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PubMed1998

Immunolocalization of leukemia inhibitory factor in normal and denervated human muscle.

The cytokine leukemia inhibitory factor (LIF) stimulates myoblast proliferation in vitro and vivo and is neurotrophic for motor neurons. In experimentally reinnervated muscle, exogenous LIF application increases muscle mass through myofiber hypertrophy. The goal of this study was to evaluate possible sources of endogenous LIF in human muscle, and whether LIF immunoreactivity (-IR) was detectable in specific myofiber types and/or re-expressed in human denervated muscle. Our study shows that LIF-IR is constitutively detectable in type I myofibers of normal human muscle. In acute and chronically denervated and reinnervated human muscle, LIF-IR is found in all type I myofibers and in addition in some atrophic and almost all angulated atrophic type II myofibers.

Adult↗
PubMed1975

Development of supersensitivity in denervated slow muscle of the frog. Its dependence on the nerve stump length.

Sensitivity to carbachol has been studied in paired normal and denervated gastrocnemius slow muscle fibers of the frog. Dose response curves showed that after 25 days the ED50 was ten times less in denervated muscle than in the normal. The denervated muscle showed a three-fold increase in affinity constant to d-tubocurarine. In studying the development of supersensitivity of paired muscles denervated near or far from the neuromuscular junction it was found that muscles with a long axon stump started to increase sensitivity three days later than muscles with a short stump. We suggested that in slow muscle fibers, denervation supersensitivity is not only due to a spread in cholinergic receptor area but also to a change in the receptor properties. As the onset of the supersensitivity depends on the length of the nerve stump, it is also suggested that it is regulated by presynaptic factors which would be transported along the axon at a rate of a few centimeters per day.

Amputation Stumps↗
PubMed1961

Effects of drugs on partially and completely denervated skeletal muscle of the frog.

The sensitivity of completely denervated and the innervated end-plate regions of partially denervated frog's sartorius muscles to stimulation by drugs has been investigated. The drugs were tested on muscles isolated 12 to 39 days following denervation. On the basis of the results obtained most of the drugs could be put into one of two main groups. The first group included choline, tetramethylammonium, carbachol and decamethonium; these drugs readily stimulated non-denervated muscles, and chronic denervation, either partial or complete, greatly increased the sensitivity of the muscles. The second group included pilocarpine and carbamate of (2-hydroxypropyl) trimethyl ammonium chloride (Bethanechol, U.S.P.). The muscles were relatively insensitive to stimulation by these two drugs. They could stimulate the muscles if applied in high enough concentrations, but the responses thus obtained could not be distinguished from responses produced by similar concentrations of sucrose and chronic denervation did not increase the sensitivity of the muscles to stimulation by these two drugs. Methacholine, like the drugs in the second group, was unable to stimulate the muscles in low concentrations, but chronic denervation rendered the muscles sensitive to stimulation by this drug. Tetraethylammonium presented a completely different pattern of activity which was consistent with a hypothesis that in low doses this drug stimulates skeletal muscle by causing a release of acetylcholine from nerve endings in the muscle.

Acetylcholine↗
PubMed1996

Tenascin in denervated human muscle.

Tenascin is a large oligomeric glycoprotein of the extracellular matrix. Its location is innervated muscle tissues. We investigated immunohistologically, using two monoclonal antibodies (mah) against Tenascin, biopsied denervated human muscle of children and adults. Tenascin was present in the interstitial space among denervated muscle fibres. Accumulation of Tenascin in denervated adult muscle tissue was frequent, accumulation in denervated muscle tissue of children was sparse and weak. The two antibodies reacted correspondingly. Tenascin was not only found in the vicinity of atrophic muscle fibres, but also close to normally sized fibres, suggesting an early stage of denervation even before reduction of muscle fibre volume.

Adult↗
PubMed1989

Increase in the amount of adenylate cyclase in rat gastrocnemius muscle after denervation.

