Influence of the nervous system on transplantation regeneration of skeletal muscle

The gastrocnemius muscles of turtles (Testudo horsfieldi) were completely detached and reimplanted in the same position with the nerve led up to the graft or with denervation. The recovery of contractile activity and innervation of the grafts from the approximated nerve were studied from their beginning 1 month after the operation until their still incomplete state 6 months after the operation. The grafts had a muscular type of structure only if their innervation was restored; otherwise, connective tissue developed in them. Two months after the operation a significant difference was found in the weight of the innervated and denervated grafts. As regards the time for recovery of innervation and of the gravimetric indices, grafts in turtles occupy an intermediate position between those studied previously in rats and frogs.Laboratory of Evolutionary Histology, A. N. Severtsov Institute of Evolutionary Morphology and Ecology of Animals, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 84, No. 10, pp. 474–477, October, 1977.     

Restorative processes in dog muscles after free auto-and homografting

Whole gastrocnemius muscles, denervated 1 month previously by division of the tibial nerve, were autografted and homografted in dogs. The transplanted muscles took at the site of grafting, but some of the transplanted material died and was resorbed; myoblasts were liberated from the viable part of the disintegrating material. As a result of further differentiation of myogenic elements in the autografts the blood supply and innervation were restored in good time and the muscle organ reconstructed. Its contractile activity also was restored. The homografts did not take permanently: The newly formed muscle died because of the incompatibility reaction. Preliminary denervation is thus an effective means of preparing muscle tissue for subsequent autografting.Laboratory of Evolutionary Histology, A. N. Severtsov Institute of Evolutionary Morphology and Ecology of Animals, Academy of Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 11, pp. 1377–1379, November, 1976     

Regeneration in grafts of normal and denervated rat muscles

Summary The soleus or extensor digitorum longus muscles of young rats were freely grafted into the bed of the corresponding contralateral muscle. The grafts were of normal muscle or muscles which had been denervated for 14 days. Grafts of normal muscle were characterized by little or no contractile activity for the first 2–4 days after transplantation. In contrast, denervated grafts contracted weakly, but consistently, throughout this early period. The patterns of contraction were complex. In early transplants, the contractions were due entirely to surviving muscle fibers in the graft, and the contractile characteristics were those of denervated muscle fibers. After the first week, contractions of newly regenerating muscle fibers within the grafts were superimposed upon and later took over those from the fibers that survived the original transplantation. The contraction time approached those of the normal soleus or extensor muscles during the second month after grafting, and the grafts contracted like fast or slow muscles.     

Autografting of previously denervated muscles in rabbits

Whole gastrocnemius muscles of rabbits were grafted after preliminary denervation. At the time of grafting (60 days after denervation) the muscles were in a state of advanced atrophy, accompanied by degenerative changes. The autografts survived at the site of transplantation and underwent structural, changes which led to the progressive development of the muscle tissue preserved in the graft, the spreading out of the tissue, and the formation of definitive muscle fibers supplied with nerve endings. Meanwhile, after a certain time secondary degeneration was observed in the muscle, leading to its replacement by connective tissue. The results confirm the writer's earlier hypothesis that free grafting of previously denervated whole muscles is possible. However, advanced denervation atrophy is evidently reflected in the late results of transplantation.Laboratory of Evolutionary Histology, A. N. Severtsov Institute of Evolutionary Morphology and Ecology of Animals, Academy of Sciences of the USSR, Moscow (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 1, pp. 67–70, January, 1978.     

Changes in electrogenic properties of striated muscle fibers in experimental botulism

Changes in the electrical parameters of fibers of fast and slow muscles were studied during the development of local botulism in rats. In the early stage of poisoning the membrane potential (MP) of fibers of both fast and slow muscles fell. In the late stage of poisoning, marked depolarization of the membrane was accompanied by a change in the input resistance and time constant (RC) of the membrane, rheobase currents, and amplitude of the action potentials evoked by direct intracellular stimulation. Changes in the electrical parameters were more marked in fast muscle fibers.A. A. Bogomolets Department of Pathological Physiology, Saratov Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR N. N. Sirotinin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 84, No. 9, pp. 262–264, September, 1977.     

