Hellström Nina A K, Björk-Eriksson Thomas, Blomgren Klas, Kuhn H Georg
Center for Brain Repair and Rehabilitation, Institute for Neuroscience and Physiology, University of Gothenburg, Sweden.
Stem Cells. 2009 Mar;27(3):634-41. doi: 10.1634/stemcells.2008-0732.
Radiation therapy is a widely used treatment for malignant central nervous system tumors. Mature neurons are terminally differentiated, whereas stem and progenitor cells have a prominent proliferative capacity and are therefore highly vulnerable to irradiation. Our aim was to investigate how cranial radiation in young rats would affect stem/progenitor cells in the two niches of adult neurogenesis, the subventricular zone (SVZ) and the dentate gyrus of the hippocampal formation. Nine weeks after irradiation we found that in irradiated animals, hippocampal neurogenesis was reduced to 5% of control levels. Similarly, the numbers of actively proliferating cells and radial glia-like stem cells (nestin+/glial fibrillary acidic protein [GFAP]+) in the dentate gyrus were reduced to 10% and 15% of control levels, respectively. In the irradiated olfactory bulb, neurogenesis was reduced to 40% of control levels, and the number of actively proliferating cells in the SVZ was reduced to 53% of control levels. However, the number of nestin+/GFAP+ cells in the SVZ was unchanged compared with controls. To evaluate the immediate response to the radiation injury, we quantified the amount of proliferation in the SVZ and dentate gyrus 1 day after irradiation. We found an equal reduction in proliferating cells both in dentate gyrus and SVZ. In summary, we show an initial response to radiation injury that is similar in both brain stem cell niches. However, the long-term effects on stem cells and neurogenesis in these two areas differ significantly: the dentate gyrus is severely affected long-term, whereas the SVZ appears to recover with time.
放射治疗是恶性中枢神经系统肿瘤广泛使用的一种治疗方法。成熟神经元是终末分化的，而干细胞和祖细胞具有显著的增殖能力，因此极易受到辐射影响。我们的目的是研究幼年大鼠的颅脑辐射如何影响成体神经发生的两个微环境（即脑室下区（SVZ）和海马结构齿状回）中的干细胞/祖细胞。辐射后9周，我们发现受辐照动物的海马神经发生减少至对照水平的5%。同样，齿状回中活跃增殖细胞和放射状胶质样干细胞（巢蛋白+/胶质纤维酸性蛋白[GFAP]+）的数量分别减少至对照水平的10%和15%。在受辐照的嗅球中，神经发生减少至对照水平的40%，SVZ中活跃增殖细胞的数量减少至对照水平的53%。然而，与对照相比，SVZ中巢蛋白+/GFAP+细胞的数量没有变化。为了评估对辐射损伤的即时反应，我们在辐照后1天对SVZ和齿状回中的增殖量进行了量化。我们发现齿状回和SVZ中增殖细胞的减少程度相同。总之，我们表明在两个脑干细胞微环境中对辐射损伤的初始反应是相似的。然而，这两个区域对干细胞和神经发生的长期影响有显著差异：齿状回长期受到严重影响，而SVZ似乎会随着时间恢复。
