Effects of tail suspension on serum testosterone and molecular targets regulating muscle mass

Introduction: The contribution of reduced testosterone levels to tail suspension (TS)‐induced muscle atrophy remains equivocal. The molecular mechanism by which testosterone regulates muscle mass during TS has not been investigated. Methods: Effects of TS on serum testosterone levels, muscle mass, and expression of muscle atrophy‐ and hypertrophy‐inducing targets were measured in soleus (SOL) and extensor digitorum longus (EDL) muscles after testosterone administration during 1, 5, and 14 days of TS in male mice. Results: TS produced an increase followed by a transient drop in testosterone levels. Muscle atrophy was associated with downregulation of Igf1 and upregulation of Mstn, Redd1, Atrogin‐1, and MuRF1 mRNA with clear differences in Igf1, Mstn, and MAFbx/Atrogin‐1 gene expression between SOL and EDL. Testosterone supplementation did not affect muscle mass or protein expression levels during TS. Conclusions The known anabolic effects of testosterone are not sufficient to ameliorate loss of muscle mass during TS. Muscle Nerve 52 : 278–288, 2015     

Low‐volume resistance exercise attenuates the decline in strength and muscle mass associated with immobilization

We determined the effectiveness of low‐volume resistance exercise (EX) for the attenuation of loss of muscle mass and strength during leg immobilization. Men (N = 5) and women (N = 12, age 24 ± 5 years, body mass index 25.4 ± 3.6 kg/m²) were divided into two groups: exercise (EX; n = 12) and control (CON; n = 5). Subjects wore a knee brace on one leg that prevented weight bearing for 14 days. Resistance exercise (EX; 80% of maximal) was performed by the immobilized limb every other day. Immobilization induced a significant reduction (P < 0.05) in muscle fiber and thigh cross‐sectional area (CSA), isometric knee extensor, and plantarflexor strength in the CON (P < 0.01) but not in the EX group. There were significant losses in triceps surae CSA in the CON and EX groups (P < 0.05), but the losses were greater in CON subjects (P < 0.01). A minimal volume (140 contractions in 14 days) of resistive exercise is an effective countermeasure against immobilization‐induced atrophy of the quadriceps femoris but is only partially effective for the triceps surae. Muscle Nerve, 2010     

Tongue muscle plasticity following hypoglossal nerve stimulation in aged rats

Introduction: Age‐related decreases in tongue muscle mass and strength have been reported. It may be possible to prevent age‐related tongue muscle changes using neuromuscular electrical stimulation (NMES). Our hypothesis was that alterations in muscle contractile properties and myosin heavy chain composition would be found after NMES. Methods: Fifty‐four young, middle‐aged, and old 344/Brown Norway rats were included in this study. Twenty‐four rats underwent bilateral electrical stimulation of the hypoglossal nerves for 8 weeks and were compared with control or sham rats. Muscle contractile properties and myosin heavy chain (MHC) in the genioglossus (GG), styloglossus (SG), and hyoglossus (HG) muscles were examined. Results: Compared with unstimulated control rats, we found reduced muscle fatigue, increased contraction and half‐decay times, and increased twitch and tetanic tension. Increased type I MHC was found, except for in GG in old and middle‐aged rats. Conclusion: Transitions in tongue muscle contractile properties and phenotype were found after NMES. Muscle Nerve, 2013     

Therapeutic effect of microcurrent on calf muscle atrophy in immobilized rabbit

Introduction: Immobilization causes significant muscle loss. In this study we assessed the regenerative effect of microcurrent electrical stimulation (MES) on gastrocnemius muscle (GCM) atrophy induced by immobilization by cast (IC) in rabbits. Methods: Fifteen rabbits were divided into 3 groups: IC (group 1); IC and free re‐ambulation for 2 weeks after cast removal (CR) (group 2); and IC and MES for 2 weeks after CR (group 3). We evaluated clinical parameters (calf circumference, compound muscle action potential of tibial nerve, and thickness of GCM by ultrasound), histomorphometric data (muscle composition and cross‐sectional area), and immunohistochemistry. Results: Mean atrophic changes in clinical parameters in group 3 were significantly less than those in groups 1 and 2 (P < 0.05). Histomophometric and immunohistochemical parameters in group 3 were significantly greater than those in groups 1 and 2, respectively (P < 0.05). Discussion: MES prevents muscle atrophy and facilitates regeneration of muscle. Muscle Nerve 58 : 270–276, 2018     

