Effects of focal cerebral ischemia and neurotrophic factor on proliferation, migration and differentiation of ependymal neural stem cells in the lateral ventricle

有人提出，侧脑室室管膜细胞（ECs）是在侧脑室下区（SV）进行细胞分裂产生祖细胞的干细胞，这些祖细胞在吻侧迁移流中迁移并产生神经元细胞。据报道，SV的祖细胞在局灶性脑缺血后增殖和分化。本研究旨在探讨EC对大鼠短暂性局灶性脑缺血的迁移、增殖和分化等反应。左左左室给予10 μl 1,1′-二十八烷基- 6,6′-二（4-磺苯基）- 3,3,3′，3′-四甲基吲哚碳菁（Dil）， 0.2%，于30 min后右大脑中动脉闭塞（MCAO）致缺血90 min或假手术。用溴脱氧尿苷（BrdU）标记增殖细胞2天后献祭动物。在单独实验中，碱性成纤维细胞生长因子（bFGF）从MCAO当日开始以1 μg / d的速率连续输注于右侧左室3天。MCAO后7、14和28天，在缺血灶附近纹状体中出现dl标记细胞。在MCAO后7、14和28天，dil标记细胞的迁移程度相似。相比之下，假手术动物在任何时间点，除了吻侧迁徙流外，只有左室的ECs被标记为Dil。迁移的dil标记细胞偶尔表达Notch1的免疫反应性，表明这些细胞最初来源于ECs。增殖细胞核抗原和BrdU的免疫组化结果显示，MCAO后7天纹状体中部分dil标记的细胞开始增殖。然而，这些细胞在MCAO后7、14和28天对β iii -微管蛋白、胶质纤维酸性蛋白和O4没有免疫反应性。这些结果提示左室壁的内皮细胞产生未成熟细胞，如前体细胞或祖细胞，这些细胞向短暂局灶性缺血引起的病变迁移。本研究中使用的bFGF给药方案对迪尔标记细胞的迁移程度和梗死灶没有显着影响。少

It has been proposed that ependymal cells (ECs) of the lateral ventricle (LV) are stem cells that undergo cell division to generate progenitor cells in the subventricular zone (SV) of LV that migrate and produce neuronal cells in the rostral migratory stream. The progenitor cells in SV have been reported to proliferate and differentiate after focal cerebral ischemia. The purpose of this study was to examine the response such as migration, proliferation and differentiation of EC to transient focal cerebral ischemia in the rat. To trace ECs 10 μl of 1, 1'-dioctadecyl-6, 6'-di(4-sulfophenyl)-3, 3, 3' ,3' -tetramethylindocarbocyanine (Dil), 0.2 %, was administered in the left LV, and 〜30 min later ischemia was induced by right middle cerebral artery occlusion (MCAO) for 90 min or sham operation was performed. Proliferating cells were labeled with bromodeoxyuridine (BrdU) over 2-day periods before sacrificing animals. In the separate experiment, basic fibroblast growth factor (bFGF) was con … More tinuously infused into the right LV at the rate of 1 μg / day for 3 days from the day of MCAO. Dil-labeled cells appeared in the striatum close to the ischemic lesion 7, 14, and 28 days after MCAO. The extent of migration of Dil-labeled cells was similar at 7, 14 and 28 days after MCAO. In contrast, only ECs of LV except for rostral migratory stream was labeled with Dil in sham-operated animals at any time point. Migrating Dil-labeled cells occasionally expressed immunoreactivity for Notch1, suggesting that these cells were originally derived from ECs. Immunohistochemistry for proliferating cell nuclear antigen and BrdU revealed that some Dil-labeled cells in the striatum were proliferating at 7 days after MCAO. However, these cells did not have immunoreactivity for βIII-tubulin, glial fibrillary acidic protein and O4 7, 14 and 28 days after MCAO. These findings suggest that ECs of LV wall generate immature cells such as precursor or progenitor cells, which migrate toward the lesion caused by transient focal ischemia. The protocol for bFGF administration used in this study did not show remarkable effects on the extent of migration of Dil-labeled cells and the infarct lesion. Less