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首页> 外文期刊>International immunopharmacology >Wnt-3a alleviates neuroinflammation after ischemic stroke by modulating the responses of microglia/macrophages and astrocytes
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Wnt-3a alleviates neuroinflammation after ischemic stroke by modulating the responses of microglia/macrophages and astrocytes

机译：通过调节小胶质细胞/巨噬细胞和星形胶质细胞的反应，WNT-3A缓解缺血性卒中后的神经炎炎症

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摘要

Neuroinflammation crucially influences functional recovery after ischemic stroke. Wnt-3a, a novel Wnt protein that specifically promotes Wnt/beta-catenin signaling pathway, has been shown to regulate apoptosis and cell proliferation, but how it affects ischemic stroke-induced toxic brain inflammation remains unknown. Using a transient middle cerebral artery occlusion (tMCAO) mouse model in this study, we found that intranasal Wnt-3a-treated tMCAO mice had apparently reduced infarct volume and decreased brain water content after being allowed to recover for 72 h, as well as better neurologic outcomes on days 3, 7, and 14. Mice received Wnt-3a had significantly fewer tMCAO-induced peri-infarct TUNEL-positive cells compared with those received vehicle. Further, Wnt-3a-delivered tMCAO mice had notably fewer peri-infarct CD68-positive cells and lower ionized calcium-binding adapter molecule (Iba)-1 protein level. Wnt-3a significantly downregulated the expression of inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-alpha, and upregulated the expression of arginase 1 (Arg1) and CD206. Finally, Wnt-3a obviously decreased the number of tMCAO-induced peri-infarct glial fibrillary acidic protein (GFAP)/C3-positive cells, increased the number of GFAP/S100A10-positive cells, attenuated the protein levels of GFAP and interleukin 15 (IL15), and elevated IL33 protein level. Our findings suggest that intranasal Wnt-3a could ameliorate toxic responses of microglia/macrophages and astrocytes in ischemic brain injury, supporting that Wnt-3a might be potentially appropriate for ischemic stroke treatment functioning as an immunomodulatory agent.
机译：神经胰腺炎在缺血性卒中后至关重要。 WNT-3A，一种特异性促进WNT /β-连环蛋白信号传导途径的新型WNT蛋白，已显示调节细胞凋亡和细胞增殖，但它如何影响缺血性卒中诱导的有毒脑炎症仍然未知。在本研究中使用瞬时中间脑动脉闭塞（TMCAO）小鼠模型，我们发现鼻内WNT-3A处理的TMCAO小鼠显然降低了梗塞体积，并且在允许恢复72小时后降低脑含水量，以及更好与所接受的载体相比，在第3,7和14天接受WNT-3A的小鼠的神经系统结果显着较少。此外，WNT-3A-递送的TMCAO小鼠尤其具有较少的PERI-IMARCT CD68阳性细胞和低离子化钙结合衔接子分子（IBA）-1蛋白水平。 WNT-3A显着下调诱导型一氧化氮合酶（InOS）和肿瘤坏死因子（TNF） - α的表达，并上调了氨基酶1（ARG1）和CD206的表达。最后，WNT-3A显然降低了TMCAO诱导的蠕虫术胶质纤维酸蛋白（GFAP）/ C3阳性细胞的数量，增加了GFAP / S100A10阳性细胞的数量，减弱了GFAP和白细胞介素15的蛋白质​​水平（ IL15）和升高的IL33蛋白质水平。我们的研究结果表明，Intranasal Wnt-3a可以改善缺血性脑损伤中的小凝血性/巨噬细胞和星形胶质细胞的毒性反应，支持Wnt-3a可能适用于作为免疫调节剂的缺血性卒中处理。

著录项

  • 来源
    《International immunopharmacology》 |2019年第2019期|共9页
  • 作者

    Zhang Di; Lu Zhengfang; Man Jiang; Cui Kefei; Fu Xiaojie; Yu Lie; Gao Yufeng; Liao Linghui; Xiao Qianqian; Guo Ruiming; Zhang Yongxin; Zhang Zhen; Liu Xianliang; Lu Hong; Wang Jianping;

  • 作者单位

    Zhengzhou Univ Dept Neurol Affiliated Hosp 5 Zhengzhou 450052 Henan Peoples R China;

    Zhengzhou Univ Dept Neurol Affiliated Hosp 5 Zhengzhou 450052 Henan Peoples R China;

    Zhengzhou Univ Dept Neurol Affiliated Hosp 5 Zhengzhou 450052 Henan Peoples R China;

    Zhengzhou Univ Dept Ultrasound Affiliated Hosp 1 Zhengzhou 450052 Henan Peoples R China;

    Zhengzhou Univ Dept Intervent Neuroradiol Affiliated Hosp 1 Zhengzhou 450052 Henan Peoples R;

    Zhengzhou Univ Dept Neurol Affiliated Hosp 1 Zhengzhou 450052 Henan Peoples R China;

    Zhengzhou Univ Dept Neurol Affiliated Hosp 5 Zhengzhou 450052 Henan Peoples R China;

    Zhengzhou Univ Dept Neurol Affiliated Hosp 5 Zhengzhou 450052 Henan Peoples R China;

    Zhengzhou Univ Dept Neurol Affiliated Hosp 5 Zhengzhou 450052 Henan Peoples R China;

    Zhengzhou Univ Dept Surg Affiliated Hosp 1 Zhengzhou 450052 Henan Peoples R China;

    Zhengzhou Univ Dept Neurol Affiliated Hosp 5 Zhengzhou 450052 Henan Peoples R China;

    Zhengzhou Univ Dept Neurol Affiliated Hosp 5 Zhengzhou 450052 Henan Peoples R China;

    Zhengzhou Univ Dept Neurol Affiliated Hosp 5 Zhengzhou 450052 Henan Peoples R China;

    Zhengzhou Univ Dept Neurol Affiliated Hosp 1 Zhengzhou 450052 Henan Peoples R China;

    Zhengzhou Univ Dept Neurol Affiliated Hosp 5 Zhengzhou 450052 Henan Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 药理学;
  • 关键词

    Wnt-3a; Ischemic stroke; Neuroinflammtion; Microglia/macrophage; Astrocyte; Polarization;

    机译：wnt-3a;缺血性卒中;神经蛋白血液;微胶质细胞/巨噬细胞;星形胶质细胞;极化;

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