Non-invasive muscle contraction assay to study rodent models of sarcopenia

Abstract

BackgroundAge-related sarcopenia is a disease state of loss of muscle mass and strength that affects physical function and mobility leading to falls, fractures, and disability. The need for therapies to treat age-related sarcopenia has attracted intensive preclinical research. To facilitate the discovery of these therapies, we have developed a non-invasive rat muscle functional assay system to efficiently measure muscle force and evaluate the efficacy of drug candidates.MethodsThe lower leg muscles of anesthetized rats are artificially stimulated with surface electrodes on the knee holders and the heel support, causing the lower leg muscles to push isometric pedals that are attached to force transducers. We developed a stimulation protocol to perform a fatigability test that reveals functional muscle parameters like maximal force, the rate of fatigue, fatigue-resistant force, as well as a fatigable muscle force index. The system is evaluated in a rat aging model and a rat glucocorticoid-induced muscle loss modelResultsThe aged rats were generally weaker than adult rats and showed a greater reduction in their fatigable force when compared to their fatigue-resistant force. Glucocorticoid treated rats mostly lost fatigable force and fatigued at a higher rate, indicating reduced force from glycolytic fibers with reduced energy reserves.ConclusionsThe involuntary contraction assay is a reliable system to assess muscle function in rodents and can be applied in preclinical research, including age-related sarcopenia and other myopathy.

A Standardized Rat Model of Volumetric Muscle Loss Injury for the Development of Tissue Engineering Therapies

“…In vivo functional measurements were performed using methodology, similar to that we have described previously for mice and rats. 28,29 A nerve cuff was implanted in each leg around the peroneal nerve. The foot was strapped using silk surgical tape to a foot plate attached to a dual-mode muscle lever system (Aurora Scientific, Inc., Mod.…”

Non‐invasive isometric force measurement of plantar flexors in rats

“…The validity of isometric force for evaluating motor function is well established, yet it has not been used in a longitudinal study of peripheral nerve reinnervation. The noninvasive techniques pioneered by Ashton‐Miller, Stieglitz, and Chiu were validated as concepts but were never applied or validated in a longitudinal study . All studies of nerve regeneration in which isometric force was used as an outcome have used invasive or noninvasive nerve stimulation coupled with invasive force measurement.…”

“…Shin et al used a combination of invasive stimulation and force measurement to determine the effect of stimulation parameters on isometric force in a rat model . Chiu et al created a novel method of noninvasive direct muscle stimulation using surface electrodes paired with noninvasive load cells to measure motor function in a rat model of sarcopenia …”

“…5 Chiu et al created a novel method of noninvasive direct muscle stimulation using surface electrodes paired with noninvasive load cells to measure motor function in a rat model of sarcopenia. 9 While both invasive and noninvasive methods have been validated, they each have strengths and pitfalls. Most notably, the invasive modalities allow a greater degree of accuracy in both nerve stimulation and force measurement.…”

Applications of <em>In Vivo</em> Functional Testing of the Rat Tibialis Anterior for Evaluating Tissue Engineered Skeletal Muscle Repair

“…In both in vitro and in situ experiments, pharmacological treatments may be applied more directly without having to account for the effects of any surrounding tissues or the impact of the circulatory system on the measured contractile responses 37 . However, in vivo function testing, as described herein, is the least invasive technique for evaluating muscle function in its native environment 38 , and can be performed repeatedly over time (i.e., longitudinally). As such, it will be the focal point of the discussion below.…”