Protective Effect of Moderate Exogenous Electric Field Stimulation on Activating Netrin-1/DCC Expression Against Mechanical Stretch-Induced Injury in Spinal Cord Neurons
Protective Effect of Moderate Exogenous Electric Field Stimulation on Activating Netrin-1/DCC Expression Against Mechanical Stretch-Induced Injury in Spinal Cord Neurons
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中等外源电场刺激激活 Netrin-1/DCC 表达对脊髓神经元机械拉伸损伤的保护作用
DOI：
10.1007/s12640-018-9885-3
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发表时间：
2018-04
影响因子：
3.7
通讯作者：
Fan Yubo
中科院分区：
文献类型：
--
作者：
Liu Meili;Yin Chuanwei;Jia Zhengtai;Li Kun;Zhang Zhifa;Zhao Yuchen;Gong Xianghui;Liu Xiaoyu;Li Ping;Fan Yubo
神经细胞在发育和再生过程中对电场刺激和外部化学引导信号进行检测和反应；因此，开发和优化一种功能神经元再生的方法对于神经损伤是必要的。在本研究中，我们建议使用电场刺激来修复严重机械拉伸负荷所引发的神经损伤。设计了一种提供连续机械拉伸和恒定电场刺激的装置。在不同时间(1、4、8、12h)用机械拉伸(2.5%~10%)刺激原代分离的脊髓神经元，建立中度神经损伤模型。用四甲基偶氮唑盐比色法和免疫荧光法对刺激样本的细胞活力、密度和轴突延长进行评估。结果表明，机械牵张(S，5%拉伸应变，4h)引起中度轴突损伤，导致细胞活力显著丧失，细胞密度降低。在双乙酸荧光素实验中，电场刺激(33 mA/m~2，4h)后，损伤的脊髓神经元开始存活。此外，与拉伸损伤的神经元相比，电场刺激后神经元的存活率、密度和延伸率显著增加。此外，与牵张损伤组相比，电场刺激显著激活了轴突引导信号Netrin-1并缺失了结直肠癌(DCC)受体的表达。这些结果表明，电刺激激活了表达的协同引导线索，以促进与神经损伤相关的轴突生长。我们的研究为神经元再生提供了新的视角。
Nerve cells detect and respond to electric field stimulation and extrinsic chemical guidance cues during development and regeneration; therefore, the development and optimization of an approach for functional neuronal regeneration are necessary for a nerve injury. In this study, we proposed using electric field stimulation to repair a nerve injury triggered by serious mechanical stretch loading. A device that provides continuous mechanical stretch and constant electric field stimulation was designed. Primary dissociated spinal cord neurons were stimulated by mechanical stretch (tensile strain 2.5–10%) at different times (1, 4, 8, and 12 h) to set up a moderate nerve injury model. Stimulated samples were evaluated with respect to cell viability, density, and axonal elongation by the MTT and immunofluorescence assays. The results indicated that mechanical stretch (S, 5% tensile strain, 4 h) caused moderate axonal injury, resulting in significant loss of cell viability and a decrease in cell density. However, injured spinal cord neurons became viable after electric field stimulation (E, 33 mA/m2, 4 h) in the fluorescein diacetate assay. In addition, neuronal viability, density, and elongation increased significantly after electric field stimulation compared with those of stretch-injured neurons. Moreover, electric field stimulation significantly activated the axonal guidance cues Netrin-1 and deleted in colorectal cancer (DCC) receptor expression compared with the stretch-injury group. These results indicate that electric stimulation activates synergistic guidance cues of expression to improve axonal growth relevant to nerve injuries. Our study provides new insight into neuronal regeneration.
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影响因子：
5.3
作者：
Pfister, BJ;Iwata, A;Smith, DH
通讯作者：
Smith, DH
影响因子：
9.5
作者：
Yueming Wang;Wen-Jin Wang;Yan Wo;Ting Gui;Hao Zhu;X. Mo;C. Chen;Qingfeng Li;W. Ding
通讯作者：
Yueming Wang;Wen-Jin Wang;Yan Wo;Ting Gui;Hao Zhu;X. Mo;C. Chen;Qingfeng Li;W. Ding
影响因子：
4.8
作者：
Pfister, Bryan J.;Huang, Jason H.;Smith, Douglas H.
通讯作者：
Smith, Douglas H.
影响因子：
3.3
作者：
Gladman, S. J.;Ward, R. E.;Priestley, J. V.
通讯作者：
Priestley, J. V.
影响因子：
3.1
作者：
Schwartzman, Robert J.;Grothusen, John R.
通讯作者：
Grothusen, John R.