Teriflunomide has been reported to inhibit microglial activation in experimental models of traumatic brain injury. However, its roles in ischemic stroke and underlying mechanisms of action are still undiscovered. In this study, we investigated the effects of teriflunomide on brain edema, neurologic deficits, infarct volume, neuroinflammation, blood-brain barrier (BBB) permeability, and neurogenesis in a mouse model of transient middle cerebral artery occlusion (tMCAO). tMCAO mice treated with teriflunomide showed lower brain water content on day 3, milder neurologic deficits and smaller infarct volume on day 7 than those treated with vehicle. Additionally, mice received teriflunomide had fewer activated Iba-1-positive microglia and lower protein levels of interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2), and 3-Nitrotyrosine (3-NT) compared with those received vehicle on day 3. Further, teriflunomide alleviated Evans blue dye leakage, increased pericyte coverage and protein levels of platelet-derived growth factor B (PDGFB), platelet-derived growth factor receptor β (PDGFRβ) and Bcl2, and decreased the number of PDGFRβ/matrix metalloproteinase 9 (MMP9)-positive cells. Moreover, teriflunomide reduced the loss of zonula occludens-1 (ZO-1) and occludin. Finally, teriflunomide significantly upregulated the number of 5-bromo-20-deoxyuridine (BrdU)/doublecortin (DCX)-positive cells and expression of mammalian achaete-scute homolog 1 (Mash1), DCX and Pbx1 in subventricular zone (SVZ) on day 7 after stroke. Our results indicate that teriflunomide exhibits protective roles in ischemic stroke by inhibiting neuroinflammation, alleviating BBB disruption and enhancing neurogenesis.

中文翻译：

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特立氟胺在短暂性中脑动脉阻塞小鼠模型中的神经保护作用。

据报道，在创伤性脑损伤的实验模型中，特立氟胺具有抑制小胶质细胞活化的作用。然而，其在缺血性中风中的作用和潜在的作用机制仍未被发现。在这项研究中，我们调查了特立氟胺对短暂性中脑动脉闭塞（tMCAO）小鼠模型中脑水肿，神经功能缺损，梗塞体积，神经炎症，血脑屏障（BBB）通透性和神经发生的影响。与媒介物治疗的小鼠相比，特立氟胺治疗的tMCAO小鼠在第3天的大脑含水量更低，在第7天的神经功能缺损更轻，梗死体积更小。此外，接受teriflunomide的小鼠活化的Iba-1阳性小胶质细胞较少，白细胞介素1β（IL-1β），环氧合酶2（COX-2）的蛋白质水平较低，和在第3天接受载药的患者使用3-硝基酪氨酸（3-NT）。此外，特立氟米特减轻了Evans蓝染料的泄漏，增加了血小板衍生的生长因子B（PDGFB），血小板衍生的生长因子受体的周细胞覆盖率和蛋白质水平β（PDGFRβ）和Bcl2，并减少了PDGFRβ/基质金属蛋白酶9（MMP9）阳性细胞的数量。此外，特立氟胺减少了小带闭合蛋白-1（ZO-1）和闭合蛋白的损失。最后，特立氟胺在当天显着上调了5-溴-20-脱氧尿苷（BrdU）/双皮质素（DCX）阳性细胞的数量以及哺乳动物achaete-scute同源物1（Mash1），DCX和Pbx1在脑室下区（SVZ）的表达。中风后7。我们的结果表明，teriflunomide可通过抑制神经炎症在缺血性中风中发挥保护作用，