Radiation effects on the blood-brain barrier

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Nuclear Science and Engineering, 2007.

Bibliographic Details
Main Author: Raabe, Rebecca L
Other Authors: Jeffrey A. Coderre.
Format: Thesis
Language:eng
Published: Massachusetts Institute of Technology 2009
Subjects:
Online Access:http://hdl.handle.net/1721.1/44779
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author Raabe, Rebecca L
author2 Jeffrey A. Coderre.
author_facet Jeffrey A. Coderre.
Raabe, Rebecca L
author_sort Raabe, Rebecca L
collection MIT
description Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Nuclear Science and Engineering, 2007.
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spelling mit-1721.1/447792019-04-10T16:35:45Z Radiation effects on the blood-brain barrier Raabe, Rebecca L Jeffrey A. Coderre. Massachusetts Institute of Technology. Dept. of Nuclear Science and Engineering. Massachusetts Institute of Technology. Dept. of Nuclear Science and Engineering. Nuclear Science and Engineering. Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Nuclear Science and Engineering, 2007. Includes bibliographical references (p. 53-56). Selective vascular irradiation enables the critical examination of the vasculature and its role in the onset of late radiation effects. It is a novel approach to expose the endothelial cells to much higher levels of ionizing radiation relative to normal cells by utilizing the boron neutron capture reaction. When boron-containing compounds are restricted to the lumen of the blood vessel, the resulting high-LET alpha and lithium particles cannot deposit their energy in the normal cells beyond the vasculature after the target is exposed to thermal neutrons. This allows for a 2- to 3-fold increase in the calculated dose to the endothelial cells. However, this technique has been criticized because there is no direct evidence that the endothelial cells receive an absorbed dose from the selective vascular irradiation. The objective of this work is to provide corroborating experimental evidence that selective vascular irradiation physically damages the endothelial cells. An established assay utilizing blood-brain barrier disruption was adopted to quantify the radiation damage to the endothelial cells in female BALB/C mice, 8-12 weeks of age. A dye that attaches to the plasma proteins in the blood and that is ordinarily kept out of the brain by the blood-brain barrier is injected into the blood supply before the irradiation, and following irradiation, damage to the vasculature will result in disruption of the blood-brain barrier that allows blood stained with the dye to enter the brain. After sacrificing, the blood in the vessel lumen is cleared by performing a trans-cardiac perfusion, and the brain is homogenized and prepared for analysis. The absorbance of the resulting supernatant of each brain sample is measured with a spectrophotometer at the optimal wavelength of the dye. (cont.) The absorbance is related to the quantity of blood that leaked through the blood-brain barrier, which is also related to the damage caused to the vasculature from exposure to ionizing radiation. Increased leakage through the blood-brain barrier was observed for those mice exposed to selective vascular irradiation, indicating a direct relationship between the leakage through the blood-brain barrier and the 10B concentration in the blood. The most significant increase in the leakage through the blood-brain barrier (p<0.002) was observed at the highest lOB concentration in the blood (161 ppm). The compound biological effectiveness (CBE) for sulfhydryl borane (BSH) was calculated to be 0.28, which is consistent with the published value of the CBE for BSH in the rat spinal cord. This suggests that the assumptions used for calculating the absorbed doses for selective vascular irradiation are reasonable and approximate to what the endothelial cells receive. by Rebecca L. Raabe. S.M. 2009-03-16T19:41:56Z 2009-03-16T19:41:56Z 2007 2007 Thesis http://hdl.handle.net/1721.1/44779 300291261 eng M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 56 p. application/pdf Massachusetts Institute of Technology
spellingShingle Nuclear Science and Engineering.
Raabe, Rebecca L
Radiation effects on the blood-brain barrier
title Radiation effects on the blood-brain barrier
title_full Radiation effects on the blood-brain barrier
title_fullStr Radiation effects on the blood-brain barrier
title_full_unstemmed Radiation effects on the blood-brain barrier
title_short Radiation effects on the blood-brain barrier
title_sort radiation effects on the blood brain barrier
topic Nuclear Science and Engineering.
url http://hdl.handle.net/1721.1/44779
work_keys_str_mv AT raaberebeccal radiationeffectsonthebloodbrainbarrier