Influence of resistance exercise intensity and metabolic stress on anabolic signaling and expression of myogenic genes in skeletal muscle

Introduction: We investigated the effect of resistance exercise intensity and exercise‐induced metabolic stress on the activation of anabolic signaling and expression of myogenic genes in skeletal muscle. Methods: Ten strength‐trained athletes performed high‐intensity [HI, 74% of 1‐repetition maximum (RM)], middle‐intensity (MI, 54% 1RM), or middle‐intensity (54% 1RM) no‐relaxation exercise (MIR). Kinase phosphorylation level and myogenic gene expression in muscle samples were evaluated before, 45 min, 5 h, and 20 h after exercise. Results: The lactate concentration in MI was approximately 2‐fold lower than in the 2 other sessions, and was highest in MIR. The phosphorylation level of extracellular kinase 1/2^{Thr202/Tyr204} after exercise was related to metabolic stress. Metabolic stress induced a decrease in myostatin mRNA expression, whereas mechano‐growth factor mRNA level depended on exercise intensity. Conclusions: This study demonstrates that both intensity and exercise‐induced metabolic stress can be manipulated to affect muscle anabolic signaling. Muscle Nerve 51: 434–442, 2015     

Effect of clenbuterol on normal and denervated muscle growth and contractility

The reported anabolic action of some beta 2 agonists may have clinical applications in certain muscle wasting states. Administration of clenbuterol (2 mg/kg diet for 14 days) to rats resulted in a limited degree of hypertrophy of normal muscles; the effect was more pronounced on fast-twitch muscles than on slow-twitch muscles. The anabolic effect was greatest in denervated muscles, where it was significantly more effective on the slow-twitch type. Clenbuterol significantly improved the contractile properties of denervated slow-twitch muscle, reverting them toward normal, but had little effect on contractile properties of denervated fast-twitch muscle. Such differential effects of clenbuterol must be taken into consideration in the evaluation of any future human intervention study.     

Neuromuscular electrical stimulation in early rehabilitation of Guillain-Barré syndrome: A pilot study

Introduction: In Guillain-Barré syndrome (GBS), patients often develop muscle atrophy from denervation and immobilization. We, therefore, conducted a pilot study of neuromuscular electrical stimulation (NMES) to evaluate feasibility, safety, and effect on muscle wasting in the early phase of GBS. Methods: Seventeen patients were randomized to receive 20 min of muscle fiber stimulation followed by 40 min of NMES of the right or left quadriceps muscle with the untreated side as control. Cross-sectional area (CSA) of the muscle measured by ultrasound and isometric knee extensor strength were the primary and secondary outcome measures. Results: No treatment related adverse effects were recorded. Change in CSA was -0.25 cm² (confidence interval [CI], -0.93–0.42) on the stimulated side versus -0.60 cm² (CI, -1.32–0.11) on the nonstimulated side (P = 0.08). No effect was observed on muscle strength. Conclusions: NMES seems safe and feasible in the early phase of GBS. Further studies are needed to explore effect on muscle function. Muscle Nerve 59:481–484, 2019     

Longitudinal study of skeletal muscle adaptations during immobilization and rehabilitation

This study describes the metabolic, morphologic, neurologic, and functional adaptations observed in the plantar flexors during 8 weeks of lower leg immobilization and 10 weeks of physical therapy following ankle surgery. A combination of magnetic resonance imaging and spectroscopy, isokinetic and isometric muscle testing, and simple functional tests revealed many adaptive changes due to immobilization, including atrophy, loss of muscle strength, reduced central activation, increase in fatigue resistance, and an increase in inorganic phosphate content. After 10 weeks of physical therapy all alterations were reversed, with the exception of a remaining 5.5% deficit in total muscle cross-sectional area. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:1006–1012, 1998.     

