Stolz Leonie, Derouiche Amin, Devraj Kavi, Weber Frank, Brunkhorst Robert, Foerch Christian
Department of Neurology, Goethe University, Schleusenweg 2-16, 60528, Frankfurt am Main, Germany.
Dr. Senckenbergische Anatomie, Institute for Anatomy II, Goethe University, Frankfurt am Main, Germany.
J Neuroinflammation. 2017 Jul 28;14(1):152. doi: 10.1186/s12974-017-0926-2.
In 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).
Female SJL/J mice treated with anticoagulants namely warfarin or rivaroxaban were immunized with PLP. 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.
In 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.
We 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.
在多发性硬化症中，凝血因子已被证明可调节炎症。在这项转化研究中，我们调查了长期使用华法林或利伐沙班进行抗凝治疗对自身免疫性实验性脑脊髓炎（EAE）病程是否具有有益影响。
用抗凝剂（即华法林或利伐沙班）治疗的雌性SJL/J小鼠用髓鞘少突胶质细胞糖蛋白（PLP）进行免疫。在整个实验过程中维持稳定的抗凝状态。仅用载体处理的未抗凝小鼠用作对照。在EAE病程中记录神经功能缺损，并对炎性病变进行组织病理学分析。
在预防性实验中，与对照组相比，华法林和利伐沙班治疗均降低了EAE的最高评分，并导致脊髓炎性病变减少。相比之下，华法林的治疗性治疗对EAE的临床病程没有有益影响。未观察到炎性病变部位实质内出血的迹象。
我们建立了长期抗凝模型，可用于探索在华法林和利伐沙班治疗下EAE的病程。我们发现华法林和利伐沙班对神经功能缺损和局部炎症均有轻微的预防作用，表明抗凝可调节疾病的诱导过程。