The response of skeletal muscles to anabolic steroid is individual and does not depend on the motor activity mode

Histochemical methods demonstrated that injection of the anabolic steroid phenobolin and exercise did not modify the content of fast and slow muscle fibers in the slow (m. soleus) and fast (m. plantaris andm. semimembranosus) muscles. Energy metabolism changed only in the fast muscles. After exercise the number of oxidative muscle fibers increased in both fast muscles and after injection of anabolic steroids inm. semimem-branosus. Combined exposure produced an additive effect. The content of glycolytic muscle fibers inm. plantaris increased under the effect of anabolic steroids. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 4, pp. 406–408, April, 1999     

Morphological and histological characteristics of frog skeletal muscle on application of colchicine to the motor nerve

After experimental application of colchicine to the motor nerve of a muscle to disturb fast axoplasmic transport the area of cross section of the muscle fibers was reduced, the number of fibers with low succinate dehydrogenase (SD) activity was increased, and the muscle fibers were more homogeneous as regards their optical density after staining for SD activity. Similar changes also were found after division of the motor nerve. However, denervation was accompanied by blocking of conduction and degenerative disturbances in the nerve endings. In preparations treated with colchicine the conduction of excitation in the nerve and through the synapse continued and miniature end-plate potentials (MEPP), end-plate potentials (EPP), and action potentials (AP) of the muscle fibers were recorded. It is concluded that fast axoplasmic transport supplies the muscle with substances maintaining the differentiated state of its fibers.Department of Histology, Kazan' Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 3, pp. 359–361, March, 1977.     

Dynamics of spinal cord changes produced by prenatal asphyxia

Changes in neurons and nerve fibers of the spinal cord at the level C4–C5 were studied in rats exposed to asphyxiain utero and killed at different times. In the first 10 days the changes in the nerve cells progressed gradually. By the age of 1–2 months the state of most neurons is back to normal, but in each hundred fields of vision pathologically changed neurons are found, mainly in zones of the collateral circulation. Changes also are observed in the nerve fibers.Laboratory for the Study of Brain Development, Scientific-Research Institute of Pediatrics, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR M. Ya. Studenikin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 3, pp. 361–364, March, 1977.     

Myelination of regenerated optic fibers in peripheral nerve graft of adult cats

Retinal ganglion cells of adult cats have the potential to regenerate their axons into autografted peripheral nerve. Two months after transplantation of the sciatic nerve to the axotomized optic stump, regenerated axons were labeled anterogradely with biocytin, and myelin formation by Schwann cells was examined electron microscopically. Both myelinated and unmyelinated fibers were labeled with biocytin. Among 511 axons labeled in three grafts, 96 fibers (18.8%) were myelinated and 415 (81.2%) were unmyelinated. Mean diameter with SD of myelinated fibers was 1.28 ± 0.39 m (range 0.71–2.47) and that of unmyelinated fibers was 0.76± 0.38 m (range 0.18–2.46). The ratio of inner to outer diameters of the myelin sheath (g value) was 0.82, which is close to the value (0.8) for the optic fibers of intact adult cats.     

Catabolic effect of anabolic steroid in skeletal muscle under conditions of impaired neurotrophic regulation

Effect of anabolic steroid nandrolone (Phenobolin) on fast (plantar) and slow (soleus) skeletal muscles was studied in guinea pigs with impaired neurotrophic regulation (denervation, axonal transport blockade) or after tenotomy. Immunohistochemical analysis with monoclonal antibodies to fast myosin heavy chains showed that injection of anabolic steroid did not modify the relative content of fast and slow muscle fibers in the studied muscles under all experimental conditions. Injection of anabolic steroid did not modify the weight of the studied muscles and did not prevent its drop after denervation or tenotomy. Axonal transport blockade by colchicine application on the nerve induced the appearance of fast muscle fibers in the slow soleus muscle and an increase in its weight; in the slow muscle, nandrolone did not prevent the induction of fast myosin synthesis. Under conditions of axonal transport blockade, the agent exerted a catabolic effect and considerably reduced the muscle weight. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol.127, No. 5, pp. 569–572, May, 1999     

Capillary density of tenotomized skeletal muscles

Summary Alterations in the capillary density of the M. biceps brachii was studied in 20 cases during 2 months after spontaneous rupture of the tendon. The fiber typing was done using succinic dehydrogenase and myofibrillar ATP-ase at pH 9.4 for the staining, the capillaries were visualized with alkaline phosphatase and PAS reactions, and in each case 1,000 muscle fibers with their capillaries were estimated.In the intact muscles the capillary count ranged from 1,500 to 1,910 (mean 1,740) per 1,000 fibers. During the 1st month following the rupture the decrease in the capillary count of the muscle occurred rapidly, being after 4–7, 8–10, and 18–29 days 36%, 52%, and 66%, respectively, as compared to the contralateral muscles.After 2 months a decrease of approx. 70% was found in the amount of capillaries compared with the contralateral muscles. The obliteration of the capillaries was particularly pronounced in the amount of anastomoses. These results indicate that the capillary supply of the human M. biceps brachii decreases enormously during the 1st month after a tenotomy.Supported by a grant from the Ministry of Health of Hungary and the National Institute of Traumatology at Budapest     

