Structural Changes In Skeletal Muscle Research Articles

Структурно-метаболические изменения скелетных мышц у пациентов с хроническим нарушением сознания – к вопросу о полинейромиопатиях критических состояний (ПЭТ-патоморфологическое исследование)

The presence of patients in a state of chronic disorders consciousness leads to the development of dysfunction (weakness, paresis) of their skeletal muscles – polyneuropathy and myopathy of critical states. It is of interest to study the mechanisms of pathology development and assess the rehabilitation potential of such patients. Positron emission computed tomography (PET/CT) with 18F-fluorodeoxyglucose (18F-FDG) and pathomorphological studies with immunohistochemistry were used to obtain data on structural and metabolic changes in the skeletal muscles of the upper extremities in 22 patients with chronic disorders consciousness. The study showed that structural changes in skeletal muscles have a non-specific degenerative-atrophic character with more pronounced manifestations on the side of paresis. The metabolic disorders of the shoulder girdle muscles revealed by the decrease in the level of 18F-FDG metabolism in patients with chronic disorders consciousness developed symmetrically, regardless of the degree of decrease in muscle tone and deep reflexes. Along with degenerative changes, including damage to the contractile elements of sarcomeres, loss of desmin and dystrophin, a decrease in the level of 18F-FDH metabolism, signs of adaptive structural and functional rearrangements were observed in the skeletal muscles of patients- modification of the phenotype of muscle fibers by the fast type and activation of the autophagic pathway.

Structural changes in skeletal muscles of the hind limbs of rats in acute ischemia-reperfusion and its correction by carbacetam, detected by polarization microscopy

Arterial tourniquets are used in clinical practice for angioplasty and arthroplasty, and in case of limb injuries, their use often occurs according to vital signs. After removing the tourniquet and blood supply restoration to the limb arises a multifactorial lesion of tissues both ischemic and distant from the site of ischemia. A number of publications have been devoted to the study of morphological disorders in muscle tissue in acute ischemia-reperfusion in the medical literature. However, the researches for effective means for drug correction of these disorders still continues. The aim of the study was to explore peculiarities of skeletal muscle remodeling of the hind limbs of rats, detected by polarization microscopy, in acute ischemia-reperfusion, caused by the application of an arterial tourniquet, and in the correction of reperfusion disorders by carbacetam. Microscopic examination of histological sections of skeletal muscles of the hind limbs of 60 rats below the site of application of the tourniquet under conditions of experimental acute ischemia-reperfusion was performed. Acute ischemia for all animals was caused by application of SWAT rubber bands on the hind limbs of animals, 5–6 mm in width, at the inguinal fold level within 2 hours under thiopental anesthesia. A reperfusion was modeled by removing the tourniquet. Half of the experimental animals in the reperfusion period for the purpose of correction intraperitoneally was administered the nootropic drug 1-oxo-3.3.6-trimethyl-1.2.3.4-tetrahydroindolo[2.3-c]quinoline (carbacetam) at a dose of 5 mg per kilogram of body weight once a day during the entire reperfusion period. The histological specimens of the skeletal muscles were stained with hematoxylin and eosin, and were examined with a light microscope with polarization nozzle. Studies with using the polarization microscopy have shown that in the early reperfusion period morphological criteria for skeletal muscle remodeling expressed by deformation and anisotropy of muscle fibers, disappearance of their transverse striation, cracks and ruptures of fibers, and in the most severe cases there were signs of necrosis of the fibers with their fragmentation into separate lumps. Subject to the correction of reperfusion disorders by carbacetam, there is a decrease in the degree of damage and consistent acceleration of restoration of the skeletal muscles structure, which was the most pronounced in groups of animals with reperfusion terms after 1 and 14 days. Complex of features indicates, that at the tissue level the administration of carbacetam as reduces the ischemic-reperfusion lesion of the muscular fibers, as also accelerates the mechanisms of reparative rhabdomyohistogenesis. Thus, structural changes in the skeletal muscles of the limb after two-hour ischemia and subsequent reperfusion increased in the early reperfusion period and reached its peak after 1 day of reperfusion, and in the late period of reperfusion their reverse development took place. With the correction of disorders by carbacetam, the degree of damage was reduced and the recovery of the skeletal muscle structure of the limb was accelerated.

