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Results for “Muscle Denervation”

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PubMed2001

Magnetic resonance imaging of denervation-induced muscle atrophy: effects of clenbuterol in the rat.

We show that magnetic resonance imaging (MRI) can be used to quantify the amount of muscle in the lower legs of adult rats and to noninvasively monitor the onset and progression of denervation-induced atrophy. Muscle cross-sectional areas determined from 2D gradient-echo MR images allow longitudinal quantification of the protective effects of a beta(2)-adrenergic agonist clenbuterol. We also show that the estimation of clenbuterol's efficacy is improved by computation of the muscle volume. Rapid animal throughput and the ability to accurately estimate efficacy make MRI an attractive technology for studying skeletal muscle atrophy and hypertrophy, allowing the evaluation of potential therapies in longitudinal studies.

Animals↗
PubMed1986

[Effect of trivalent iron on denervated skeletal muscles].

The activity of succinic dehydrogenase, myosin ATPase, as well as lactic dehydrogenase (LDG) spectrum and cross-section area of different type of muscle fibers have been studied for 3 weeks after denervation (control) and after denervation and intraperitoneal injection of 10(-6) M FeCl3. Intraperitoneal injection of FeCl3 prevented the development of denervation phenomena (increase in cross-section area of muscle fibers, changes in LDG spectrum).

Adenosine Triphosphatases↗
PubMed1987

Fiber types in normal and neonatally denervated fast muscles of the rat: immunocytochemical study with an antimyosin monoclonal antibody.

The differentiation of fiber types in normal and neonatally denervated gastrocnemius muscles of the rat was compared by myosin ATPase histochemistry and immunocytochemistry using a monoclonal antibody, HM-1.2. The specificity of HM-1.2 for the fast myosin heavy chain was determined by radioimmunoassay, immunoautoradiography, and indirect immunofluorescence techniques. In normal 1-month-old and adult rats, the type IIB (fast glycolytic) fibers of the gastrocnemius could be clearly divided into three subtypes by their graded immunofluorescence staining with the myosin heavy chain-specific monoclonal antibody. In the gastrocnemius muscle of the newborn rat, all fibers were negative with the monoclonal antibody. The transition from negative to three grades of immunoreactivity occurred 1 to 2 weeks postnatally. After neonatal denervation of the gastrocnemius muscle, however, uniformly positive monoclonal antibody immunofluorescence staining for the myosin heavy chain was observed without subtype differentiation. This study, thus, gave clear immunocytochemical evidence that the type IIB muscle fibers are heterogeneous with respect to their myosin isoform and that the expression of this heterogeneity is dependent on the normal developmental influence of motor innervation on the muscle fibers.

Adenosine Triphosphatases↗
PubMed1985

Rapid changes in levels of individual molecular forms of acetylcholinesterase after denervation of mouse sternocleidomastoid muscle.

Experimental denervation of adult mouse sternocleidomastoid muscle results in a decrease in total AChE. The most rapid change essentially affects the tailed, asymmetric 16 S AChE, since one day after nerve section, "16S" AChE is already significantly decreased to about 70% of its control value. We found that both background and junctional "16S" AChE are affected by this rapid decrease. Later, a sharp fall in "10S" and "4S" AChE occurs about seven days after denervation when muscle atrophy develops with loss of weight and proteins. A gaussian analysis of the sedimentation profiles of AChE extracted from denervated muscle shows that there is not only an early rapid decrease in 16 S AChE but also a decrease in the monomeric 3.3S AChE. This result suggests that there is a very rapid turn-over of two molecular forms of AChE, the supposedly monomeric precursor and the complex asymmetric 16S AChE.

Acetylcholinesterase↗
PubMed1986

[Functional electrostimulation of the denervated posticus muscle in an animal experiment: histo- and biochemical results].

Histochemical and biochemical investigations have been carried out in 2 sheep following unilateral recurrent laryngeal nerve paralysis and direct electrical stimulation of the denervated posticus muscles. The stimulation effect was determined histochemically (standard ATP-ase staining) and compared with the fibre pattern of normal posticus muscles. In addition, one-dimensional gel electrophoresis of myosin heavy-chain isoforms was carried out and correlated with the histochemical results. A dramatic increase of type I fibres could be seen after long-term low-frequency direct electrical stimulation of denervated posticus muscles of the sheep. Biochemically the amount of slow myosin heavy-chain isoforms was higher than in normal muscles.

Animals↗
PubMed1984

[Innervation of the rat urinary bladder. II. Effects of prostaglandins on the denervated detrusor muscle after bilateral pelvic ganglionectomy].