Comparative analysis of plastic activity of muscle and nerve tissues after trauma and transplantation of minced muscle

Repair processes in the body muscle ofVaricorhinus capoëta sevangi were studied after removal of part of three muscle segments and after autografting the resulting defect with minced muscle. As a result of trauma a focus of injury developed in the muscle, including the defect and the surrounding zone of degeneration. The inflammatory reaction, resorption of the necrotic masses, and regeneration of the muscle and nerve tissue continued for a long time. The formation of myogenic components did not begin until the 3rd week and single regenerating nerve fibers appeared in the region of injury after 2 months. Filling the defect with minced muscle accelerated regeneration. The transplanted fragments of muscle fibers not only participated themselves in the repair process but also stimulated the plastic activity of the muscle and nerve tissues of the graft bed.Laboratory of Evolutionary Histology, A. N. Severtsov Institute of Evolutionary Morphology and Ecology of Animals, Academy of Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 3, pp. 373–376, March, 1978.     

Critical period in muscle spindle regeneration in grafts of developing rat muscles

Extensor digitorum longus (EDL) muscles from rats at various intervals after birth were grafted into EDL muscles of adult recipients. Three to twelve months after the operation, host muscles containing the grafts were removed and examined for the presence of muscle spindles in the graft. The aim of the study was to establish when muscle spindles become capable of regeneration during development. Regenerated muscles grafted during the first week after birth were virtually spindleless. Grafts of muscles transplanted 10 and 15 days postnatally contained only 5–8 muscle spindles on average. In contrast, the regenerated grafts originating from muscles of 24- and 28-day-old rats were spindle-rich as in mature muscle grafts; the number of spindles in the transplanted EDL muscles (25.0±2.3; mean ±SE) attained values comparable to free standard autografts of these muscles in adult animals. Thus, the critical period after grafting, which also involves the loss of a vascular supply, is considerably longer than the critical period for muscle-spindle survival after nerve injury. Fifteen days after birth, when muscle spindles still survive denervation, only a few regenerated spindles were present in the individual muscle regenerates. We assume that the low resistance of immature spindle capsules to ischaemia accounts for their massive degeneration and abortive spindle regeneration in grafts from 10- to 15-day-old rats.     

Expression of the Proto-oncogene c-myc in Human Stenotic Aortocoronary Bypass Grafts

Proliferation and differentiation of vascular smooth muscle cells (VSMC) are central events in vascular pathobiology and play a major role in the development of stenotic and restenotic lesions [15, 27]. The proto-oncogene c-myc and other early cell cycle-regulating genes have been implicated in the induction of cell proliferation and differentiation under diverse pathophysiological conditions [11, 13]. In the present study we analyzed c-myc mRNAexpression by indirect nonradioactive in situ hybridization technique (NISH) in human stenotic venous bypass grafts (n = 32) retrieved during re-do operations of coronary artery disease and compared the results with 28 native veins (vena saphena magna) from the same patients.Stenotic bypass grafts showed enhanced c-myc expression located predominantly in VSMCin the media and neointima (severity score: ++–+++, 32/32 stenotic veins). In native veins we observed only low levels of – c-myc mRNA(severity score: +, 28/28 native veins), all signals were restricted to endothelial cells of either the innermost intimal layer or of the vasa vasorum.Our in situ hybridization studies demonstrate enhanced mRNAexpression of the proto-oncogene c-myc in stenotic venous bypass grafts. These results suggest that – in analogy to other pathophysiological conditions – c-myc exerts essential regulatory functions in cellular events operative during the initiation and progression of venous bypass graft disease.     

Electron-microscopic investigation of satellite cell formation in skeletal muscle during physical exertion

The content of condensed chromatin is increased in nuclei of skeletal muscle fibers of rats after repeated physical exertion continued until exhaustion. Some muscle fiber nuclei, together with part of the sarcoplasm, were separated from the muscle fibers. Satellite cells formed from the separated parts of the muscle fibers.Laboratory of Functional Morphology, All-Union Scientific-Research Institute of Physical Culture, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Kupriyanov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 11, pp. 1385–1388, November, 1976.     

