A Murine Model of Muscle Training by Neuromuscular Electrical Stimulation

Abstract

Neuromuscular electrical stimulation (NMES) is a common clinical modality that is widely used to restore 1 , maintain 2 or enhance 3-5 muscle functional capacity. Transcutaneous surface stimulation of skeletal muscle involves a current flow between a cathode and an anode, thereby inducing excitement of the motor unit and the surrounding muscle fibers.NMES is an attractive modality to evaluate skeletal muscle adaptive responses for several reasons. First, it provides a reproducible experimental model in which physiological adaptations, such as myofiber hypertophy and muscle strengthening 6 , angiogenesis [7][8][9] , growth factor secretion [9][10][11] , and muscle precursor cell activation 12 are well documented. Such physiological responses may be carefully titrated using different parameters of stimulation (for Cochrane review, see 13). In addition, NMES recruits motor units non-selectively, and in a spatially fixed and temporally synchronous manner 14 , offering the advantage of exerting a treatment effect on all fibers, regardless of fiber type. Although there are specified contraindications to NMES in clinical populations, including peripheral venous disorders or malignancy, for example, NMES is safe and feasible, even for those who are ill and/or bedridden and for populations in which rigorous exercise may be challenging.Here, we demonstrate the protocol for adapting commercially available electrodes and performing a NMES protocol using a murine model. This animal model has the advantage of utilizing a clinically available device and providing instant feedback regarding positioning of the electrode to elicit the desired muscle contractile effect. For the purpose of this manuscript, we will describe the protocol for muscle stimulation of the anterior compartment muscles of a mouse hindlimb.

Repeated bouts of resistance exercise with short recovery periods activates mTOR signaling, but not protein synthesis, in mouse skeletal muscle

“…Contraction of tibialis anterior muscle was induced via percutaneous stimulation of the deep peroneal nerve following the protocol described by Ambrosio et al. (). Resistance exercise and muscle sampling were carried out according to the protocol described by Ogasawara et al.…”

Neuromuscular Electrical Stimulation as a Method to Maximize the Beneficial Effects of Muscle Stem Cells Transplanted into Dystrophic Skeletal Muscle

“…To investigate the ability of muscle contractile activity to dictate donor cell behavior in vivo , NMES was performed using a Neuromuscular Stimulator (Empi 300 PV, St Paul, USA) and modified surface electrodes, as previously described [17]. Prior to stimulation, the anterior lower limb was shaved.…”

Neuromuscular electrical stimulation promotes development in mice of mature human muscle from immortalized human myoblasts

“…The literature is also mute regarding the effects of electrical stimulation on the development of fibrosis in developing, damaged, or regenerating muscle. Electrical stimulation has, however, been reported to increase angiogenesis in muscle [ 25 , 26 ] and regeneration of motor neurons [ 65 , 66 ], perhaps by increasing the levels of trophic factors such as vascular endothelial growth factor (VEGF) and neurotrophins [ 67 , 68 ]. Furthermore, iNMES can promote the proliferation and differentiation of both myoblasts and myotubes in vitro [ 22 , 24 , 69 , 70 ].…”

“…We periodically subject the engrafted leg to intermittent neuromuscular electrical stimulation (iNMES) via the peroneal nerve. Electrical stimulation has long been known to promote muscle differentiation in vitro [ 22 – 24 ] and in vivo [ 25 , 26 ], and iNMES has been used therapeutically in man to promote the recovery of skeletal muscle from injury [ 27 – 30 ]. We report that iNMES significantly increases the number and size of the human myofibers and improves the morphology of the human skeletal muscle tissue in the grafts.…”