation factors have been shown to modulate inflammation In this translational study, we investigated whether long-term anticoagulation with warfarin or rivaroxaban has beneficial effects on the course of autoimmune experimental encephalomyelitis (EAE). Deficiency of the coagulation factor XII (the starting point of the intrinsic coagulation cascade) was shown to mitigate immune response in an experimental autoimmune encephalomyelitis (EAE) model [8]. In this explorative study, we investigated whether anticoagulation with the vitamin K antagonist warfarin or the factor Xa-inhibitor rivaroxaban has anti-inflammatory properties in EAE.
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