The effects of different training programs on the trapezius muscle of women with work-related neck and shoulder myalgia

The aim of this study was to examine the effects of training on the structural characteristics of the trapezius muscle in women with work-related trapezius myalgia. Muscle biopsies were taken before and after 10 weeks of three different training programs (strength, endurance and coordination). Enzyme-immunohistochemical analysis was performed to assess muscle fibre types, fibre area, capillary supply and cytochrome c oxidase (COX) activity. There was an increase in the proportion of type IIA fibres in strength trained group (P < 0.05). Strength training elicited a preferential increase in the area of type II fibres (P < 0.05); both strength and endurance programs induced an increase in the number of capillaries around type I and IIA muscle fibres. Finally, all training programs induced a decrease in the proportion of COX-negative fibres. In conclusion, the trapezius muscle of women with neck and shoulder myalgia is characterised by a great potential of adaptation to physical exercise over a period of 10 weeks. The significant changes in the number of capillaries and the specific changes induced by training at the level of muscle fibres might well explain the improvement of muscle function. Received: 18 August 1999 / Revised, accepted: 17 November 1999     

Balance and coordination training after sciatic nerve injury

Introduction: Numerous therapeutic interventions have been tested to enhance functional recovery after peripheral nerve injuries. Methods: After sciatic nerve crush in rats we tested balance and coordination and motor control training in sensorimotor tests and analyzed nerve and muscle histology. Results: The balance and coordination training group and the sham group had better results than the sedentary and motor control groups in sensorimotor tests. The sham and balance and coordination groups had a significantly larger muscle area than the other groups, and the balance and coordination group showed significantly better values than the sedentary and motor control groups for average myelin sheath thickness and g‐ratio of the distal portion of the nerve. Conclusions: The findings indicate that balance and coordination training improves sciatic nerve regeneration, suggesting that it is possible to revert and/or prevent soleus muscle atrophy and improve performance on sensorimotor tests. Muscle Nerve 44: 55–62, 2011.     

A differential pattern of gene expression in skeletal muscle of tumor‐bearing rats reveals dysregulation of excitation–contraction coupling together with additional muscle alterations

Introduction: Cachexia is a wasting condition that manifests in several types of cancer. The main characteristic of this condition is a profound loss of muscle mass. Methods: By using a microarray system, expression of several hundred genes was screened in skeletal muscle of rats bearing a cachexia‐inducing tumor, the AH‐130 Yoshida ascites hepatoma. This model induced a strong decrease in muscle mass in the tumor‐bearing animals, as compared with their healthy counterparts. Results: The results show important differences in gene expression in EDL skeletal muscle between tumor‐bearing animals with cachexia and control animals. Conclusions: The differences observed pertain to genes related to intracellular calcium homeostasis and genes involved in the control of mitochondrial oxidative phosphorylation and protein turnover, both at the level of protein synthesis and proteolysis. Assessment of these differences may be a useful tool for the design of novel therapeutic strategies to fight this devastating syndrome. Muscle Nerve 49 : 233–248, 2014     

Gender‐specific neuromuscular adaptations to unloading in isolated rat soleus muscles

Introduction: The potential of gender to affect unloading‐induced neuromuscular adaptations was investigated. Methods: Twenty male and 20 female rats were assigned to control (CTL), or unloaded (UL) conditions. After 2 weeks of unloading, soleus muscles were removed, and neuromuscular function was assessed during a train of alternating indirect (neural) and direct (muscle) stimuli. Results: In rested muscle, strength showed significant (P ≤ 0.05) main effects for gender (male > female) and treatment (CTL > UL). By the end of the testing protocol, when muscles showed fatigue, gender‐related and treatment‐related differences in strength had disappeared. Neuromuscular transmission efficiency and strength suffered a greater decline during the testing protocol in males than females. Unloaded male muscles displayed greater contractile velocity than female muscles both when rested and fatigued. Conclusions: Gender affected unloading‐induced neuromuscular adaptations. The greater strength of rested male muscles was due to greater muscle mass and neuromuscular transmission efficiency. Muscle Nerve 54 : 300–307, 2016     

Time‐course study of macrophage infiltration and inflammation in cast immobilization–induced atrophied muscle of mice

