Neural Stem Cells Over-Expressing Brain-Derived Neurotrophic Factor (BDNF) Stimulate Synaptic Protein Expression and Promote Functional Recovery Following Transplantation in Rat Model of Traumatic Brain Injury
Neural Stem Cells Over-Expressing Brain-Derived Neurotrophic Factor (BDNF) Stimulate Synaptic Protein Expression and Promote Functional Recovery Following Transplantation in Rat Model of Traumatic Brain Injury
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DOI：
10.1007/s11064-011-0584-1
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发表时间：
2012-01-01
影响因子：
4.4
通讯作者：
Shi, Yuxiu
中科院分区：
文献类型：
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作者：
Ma, Haiying;Yu, Bo;Shi, Yuxiu
脑源性神经营养因子（BDNF）在脑发育和损伤后对各种神经细胞的存活和分化起着重要的调节作用。在本研究中，我们使用神经干细胞（NSCs）基因修饰编码BDNF基因（BDNF/NSCs）和幼稚NSCs移植，发现BDNF/NSCs显着改善创伤性脑损伤（TBI）后的神经运动功能在选定的行为测试。我们的数据清楚地表明，脑源性神经营养因子/神经干细胞的移植导致脑源性神经营养因子在脑外伤大鼠的大脑中的过度表达。脑源性神经营养因子/神经干细胞中存活的移植细胞数量和具有神经元表型的移植细胞比例显着高于幼稚神经干细胞移植大鼠。BDNF/NSCs联合移植组大鼠突触前、突触后蛋白和再生相关基因的表达较NSCs移植组明显增强，尤其是在移植后早期。这些数据表明，在BDNF/NSC-transplanted大鼠的神经突起生长和突触蛋白的过表达与BDNF的过表达，这被假设为在TBI后的细胞移植的早期阶段的运动行为的改善的功能恢复的机制之一。因此，BDNF修饰的神经干细胞移植的保护作用大于幼稚神经干细胞移植。
Brain-derived neurotrophic factor (BDNF) plays an essential regulatory role in the survival and differentiation of various neural cell types during brain development and after injury. In this study, we used neural stem cells (NSCs) genetically modified to encode BDNF gene (BDNF/NSCs) and naive NSCs transplantation and found that BDNF/NSCs significantly improved neurological motor function following traumatic brain injury (TBI) on selected behavioral tests. Our data clearly demonstrate that the transplantation of BDNF/NSCs causes overexpression of BDNF in the brains of TBI rats. The number of surviving engrafted cells and the proportion of engrafted cells with a neuronal phenotype were significantly greater in BDNF/NSCs than in naive NSCs-transplanted rats. The expression of pre- and post-synaptic proteins and a regeneration-associated gene in the BDNF/NSCs-transplanted rats was significantly increased compared to that in NSCs-transplanted rats, especially at the early stage of post-transplantation. These data suggest that neurite growth and overexpression of synaptic proteins in BDNF/NSC-stransplanted rats are associated with the overexpression of BDNF, which is hypothesized to be one of the mechanisms underlying the improved functional recovery in motor behavior at the early stage of cell transplantation following TBI. Therefore, the protective effect of the BDNF-modified NSCs transplantation is greater than that of the naive NSCs transplantation.