Microbeam radiation-induced tissue damage depends on the stage of vascular maturation

Sara Sabatasso1, Jean Albert Laissue, Ruslan Hlushchuk

  • 1Institute of Anatomy, University of Fribourg, Fribourg, Switzerland.

Abstract

Insights

Microbeam radiation (MR) severely damages immature capillaries but spares mature ones, causing localized vascular injury. Broad beam radiation (SLR) causes widespread damage by inhibiting cell proliferation.

Area of Science:

  • Vascular Biology
  • Radiation Oncology
  • Developmental Biology

Background:

  • The chick chorioallantoic membrane (CAM) model offers a unique system to study vascular biology due to its immature and mature vascular networks.
  • Understanding the differential effects of radiation on vascular development is crucial for optimizing radiation therapies and minimizing side effects.

Purpose of the Study:

  • To investigate the impact of microbeam radiation (MR) on vascular biology using the CAM model at different developmental stages (Day 8 immature vs. Day 12 mature vessels).
  • To compare the effects of MR with conventional broad beam radiation (SLR) on vascular integrity and function.

Main Methods:

  • Irradiation of CAMs with microplanar beams (25 μm width, 200 μm spacing) at 200-300 Gy and broad beams (SLR) at 5-40 Gy.
  • In vivo monitoring of vascular response and morphological evaluation using light and electron microscopy.
  • Assessment of vascular damage, interendothelial junction integrity, and cellular changes post-irradiation.

Main Results:

  • 200 Gy MR caused near-complete destruction of immature Day-8 CAM capillaries but had minimal effect on mature Day-12 vessels.
  • Higher MR doses (300 Gy) on Day-12 CAMs induced opened interendothelial junctions and transient edema, with endothelial cell vacuolization and luminal obstruction observed.
  • MR created a metronomic pattern of damage, while 10 Gy SLR caused growth retardation and reduced vascular density, and 40 Gy SLR damaged the entire vasculature.

Conclusions:

  • MR-induced tissue injury is primarily mediated by capillary damage, with effects dependent on capillary maturation stage and occurring rapidly (15-60 min post-irradiation).
  • SLR effects, stemming from cell proliferation arrest, manifest over a longer duration compared to MR.
  • The differential response highlights the importance of vascular maturity in determining radiation sensitivity.

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