After section of the sciatic nerve, the basal adenylate cyclase (AC) activity in rat gastrocnemius muscle increased 6-7 times per membrane protein and about 2 times per whole muscle in the following 30 or 40 days. The AC activity in the muscle 30 days after denervation was increased about 4 times by forskolin. Calcitonin gene-related peptide (CGRP) also increased the adenylate cyclase activity in the denervated muscle. The binding of [3H]-forskolin (10nM) to cells isolated from gastrocnemius muscle was examined to determine the amount of AC molecules. Inhibition of [3H]-forskolin binding by increasing amounts of unlabeled forskolin gave a sigmoid curve with a IC50 value of 3 x 10(-7) M. Results showed that the number of [3H]-forskolin binding sites per cell was higher on the denervated side than on the control side, like the basal AC activity. The IC50 values for inhibition by unlabeled forskolin of binding of [3H]-forskolin were similar to muscles on the control and denervated sides. These results suggest that an increase in the AC activity induced by denervation was due to an increase in the numbers of AC molecules in the muscle.

Adenylyl Cyclases↗
PubMed1996

Remodeling of the cytoskeletal lattice in denervated skeletal muscle.

The effect of denervation-induced atrophy on the cytoskeletal lattice in rat fast- and slow-twitch skeletal muscle has been investigated. Immunochemical analyses and immunofluorescence microscopy experiments employing monospecific antibodies to dystrophin, desmin, and alpha-tubulin were carried out on intact and denervated muscles. The relative cellular content of dystrophin and desmin were reduced in the soleus muscle (slow-twitch), while significant increases were shown in the gastrocnemius muscle (fast-twitch). In both muscles, alpha-tubulin levels increased up to 12-fold as a function of time compared to control values. Immunofluorescence microscopy revealed a distinct rearrangement of the microtubule network toward a predominantly longitudinal alignment, which was accompanied by an increase in the density of the fluorescence. It is concluded that the relative increase of the three structural proteins in the fast-twitch gastrocnemius muscle may be related to the apparent resistance of this muscle type to denervation-induced atrophy. The increased alpha-tubulin content in denervated slow- and fast-twitch muscles could be indicative of an adaptive mechanism designed to maintain the integrity of the muscle fiber in view of eventual regenerative activities.

Animals↗
PubMed2001

Range of motion physiotherapy reduces the force deficit in antagonists to denervated rat muscles.

BACKGROUND: We used a rat hindlimb model of tibial nerve transection to determine if a loss of mechanical function exists in innervated antagonists compared with denervated muscles. We tested two hypotheses: (1) denervation of the rat ankle plantar flexors results in decreased force production of the ankle dorsiflexors, and (2) daily passive ankle range of motion (ROM) physiotherapy prevents or reduces the force deficit. METHODS: Adult Lewis rats were assigned to one of three groups: (1) a sham (S) group, in which the tibial nerve was exposed but not transected; (2) a no rehabilitation (NR) group, in which a 2-cm segment of tibial nerve was excised at midthigh to denervate the ankle plantar flexors; or (3) a rehabilitation (R) group, in which a 2-cm segment of tibial nerve was excised and the animals were subjected to ankle passive ROM physiotherapy for two 5-min sessions each day. After 14 days, maximum isometric tetanic force (F(0)) and specific force (sF(0)) were measured in the extensor digitorum longus (EDL) muscle, an ankle dorsiflexor. RESULTS: Compared with those from animals in the S group, EDL muscles from animals in the NR group demonstrated a 22% decrease in both F(0) and sF(0). In the EDL from animals in the R group, daily passive ROM physiotherapy diminished the deficit in F(0) but not in sF(0). CONCLUSIONS: These data support the hypotheses that nerve injuries result in impaired mechanical function in the innervated antagonists to denervated muscles and that passive ROM physiotherapy can improve force production in these muscles.

Animals↗
PubMed1989

Changes in leaching properties of chick skeletal muscles on denervation.

The leaching of electrolytes in normal and denervated chick gastrocnemius muscle has been studied by recording electroconductivity changes in donor-solvent (muscle-water) system at 11 intervals leading to a total immersion of 5 hr 15 min, at days 1,5,10,21 and 28, post-hatching. The results show age related changes in the permeability properties of normal muscle membrane system. The loss of neural control induces a blocking of electrolytes 10 days post-denervation. The possible nature of blocking mechanism has been related to the non-availability of neuro-trophic factors in the tissue.

Animals↗
PubMed1991

Why the denervated gastrocnemius muscle flap should be encouraged.