Effect of the helium-neon laser beam on postradiation repair in skeletal muscle tissues

Three series of experiments were carried out on the rat gastrocnemius muscle. Whole muscles were autografted in series I. Both hind limbs of the animals were irradiated in a dose of 1000 R before autografting of the muscles in series II. In series III x-ray irradiation in the same dose was followed by exposure of the hind limbs for 10 days to the action of a helium-neon laser, after which the muscles were autografted. The process of transplantation regeneration was investigated histologically 2 weeks and 1 and 2 months later. Exposure to the laser beam was shown to stimulate repair in skeletal muscle tissues and to normalize the process of posttraumatic regeneration when depressed by x-rays.Laboratory of Evolutionary Histology, A. N. Severtsev Institute of Evolutionary Morphology and Ecology of Animals, Academy of Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 2, pp. 222–224, February, 1980.     

Neutrophic interaction between spinal ganglia and various tissues

Spinal ganglia L5–L6, together with the mesentery of the large intestine (innervated from these ganglia) and the epithelium of the tongue, were transplanted into the anterior chamber of the eye in cats. After 2 months survival of some of the sensory neurons and intensive regeneration of their nerve fibers were observed. Meanwhile the tissue of the mesentery together with its mechanoreceptors (Pacinian corpuscles) remained intact. The epithelium of the tongue was destroyed. The trophic influence of these particular sensory ganglia on the corresponding tissue ensured the structural integrity of that tissue and of its receptor apparatus. The need for metabolic conformity between the sensory ganglia and the tissue innervated by them is revealed.Laboratory of General Physiology of Reception, I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. (Presented by Academician V. N. Chernigovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 3, pp. 355–359, March, 1977.     

Development of the graft versus host reaction and its effect on pregnancy in mice after heparin administration

The effect of heparin on the graft versus host reaction (GVHR) was studied in mice and the character of development of pregnancy in females surviving after the GVHR was noted. Preliminary injection of heparin into the recipients prevented their death from the GVHR or lengthened their life span. After injection of heparin into the donors or its addition to the transplanted cells, the GVHR was intensified. In mice surviving after the GVHR as a result of heparin administration, in 60–100% of cases abortion or intrauterine death of the fetus was observed during pregnancy (3–6 months after transplantation of the cells). When these females were again mated pathological pregnancies were observed less frequently, but some of the prog eny developed runt disease. No such disturbances of pregnancy were observed in mice receiving heparin alone or surviving after transplantation of lymphocytes alone. Pregnancy enhanced the GVHR induced previously in females after injection of heparin.Department of Microbiology, Smolensk Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. M. Zhdanov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 3, pp. 312–315, March, 1977.     

Muscle fibre loss and reinnervation after long-term denervation

Summary Cutaneus pectoris muscles of frog (Rana temporaria) were investigated 19.5–40 months after denervation. On whole mounts a heavy reduction in size and number of muscle fibres is noticed; in two muscles studied with semithin and ultrathin sections the number of remaining muscle fibres is 149 and around 120, while one of the contralateral muscles contains 250 and control muscles of equal sized frogs between 220 and 320 (n=18) fibres. By electron microscopy muscle fibres undergoing degeneration or phagocytosis can be seen (3 of 20 muscle fibres present in a single ultrathin cross-section). On the other hand several profiles contained within one common basal lamina sheath are present in 14 of 20 fibres, indicating satellite cell proliferation. In one preparation 40 months after denervation not a single muscle fibre or axon is present, suggesting that eventually, without nerve supply, muscle fibres entirely disappear.Upon spontaneous reinnervation or implantation of the hypoglossal nerve 16 months after denervation, synapses are formed with the remaining muscle fibres. When studied 3.5–24 months after nerve implantation muscles innervated by few axons only (< 10, 10–20 axons) contain a low number of muscle fibres (mean 44 ± 41sd,n=6), while all muscles with a larger number of axons have more than 150 muscle fibres (n=6). This indicates that unless large numbers of axons regenerate and/or when reinnervation is delayed muscle fibre loss continues to occur. The presence in one muscle of motor axons but only six muscle fibres 24 months after nerve implantation indicates that muscle fibre loss cannot be reversed, or recovery is extremely slow. This observation is interpreted as evidence for the exhaustibility of the satellite cell pool.     

Resting membrane potentials and miniature postsynaptic potentials of frog intrafusal muscle fibers

By recording intracellular potentials the electrophysiological characteristics of the intrafusal muscle fibers of the frog muscle spindle were investigated. Analysis of the distribution of amplitudes of the miniature postsynaptic potentials indicates heterogeneity of the intrafusal muscle fibers. It is concluded that the frog muscle spindle contains three types of muscle fibers: those with single innervation, and those combining the two types of innervation.Laboratory of Neuromuscular Physiology, Physiological Institute, Leningrad University. (Presented by Academician V. N. Chernigovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 2, pp. 136–139, February, 1977.