A new murine highly localized high-dose muscle radiation model as a tool to develop innovative countermeasures to treat radio-induced muscular lesions: preliminary studies

Acute localized irradiation accidents may evolve into a cutaneous radiation-induced syndrome (CRS) which leaves a significant underlying muscle defect despite a standard treatment. It is therefore necessary to identify new therapeutic targets to improve post-irradiation muscle regeneration.

Thus, the validation of an in vivo model of spontaneously regenerating radiation-induced muscle lesions has been initiated. The left gastrocnemius/soleus muscles of C57Bl/6 mice were irradiated with a 60 Gy X-ray dose, with a beam collimation of 9x3mm. A weekly follow-up of muscle strength and lesions was carried. Then macroscopic, biochemical and histological muscular radiation-induced effects were analyzed at day 90 post-irradiation.

The functional test revealed a contraction of the irradiated left paw compared to the right paw of the same mice. Scoring of skin lesions located on the left paw showed an increase in skin damage over time. Interestingly, studies performed at day 90 on tissue samples showed muscle atrophy after radiation exposure with a decrease of muscle weight and fibers diameter, suggesting a degeneration concomitant or not with regeneration. Finally, variations in specific muscle (Pax7, Myf5, MyoG, Myosin isoforms) and inflammatory (IL-1 beta, TGF beta, IL-10) markers have been highlighted between irradiated and control groups by gene expression analysis.

Following this preliminary study, a more complete kinetic study is underway, performed at early, intermediate and late time points, in order to analyze the spontaneous muscle regeneration capacity of the muscle after a highly localized irradiation at different doses. Thus, a major scientific interest lies in this project to improve the understanding of muscle degeneration and regeneration in CRS, allowing the identification of new therapeutic targets and the development of innovative medical countermeasures.