Radiation-Induced Alterations in Mouse Brain Development Characterized by Magnetic Resonance Imaging

Radiation-Induced Alterations in Mouse Brain Development Characterized by Magnetic Resonance Imaging
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DOI:
10.1016/j.ijrobp.2012.06.053
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发表时间:
2012-12-01
影响因子:
7
通讯作者:
Nieman, Brian J.
Nieman, Brian J.
中科院分区:
医学1区
文献类型:
--
作者:
Gazdzinski, Lisa M.;Cormier, Kyle;Nieman, Brian J.

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目的:本研究的目的是确定区域的改变后,使用纵向磁共振成像(MRI)颅照射小鼠大脑的发展:方法和材料:雌性C57 B1/6小鼠接受全脑辐射剂量为7戈伊在婴儿等效年龄为2.5周。在照射前和照射后3个时间点进行MRI检查。变形为基础的形态计量学被用来量化的体积和增长率的变化后irradiation.Results:广泛的发育缺陷,观察到在这两个白色和灰质区域照射后。大多数受影响的大脑区域遭受了最初的体积不足,随后以正常的速度增长,在所有检查的时间点与对照组相比,照射后的大脑仍然较小。一个例外是嗅球,除了早期的体积赤字,增长速度较慢,此后,在一个渐进的体积赤字相对于控制。免疫组化评估显示脱髓鞘的白色物质和损失的齿状回和脑室下区的颗粒下区的神经祖细胞。结论:MRI可以检测到区域差异的神经解剖和脑生长后,全脑照射在发展中的小鼠。神经解剖学的发育缺陷持续存在,甚至进展,并可能作为有用的标记物在小鼠模型中的晚期效应。这些方法对大脑发育的高通量评估可能有助于测试减轻儿科颅脑照射后晚期效应的策略。(C)2012 Elsevier Inc.
Purpose: The purpose of this study was to identify regions of altered development in the mouse brain after cranial irradiation using longitudinal magnetic resonance imaging (MRI).Methods and Materials: Female C57Bl/6 mice received a whole-brain radiation dose of 7 Gy at an infant-equivalent age of 2.5 weeks. MRI was performed before irradiation and at 3 time points following irradiation. Deformation-based morphometry was used to quantify volume and growth rate changes following irradiation.Results: Widespread developmental deficits were observed in both white and gray matter regions following irradiation. Most of the affected brain regions suffered an initial volume deficit followed by growth at a normal rate, remaining smaller in irradiated brains compared with controls at all time points examined. The one exception was the olfactory bulb, which in addition to an early volume deficit, grew at a slower rate thereafter, resulting in a progressive volume deficit relative to controls. Immunohistochemical assessment revealed demyelination in white matter and loss of neural progenitor cells in the subgranular zone of the dentate gyrus and subventricular zone.Conclusions: MRI can detect regional differences in neuroanatomy and brain growth after whole-brain irradiation in the developing mouse. Developmental deficits in neuroanatomy persist, or even progress, and may serve as useful markers of late effects in mouse models. The high-throughput evaluation of brain development enabled by these methods may allow testing of strategies to mitigate late effects after pediatric cranial irradiation. (C) 2012 Elsevier Inc.