Effects of fractionated radiation on the brain vasculature in a murine model: Blood-brain barrier permeability, astrocyte proliferation, and ultrastructural changes
- Department of BioImaging, College of Health Science Engineering, University of Tennessee Health Science Center, Memphis, TN (United States)
- Animal Research Center, St. Jude Children's Research Hospital, Memphis, TN (United States)
- Departments of Mechanical Engineering and Radiation Oncology, Temple University, Philadelphia, PA (United States)
- Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, TN (United States)
Purpose: Radiation therapy of CNS tumors damages the blood-brain barrier (BBB) and normal brain tissue. Our aims were to characterize the short- and long-term effects of fractionated radiotherapy (FRT) on cerebral microvasculature in mice and to investigate the mechanism of change in BBB permeability in mice. Methods and Materials: Intravital microscopy and a cranial window technique were used to measure BBB permeability to fluorescein isothiocyanate (FITC)-dextran and leukocyte endothelial interactions before and after cranial irradiation. Daily doses of 2 Gy were delivered 5 days/week (total, 40 Gy). We immunostained the molecules to detect the expression of glial fibrillary acidic protein and to demonstrate astrocyte activity in brain parenchyma. To relate the permeability changes to endothelial ultrastructural changes, we used electron microscopy. Results: Blood-brain barrier permeability did not increase significantly until 90 days after FRT, at which point it increased continuously until 180 days post-FRT. The number of adherent leukocytes did not increase during the study. The number of astrocytes in the cerebral cortex increased significantly; vesicular activity in endothelial cells increased beginning 90 days after irradiation, and most tight junctions stayed intact, although some were shorter and less dense at 120 and 180 days. Conclusions: The cellular and microvasculature response of the brain to FRT is mediated through astrogliosis and ultrastructural changes, accompanied by an increase in BBB permeability. The response to FRT is delayed as compared with single-dose irradiation treatment, and does not involve leukocyte adhesion. However, FRT induces an increase in the BBB permeability, as in the case of single-dose irradiation.
- OSTI ID:
- 20850173
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Vol. 66, Issue 3; Conference: 48. annual meeting of the American Society for Therapeutic Radiology and Oncology, Pennsylvania, PA (United States), 5-9 Nov 2006; Other Information: DOI: 10.1016/j.ijrobp.2006.06.043; PII: S0360-3016(06)01114-X; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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