Aging‐associated skeletal muscle defects in HER2/Neu transgenic mammary tumour model

AbstractBackgroundLoss of skeletal muscle volume and functional limitations are poor prognostic markers in breast cancer patients. Several molecular defects in skeletal muscle including reduced myoblast determination protein 1 (MyoD) levels and increased protein turn over due to enhanced proteosomal activity have been suggested as causes of skeletal muscle loss in cancer patients. However, it is unknown whether molecular defects in skeletal muscle are dependent on tumour aetiology.MethodsWe characterized functional and molecular defects of skeletal muscle in mouse mammary tumour virus (MMTV)‐Neu (Neu+) mice (n = 6–12), an animal model that represents HER2 + human breast cancer, and compared the results with well‐characterized luminal B breast cancer model MMTV‐PyMT (PyMT+). Functional studies such as grip strength, rotarod performance, and ex vivo muscle contraction were performed to measure the effects of cancer on skeletal muscle. Expression of muscle‐enriched genes and microRNAs as well as circulating cytokines/chemokines were measured. Because nuclear factor‐kappaB (NF‐κB) pathway plays a significant role in skeletal muscle defects, the ability of NF‐κB inhibitor dimethylaminoparthenolide (DMAPT) to reverse skeletal muscle defects was examined.ResultsNeu+ mice showed skeletal muscle defects similar to accelerated aging. Compared with age and sex‐matched wild type mice, Neu+ tumour‐bearing mice had lower grip strength (202 ± 6.9 vs. 179 ± 6.8 g grip force, P = 0.0069) and impaired rotarod performance (108 ± 12.1 vs. 30 ± 3.9 s, P < 0.0001), which was consistent with reduced muscle contractibility (P < 0.0001). Skeletal muscle of Neu+ mice (n = 6) contained lower levels of CD82 + (16.2 ± 2.9 vs. 9.0 ± 1.6) and CD54 + (3.8 ± 0.5 vs. 2.4 ± 0.4) muscle stem and progenitor cells (P < 0.05), suggesting impaired capacity of muscle regeneration, which was accompanied by decreased MyoD, p53, and miR‐486 expression in muscles (P < 0.05). Unlike PyMT+ mice, which showed skeletal muscle mitochondrial defects including reduced mitochondria levels and peroxisome proliferator‐activated receptor gamma co‐activator 1 (beta), Neu + mice displayed accelerated aging‐associated changes including muscle fibre shrinkage and increased extracellular matrix deposition. Circulating ‘aging factor’ and cachexia and fibromyalgia‐associated chemokine C‐C motif chemokine ligand 11 (Ccl11) was elevated in Neu+ mice (1439.56 ± 514 vs. 1950 ± 345 pg/mL, P < 0.05). Treatment of Neu+ mice with DMAPT significantly restored grip strength (205 ± 6 g force), rotarod performance (74 ± 8.5 s), reversed molecular alterations associated with skeletal muscle aging, reduced circulating Ccl11 (1083.26 ± 478 pg/mL), and improved animal survival.ConclusionsThese results suggest that breast cancer subtype has a specific impact on the type of molecular and structural changes in skeletal muscle, which needs to be taken into consideration while designing therapies to reduce breast cancer‐induced skeletal muscle loss and functional limitations.