The effects of prostaglandin (PG) F2 alpha and E2 on the denervated smooth muscle of the urinary bladder in female rats were studied in vivo by histochemistry and electron microscopy. The urinary bladder denervated by bilateral removal of the pelvic ganglion was markedly distended, being filled with urine. Daily intravenous administration of PGF2 alpha or PGE2 for 6 days following the operation showed that rats receiving PGE2 urinated remarkably more than those receiving PGF2 alpha. But the ultrastructural changes on the smooth muscle cells, such as dilated tubules of rough endoplasmic reticulum and large Golgi vacuoles, were more prominent in the PGF2 alpha administrated urinary bladders than in PGE2 administrated ones. On occasion, cholinergic ganglion cells happened to be encountered in the muscular layer of a rat urinary bladder. These intramural ganglion cells and the cholinergic nerve fibers surrounding the cells displayed strong acetylcholinesterase activity, unaffected by bilateral pelvic ganglionectomy.

Animals↗
PubMed2005

The immunophilin ligand FK506, but not the P38 kinase inhibitor SB203580, improves function of adult rat muscle reinnervated from transplants of embryonic neurons.

Injury to the adult CNS often involves death of motoneurons, resulting in the paralysis and progressive atrophy of muscle. There is no effective therapy to replace motoneurons in the CNS. Our strategy to replace neurons and to rescue denervated muscles is to transplant dissociated embryonic day 14-15 (E14-15) ventral spinal cord cells into the distal stump of a peripheral nerve near the denervated muscles. Here, we test whether long-term delivery of two pharmacological inhibitors to denervated muscle, FK506 or SB203580, enhances reinnervation of muscle from embryonic cells transplanted in the tibial nerve of adult Fischer rats. FK506, SB203580 (2.5 mg/kg) or saline was delivered under the fascia of the medial gastrocnemius muscle for 4 weeks, beginning when muscles were denervated by section of the sciatic nerve. After 1 week of nerve degeneration, one million E14-15 ventral spinal cord cells were transplanted into the distal tibial nerve stump of each rat in the three treatment groups. Ten weeks later, all cell transplants had neuron-specific nuclear protein (NeuN) positive neurons. Neuron survival and axon regeneration were similar across treatments. An average (+/-S.E.) of 210+/-66, 100+/-36 and 176+/-58 myelinated axons grew distally from the cell transplants of rats with muscles treated with FK506, SB203580 or saline, respectively. Regenerating axons in muscles of all three treatments groups were detected with antibodies against phosphorylated neurofilaments and synaptophysin, and motor end plates were labeled with alpha-bungarotoxin. Muscles of rats that received transplants of media only had no axon growth, indicating that the muscles were denervated. The mean muscle fiber areas of rats that received cell transplants and had long-term delivery of FK506, SB203580 or saline to muscles were significantly larger than those of denervated muscle fibers. Thus, cell transplantation reduced muscle atrophy. Transplantation of embryonic cells also resulted in functional muscle reinnervation. Electromyographic activity and force were evoked from >90% of the muscles of rats with cell transplants, but not from denervated muscles. FK506-treated muscles were significantly more fatigue resistant than naive control muscles. FK506-treated muscles also had significantly stronger motor units than those in SB203580 or saline-treated muscles. These data suggest that a pathway regulated by FK506 improves the function of muscles reinnervated by embryonic neurons placed in peripheral nerve.

Animals↗
PubMed1978

Cell proliferation in skeletal muscle following denervation or tenotomy. A series of autoradiographic studies.

Autoradiographic experiments using 3H-thymidine were designed to analyse cell proliferation which occurs in skeletal muscle after denervation and after tenotomy. In mouse tibialis anterior and tongue muscles during the first 24 h after denervation or tenotomy labelling levels were low and did not differ significantly from sham operated control muscles. By 48 h after denervation and tenotomy of tibialis anterior muscles, increased levels of labelling occurred in both muscle and connective tissue nuclei. Daily pulse labelling for 7 days after denervation produced a labelling level which was 8 times that of sham operated controls, 25--30% of the total nuclear population being labelled. Denervated muscles had twice the level of labelling compared to tenotomised muscles. These results provide conclusive evidence that both denervation and tenotomy stimulate cell proliferation in skeletal muscle and it is suggested that the increased numbers of labelled muscle nuclei are likely to be the result of mitotic activity in muscle satellite cells.

Animals↗
PubMed1980

Protease inhibitors reduce effects of denervation on muscle end-plate acetylcholinesterase.

The effects of certain protease inhibitors on end-plate acetylcholinesterase (AChE) activity, as well as on wet weight and total protein, were studied in vivo in intact and denervated anterior gracilis muscles from the rat. A combination of leupeptin, pepstatin, and aprotinin, administered intraarterially, partly prevented the early (24 h) denervation-induced decrease in muscle weight and protein content. In turn, leupeptin and aprotinin, either alone or in combination, markedly reduced the decay of AChE activity in the denervated muscles, whereas pepstatin alone was ineffective. Such effects were additive in that the inhibitors in combination were more effective than when they were used separately. Additional experiments indicated that none of the inhibitors, at the concentrations used, affected AChE activity directly, nor did they have a significant effect during processing of the muscle samples. These findings indicate that the initial decay of AChE activity with denervation was effectively reduced by the inhibitors, probably through inactivation of proteolytic enzymes which, otherwise, would be increase in denervated muscle.