Introduction: Macrophage infiltration may play an important role in mediating the development of muscle atrophy. However, temporal differences in the activation of muscle atrophy signaling pathways and the progress of macrophage infiltration during the atrophic phases of cast immobilization are currently unknown. Methods: C57BL/6J mice were euthanized after cast immobilization at 1, 3, 7, and 14 days. Results: Skeletal muscle macrophage numbers were unchanged on days 1 and 3 after immobilization, but were elevated on days 7 (2.7‐fold, P < 0.01) and 14 (4.1‐fold, P < 0.01). Ubiquitin ligase expression was increased 1 and 3 days after cast immobilization, as was the LC3‐II/LC3‐I ratio. Discussion: Atrophy signaling pathway activation, but not macrophage infiltration, was observed during the early phase after cast immobilization. Our findings indicate that macrophage infiltration may contribute very little to the early phase of muscle atrophy after cast immobilization. Muscle Nerve 57 : 1006–1013, 2018     

Balance and coordination training and endurance training after nerve injury

Introduction: Different rehabilitation treatments have proven useful in accelerating regeneration. Methods: After sciatic nerve crush in rats, we tested balance and coordination training (BCT) and endurance training (ET) through sensorimotor tests and analyzed nerve and muscle morphology. Results: After BCT and ET, rats performed better in sensorimotor tests than did non‐trained animals. However, only BCT maintained sensorimotor function during training. Furthermore, BCT and ET produced significantly larger muscle area than in non‐trained animals. Conclusions: These findings indicate that BCT and ET, when initiated in the early phase after sciatic nerve injury, improve morphological properties of the soleus muscle and sciatic nerve, but only the task‐oriented BCT maintained sensorimotor function. The success of rehabilitative strategies appears to be highly task‐specific, and strategies that stimulate sensory pathways are the most effective in improving balance and/or coordination parameters. Muscle Nerve 51 : 83–91, 2015     

Muscle strength and fatigue in newly diagnosed patients with myasthenia gravis

Introduction: Dynamometry is increasingly used as an objective measurement of muscle strength in neurological diseases. No study has applied dynamometry in untreated newly diagnosed patients with myasthenia gravis (MG). Methods: Isometric muscle strength at the shoulder, knee, and ankle was determined in 21 MG patients before and after initial anti‐myasthenic treatment. Isometric strength was compared with MG evaluation scales. Results: Muscle strength was reduced for knee extensors and shoulder abductors but normal for ankle extensors. Isometric muscle strength did not correlate significantly with manual muscle testing (MG Composite). Dynamometry revealed improved muscle strength of up to 50% (median 17%; range ‐1.8–49.8) despite no change in the MG Composite score. Conclusions: Dynamometry appears to be a more sensitive method of identifying changes in limb strength than MG evaluation scales. This supports the use of dynamometry in MG patients, especially for evaluation of the effect of anti‐myasthenic treatment. Muscle Nerve 54 : 709–714, 2016     

Reduced Nerve Blood Flow In Diabetic Rats Is A Reflection Of Hindlimb Muscle Wasting

We examined the influence of muscle wasting, as a result of streptozotocin-induced diabetes, on sciatic nerve laser Doppler flux (SNLDF), as an index of nerve blood flow, and conduction velocity (NCV). We compared dietary-restricted weight-reduced non-diabetic rats with controls and with diabetic rats and we studied the effects of clenbuterol, an anabolic β-adrenoceptor agonist, in control and diabetic rats. Dietary restriction reduced the weights of hindlimb muscles—extensor digitorum longus, soleus and gastrocnemius—half as much as did streptozotocin-diabetes and clenbuterol increased muscle weights in control and diabetic rats. This gave a hierarchy of muscle weights in the order—clenbuterol-controls, untreated controls, weight-reduced non-diabetics, clenbuterol-diabetics and untreated diabetics. Diabetes without treatment reduced SNLDF by 51% (p < 0.01); dietary restriction by 25% (p < 0.01) and there were proportional increases associated with clenbuterol treatment. Combined muscle weights regressed closely with SNLDF (r²=0.69; p < 0.001) and, when the latter was expressed relative to muscle weights, a similar value was obtained for all five groups—there were no significant differences. Thus, sciatic nerve blood flow is closely related to hindlimb muscle weight and the effect of diabetes on nerve blood flow may be secondary to muscle wasting. Sciatic/tibialis motor and sensory conduction velocities were also reduced by muscle wasting in the dietary restricted group of non-diabetic rats, but, unlike nerve Doppler flux, it was unaffected by clenbuterol.     

