Altered brain morphology after focal radiation reveals impact of off-target effects: implications for white matter development and neurogenesis.
Altered brain morphology after focal radiation reveals impact of off-target effects: implications for white matter development and neurogenesis.
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DOI：
10.1093/neuonc/nox211
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发表时间：
2018-05-18
期刊：
影响因子：
15.9
通讯作者：
Nieman BJ
中科院分区：
文献类型：
--
作者：
Beera KG;Li YQ;Dazai J;Stewart J;Egan S;Ahmed M;Wong CS;Jaffray DA;Nieman BJ
接受颅脑放射治疗(RT)的脑肿瘤儿童通常表现出认知迟发效应，通常与脑白质(WM)体积减少和神经发生减少有关。特定区域或组织的辐射损伤对整个大脑发育的影响尚未阐明。对幼鼠进行全脑或局灶性照射(8Gy单剂量)。局部治疗针对白质(前连合)、神经元(嗅球)或神经源性(脑室下区)区域。高分辨率的体外磁共振成像被用来评估辐射引起的体积差异。髓鞘碱性蛋白和双重皮质素的免疫组织化学染色分别评估白质内相关的细胞变化和与神经发生有关的细胞变化。婴儿期的全脑RT和局灶性RT都会导致青壮年的体积缺陷，其中全脑RT的缺陷最大。令人惊讶的是，前连合的RT对其体积或整个大脑发育没有影响。相反，嗅球RT导致前连合的非靶点体积减少，并减少了室下区神经发生。室下区的RT同样在嗅球和前连合产生容量缺陷。类似的非靶点效应也出现在胼胝体和顶叶皮质中。我们的结果表明，局部辐射损伤可能会对大脑发育产生重要的非靶点后果。这些数据表明，WM对辐射的敏感性可能不像仅有体积变化所显示的那样敏感，并对旨在减少认知迟发效应的区域保留放射治疗有影响。
Children with brain tumors treated with cranial radiation therapy (RT) often exhibit cognitive late effects, commonly associated with reduced white matter (WM) volume and decreased neurogenesis. The impact of radiation damage in particular regions or tissues on brain development as a whole has not been elucidated. We delivered whole-brain or focal radiation (8 Gy single dose) to infant mice. Focal treatments targeted white matter (anterior commissure), neuronal (olfactory bulbs), or neurogenic (subventricular zone) regions. High-resolution ex vivo MRI was used to assess radiation-induced volume differences. Immunohistochemistry for myelin basic protein and doublecortin was performed to assess associated cellular changes within white matter and related to neurogenesis, respectively. Both whole-brain and focal RT in infancy resulted in volume deficits in young adulthood, with whole-brain RT resulting in the largest deficits. RT of the anterior commissure, surprisingly, showed no impact on its volume or on brain development as a whole. In contrast, RT of the olfactory bulbs resulted in off-target volume reduction in the anterior commissure and decreased subventricular zone neurogenesis. RT of the subventricular zone likewise produced volume deficits in both the olfactory bulbs and the anterior commissure. Similar off-target effects were found in the corpus callosum and parietal cortex. Our results demonstrate that radiation damage locally can have important off-target consequences for brain development. These data suggest that WM may be less radiosensitive than volume change alone would indicate and have implications for region-sparing radiation treatments aimed at reducing cognitive late effects.
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影响因子：
5.2
作者：
Achanta, Pragathi;Capilla-Gonzalez, Vivian;Purger, David;Reyes, Juvenal;Sailor, Kurt;Song, Hongjun;Manuel Garcia-Verdugo, Jose;Gonzalez-Perez, Oscar;Ford, Eric;Quinones-Hinojosa, Alfredo
通讯作者：
Quinones-Hinojosa, Alfredo
影响因子：
3.6
作者：
Moore, BD
通讯作者：
Moore, BD
影响因子：
9
作者：
通讯作者：
--
DOI：
10.1016/j.ijrobp.2012.06.053
发表时间：
2012-12-01
影响因子：
7
作者：
Gazdzinski, Lisa M.;Cormier, Kyle;Nieman, Brian J.
通讯作者：
Nieman, Brian J.
影响因子：
5.7
作者：
de Guzman, A. Elizabeth;Wong, Michael D.;Nieman, Brian J.
通讯作者：
Nieman, Brian J.