Exercise physiology basis and necessity of hypoxic training to improve exercise performance in elite athletes

Purpose The purpose of this study is to emphasize the need for the establish and the use of altitude training center via examining exercise training method in natural or artificial altitude environment that is applied to various elite athletes in various advanced countries to maximize exercise performance and its effectiveness. Results Altitude training in natural or artificial altitude environment enhances aerobic and anaerobic exercise performance baesd on the hematological and nonhematological adaptations to hypoxic conditions. These altitude training methods can be classified into living high training high (LHTH), living high training low (LHTL), and living low training high (LLTH). LHTH (i.e., developed since the 1968 Mexico Olympics) and LHTL (i.e., developed in the 1990s by Levine and Stray-Gundersen) improve exercise performance via hematologic changes through erythropoiesis such as increased hemoglobin mass and erythrocyte volume. On the other hand, LLTH (i.e., has been developed variously since the 2000s) is composed continuous hypoxic training (CHT), intermittent hypoxic training (IHT) and repeated sprint training in hypoxia (RSH), and the altitude environment is constructed using a vacuum pump and a nitrogen generator. In general, LLTH method dose not induce hematological change in a short time within 3 hours. However, CHT and IHT enhance aerobic exercise capacity by improved exercise economy, supply and utilization of blood to tissues, capillary and mitochondrial densities, and oxidative enzyme activity through various biochemical and structural changes in skeletal muscle and cardiac muscle. RSH enhances anaerobic power and repetitive sprint performance by improving glycolytic enzyme, glucose transport, and pH control. In Korea, however, there are almost no facilities for altitude training that is applied to enhance athletic performance in advanced sports countries and recognition of the need for altitude training is also very poor. Conclusions Therefore, it is very urgent to develop altitude training for maximizing athletic performance in Korea and a lot of support and efforts are needed from the government and local governments.

Structural changes in skeletal muscles in hypokinesia and physical loading in the posthypokinetic period of recovery of rats’ organisms

This article reports the study of histo-ultrastructural changes of different structural components of the direct muscle of the thigh of sexually mature male rats over a prolonged period of hypokinesia and subsequent application of physical loading of average aerobic power. Using a light optical, electron microscope (for the exposure of structural transformations of muscle components) and histochemical (for determination of activity of succinate dehydrogenase according to the Nahlas method to identify muscle fibers with different phenotypes) methods, we studied the structural manifestations of adaptation of muscle fibres under prolonged (240 day) hypokinesia and 15–30 episodes of physical loading of average aerobic power in the posthypokinetic period among 55 sexually mature rats. Under prolonged hypokinesis we primarily observed changes in the intramuscular network and morphometric changes in the blood vessels. These data closely correlate with the progression of changes of the subcellular components responsible for energetic and flexible balance of muscle fibres. We found that fast oxygen-glycolytic muscle fibers and their peripheral nervous apparatus are the most sensitive to prolonged hypokinesia. As a result of application of physical loading of average aerobic power, reparative regeneration is intensified, which substantially shortens the period of recovery of structural-functional properties of skeletal muscles in the conditions of hypokinetic disorders. Thus, in prolonged hypokinesia, changes primarily affect the sources of blood supply to skeletal muscles, with the secondary development of reverse processes in muscle fibers and peripheral nervous apparatus with certain morphometric signs.

Muscular Adaptations and Novel Magnetic Resonance Characterizations of Spinal Cord Injury

The spinal cord is highly complex, consisting of a specialized neural network that comprised both neuronal and non-neuronal cells. Any kind of injury and/or insult to the spinal cord leads to a series of damaging events resulting in motor and/or sensory deficits below the level of injury. As a result, muscle paralysis (or paresis) leading to muscle atrophy or shrinking of the muscle along with changes in muscle fiber type, and contractile properties have been observed. Traditionally, histology had been used as a gold standard to characterize spinal cord injury (SCI)-induced adaptation in spinal cord and skeletal muscle. However, histology measurements is invasive and cannot be used for longitudinal analysis. Therefore, the use of conventional magnetic resonance imaging (MRI) is promoted to be used as an alternative non-invasive method, which allows the repeated measurements over time and secures the safety against radiation by using radiofrequency pulse. Currently, many of pathological changes and adaptations occurring after SCI can be measured by MRI methods, specifically 3-dimensional MRI with the advanced diffusion tensor imaging technique. Both techniques have shown to be sensitive in measuring morphological and structural changes in skeletal muscle and the spinal cord.

