New model for long-term investigations of cutaneous microcirculatory and inflammatory changes following irradiation

Abstract

Radiotherapy is used for curative and palliative treatment. However, its negative effect on normal tissue is a limiting factor for the deliverable dose. Microcirculatory breakdown and prolonged inflammation in particular are major features of late side effects. The purpose of this study was to develop a reliable animal model that will allow a long-term in vivo analysis of microcirculation and inflammation following irradiation. A single dose of 90 Gy was delivered to the ears of hairless mice (n = 15). Intravital fluorescent microscopy was used to assess microcirculatory parameters and leukocyte behaviour. Values for the identical (control) areas were obtained before as well as during the following days, weeks and months following irradiation. The arteriolar and venular diameter increased up to Day 14, decreased during the following months, and increased again after one year. The red blood cell velocity increased up to 145% on Day 3, decreased on Day 7 to 115%, and stayed above baseline value the whole year. The integrity loss of the endothelium increased up to Day 7 and continued up to Day 75 after radiation. After one year, the oedema was at the baseline level. Leukocytes showed their maximal activity at one year after trauma. An increase was measured up to Day 25; the lowest values were measured at Day 40 post-irradiation, followed by a repeated increase. The present model allows a certain visualization of microcirculatory disturbances and inflammation over a period of months. This permits the possibility of long-term investigations of the underlying pathophysiology following irradiation, including possible drug interactions.