Local application of MDL28170-loaded PCL film improves functional recovery by preserving survival of motor neurons after traumatic spinal cord injury
Local application of MDL28170-loaded PCL film improves functional recovery by preserving survival of motor neurons after traumatic spinal cord injury
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局部应用负载 MDL28170 的 PCL 薄膜可通过保留创伤性脊髓损伤后运动神经元的存活来改善功能恢复
DOI：
10.1016/j.neulet.2018.12.006
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发表时间：
2019-02
影响因子：
2.5
通讯作者：
Lin-lin Wang
中科院分区：
文献类型：
--
作者：
Dongling Shi;Teng He;Weijian Tang;Heyangzi Li;Chao Wang;Mingzhi Zheng;Jue Hu;Xinghui Song;Yuemin Ding;Ying-ying Chen;Yueliang Shen;Hongfeng Jin;Lin-lin Wang
脊髓损伤(SCI)后可发生神经元死亡和组织变性，导致神经功能障碍。我们的目的是确定局部应用细胞渗透性钙蛋白酶I抑制剂(MDL28170)是否可以通过提高神经细胞的活力来促进脊髓损伤的恢复。制备了MDL28170负载的聚己内酯(PCL)薄膜。扫描电子显微镜显示，PCL膜表面光滑，有孔洞(直径为μM级)。PCL膜无毒、生物相容性好，具有良好的神经元粘附性和缓释特性。MDL28170增加衣霉素(一种内质网应激)损伤下VSC4.1运动神经元的存活率。在创伤性脊髓损伤大鼠模型中，负载MDL28170的PCL膜缩小了损伤腔的面积，促进了运动行为的恢复。经MDL28170负载的PCL膜处理后，GAP-43的表达上调。因此，我们的研究结果表明，MDL28170的局部应用可以抑制内质网应激，保护运动神经元的存活，从而促进脊髓损伤的恢复，这可能为脊髓损伤患者的治疗提供了一个有前途的治疗靶点。
Neuronal death and organization degeneration can happen inordinately after spinal cord injury (SCI), which lead to nerve dysfunction. We aimed to determine whether local application of a cell permeable calpain I inhibitor (MDL28170) can promote SCI recovery by increasing neuronal cell viability. MDL28170-loaded polycaprolactone (PCL) film was fabricated. Scanning electron microscopy showed the surface of PCL film was smooth with holes (diameter at μM level). The PCL film was non-toxic, biological compatibility, and had good neuron adhension and slow release characteristic. MDL28170 increased VSC4.1 motor neurons’ viability under tunicamycin (an endoplasmic reticulum stress) induced injury. In a traumatic SCI rat model, MDL28170-loaded PCL film reduced the area of lesion cavity, and promoted recovery of locomotor behavior. Moreover, the expression of GAP-43 was upregulated after MDL28170-loaded PCL film treatment. Thus, our findings demonstrated that localized delivery of MDL28170 could promote SCI recovery by inhibiting endoplasmic reticulum stress, preserving survival of the motor neurons, which may point out a promising therapeutic target for treating SCI patient.
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DOI：
--
发表时间：
2017
期刊：
--
影响因子：
--
作者：
Marc Bernard;L. Boyer;Amaury Habrard;M. Sebban
通讯作者：
Marc Bernard;L. Boyer;Amaury Habrard;M. Sebban
影响因子：
2.8
作者：
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通讯作者：
Banik, NL
影响因子：
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影响因子：
14
作者：
Junjuan Wang;Jiaqiu Wang;Ping Lu;Youzhi Cai;Yafei Wang;Lan Hong;Hao Ren;B. Heng;Hua Liu-Hua-Li
通讯作者：
Junjuan Wang;Jiaqiu Wang;Ping Lu;Youzhi Cai;Yafei Wang;Lan Hong;Hao Ren;B. Heng;Hua Liu-Hua-Li
影响因子：
1.9
作者：
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通讯作者：
Fan, Shunwu