Diurnal and day‐to‐day variation of isometric muscle strength in myasthenia gravis

Introduction: In patients with myasthenia gravis (MG), muscle strength is expected to decrease gradually during the day due to physical activities. Methods: Isometric muscle strength at the shoulder, knee, and ankle was determined in 10 MG patients (MGFA class II–IV) who were receiving usual medical treatment and in 10 control subjects. To determine diurnal and day‐to‐day variation, muscle strength was measured 4 times during day 1 and once at day 2. Results: Knee extension strength decreased during the day in both patients and controls. Neither diurnal nor day‐to‐day variation of muscle strength was higher in patients compared with controls. Conclusions: Patients with mild to moderate MG did not have increased variation of isometric muscle strength during the day or from day‐to‐day compared with controls. This suggests that isometric muscle performance can be determined with high reproducibility in similar groups of MG patients without regard to time of day. Muscle Nerve 53 : 67–72, 2016     

Effect of physical training on pain sensitivity and trapezius muscle morphology

The objective of this study was to investigate morphological and physiological characteristics of painful muscles in women with (MYA, n= 42) and without (CON, n = 20) trapezius myalgia, and assess changes in response to a 10‐week, randomized, controlled trial. MYA accomplished: (1) specific strength training (SST); (2) general fitness training (GFT); or (3) reference intervention (REF). Differences in muscle morphology could not be detected by ultrasound imaging. Significantly lower pressure pain threshold (PPT) and shoulder torque were observed for MYA, indicating pain‐related lack of full activation. After 10 weeks, increased shoulder torque and PPT of the painful trapezius were observed in SST solely. The PPT of a pain‐free reference muscle was increased in response to both SST and GFT, indicating a general effect of physical activity on pain perception. This study shows clinically relevant improvement in pain sensitivity and muscle strength capacity in response to SST. Muscle Nerve, 2010     

The problem Of muscle hypertrophy: Revisited

In this paper we revisit a topic originally discussed in 1955, namely the lack of direct evidence that muscle hypertrophy from exercise plays an important role in increasing strength. To this day, long‐term adaptations in strength are thought to be primarily contingent on changes in muscle size. Given this assumption, there has been considerable attention placed on programs designed to allow for maximization of both muscle size and strength. However, the conclusion that a change in muscle size affects a change in strength is surprisingly based on little evidence. We suggest that these changes may be completely separate phenomena based on: (1) the weak correlation between the change in muscle size and the change in muscle strength after training; (2) the loss of muscle mass with detraining, yet a maintenance of muscle strength; and (3) the similar muscle growth between low‐load and high‐load resistance training, yet divergent results in strength. Muscle Nerve 54 : 1012–1014, 2016     

Muscle weakness and functional disability in patients with myasthenia gravis

Introduction: Muscle weakness and functional disability have not been evaluated in a population-based study of patients with myasthenia gravis (MG). Methods: All patients with MG in a well-defined catchment area were identified in the Danish National Patient Registry. Of the 175 eligible patients, 90 participated and were studied using MG-specific scales, isometric dynamometry, and functional tests. Fifty age- and sex-matched subjects served as controls. Results: Muscle strength was reduced by 13%, 21%, and 12% for shoulder abduction, knee extension, and ankle extension, respectively (P < 0.05). Chair stand and 400-meter walking were impaired by 24% and 23%, respectively (P < 0.05). Muscle strength and functional performances were related to MG-specific scales. Discussion: MG patients have moderately reduced isometric muscle strength and impaired physical performance. Muscle weakness and functional tests relate closely to MG-specific scales, suggesting that dynamometry and functional tests can be used to monitor MG patients and as efficacy parameters in clinical trials. Muscle Nerve 59 :218–223, 2019