Netrin-1 attenuates brain injury after middle cerebral artery occlusion via downregulation of astrocyte activation in mice.
Netrin-1 attenuates brain injury after middle cerebral artery occlusion via downregulation of astrocyte activation in mice.
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Netrin-1 通过下调小鼠星形胶质细胞活化减轻大脑中动脉闭塞后的脑损伤
DOI：
10.1186/s12974-018-1291-5
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发表时间：
2018-09-18
影响因子：
9.3
通讯作者：
Yang GY
中科院分区：
文献类型：
--
作者：
He X;Liu Y;Lin X;Yuan F;Long D;Zhang Z;Wang Y;Xuan A;Yang GY
背景Netrin-1主要通过结合受体和下游效应器发挥作用。有证据表明，星形胶质细胞表达netrin-1受体，包括DCC和UNC 5 H2。然而，netrin-1是否影响星形胶质细胞的功能是以前unknow.MethodsLipopolysaccharide刺激原代培养的星形胶质细胞，白细胞介素释放用于跟踪星形胶质细胞活化。在体内，将shRNA和netrin-1蛋白注射到小鼠脑中。脑体积，星形胶质细胞活化，白细胞介素释放被用来观察netrin-1在神经炎症和脑损伤后大脑中动脉occlusion.ResultsOur结果表明，netrin-1减少脂多糖诱导的白细胞介素-1 β和白细胞介素-12 β释放在培养的星形胶质细胞，和与抗体的UNC 5 H2受体阻断逆转这种效果。此外，netrin-1增加了原代培养的星形胶质细胞中p-AKT和PPAR-γ的表达。体内研究表明，在大脑中动脉闭塞后，netrin-1的敲低增加了小鼠脑中星形胶质细胞的活化（p< 0.05）。此外，注射netrin-1可减弱GFAP表达，（netrin-10.27 ± 0.06vs.BSA 0.62 ± 0.04，p < 0.001）和白细胞介素的释放以及脑缺血后梗死体积的减少（netrin-1 0.27 ± 0.06 vs. BSA 0.62 ± 0.04 mm3，p< 0.05）。结论我们的结果表明，netrin-1是调节脑缺血时星形胶质细胞活化和神经炎症的重要分子，为缺血性脑卒中的治疗提供了潜在的靶点。
BackgroundNetrin-1 functions largely via combined receptors and downstream effectors. Evidence has shown that astrocytes express netrin-1 receptors, including DCC and UNC5H2. However, whether netrin-1 influences the function of astrocytes was previously unknown.MethodsLipopolysaccharide was used to stimulate the primary cultured astrocytes; interleukin release was used to track astrocyte activation. In vivo, shRNA and netrin-1 protein were injected in the mouse brain. Infarct volume, astrocyte activation, and interleukin release were used to observe the function of netrin-1 in neuroinflammation and brain injury after middle cerebral artery occlusion.ResultsOur results demonstrated that netrin-1 reduced lipopolysaccharide-induced interleukin-1β and interleukin-12β release in cultured astrocytes, and blockade of the UNC5H2 receptor with an antibody reversed this effect. Additionally, netrin-1 increased p-AKT and PPAR-γ expression in primary cultured astrocytes. In vivo studies showed that knockdown of netrin-1 increased astrocyte activation in the mouse brain after middle cerebral artery occlusion (p< 0.05). Moreover, injection of netrin-1 attenuated GFAP expression (netrin-1 0.27 ± 0.06 vs. BSA 0.62 ± 0.04,p< 0.001) and the release of interleukins and reduced infarct volume after brain ischemia (netrin-1 0.27 ± 0.06 vs. BSA 0.62 ± 0.04 mm3,p< 0.05).ConclusionOur results indicate that netrin-1 is an important molecule in regulating astrocyte activation and neuroinflammation in cerebral ischemia and provides a potential target for ischemic stroke therapy.
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影响因子：
3.3
作者：
Liu, N.;Huang, H.;Du, H.
通讯作者：
Du, H.
影响因子：
3.1
作者：
Aherne CM;Collins CB;Eltzschig HK
通讯作者：
Eltzschig HK
通过共移植神经和血管祖细胞的神经血管恢复可以改善大鼠缺血性中风后的功能恢复。
影响因子：
5.9
作者：
Li, Jia;Tang, Yaohui;Wang, Yongting;Tang, Rongbiao;Jiang, Weifang;Yang, Guo-Yuan;Gao, Wei-Qiang
通讯作者：
Gao, Wei-Qiang
DOI：
10.1186/cc9301
发表时间：
2010
期刊：
Critical care (London, England)
影响因子：
--
作者：
Mutz C;Mirakaj V;Vagts DA;Westermann P;Waibler K;König K;Iber T;Nöldge-Schomburg G;Rosenberger P
通讯作者：
Rosenberger P
DOI：
10.1073/pnas.0511011103
发表时间：
2006-04-25
影响因子：
11.1
作者：
Nguyen, A;Cai, H
通讯作者：
Cai, H