Age-dependent sensitivity of the developing brain to irradiation is correlated with the number and vulnerability of progenitor cells
Age-dependent sensitivity of the developing brain to irradiation is correlated with the number and vulnerability of progenitor cells
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DOI：
10.1111/j.1471-4159.2004.02894.x
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发表时间：
2005-02-01
影响因子：
4.7
通讯作者：
Blomgren, K
中科院分区：
文献类型：
--
作者：
Fukuda, A;Fukuda, H;Blomgren, K
在一个新建立的单侧，辐照（IR）诱导的损伤模型中，我们分别在出生后9天和23天使用大鼠，比较了辐照后未成熟和幼年脑的结果。结果表明：(1)与青少年相比，未成熟大脑在脑室下区（SVZ）和亚颗粒区（SGZ）含有更多的祖细胞；（ii）通过caspase 3和p53的激活以及硝基酪氨酸的形成来判断，IR后6小时未成熟脑SVZ和SGZ的细胞损伤更为明显；（iii） ir后6 h和7 d， SVZ和SGZ的祖细胞和未成熟细胞数量分别减少，对应于人类急性和亚急性作用，这些作用在未成熟大脑中更为明显；（iv）两个年龄的大脑在IR后髓鞘形成均受损，且在未成熟的大脑IR后更为明显；(v)红外诱导的变化至少在10周内保持显著，与人类的晚期效应相对应，并且在红外对未成熟大脑后最为明显。IR似乎通过细胞凋亡诱导了祖细胞的急性丧失，并扰乱了与正常增殖和分化不相容的微环境，这在未成熟的大脑中更为明显。
In a newly established model of unilateral, irradiation (IR)-induced injury we compared the outcome after IR to the immature and juvenile brain, using rats at postnatal days 9 or 23, respectively. We demonstrate that (i) the immature brains contained more progenitors in the subventricular zone (SVZ) and subgranular zone (SGZ) compared with the juvenile brains; (ii) cellular injury, as judged by activation of caspase 3 and p53, as well as nitrotyrosine formation, was more pronounced in the SVZ and SGZ in the immature brains 6 h after IR; (iii) the number of progenitor and immature cells in the SVZ and SGZ decreased 6 h and 7 days post-IR, corresponding to acute and subacute effects in humans, respectively, these effects were more pronounced in immature brains; (iv) myelination was impaired after IR at both ages, and much more pronounced after IR to immature brains; (v) the IR-induced changes remained significant for at least 10 weeks, corresponding to late effects in humans, and were most pronounced after IR to immature brains. It appears that IR induces both an acute loss of progenitors through apoptosis and a perturbed microenvironment incompatible with normal proliferation and differentiation, and that this is more pronounced in the immature brain.