Physical Activity Attenuates Brain Irradiation-Associated Skeletal Muscle Damage in the Rat

Abstract

Purpose: Radiation therapy 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 radiation therapy on skeletal muscle may be involved in fatigue. The present study aims to assess the effect of brain irradiation on skeletal muscles and its relationship with fatigue and to analyze whether physical activity could counteract brain radiation-induced side effects.

Methods and materials: Adult Wistar rats were randomly distributed between 4 groups: control (CTL), irradiated (IR), nonirradiated with physical activity (PA), and irradiated with physical activity (IR+PA). IR 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 for 6 months. The effects of WBI on muscles were evaluated by complementary approaches: behavioral tests (fatigue, locomotion activity), magnetic resonance imaging, and histologic analyses.

Results: IR rats displayed a significant fatigue and a reduced locomotor activity at short term compared with the CTL group, which were attenuated with PA at 6 months after WBI. The IR rat's gastrocnemius mass decreased compared with CTL rats, which was reversed by physical activity at 14 days after WBI. Multiparametric magnetic resonance 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 histologic analyses: the number of type I fibers was decreased, whereas that of type IIa fibers was increased in IR animals but not in the IR+PA group.

Conclusions: The data show that WBI induces skeletal muscle damage, which is attenuated by PA. This muscle damage may explain, at least in part, the fatigue of patients treated with radiation therapy.