Direct hippocampal injection of pseudo lentivirus-delivered nerve growth factor gene rescues the damaged cognitive function after traumatic brain injury in the rat
Direct hippocampal injection of pseudo lentivirus-delivered nerve growth factor gene rescues the damaged cognitive function after traumatic brain injury in the rat
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直接海马注射伪慢病毒传递的神经生长因子基因可挽救大鼠脑外伤后受损的认知功能
DOI：
10.1016/j.biomaterials.2015.08.010
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发表时间：
2015-11-01
期刊：
影响因子：
14
通讯作者：
Jiang, Ji-yao
中科院分区：
文献类型：
--
作者：
Lin, Yong;Wan, Jie-qing;Jiang, Ji-yao
创伤性脑损伤（TBI）的治疗是一个长期的过程，需要反复给药，然而，这会给患者造成高昂的费用、感染和出血。为探讨神经生长因子（Nerve growth factor，Ngf）基因的长期表达对脑损伤后海马功能的影响，本研究构建了一种携带有绿色荧光蛋白（green fluorescence protein，GFP）基因的β-Ngf融合基因的假慢病毒，并在体外研究了该基因的表达及其对脑损伤后海马细胞氧化损伤的保护作用。然后，将携带β-Ngf融合基因的假慢病毒直接注射到损伤的脑内，以评估其对TBI后损伤的海马功能的影响。结果表明，pseudo慢病毒介导的β-NGF融合基因在PC 12细胞中的表达可持续4周以上，并能诱导PC 12细胞向神经元样细胞分化。此外，海马注射假慢病毒携带的β-Ngf融合基因加速了TBI大鼠受损的认知功能恢复。总之，我们的研究结果表明，通过假慢病毒递送的β-Ngf融合基因的长期表达，可以促进神经元样细胞的轴突生长，并保护细胞免受体外氧化损伤，并且直接和单剂量海马注射的假慢病毒携带的β-Ngf融合基因能够拯救大鼠TBI后的海马功能。(C)2015爱思唯尔有限公司版权所有。
Traumatic brain injury (TBI) treatment is a long-term process and requires repeated medicine administration, which, however, can cause high expense, infection, and hemorrhage to patients. To investigate how a long-term expression of nerve growth factor (Ngf) gene affects the injured hippocampus function post-TBI, in this study, a pseudo lentivirus carrying the beta-Ngf fusion gene, with green fluorescence protein (GFP) gene, was constructed to show the gene expression and its ability of protecting cells from oxidative damage in vitro. Then, the pseudo lentivirus-carried beta-Ngf fusion gene was directly injected into the injured brain to evaluate its influence on the injured hippocampus function post-TBI in vivo. We found that the expression of the pseudo lentivirus-delivered beta-Ngf fusion gene lasted more than four-week after the cell transduction and the encoded beta-NGF fusion protein could induce the neuron-like PC12 cell differentiation. Moreover, the hippocampal injection of the pseudo lentivirus-carried beta-Ngf fusion gene sped the injured cognitive function recovery of the rat subjected to TBI. Together, our findings indicate that the long-term expression of the beta-Ngf fusion gene, delivered by the pseudo lentivirus, can promote the neurite outgrowth of the neuron-like cells and protect the cells from the oxidative damage in vitro, and that the direct and single dose hippocampal injection of the pseudo lentivirus-carried beta-Ngf fusion gene is able to rescue the hippocampus function after the TBI in the rat. (C) 2015 Elsevier Ltd. All rights reserved.