Glycine receptor subunit-ß-deficiency in a mouse model of spasticity results in attenuated physical performance, growth, and muscle strength.

Spasticity is the most common neurological disorder associated with increased muscle contraction causing impaired movement and gait. The aim of this study was to characterize the physical performance, skeletal muscle function, and phenotype of mice with a hereditary spastic mutation (B6.Cg-Glrbspa/J). Motor function, gait, and physical activity of juvenile and adult spastic mice and the morphological, histological, and mechanical characteristics of their soleus and gastrocnemius medialis muscles were compared with those of their wild-type (WT) littermates. Spastic mice showed attenuated growth, impaired motor function, and low physical activity. Gait of spastic mice was characterized by a typical hopping pattern. Spastic mice showed lower muscle forces, which were related to the smaller physiological cross-sectional area of spastic muscles. The muscle-tendon complex length-force relationship of adult gastrocnemius medialis was shifted toward shorter lengths, which was explained by attenuated longitudinal tibia growth. Spastic gastrocnemius medialis was more fatigue resistant than WT gastrocnemius medialis. This was largely explained by a higher mitochondrial content in muscle fibers and relatively higher percentage of slow-type muscle fibers. Muscles of juvenile spastic mice showed similar differences compared with WT juvenile mice, but these were less pronounced than between adult mice. This study shows that in spastic mice, disturbed motor function and gait is likely to be the result of hyperactivity of skeletal muscle and impaired skeletal muscle growth, which progress with age.

Stimuli for Adaptations in Muscle Length and the Length Range of Active Force Exertion-A Narrative Review.

Treatment strategies and training regimens, which induce longitudinal muscle growth and increase the muscles' length range of active force exertion, are important to improve muscle function and to reduce muscle strain injuries in clinical populations and in athletes with limited muscle extensibility. Animal studies have shown several specific loading strategies resulting in longitudinal muscle fiber growth by addition of sarcomeres in series. Currently, such strategies are also applied to humans in order to induce similar adaptations. However, there is no clear scientific evidence that specific strategies result in longitudinal growth of human muscles. Therefore, the question remains what triggers longitudinal muscle growth in humans. The aim of this review was to identify strategies that induce longitudinal human muscle growth. For this purpose, literature was reviewed and summarized with regard to the following topics: (1) Key determinants of typical muscle length and the length range of active force exertion; (2) Information on typical muscle growth and the effects of mechanical loading on growth and adaptation of muscle and tendinous tissues in healthy animals and humans; (3) The current knowledge and research gaps on the regulation of longitudinal muscle growth; and (4) Potential strategies to induce longitudinal muscle growth. The following potential strategies and important aspects that may positively affect longitudinal muscle growth were deduced: (1) Muscle length at which the loading is performed seems to be decisive, i.e., greater elongations after active or passive mechanical loading at long muscle length are expected; (2) Concentric, isometric and eccentric exercises may induce longitudinal muscle growth by stimulating different muscular adaptations (i.e., increases in fiber cross-sectional area and/or fiber length). Mechanical loading intensity also plays an important role. All three training strategies may increase tendon stiffness, but whether and how these changes may influence muscle growth remains to be elucidated. (3) The approach to combine stretching with activation seems promising (e.g., static stretching and electrical stimulation, loaded inter-set stretching) and warrants further research. Finally, our work shows the need for detailed investigation of the mechanisms of growth of pennate muscles, as those may longitudinally grow by both trophy and addition of sarcomeres in series.

Remodeling of Rat M. Gastrocnemius Medialis During Recovery From Aponeurotomy.

Aponeurotomy is a surgical intervention by which the aponeurosis is transsected perpendicularly to its longitudinal direction, halfway along its length. This surgical principle of aponeurotomy has been applied also to intramuscular lengthening and fibrotomia. In clinics, this intervention is performed in patients with cerebral palsy in order to lengthen or weaken spastic and/or short muscles. If the aponeurotomy is performed on the proximal aponeurosis, as is the case in the present study, muscle fibers located distally from the aponeurosis gap that develops lose their myotendinous connection to the origin. During recovery from this intervention, new connective (scar) tissue repairs the gap in the aponeurosis, as well as within the muscle belly. As a consequence, the aponeurosis is longer during and after recovery. In addition, the new connective tissue is more compliant than regular aponeurosis material. The aim of this study was to investigate changes in muscle geometry and adaptation of the number of sarcomeres in series after recovery from aponeurotomy of the proximal gastrocnemius medialis (GM) aponeurosis, as well as to relate these results to possible changes in the muscle length-force characteristics. Aponeurotomy was performed on the proximal aponeurosis of rat muscle GM and followed by 6 weeks of recovery. Results were compared to muscles of a control group and those of a sham-operated group. After recovery from aponeurotomy, proximal and distal muscle fiber lengths were similar to that of the control group. The mean sarcomere length from fibers located proximally relative to the aponeurosis gap remained unchanged. In contrast, fibers located distally showed 16-20% lower mean sarcomere lengths at different muscle lengths. The number of sarcomeres in series within the proximal as well as distal muscle fibers was unchanged. After recovery, muscle length-force characteristics were similar to those of the control group. A reversal of proximal-distal difference of fibers mean sarcomere lengths within muscles during recovery from aponeurotomy is hypothesized to be responsible for the lack of an effect. These results indicate that after recovery from aponeurotomy, geometrical adaptations preserved the muscle function. Moreover, it seems that the generally accepted rules of adaptation of serial sarcomere numbers are not applicable in this situation.