The superiorly based, denervated gastrocnemius muscle flap is able to perform an aesthetically excellent and functionally good cover for defects of the upper one-third of the calf, including the knee, and the lower one-third of the thigh. A consecutive series of 41 muscle and musculocutaneous gastrocnemius flaps was analyzed. Thirty-six patients (88% of the patients who underwent surgery) could be reexamined. The mean follow-up time was 36 months, with a minimum time of 12 months. At the time of examination, all skin defects as well as the incidental concomitant osteomyelitis had completely healed; however, 40% of the patients have required secondary operations. One-half of the patients have a functional deficiency, and 20% showed areas with loss of sensation. After surgery with musculocutaneous flaps, all patients complained about the sensory loss of the saphenous nerve, and peripheral edema was seen more often than after surgery with a simple muscle flap. Muscle flaps with residual innervation showed more secondary wound breakdown and more contraction pain, due to spasms. The best results concerning function and aesthetics are achieved with denervated muscle flaps covered by a split-thickness skin graft. In this variation, the flap showed good and stable coverage without bulk, as well as minimal donor-site deformity; therefore, primary denervation must be considered. The anatomy of the motor nerves to the gastrocnemius muscle is shown.

Adolescent↗
PubMed1988

[The electrical and contractile activity of denervated smooth muscle].

The effect of norepinephrine, histamine, serotonin and potassium chloride on electrogenesis and contraction was studied on innervated and denervated smooth muscles of cat's nictitating membrane. Denervated smooth muscles generate slow depolarizing potentials with the APs corresponding to tonic and phasic contractions, resp. Tonic contractions occur with no considerable change fo the MP in innervated muscles, phasic contractions being absent. Spontaneous generation of the APs is only possible in denervated muscles. Pharmacomechanical type of coupling between excitation and contraction seems to be characteristic of innervated smooth muscles, whereas electromechanical type is characteristic of denervated muscles. The denervation seems to result not only in the change of cells' sensitivity to transmitters but in the abnormality of coupling processes between excitation and contraction as well.

Animals↗
PubMed2005

Monitoring muscle growth and tissue changes induced by electrical stimulation of denervated degenerated muscles with CT and stereolithographic 3D modeling.

In the frame of the EU-funded RISE project, patients with lower motor neuron lesion and denervated and degenerated muscles are treated with electrical stimulation, with the aim of restoring muscle mass and force. Spiral computer tomography from the hip joint down to the knee joint is used to gather three-dimensional data on the upper leg tissue. These data are analyzed in order to monitor tissue changes induced by the electrical stimulation treatment. Especially the data representing muscle tissue and bone tissue were isolated for measurement purposes. Computer models and models made with rapid prototyping methods were used to display and demonstrate changes in muscle shape and size, as well as position relative to bone. Results showed that time and spatial dependencies of muscle growth can be monitored and studied quantitatively and qualitatively with the aid of a three-dimensional data set displayed on the computer screen or in the form of plastic models. These first results indicate muscle growth and an increase in bone density.

Electric Stimulation Therapy↗
PubMed1988

Characteristics of Schwann-cell miniature end-plate currents in denervated frog muscle.

End-plates in denervated frog sartorius muscles were investigated, under voltage clamp, to determine the characteristics of miniature endplate currents (mepc) caused by the release of acetylcholine (ACh)-quanta from Schwann-cells. Staining for acetylcholinesterase ascertained that in most cases Schwann-cell mepc had been recorded focally from the end-plate. The mean amplitude of Schwann-cell mepc (about 1 nA) was smaller than the amplitude (3-4nA) of normal nerve evoked mepc. The amplitude distribution of Schwann-cell mepc was skewed, as were also the distributions of decay time constants and of rise times. Some Schwann-cell mepc appeared to be of composite nature, as shown by an inflexion on either the rising of falling phase. The decay time constant tau of both fast and slowly decaying Schwann-cell mepc increased with membrane hyperpolarization suggesting an exponential correlation. The potential dependence was 118 +/- 37 mV (means +/- SD from 6 experiments) for an e-fold change of tau, which does not differ significantly from that for neural mepc (98 mV). The cholinesterase inhibitor neostigmine increased the amplitude and prolonged the time course of Schwann-cell mepc to a similar degree after short and long term denervation, which indicates that cholinesterase was still functional after 3-4 months of denervation. The results show that the characteristics of Schwann-cell mepc resemble in many respects those of neural mepc but are more variable in shape and amplitude.

