SERIAL IN-VIVO OBSERVATIONS OF CEREBRAL VASCULATURE AFTER TREATMENT WITH A LARGE SINGLE FRACTION OF RADIATION

To test whether single high doses of radiation, similar to those used with radiosurgery, given to normal cerebral vasculature can cause chan ges in leukocyte-vessel wall interactions and tissue perfusion, a rat pial window model was used to view the cerebral vasculature, facilitat ing repeated in vivo observations of microcirculatory function. An att achment for a 4 MV linear accelerator was designed to deliver a well-c ollimated 2.2-mm beam of radiation to a selected region of rat brain. Sequential measurements of leukocyte-endothelial cell interactions, re lative change in blood flow with laser Doppler flowmetry and vessel le ngth density were performed prior to and at 24 h and 3 weeks after tre atment with 15, 22.5 or 30 Gy, given in a single fraction. Significant increases in leukocyte-endothelial cell interactions were seen 24 h a nd 3 weeks after irradiation that were dependent on dose, particularly in arteries. Changes were apparent in both arteries and veins at 24 h , but by 3 weeks the effects in arteries predominated. Decreases in ve ssel length density and blood flow were observed and became greater wi th time after treatment. A variety of morphological changes were obser ved in irradiated arteries, including formation of aneurysmal structur es, endothelial denudation and thrombus formation. These results sugge st that: (1) An increase in leukocyte-vessel wall interactions occurs after irradiation; (2) cerebral arterioles are more sensitive than vei ns to radiation administered in this fashion; and (3) the increase in leukocyte-vessel wall interactions likely contributes to reduction of or loss of arteriolar flow, with resultant loss of flow to dependent m icrovascular vessels. (C) 1998 by Radiation Research Society.