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

局灶性脑缺血和神经营养因子对侧脑室室管膜神经干细胞增殖、迁移和分化的影响

• 批准号: 12671480
• 负责人: YANO Toshiyuki
• 金额: $ 0.7万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671480/
• 关键词: ependymal cell; fibroblast growth factor; focal cerebral ischemia; middle cerebral artery occlusion; neural stem cell; rat; subventricular zone; Subventricular zone; eppendymal cell; 神経幹細胞; 上衣細胞; 細胞膜マーカー; DiI

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

已经提出侧脑室（LV）的室管膜细胞（EC）是干细胞，其经历细胞分裂以在LV的室管膜下区（SV）中产生祖细胞，所述祖细胞在嘴侧迁移流中迁移并产生神经元细胞。据报道，SV中的祖细胞在局灶性脑缺血后会增殖和分化。本研究旨在观察大鼠局灶性脑缺血后内皮细胞迁移、增殖和分化的变化。左室注射0.2%的1，1 '-双十八烷基-6，6'-二（4-磺基苯基）-3，3，3'，3' -四甲基吲哚羰花青（Dil）10 μl，30 min后行右侧大脑中动脉阻断（MCAO）90 min或假手术。在处死动物之前，用溴脱氧尿苷（BrdU）标记增殖细胞2天。在单独实验中，碱性成纤维细胞生长因子（bFGF）在体外培养条件下， ...更多信息 从MCAO当天起，以1 μg /天的速率持续输注至右侧LV，持续3天。Dil标记的细胞出现在纹状体靠近缺血病变后7，14，28天。Dil标记的细胞在MCAO后7、14和28天的迁移程度相似。而假手术组在任何时间点，除左室吻侧移行流外，左室内皮细胞均被Dil标记。迁移的Dil标记的细胞偶尔表达Notch 1的免疫反应性，表明这些细胞最初来自EC。增殖细胞核抗原和BrdU的免疫组化显示，在MCAO后7天，纹状体中的一些Dil标记的细胞增殖。而在MCAO后7、14和28天，这些细胞均无β Ⅲ-微管蛋白、胶质细胞酸性蛋白和O_4的免疫反应。这些结果表明，左室壁的内皮细胞产生不成熟的细胞，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Dil标记细胞的迁移程度和梗死病变没有显着影响。少

项目成果

Nkayama R, Yano T, Ushihima K, Abe E, Terasaki H: "Effects of dantrolene on extracellular glutamate concentration and neuronal death in the rat hippocampal CA1 region subjected to transient ischemia"Anesthesiology. 96. 705-710 (2002)

Nkayama R、Yano T、Ushihima K、Abe E、Terasaki H：“丹曲林对短暂性缺血大鼠海马 CA1 区细胞外谷氨酸浓度和神经元死亡的影响”麻醉学。

Nakayama R, Yano T, Ushijima K, Abe E, Terasaki H: "Effects of dantrolene on extracellular glutamate concentration and neuronal death in the rat hippocampal CA1 region subjected to transient ischemia"Anesthesiology. 96. 705-710 (2002)

Nakayama R、Yano T、Ushijima K、Abe E、Terasaki H：“丹曲林对短暂性缺血大鼠海马 CA1 区细胞外谷氨酸浓度和神经元死亡的影响”麻醉学。

Nakayama R, Yano T, Ushijima K, Abe E. Terasaki H.: "Effects of dantrolene on extracellular glutamate concentration and neuronal death in the rat hippocampal CA1 region subjected to transient ischemia"Anesthesiology. 96. 705-710 (2002)

Nakayama R、Yano T、Ushijima K、Abe E. Terasaki H.：“丹曲林对短暂性缺血大鼠海马 CA1 区细胞外谷氨酸浓度和神经元死亡的影响”麻醉学。