Acker J C, Marks L B, Spencer D P, Yang W, Avery M A, Dodge R K, Rosner G L, Dewhirst M W
Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Radiat Res. 1998 Apr;149(4):350-9.
To test whether single high doses of radiation, similar to those used with radiosurgery, given to normal cerebral vasculature can cause changes in leukocyte-vessel wall interactions and tissue perfusion, a rat pial window model was used to view the cerebral vasculature, facilitating repeated in vivo observations of microcirculatory function. An attachment for a 4 MV linear accelerator was designed to deliver a well-collimated 2.2-mm beam of radiation to a selected region of rat brain. Sequential measurements of leukocyte-endothelial cell interactions, relative change in blood flow with laser Doppler flowmetry and vessel length density were performed prior to and at 24 h and 3 weeks after treatment with 15, 22.5 or 30 Gy, given in a single fraction. Significant increases in leukocyte-endothelial cell interactions were seen 24 h and 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 vessel length density and blood flow were observed and became greater with time after treatment. A variety of morphological changes were observed in irradiated arteries, including formation of aneurysmal structures, endothelial denudation and thrombus formation. These results suggest that: (1) An increase in leukocyte-vessel wall interactions occurs after irradiation; (2) cerebral arterioles are more sensitive than veins 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 microvascular vessels.
为了测试给予正常脑循环系统类似于放射外科手术中使用的单次高剂量辐射是否会引起白细胞与血管壁相互作用及组织灌注的变化，采用大鼠软脑膜窗模型来观察脑循环系统，便于对微循环功能进行反复的体内观察。设计了一种用于4兆伏直线加速器的附件，以便向大鼠脑的选定区域输送一束准直良好的2.2毫米辐射束。在单次给予15、22.5或30戈瑞辐射治疗前、治疗后24小时和3周时，对白细胞与内皮细胞的相互作用、用激光多普勒血流仪测量的血流相对变化以及血管长度密度进行了连续测量。照射后24小时和3周时可见白细胞与内皮细胞的相互作用显著增加，且这种增加依赖于剂量，尤其是在动脉中。24小时时动脉和静脉均出现明显变化，但到3周时，动脉中的影响占主导。观察到血管长度密度和血流减少，且治疗后随时间推移变得更加明显。在受照射的动脉中观察到多种形态学变化，包括动脉瘤样结构的形成、内皮剥脱和血栓形成。这些结果表明：（1）照射后白细胞与血管壁的相互作用增加；（2）以这种方式给予辐射时，脑小动脉比静脉更敏感；（3）白细胞与血管壁相互作用的增加可能导致小动脉血流减少或丧失，进而导致依赖的微血管血流丧失。
