title: Localized CT-guided irradiation inhibits neurogenesis in specific regions of the adult mouse brain.
abstract: 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 γ-H2AX, a marker of DNA double-strand breaks. γ-H2AX stains showed that the lateral ventricle wall could be targeted with an accuracy of 0.19 mm (n = 10). In the hippocampus, γ-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.
authors: Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA. eric.ford@jhmi.edu
authors: E C
authors: EC
authors: Ford
authors: P
authors: P
authors: Achanta
authors: D
authors: D
authors: Purger
authors: M
authors: M
authors: Armour
authors: J
authors: J
authors: Reyes
authors: J
authors: J
authors: Fong
authors: L
authors: L
authors: Kleinberg
authors: K
authors: K
authors: Redmond
authors: J
authors: J
authors: Wong
authors: M H
authors: MH
authors: Jang
authors: H
authors: H
authors: Jun
authors: H-J
authors: HJ
authors: Song
authors: A
authors: A
authors: Quinones-Hinojosa
mesh_terms: D000818:Animals; D016371:Cranial Irradiation; D006657:Histones / Q000032:analysis; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000528:radiation effects*; D014057:Tomography, X-Ray Computed / Q000379:methods*
chemical_list: D006657:Histones; D019394:Ki-67 Antigen; C498355:Mki67 protein, mouse; C475961:gamma-H2AX protein, mouse