Dose Response of Brain Vasculature to Proton Irradiation: a Progress Report

PURPOSE The aim of this study was to estimate the risk of brain microvessel radiation damage produced by exposure to proton irradiation. The microvessel endothelial populations and vessel topology to proton irradiation were quantified in the rat brain cortex and white matter following single and split dose schedules of protons using unbiased stereological techniques. This was a work in progress that reported on the dose response of the microvessels observed up to 12 month over a period of two years. MATERIAL AND METHODS Male Sprague-Dawley rats received single or split dose of proton irradiation at 8, 14 or 20Gy 6 or 12 month earlier. The brain microvessel endothelial cell population numbers, vessel lengths, vessel branches and Euler number in cortex and corpus callosum were measured using confocal laser scanning microscopic stereological protocol. RESULTS At 12 months, rats received proton irradiation at high dose (20Gy) exhibited significant decrease of endothelial cell and microvessel branching density (p<0.05) in corpus callosum compared to that of control, but with no significant difference in cortex. The vessel density changes and Euler numbers were not different from age-matched controls in both cortex and corpus callosum. CONCLUSION The dose response of the microvessels in cortex was quantitively more resistant than the changes in the white matter. The dose response of split-dose was same as that of single dose. No cell proliferation or recovery was observed in the irradiated vasculature, suggesting brain microvessels were non-proliferative. BACKGROUND Inflammatory tissue damage, associated with irradiation, may have a superoxide component. A previously developed model with rat rectal tissue was used to quantify the protective ability of Manganic Porphyrins as a SOD mimic. The quantification of crypts on the circumference of the rectum established the effective ability of a MnSOD to scavenge superoxides. METHODS Sprague Dawley male rats weighing approximately 500g were given a low residue diet to limit feces formation. Prior to irradiation the rats were given a water only diet to limit feces in the bowel. Rats were anesthetized with isoflurane and given systemic Mn-TE-2-PyP subcutaneously. Groups were given the drug: 1hr prior to irradiation, and 1hr post-irradiation. The rats were suspended head down localizing the beam light field to an area starting 2.5cm from the anus. Radiation was delivered at 21.5Gy (LD-50%) and animals were removed and placed in a cage to recover under observation. Animals were sacrificed at 10 and 150 days intervals to observe acute and long …