Abstract

Muscle atrophy is a widespread ill condition occurring in many diseases, which can reduce quality of life and increase morbidity and mortality. We developed a new method using non-invasive ultrasonography to measure soleus and gastrocnemius lateralis muscle atrophy in the hindlimb-unloaded rat, a well-accepted model of muscle disuse. Soleus and gastrocnemius volumes were calculated using the conventional truncated-cone method and a newly-designed sinusoidal method. For Soleus muscle, the ultrasonographic volume determined in vivo with either method was linearly correlated to the volume determined ex-vivo from excised muscles as muscle weight-to-density ratio. For both soleus and gastrocnemius muscles, a strong linear correlation was obtained between the ultrasonographic volume and the muscle fiber cross-sectional area determined ex-vivo on muscle cryosections. Thus ultrasonography allowed the longitudinal in vivo evaluation of muscle atrophy progression during hindlimb unloading. This study validates ultrasonography as a powerful method for the evaluation of rodent muscle atrophy in vivo, which would prove useful in disease models and therapeutic trials.

Highlights

  • Muscle atrophy is a widespread ill condition occurring during inactivity, aging, and various diseases, including neuromuscular disorders, cancer, bacterial and viral infections, chronic lung and kidney diseases, diabetes, and drug side effects[1,2]

  • Ultrasound B-Mode acquisitions of Sol and gastrocnemius lateralis (Gas) muscle images were performed at day 0 (D0), 7 (D7) and 14 (D14) in control (CTRL) and hindlimb unloaded (HU) adult rats

  • It was possible to visualize the whole length of the Sol and Gas muscles tendon-to-tendon by shifting the probe along the longitudinal axis

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Summary

Introduction

Muscle atrophy is a widespread ill condition occurring during inactivity, aging, and various diseases, including neuromuscular disorders, cancer, bacterial and viral infections, chronic lung and kidney diseases, diabetes, and drug side effects[1,2]. While exercise is today the only recognized counteracting measure to slow atrophy, a number of studies in the last decade have shed light on the underlying molecular mechanisms, paving the way for drug development. This later will require preclinical models and associated powerful techniques to evaluate trial outcomes. To date the measure of muscle atrophy in animal disease models usually requires animal sacrifice in order to weigh excised muscles and perform histological and biochemical studies This approach is invasive and expensive involving the use of a large number of animals to obtain significant results. We performed a longitudinal ultrasonographic study of rat soleus (Sol) and gastrocnemius lateralis (Gas) muscle volume variation during a 14-days hindlimb-unloading (HU) period, which is a widely acknowledged model of disuse-induced muscle atrophy[10,11]

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