Localized CT-Guided Irradiation Inhibits Neurogenesis in Specific Regions of the Adult Mouse Brain

被引:48
作者
Ford, E. C. [1 ]
Achanta, P. [3 ]
Purger, D. [3 ]
Armour, M. [1 ]
Reyes, J. [1 ]
Fong, J. [1 ]
Kleinberg, L. [1 ]
Redmond, K. [1 ]
Wong, J. [1 ]
Jang, M. H. [4 ,5 ]
Jun, H. [4 ]
Song, H-J. [4 ,5 ,6 ]
Quinones-Hinojosa, A. [2 ,3 ]
机构
[1] Johns Hopkins Univ, Dept Radiat Oncol & Mol Radiat Sci, Sch Med, Baltimore, MD 21231 USA
[2] Johns Hopkins Univ, Dept Oncol, Sch Med, Baltimore, MD 21231 USA
[3] Johns Hopkins Univ, Dept Neurosurg, Sch Med, Baltimore, MD 21231 USA
[4] Johns Hopkins Univ, Inst Cell Engn, Sch Med, Baltimore, MD 21231 USA
[5] Johns Hopkins Univ, Dept Neurol, Sch Med, Baltimore, MD 21231 USA
[6] Johns Hopkins Univ, Dept Neurosci, Sch Med, Baltimore, MD 21231 USA
基金
美国国家卫生研究院;
关键词
RADIATION RESEARCH PLATFORM; ANIMAL CONFORMAL IRRADIATOR; HIPPOCAMPAL NEUROGENESIS; DENTATE GYRUS; SUBVENTRICULAR ZONE; X-IRRADIATION; CRANIAL IRRADIATION; H2AX PHOSPHORYLATION; IONIZING-RADIATION; MAMMALIAN BRAIN;
D O I
10.1667/RR2214.1
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Radiation is used in the study of neurogenesis in the adult mouse both as a model for patients undergoing radiation therapy for CNS malignancies and as a tool to interrupt neurogenesis. We describe, the use of a dedicated CT-guided precision device to irradiate specific sub-regions of the adult mouse brain. Improved CT visualization was accomplished with intrathecal injection of iodinated contrast agent, which enhances the lateral ventricles. T2-weighted MRI images were also used for target localization. Visualization of delivered beams (10 Gy) in tissue was accomplished with immunohistochemical staining for the protein gamma-H2AX, a marker of DNA double-strand breaks. gamma-H2AX stains showed that the lateral ventricle wall could be targeted with an accuracy of 0.19 mm (n = 10). In the hippocampus, gamma-H2AX staining showed that the dentate gyrus can be irradiated unilaterally with a localized arc treatment. This resulted in a significant decrease of proliferative neural progenitor cells as measured by Ki-67 staining (P < 0.001) while leaving the contralateral side intact. Two months after localized irradiation, neurogenesis was significantly inhibited in the irradiated region as seen with EdU/NeuN double labeling (P < 0.001). Localized radiation in the rodent brain is a promising new tool for the study of neurogenesis. (C) 2011 by Radiation Research Society
引用
收藏
页码:774 / 783
页数:10
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