Bone Marrow Endothelial Progenitor Cell Transplantation After Ischemic Stroke: An Investigation Into Its Possible Mechanism
Bone Marrow Endothelial Progenitor Cell Transplantation After Ischemic Stroke: An Investigation Into Its Possible Mechanism
复制标题
缺血性中风后骨髓内皮祖细胞移植：对其可能机制的研究
DOI：
10.1111/cns.12447
复制
发表时间：
2015-11-01
影响因子：
5.5
通讯作者：
Ju, Sheng-Hong
中科院分区：
文献类型：
--
作者：
Bai, Ying-Ying;Peng, Xin-Gui;Ju, Sheng-Hong
AimsWe测试的假设，内皮祖细胞（EPC）介导的功能恢复中风后可能与内皮型一氧化氮合酶（eNOS）/脑源性神经营养因子（BDNF）信号通路。EPC治疗的小鼠也接受静脉注射的N-硝基-L-精氨酸甲酯（L-NAME，NOS抑制剂）或salines. ResultseNOS的激活和BDNF的表达显着增加缺血脑的EPC治疗的小鼠，沿着增加血管生成和神经发生。在扩散张量成像（DTI）上，观察到白色物质的各向异性分数和纤维计数显著增加，表明EPCs刺激轴突生长。然而，接受L-NAME注射的EPC治疗的小鼠未能表现出所观察到的血管生成、神经发生和轴突生长的增加。与对照组相比，EPCs体外共培养的神经元缺氧缺糖后BDNF表达增加，凋亡减少。这种EPC诱导的保护作用在L-NAME治疗组中几乎不存在。结论eNOS/BDNF通路可能参与EPC介导的脑卒中小鼠功能恢复。DTI技术可以动态跟踪EPC治疗后轴突投射的方向。
AimsWe tested the hypothesis that endothelial progenitor cell (EPC)-mediated functional recovery after stroke may be associated with the endothelial nitric oxide synthase (eNOS)/brain-derived neurotrophic factor (BDNF) signaling pathway.MethodsMice were infused with either EPCs or saline after being subjected to middle cerebral artery occlusion. The EPC-treated mice also received intravenous injections of either N-nitro-l-arginine methyl ester (L-NAME, the NOS inhibitor) or saline.ResultsThe activation of eNOS and the expression of BDNF were significantly increased in ischemic brain of the EPC-treated mice, along with increased angiogenesis and neurogenesis. On diffusion tensor imaging (DTI), significant increases in fractional anisotropy and fiber count were observed in white matter, indicating axonal growth stimulated by EPCs. However, the EPC-treated mice that were received an L-NAME injection failed to exhibit the observed increases in angiogenesis, neurogenesis, and axonal growth. In addition, the neurons cocultured with EPCs in vitro exhibited the increased expression of BDNF and decreased apoptosis after oxygen-glucose deprivation compared with the control group. This EPC-induced protective effect was virtually absent in the L-NAME treatment group.ConclusionThe eNOS/BDNF pathway may be involved in the EPC-mediated functional recovery of stroke mice. DTI is feasible for dynamically tracking the orientation of axonal projections after EPC treatment.