Impaired protein metabolism: interlinks between obesity, insulin resistance and inflammation

Metabolic and structural changes in skeletal muscle that accompany obesity are often associated with the development of insulin resistance. The first events in the pathogenesis of this disorder are considered as an accumulation of lipids within skeletal muscle due to blunted muscle capacity to oxidize fatty acids. Fat infiltration is also associated with muscle fibre typology modification, decrease in muscle mass and impairments in muscle strength. Thus, as a result of obesity, mobility and quality of life are affected, and this is in part due to quantitative and qualitative impairments in skeletal muscle. In addition, the insulin resistance related to obesity results not only in defective insulin-stimulated glucose disposal but has also detrimental consequences on protein metabolism at the skeletal muscle level and whole-body level. This review highlights the involvement of fat accumulation and insulin resistance in metabolic disorders occurring in skeletal muscle during the development of obesity, and the impairments in the regulation of protein metabolism and protein turnover in the links between obesity, metabolic inflammation and insulin resistance.

MRI analysis of structural changes in skeletal muscles and surrounding tissues following long-term walking exercise with training equipment

Muscular recovery after exercise is an important topic in sports medicine, and accurate and quantitative measurements of changes in muscle are required to assess muscular recovery. In the present study, we report a new analytical method to measure muscular changes quantitatively. The technique consists of three independent methods: image processing of two-dimensional MR images, morphological analysis using three-dimensional MR images, and diffusion tensor MRI. Using this method, we investigated changes in the quadriceps and biceps femoris and gluteus maximus muscles and surrounding tissues before and after 1 mo of exercise wearing training equipment. The subjects were 21 healthy adult female volunteers, 14 of whom wore training equipment and 7 who wore normal equipment. The percentage of adipose tissue in muscle after exercise in subjects who wore training equipment was on average 4.4% (P < 0.001) lower than that before exercise, and the peak point of the dorsal hip after exercise with use of the equipment was on average 10.8 mm higher than that before exercise. Further, the fractional anisotropy of water diffusion in muscles increased by an average of 0.039 (P < 0.001) after exercise with use of training equipment. In contrast, there was no significant difference before and after exercise in subjects who wore normal equipment. These results show that walking exercise while wearing training equipment thickens and tightens the muscular fiber tissues. This noninvasive measurement approach may allow quantitation of the athletic ability of the muscles, which is not measured conventionally, and is an effective method for analyzing skeletal muscles.

Structural changes in skeletal muscles of Ossabaw miniature swine with metabolic syndrome

Ossabaw swine fed excess kcal and atherogenic diets develop metabolic syndrome (MetS) characterized by obesity, dyslipidemia, hypertension, insulin resistance, and glucose intolerance. The purpose of this study was to test the hypothesis that MetS could have a detrimental effect on skeletal muscle structure and function. Adult Ossabaw swine were fed Control (C), high fructose (F) or high fat/cholesterol/fructose (H) diets for 28 weeks. Biceps femoris and plantaris muscles were analyzed. F swine showed mild MetS, lacking increase in LDL and total cholesterol, both of which were highly up‐regulated in H swine. There were no significant differences in cross sectional areas of muscle fibers of swine on C and F diets. Ossabaw swine fed H diet showed a 20% decrease in size of Type 2B fibers in biceps femoris muscles and a 30% increase in plantaris muscles. Physiological differences between these two muscles might explain these disparate findings. H diet caused increased accumulation of intramyocellular lipid droplets. This finding correlates well with a 5‐fold increase in total plasma cholesterol of H fed Ossabaw swine and suggests a role of dyslipidemia in structural defects in MetS. Support: NIH HL013223 (MS), HL062552 (MS) and IUSM‐Northwest (TK).

