title: Microbeam radiation-induced tissue damage depends on the stage of vascular maturation.
abstract: OBJECTIVE
  To explore the effects of microbeam radiation (MR) on vascular biology, we used the chick chorioallantoic membrane (CAM) model of an almost pure vascular system with immature vessels (lacking periendothelial coverage) at Day 8 and mature vessels (with coverage) at Day 12 of development.
  
  
  METHODS
  CAMs were irradiated with microplanar beams (width, ∼25 μm; interbeam spacing, ∼200 μm) at entrance doses of 200 or 300 Gy and, for comparison, with a broad beam (seamless radiation [SLR]), with entrance doses of 5 to 40 Gy.
  
  
  RESULTS
  In vivo monitoring of Day-8 CAM vasculature 6 h after 200 Gy MR revealed a near total destruction of the immature capillary plexus. Conversely, 200 Gy MR barely affected Day-12 CAM mature microvasculature. Morphological evaluation of Day-12 CAMs after the dose was increased to 300 Gy revealed opened interendothelial junctions, which could explain the transient mesenchymal edema immediately after irradiation. Electron micrographs revealed cytoplasmic vacuolization of endothelial cells in the beam path, with disrupted luminal surfaces; often the lumen was engorged with erythrocytes and leukocytes. After 30 min, the capillary plexus adopted a striated metronomic pattern, with alternating destroyed and intact zones, corresponding to the beam and the interbeam paths within the array. SLR at a dose of 10 Gy caused growth retardation, resulting in a remarkable reduction in the vascular endpoint density 24 h postirradiation. A dose of 40 Gy damaged the entire CAM vasculature.
  
  
  CONCLUSIONS
  The effects of MR are mediated by capillary damage, with tissue injury caused by insufficient blood supply. Vascular toxicity and physiological effects of MR depend on the stage of capillary maturation and appear in the first 15 to 60 min after irradiation. Conversely, the effects of SLR, due to the arrest of cell proliferation, persist for a longer time.
authors: Institute of Anatomy, University of Fribourg, Fribourg, Switzerland.
authors: Sara
authors: S
authors: Sabatasso
authors: Jean Albert
authors: JA
authors: Laissue
authors: Ruslan
authors: R
authors: Hlushchuk
authors: Werner
authors: W
authors: Graber
authors: Alberto
authors: A
authors: Bravin
authors: Elke
authors: E
authors: Bräuer-Krisch
authors: Stéphanie
authors: S
authors: Corde
authors: Hans
authors: H
authors: Blattmann
authors: Guenther
authors: G
authors: Gruber
authors: Valentin
authors: V
authors: Djonov
mesh_terms: D000818:Animals; D001160:Arterioles / Q000473:pathology / Q000528:radiation effects* / Q000648:ultrastructure; D002196:Capillaries / Q000473:pathology / Q000528:radiation effects* / Q000648:ultrastructure; D049109:Cell Proliferation / Q000528:radiation effects; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply* / Q000196:embryology / Q000528:radiation effects*; D042783:Endothelial Cells / Q000473:pathology / Q000528:radiation effects; D004730:Endothelium, Vascular / Q000473:pathology / Q000528:radiation effects; D007365:Intercellular Junctions / Q000473:pathology / Q000528:radiation effects; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000473:pathology*; D011836:Radiation Tolerance / Q000502:physiology; D017356:Synchrotrons; D013997:Time Factors; D014699:Venules / Q000473:pathology / Q000528:radiation effects* / Q000648:ultrastructure