Synchrotron microbeam irradiation induces neutrophil infiltration, thrombocyte attachment and selective vascular damage in vivo

Abstract

Our goal was the visualizing the vascular damage and acute inflammatory response to micro- and minibeam irradiation in vivo. Microbeam (MRT) and minibeam radiation therapies (MBRT) are tumor treatment approaches of potential clinical relevance, both consisting of parallel X-ray beams and allowing the delivery of thousands of Grays within tumors. We compared the effects of microbeams (25–100 μm wide) and minibeams (200–800 μm wide) on vasculature, inflammation and surrounding tissue changes during zebrafish caudal fin regeneration in vivo. Microbeam irradiation triggered an acute inflammatory response restricted to the regenerating tissue. Six hours post irradiation (6 hpi), it was infiltrated by neutrophils and fli1a+ thrombocytes adhered to the cell wall locally in the beam path. The mature tissue was not affected by microbeam irradiation. In contrast, minibeam irradiation efficiently damaged the immature tissue at 6 hpi and damaged both the mature and immature tissue at 48 hpi. We demonstrate that vascular damage, inflammatory processes and cellular toxicity depend on the beam width and the stage of tissue maturation. Minibeam irradiation did not differentiate between mature and immature tissue. In contrast, all irradiation-induced effects of the microbeams were restricted to the rapidly growing immature tissue, indicating that microbeam irradiation could be a promising tumor treatment tool.

Synchrotron Microbeam Radiation Therapy as a New Approach for the Treatment of Radioresistant Melanoma: Potential Underlying Mechanisms

“…2A), indicating its potential to act as a vascular disruption agent in radio-oncology. Studies on chick chorioallantoic membrane and zebrafish caudal fin regeneration models, showing 2 types of immature vessels, demonstrated that MRT induced notable morphologic and functional damage 10 and severely impaired vascular perfusion 12 of immature blood vessels. Two main mechanisms were identified: (1) direct disruption of immature capillaries along the beam path, which caused endothelial cell detachment and consequent folding into the lumen; and (2) local adhesion of blood cells at the site of vascular damage.…”

Animal Models in Microbeam Radiation Therapy: A Scoping Review

“…Vasculature organization of the irradiated tissue depends on the stage of tissue maturation and as a result, determines tolerance to MRT. Models of immature vasculature have been the regenerating fin of the zebrafish [70] and the early chick chorioallantoic membrane [71]. The susceptibility of immature vessels to MRT-induced damage is significantly higher than the mature vessels which show very little post-MRT alterations (vascular lesions, reduced perfusion) when the MRT spacing is kept below 200 µm [71].…”

“…No changes in animal behaviour have been observed [72]. Data from chick chorioallantoic membrane [71] and zebrafish fin regeneration [70] models demonstrate the disruptive vascular effect of MRT on immature blood vessels. Work in adult organisms confirmed that the disruptive vascular effects of MRT depend on the vascular maturation status.…”

Removal of behavioural and electrophysiological signs of chronic pain byin vivomicrosections of rat somatosensory cortex with parallel X-ray microbeams

“…Redundant cortical functions may be thus more efficient in the closed context of moduli, as in control animals where the network redundancy is resilient to the low grade degradation from MB (Gao, Barzel, and Barabási 2016). The alternative hypothesis of regeneration of properties appears weaker, in that no specific neurogenesis after irradiation has been observed in the literature (Brönnimann et al 2016) (except for poor potential cell extensions as shown in Figure 7). The irradiation induces also local vascular regenerative episodes where signs of novel vessel branches transpassing narrower MB tracks (25 µm, 500 Gy) have been observed (Serduc et al 2008).…”