Long-term impairment of subependymal repopulation following damage by ionizing irradiation.
Long-term impairment of subependymal repopulation following damage by ionizing irradiation.
复制标题
电离辐射损伤后室管膜下再生的长期损害。
DOI：
10.1006/exnr.1999.7172
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Fike,JR
中科院分区：
文献类型：
--
作者：
Tada,E;Yang,C;Gobbel,GT;Lamborn,KR;Fike,JR
在哺乳动物脑中，室管膜下（subependyma，SE）含有能够产生神经元和神经胶质的干细胞。在正常脑中，这些干细胞部分负责维持SE的形态和功能完整性; SE细胞在脑损伤中发挥的作用尚未阐明。本研究旨在确定大鼠SE在干细胞显著耗竭后的长期再生潜力。电离辐射被用来消耗SE细胞和随后的细胞反应进行定量使用福尔马林固定，石蜡包埋组织的免疫组织化学分析。采用组织形态学方法定量测定总细胞数、增殖细胞数、未成熟神经元数、星形胶质细胞数和SE未分化成分。由于没有干细胞特异性标记，我们使用再生试验作为损伤后干细胞反应的间接测量。我们的数据显示，在我们的定量终点中有明确的辐射剂量依赖性，这意味着随着辐射剂量的增加，干细胞损伤逐渐增加。在治疗后180天内，SE在总细胞数、增殖细胞数和未成熟神经元数方面的再增殖以剂量依赖性方式受损。这些数据表明，照射后，存活的干细胞不能再生SE。干细胞损伤/耗竭后不能再生可能对SE的正常功能和脑损伤后SE的功能具有重要意义。
In the mammalian brain, the subependyma (SE) contains stem cells capable of producing neurons and glia. In normal brain these stem cells are responsible, in part, for maintaining the morphologic and functional integrity of the SE; what role the cells of the SE play in brain injury has not yet been elucidated. The present study was designed to determine the long-term regenerative potential of the rat SE after significant depletion of stem cells. Ionizing irradiation was used to deplete cells of the SE and subsequent cellular responses were quantified using immunohistochemical analyses on formalin-fixed, paraffin-embedded tissues. A histomorphometric approach was used to quantify total cell number, number of proliferating cells, number of immature neurons, astrocytes, and undifferentiated components of the SE. Because there are no markers specific for stem cells, we used a repopulation assay as an indirect measure of stem cell response after injury. Our data showed clear radiation dose-dependencies in our quantitative endpoints, implying that there was progressively more stem cell damage with increasing radiation dose. Repopulation of the SE in terms of total cell number, number of proliferating cells and numbers of immature neurons was impaired in a dose-dependent fashion up to 180 days after treatment. These data suggest that after irradiation, surviving stem cells are unable to regenerate the SE. This inability to regenerate after stem cell damage/depletion could have important implications with respect to the normal function of the SE and the function of the SE after brain injury.