Acetylcholine↗
PubMed2005

Osteoactivin upregulates expression of MMP-3 and MMP-9 in fibroblasts infiltrated into denervated skeletal muscle in mice.

In this study, we examined pathophysiological roles of osteoactivin, a functionally unknown type I membrane glycoprotein, in mouse skeletal muscle atrophied by denervation (sciatic neurectomy). Denervation increased the amounts of osteoactivin, vimentin, matrix metalloproteinase-3 (MMP-3), and MMP-9 in mouse gastrocnemius muscle. Interestingly, immunohistochemical analysis revealed that vimentin, MMP-3, and MMP-9 were mainly present in fibroblast-like cells infiltrated into denervated mouse gastrocnemius muscle, whereas osteoactivin was expressed in the sarcolemma of myofibers adjacent to the fibroblast-like cells. On the basis of these findings, we reasoned that osteoactivin in myocytes was involved in activation of the infiltrated fibroblasts. To address this issue, we examined effects of osteoactivin on expression of MMPs in fibroblasts in vitro and in vivo. Overexpression of osteoactivin in NIH-3T3 fibroblasts induced expression of MMP-3, but not in mouse C(2)C(12) myoblasts, indicating that osteoactivin might functionally target fibroblasts. Treatment with recombinant mouse osteoactivin increased the amounts of collagen type I, MMP-3, and MMP-9 in mouse NIH-3T3 fibroblasts. The upregulated expression of these fibroblast marker proteins was significantly inhibited by heparin, but not by an integrin inhibitor, indicating that a heparin-binding motif in the extracellular domain might be an active site of osteoactivin. In osteoactivin-transgenic mice, denervation further enhanced expression of MMP-3 and MMP-9 in fibroblasts infiltrated into gastrocnemius muscle, compared with wild-type mice. Our present results suggest that osteoactivin might function as an activator for fibroblasts infiltrated into denervated skeletal muscles and play an important role in regulating degeneration/regeneration of extracellular matrix.

Animals↗
PubMed1987

[Long-term experimental electric stimulation of denervated laryngeal muscles in dogs. Myopathologic findings].

The recurrent laryngeal nerve was transsected unilaterally and a device for electrical stimulation of the denervated muscles was implanted in 6 dogs. After 3 to 11 months the laryngeal muscles were obtained and histopathologically demonstrated a striking neurogenic pattern. In place of homogeneous muscle fiber atrophy, a patchwork of grouped fibre atrophy, compensational hypertrophy, fibre regeneration and reinnervation as well as muscle fibre type grouping were observed. Muscle fibre type distribution in the m. cricoarytenoideus posterior, m. vocalis and m. cricothyroideus was determined and compared between the normal and denervated sites. All muscles showed some changes in the fibre type distribution, including type grouping, but these were most pronounced in m. vocalis. The average fibre diameter decreased whereas fibre size variability increased. Mixed muscle fibre atrophy with compensatory hypertrophy of a single fibre type predominated. There was no evidence of disuse atrophy. The electrically stimulated muscles could be maintained at a reduced functional level throughout the study period.

Animals↗
PubMed1995

Neomyogenesis in neonatally de-efferented and postnatally denervated rat muscle spindles.

