Institute of Pediatrics, Children's Hospital of Fudan University, China.
Biochem Biophys Res Commun. 2010 Mar 26;394(1):146-52. doi: 10.1016/j.bbrc.2010.02.132. Epub 2010 Feb 24.
This study investigated the effects of angiogenesis on the proliferation and differentiation of neural stem cells in the premature brain. We observed the changes in neurogenesis that followed the stimulation and inhibition of angiogenesis by altering vascular endothelial growth factor (VEGF) expression in a 3-day-old rat model. VEGF expression was overexpressed by adenovirus transfection and down-regulated by siRNA interference. Using immunofluorescence assays, Western blot analysis, and real-time PCR methods, we observed angiogenesis and the proliferation and differentiation of neural stem cells. Immunofluorescence assays showed that the number of vWF-positive areas peaked at day 7, and they were highest in the VEGF up-regulation group and lowest in the VEGF down-regulation group at every time point. The number of neural stem cells, neurons, astrocytes, and oligodendrocytes in the subventricular zone gradually increased over time in the VEGF up-regulation group. Among the three groups, the number of these cells was highest in the VEGF up-regulation group and lowest in the VEGF down-regulation group at the same time point. Western blot analysis and real-time PCR confirmed these results. These data suggest that angiogenesis may stimulate the proliferation of neural stem cells and differentiation into neurons, astrocytes, and oligodendrocytes in the premature brain.
本研究探讨了血管生成对早产儿大脑中神经干细胞增殖和分化的影响。我们通过改变血管内皮生长因子（VEGF）在 3 日龄大鼠模型中的表达，观察了血管生成刺激和抑制后神经发生的变化。通过腺病毒转染过表达 VEGF，通过 siRNA 干扰下调 VEGF 表达。我们使用免疫荧光分析、Western blot 分析和实时 PCR 方法观察血管生成以及神经干细胞的增殖和分化。免疫荧光分析显示，vWF 阳性区域的数量在第 7 天达到峰值，在每个时间点，VEGF 上调组最高，VEGF 下调组最低。VEGF 上调组侧脑室区的神经干细胞、神经元、星形胶质细胞和少突胶质细胞数量随时间逐渐增加。在这三组中，同一时间点 VEGF 上调组的这些细胞数量最高，VEGF 下调组的细胞数量最低。Western blot 分析和实时 PCR 验证了这些结果。这些数据表明，血管生成可能刺激早产儿大脑中神经干细胞的增殖，并分化为神经元、星形胶质细胞和少突胶质细胞。