Acetylcholinesterase↗
PubMed1981

Changes in lipid levels of three skeletal muscles following denervation.

Nonpolar and polar lipids extracted from denervated rat gastrocnemius, plantaris, and soleus muscles were measured 7-9 days after unilateral sciatic nerve transection. The contralateral muscle (CCON) was used to obtain control lipid levels. After denervation changes in lipid concentrations were found in all three muscles. These alterations in lipid levels were generally in same direction but not to the same extent. The change in total nonpolar lipids (NL) was an increase in soleus greater than gastrocnemius greater than plantaris concentration. This change in lipid concentration was more apparent than real since the wet weight of muscle was decreased after denervation. Since polar lipid (PL) concentrations were not increased under these conditions of muscle weight loss, an actual decrease of polar lipids after denervation may be inferred. In contrast to the other two muscles, a marked difference was noted for polar lipids of denervated gastrocnemius muscle. An unidentified spot near the origin was detected. This area is the location of a nerve sprouting factor(s). The compound(s) was not detectable for the other two muscles. When the gastrocnemius from an unoperated animal rather than a CCON muscle was used as a benchmark, slight increases were found for total nonpolar, polar, and plasmalogen fractions following denervation. The changes for individual lipid fractions were less definable, except for the significant increase for the unknown polar compound near the origin. This spot was noted in extracts from CCON and DEN muscles but not in untouched control muscle. The CCON gastrocnemius muscle is therefore a poor control for determining effects of denervation on lipid levels and perhaps other biochemical parameters as well.

Animals↗
PubMed1989

Influence of overload on recovery of rat plantaris from partial denervation.

A functional index of neural adaptability is the capacity of motoneurons to extend and establish supernumerary connections with neighboring denervated muscle fibers. The purpose of this study was to guage this response in rat plantaris muscles subjected to increased levels of activity resulting from the surgical removal of the synergistic gastrocnemius and soleus muscles. Thirty-seven days of overload increased plantaris absolute (69%) and relative (82%) weight, whole muscle (35%) and individual fiber (37%) mean cross-sectional area, half-relaxation time (1/2RT; 25%), and maximum tetanic tension (P0; 21%). In a separate group of animals that had undergone 30 days of overload, three-quarters of the plantaris muscle fibers were denervated by sectioning radicular nerve L4. At 7 days postlesion, contractile responses were obtained from sprouting motor units remaining in radicular nerve L5, and the results compared to a nonoverloaded group that had undergone this same procedure. Twitch time to peak tension and 1/2RT were prolonged in normal partially denervated (PD) and overloaded partially denervated (OPD) muscles, and this response was significantly greater in the overloaded muscles. Both PD and OPD muscles increased twitch tension (38%) and peak tension developed at 25 Hz (34%) to a similar extent, during recovery from partial denervation. These increases, attributable to sprouting of L5 motor axon collaterals, were matched in PD muscles with a corresponding increase in P0, a response which did not occur in OPD muscles. Additionally, a more extensive decrease in P0 occurred as a result of partial denervation in OPD muscles compared with whole muscle P0 of nondenervated muscle (L4 plus L5 stimulation).(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1986

Expression of several adhesive macromolecules (N-CAM, L1, J1, NILE, uvomorulin, laminin, fibronectin, and a heparan sulfate proteoglycan) in embryonic, adult, and denervated adult skeletal muscle.

Levels of the neural cell adhesion molecule N-CAM in muscle are regulated in parallel with the susceptibility of muscle to innervation: N-CAM is abundant on the surface of early embryonic myotubes, declines in level as development proceeds, reappears when adult muscles are denervated or paralyzed, and is lost after reinnervation (Covault, J., and J. R. Sanes, 1985, Proc. Natl. Acad. Sci. USA, 82:4544-4548). Here we used immunocytochemical methods to compare this pattern of expression with those of several other molecules known to be involved in cellular adhesion. Laminin, fibronectin, and a basal lamina-associated heparan sulfate proteoglycan accumulate on embryonic myotubes after synapse formation, and their levels change little after denervation. L1, J1, nerve growth factor-inducible large external protein, uvomorulin, and a carbohydrate epitope (L2/HNK-1) shared by several adhesion molecules are undetectable on the surface of embryonic, perinatal, adult, or denervated adult muscle fibers. Thus, of the molecules tested, only N-CAM appears on the surface of muscle cells in parallel with the ability of the muscle cell surface to accept synapses. However, four antigens--N-CAM, J1, fibronectin, and a heparan sulfate proteoglycan--accumulate in interstitial spaces near denervated synaptic sites; regenerating axons traverse these spaces as they preferentially reinnervate original synaptic sites. Of particular interest is J1, antibodies to which block adhesion of central neurons to astrocytes (Kruse, J., G. Keihauer, A. Faissner, R. Timpl, and M. Schachner, 1985, Nature (Lond.), 316:146-148). J1 is associated with collagen and other fibrils in muscle and thus may be an extracellular matrix molecule employed in both the central and peripheral nervous systems.

Animals↗