The ultrastructure of muscle spindles de-efferented by the extirpation of the lumbosacral spinal cord at the age of 2 days and subsequently deprived of their sensory innervation by the section of the sciatic nerve at 3-4 weeks of age was studied in serial sections of 2-month-old rat hindlimb muscles. De-efferentation leaves the primary sensory neurons and their peripheral axons intact and capable of inducing the muscle spindle morphogenesis during the critical period of their development. In de-efferented and subsequently denervated muscle spindles, new supernumerary intrafusal muscle profiles (SIPs) appeared in the muscle spindle A region. They were formed in intimate spatial relation with the original intrafusal muscle fibres (IMFs) predominantly from activated satellite cells derived from both nuclear bag (larger diameter) and nuclear chain fibres. SIPs, however, lacked the typical nuclear accumulations, as well as other ultrastructural distinctions present in control IMFs. The majority of differentiated SIPs separated from original IMFs, whereas the less differentiated SIPs were usually closely apposed to the surface of the parent IMFs and both were covered by the common basal lamina. In some spindles, the original IMFs and/or new SIPs at different stages of their differentiation were found together and they formed clusters of variable shape and composition. In the majority of clusters, all profiles seemed to be isolated along their entire length, although in few clusters, occasional cytoplasmic connections of variable length between intrafusal profiles were found. This result is important for the interpretation of the forthcoming study of expression of muscle spindle-specific myosin heavy chain isoforms in denervated SIPs in rat muscle spindles gradually deprived of their motor and sensory innervation.

Animals↗
PubMed2002

Survival of Schwann cells in chronically denervated skeletal muscles.

It is well established that over time Schwann cells disappear from the endoneurial space of the distal stump of a chronically transected sciatic nerve trunk. Nevertheless, the status of the Schwann cells within terminal branches of the transected sciatic nerve remains poorly understood. To elucidate this issue we examined the endoneurial space of the intramuscular nerves in rat hindlimb skeletal muscles, which had been denervated for a 25-month period. Based on specific ultrastructural characteristics, we identified a small population of viable Schwann cells within the intramuscular nerve trunks. The surviving Schwann cells continued to be immunopositive for both S-100 protein and neural cell adhesion molecule. In addition, reverse transcription-polymerase chain reaction and/or Western blot analyses have shown that at least two molecules, brain-derived neurotrophic factor and a non-catalytic truncated form of tyrosine protein kinase receptor B, which could potentially participate in the process of nerve repair, were detectable in chronically denervated skeletal muscle. Our results demonstrate that Schwann cells can survive inside the intramuscular nerve trunks of denervated skeletal muscle for a 25-month period without axonal contact.

Animals↗
PubMed1993

Increase in the number of intrafusal muscle fibres in rat muscles after neonatal motor denervation.

Rat muscle spindles disintegrate after total neonatal muscle denervation in which both sensory and motor axons are cut, but develop almost normally during the first three weeks after neonatal de-efferentation, attaining the usual complement of four intrafusal fibres, two bag and two chain fibres. Thereafter additional intrafusal fibres differentiate in most of the de-efferented spindles. We have examined the development of supernumerary fibres in muscle spindles of the rat hind limb muscles one to four months after neonatal de-efferentation using transmission electron microscopy. Additional intrafusal fibres originate both from activated intrafusal myosatellites and by different forms of fibre division. In a sample of 27 muscle spindles examined along the A zone five weeks after de-efferentation, the mean number of intrafusal fibre profiles increased almost two-fold to 7.9 +/- 3.3 (S.D.). Up to 20 intrafusal fibre profiles per spindle cross-section were found in muscles de-efferented for four months. The supernumerary fibres were apparently derived from all three intrafusal fibre types, but predominantly from the chain fibres. It is noteworthy that de-efferentation which causes wasting of extrafusal muscle initiates myogenesis and maintains additional intrafusal fibres within the spindle capsules.

Animals↗
PubMedDate not supplied

Ca2+-ATPase activity and lipid composition of sarcoplasmic reticulum of the gastrocnemius muscle of denervated frog.

Abnormalities have been noticed in the phospholipid and cholesterol composition of the atrophied gastrocnemius muscle of frog denervated for 1 month. Cholesterol : phospholipid molar ratios in the muscle increased on denervation. Sphingomyelin and cardiolipin fractions increased in contrast to phosphatidyl choline, phosphatidyl serine and phosphatidyl ethanolamine in the sarcoplasmic reticulum (SR) of denervated muscle. Na-azide sensitive Ca2+ ATPase activity of the mitochondria did not alter whereas that of SR decreased on denervation. Phospholipase C digestion impaired the organelle Ca2+-ATPase activity. The above abnormalities in enzyme activities have been correlated to the changes in the lipid composition of the denervated muscle. On the basis of these changes it is discussed that the primary change in the muscle due to denervation is the change in the permeability of the membrane.

Adenosine Triphosphatases↗