Yuan Ti-Fei, Liang Yu-Xiang, Tay David, So Kwok-Fai, Ellis-Behnke Rutledge
School of Psychology, Nanjing Normal University, Nanjing, China.
Cell Transplant. 2015;24(3):377-90. doi: 10.3727/096368915X686878. Epub 2015 Feb 10.
Neurovascular niches serve as the hosts for adult neural stem cells in both the hippocampus and subventricular zone. The rostral migratory stream (RMS) vasculature has been found to be important for neuroblast migration, while its roles in hosting putative neural stem cells have not been investigated. Here we investigated the organization of RMS vasculature and its contribution to the production of new neurons. A single pulse of bromodeoxyuridine (BrdU) administration revealed locally formed new neurons within RMS were located adjacent to blood vessels. In addition, BrdU label-retaining cells that are putative neural stem cells were also found close to the vasculature. Sodium fluorescein perfusion assay demonstrated that the blood-brain barrier (BBB) organization was especially "leaky" in the neurogenic niches. Immunohistochemical visualization of some BBB component molecules indicated a thinner BBB in the RMS region, compared to that in the frontal cortex of adult rats. Finally, the expression of vascular endothelial growth factor was strong and specialized in the RMS region, implying that the region was active in cell proliferation and migration. Here we show that the RMS vasculature associated with surrounding astrocytes provides a highly organized neurovascular niche for adult neural stem cell proliferation, in addition to the function of neuroblast migration support. This result points to a new vasculature supporting neurogenic region in the brain.
神经血管微环境是海马体和脑室下区成年神经干细胞的宿主。已发现吻侧迁移流(RMS)脉管系统对神经母细胞迁移很重要,但其在容纳假定神经干细胞方面的作用尚未得到研究。在此,我们研究了RMS脉管系统的组织及其对新神经元产生的贡献。单次注射溴脱氧尿苷(BrdU)显示,RMS内局部形成的新神经元位于血管附近。此外,还发现作为假定神经干细胞的BrdU标记保留细胞也靠近脉管系统。荧光素钠灌注试验表明,血脑屏障(BBB)组织在神经源性微环境中特别“渗漏”。一些BBB组成分子的免疫组织化学可视化显示,与成年大鼠额叶皮质相比,RMS区域的BBB更薄。最后,血管内皮生长因子在RMS区域的表达强烈且具有特异性,这意味着该区域在细胞增殖和迁移方面很活跃。我们在此表明,与周围星形胶质细胞相关的RMS脉管系统除了具有支持神经母细胞迁移的功能外,还为成年神经干细胞增殖提供了高度组织化的神经血管微环境。这一结果指出了大脑中一个新的支持神经发生的脉管系统区域。