Effect of a single dose of ethanol on developing skeletal muscle of chick embryos

Fetal alcohol syndrome is a condition occurring in some children of mothers who have consumed alcohol during pregnancy. Many of these affected children show retarded physical growth in the postnatal period despite adequate nutrition. On the basis of findings from studies with animals, it has been proposed that this is due to allometric retardation of growth of skeletal muscle, although the exact reasons for this are not known. The aim of the current study was to examine the structural changes in skeletal muscle in fetal alcohol syndrome in an attempt to understand the mechanisms of growth retardation in fetal alcohol syndrome. Chick embryos were exposed to single doses of 5%, 10%, and 15% ethanol, and the effects on the general growth and development, as well as on the skeletal muscle, of these chicks were studied. There was a significant retardation in crown rump length, head circumference, and body weight in ethanol-exposed chicks when these parameters were compared with findings for appropriate control groups. This retardation was associated with significant and proportionate reductions in the weights of skeletal muscles. Microscopic examination of skeletal muscle showed areas of neutrophil infiltration and necrosis, suggestive of muscle damage, in chicks exposed to 10% and 15% ethanol. Thus, findings of the current study demonstrate the direct toxic effects of a single dose of ethanol on developing embryos in general and skeletal muscle in particular. The pathologic changes seen in skeletal muscle could account for the failure in postnatal growth in fetal alcohol syndrome.

Structural changes in rat skeletal muscle induced by swimming at high temperatures (28 and 42°C)

Structural changes in rat skeletal muscle induced by swimming to exhaustion were investigated by light and electron microscopy. Male Wistar rats were divided into four groups: a 28°C swimming groups, a 42°C swimming group, and non-swimming control groups at each of these temperatures. The experimental animals were tested in water for 32 min. Immediately after the swimming test, under pentobarbital intravenous anesthesia, the extensor digitorum longus muscle (EDL) and the soleus muscle (SOL) of each animal were removed from the right hindleg. Light microscopy revealed structural changes such as atrophy and focal necrosis in both muscles in animals swimming at 28 and 42°C. In some animals swimming at 42°C, an inflammatory reaction was noted around severely necrotic lesions in the EDL. A few structural changes indicative of mild atrophy were observed in the control animals. Electron microscopy revealed swelling of the sarcoplasm, swelling of the mitochondria, and disorganization or disappearance of myofilaments in various degrees in the atrophic and focal necrotic muscles of the animals swimming at 28 and 42°C. The degree of these structural changes in skeletal muscle fibers was more conspicuous in the animals swimming at 42°C than at 28°C, and more marked in the EDL than in the SOL.

Metabolic and structural changes In skeletal muscle during hypocaloric dieting

Hypocaloric dieting and fasting alter the contraction-relaxation characteristics of skeletal muscle and result in low frequency fatigue. We report the metabolic and structural changes in skeletal muscle in five morbidly obese female subjects who had biopsies of the gastrocnemius muscle on a base-line diet (2500 kcal/day) followed by a repeat biopsy after 2 wk of a 400-kcal/day carbohydrate diet. Hypocaloric dieting resulted in a signficant increase in the intracellular muscle calcium content (p < 0.05), which may account for the observed changes in muscle function. There were no significant changes in muscle glycogen, lactate, pyruvate, or free energy stores. There was a significant decrease in muscle enzymes [phosphofructokinase (p < 0.05), succinate dehydrogenase (p < 0.02)] and some muscle amino acid levels [glutamine (p < 0.025), glycine (p < 0.01), and alanine (p < 0.02)], while muscle histochemistry showed type II fiber atrophy (p < 0.025). However, these changes reflect a generalized response to hypocaloric dieting and probably do not explain the specific functional changes. Change in the muscle calcium content is probably an important mediator of the adverse functional effects of malnutrition.

Changes in myosin light chains in the rat soleus after thyroidectomy

The occurrence of physiological and structural changes in skeletal muscle in hypothyroidism is well-documented...