Abstract
Background: Radiotherapy for brain tumors increases patient survival. Nonetheless, side effects are increasingly reported such as cognitive deficits and fatigue. The etiology of fatigue remains poorly described. Our hypothesis is that the abscopal effects of radiotherapy on skeletal muscle may be involved in fatigue. The present study aims to assess the impact of brain irradiation on skeletal muscles, its relationships with fatigue and to analyze whether physical activity could counteract brain radiation-induced side effects. Methods: Adult Wistar rats were randomly distributed between 4 groups: control (CTL), irradiated (IR), non-irradiated with physical activity (PA) and irradiated with physical activity (IR+PA). Irradiated rats were exposed to a whole-brain irradiation (WBI) of 30 Gy (3×10 Gy). Rats subjected to PA underwent sessions of running on a treadmill, 3 times/week during 6 months. The effects of WBI on muscles were evaluated by complementary approaches: behavioral tests (fatigue, locomotion activity), magnetic resonance imaging (MRI) and histological analyses. Results: Irradiated rats displayed a significant fatigue and a reduced locomotor activity at short term compared to the CTL group which were attenuated with PA at 6 months after whole-brain irradiation. The IR rat's gastrocnemius mass decreased compared to CTL rats which was reversed by physical activity at 14 days after WBI. Multiparametric MRI imaging of the skeletal muscle highlighted an alteration of the fiber organization in IR rats as demonstrated by a significant decrease of the mean diffusivity in the gastrocnemius at short term. Alteration of fibers was confirmed by histological analyses: the number of type I fibers was decreased while that of type IIa fibers was increased in irradiated animals but not in IR+PA group. Conclusions: The data show that whole-brain irradiation induces skeletal muscle damage which are attenuated by PA. This muscle damage may explain, at least in part, the fatigue of patients treated with radiotherapy.
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