Involvement of Shh/Gli1 signaling in the permeability of blood-spinal cord barrier and locomotion recovery after spinal cord contusion
Involvement of Shh/Gli1 signaling in the permeability of blood-spinal cord barrier and locomotion recovery after spinal cord contusion
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Shh/Gli1 信号传导参与血脊髓屏障通透性和脊髓挫伤后运动恢复
DOI：
10.1016/j.neulet.2020.134947
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发表时间：
2020-04
影响因子：
2.5
通讯作者：
Fan Hong
中科院分区：
文献类型：
--
作者：
Yue Yili;Zhao Jiqian;Li Xiaoji;Zhang Li;Su Yuhong;Fan Hong
Shh/Gli 1信号通路在脊髓发育过程中起重要作用。它如何参与脊髓损伤（SCI）仍不清楚。本研究利用Shh信号转导通路阻断Gli 1 lz/lz小鼠和Gli 1信号转导通路阻断Gli 1 lz/lz小鼠，探讨Shh/Gli 1信号转导通路在脊髓损伤中的作用。为检测SCI后Shh/Gli 1信号通路的变化，在Gli 11 z小鼠损伤后第3天（dpi）进行X-gal染色和Shh/PDGFR-β、Shh/GFAP和LacZ/GFAP的免疫双标染色。为探讨Gli 1基因突变对脊髓损伤后病理变化的影响，于脊髓损伤后7 d，检测野生型和Gli 1 lz/lz小鼠星形胶质细胞增殖和脑实质内伊文思蓝含量。此外，在1、3、5和7 dpi通过BMS评分评估运动恢复。X-gal染色和免疫组化结果显示，SCI后Shh/Gli 1信号主要在反应性星形胶质细胞中激活。5-溴脱氧尿苷（BrdU）掺入实验表明Gli 1基因突变对星形胶质细胞增殖无影响。然而，与野生型小鼠相比，Gli 1 lz/lz小鼠受损脊髓中伊文思蓝的渗漏显著增加。此外，Gli 1 lz/lz小鼠的运动恢复明显受损。结果表明，SCI后反应性星形胶质细胞中Shh/Gli 1信号通路被诱导，并在血-脊髓屏障（BSCB）通透性和SCI后运动功能恢复中发挥重要作用。
Shh/Gli1 signaling plays important roles in development of spinal cord. How it is involved in spinal cord injury (SCI) remains unclear. In this study, we explored the roles of Shh/Gli1 signaling in SCI by using Shh signaling reporterGli1lzmice and Gli1 mutantGli1lz/lzmice. For detecting the Shh/Gli1 signaling after SCI, X-gal staining and double-immunostaining of Shh/PDGFR-β, Shh/GFAP and LacZ/GFAP was conducted at 3 days post injury (dpi) onGli1lzmice. To investigate the effects ofGli1mutation on pathological changes after SCI, astrocytic proliferation and the content of intra-parenchymal Evans Blue were evaluated at 7dpi in wild-type andGli1lz/lzmice. Furthermore, locomotor recovery was assessed by BMS scoring at 1, 3, 5 and 7dpi. The results of X-gal staining and immunohistochemistry showed that Shh/Gli1 signaling was mainly activated in reactive astrocytes after SCI. The 5-bromo-2-deoxyuridine (BrdU) incorporation assay showed that mutation ofGli1did not affect the proliferation of astrocytes. However, the leakage of Evans Blue was significantly increased in the injured cord ofGli1lz/lzmice compared to wild-type mice. In addition, locomotor recovery was significantly impaired in theGli1lz/lzmice. The findings demonstrated that Shh/Gli1 signaling could be induced in reactive astrocytes by SCI, and plays important role in permeability of blood-spinal cord barrier (BSCB) and locomotor recovery after SCI.
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影响因子：
3.3
作者：
Nicchia, GP;Nico, B;Friger, A
通讯作者：
Friger, A
影响因子：
5.3
作者：
Amankulor, Nduka M.;Hambardzumyan, Dolores;Holland, Eric C.
通讯作者：
Holland, Eric C.
DOI：
10.1093/jnen/64.5.404
发表时间：
2005-05-01
影响因子：
3.2
作者：
Seifert, T;Bauer, J;Storch, MK
通讯作者：
Storch, MK
影响因子：
5.1
作者：
Kumar, Hemant;Ropper, Alexander E.;Han, Inbo
通讯作者：
Han, Inbo
影响因子：
5.6
作者：
Ikeshima-Kataoka H
通讯作者：
Ikeshima-Kataoka H