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PubMed2004

Effects of insulin-like growth factor-1 gene transfer on myosin heavy chains in denervated rat laryngeal muscle.

OBJECTIVES/HYPOTHESIS: To determine whether the myotrophic activity of human insulin-like growth factor (hIGF)-1 promotes restoration of normal myosin heavy chain (MHC) composition after nerve injury, MHC composition was analyzed after hIGF-1 gene transfer in denervated rat laryngeal muscle. STUDY DESIGN: Animal model to study effects of gene transfer on laryngeal paralysis. METHODS: In anesthetized rats, the left recurrent and superior laryngeal nerves are cut and suture ligated. A midline thyrotomy is performed, and the thyroarytenoid muscle is injected with a polyvinyl-based formulation containing a muscle specific expression system and hIGF-1 DNA (treatment group) or saline (control group). After 30 days, animals were killed, and the thyroarytenoid muscle was removed and processed for sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Densitometric measurements were obtained to determine composition of MHCs. RESULTS: As previously described, MHC composition in denervated laryngeal muscle was characterized by a decrease in type IIB and IIL and up-regulation of IIA/IIX. Compared with controls, hIGF-1 treated animals demonstrated a significant increase in expression of type IIB and IIL and a significant decrease in expression of type IIA/X. CONCLUSIONS: These findings suggest that the myotrophic effect of hIGF-1 gene transfer results in normalization of MHC composition in denervated muscle, with suppression of type IIA/X MHC and promotion of type IIL expression.

Animals↗
PubMed1994

Effects of denervation and nerve crushing on chicken muscle.

When compared with the standard free muscle grafts, predenervated and nerve crushed chick gastrocnemius muscle grafts followed an identical and ordered sequence of tissue degeneration-regeneration. Atrophy of the fibres during ischaemic degeneration was accompanied by loss of weight, noncollagenous proteins and increment in lytic enzymes (acid and alkaline phosphatase), glucose 6-phosphatase, glycogen and succinate dehydrogenase. Regeneration was more rapid in standard free muscle grafts. Trophic insults to muscle via denervation and nerve crushing prior to transplantation did not influence graft renewal when compared with standard free muscle grafts though relatively increased recovery was shown by predenervated muscle grafts.

Animals↗
PubMed1985

Enzymatic activities in slow and fast denervated old rat muscles.

The activities of five enzymes have been studied quantitatively in denervated extensor digitorum longus, gastrocnemius and soleus muscles of 24-month-old rats. The results have been compared with those obtained from normal muscles of a similar age group of rats. Three weeks after denervation, the activity of hexokinase was increased in gastrocnemius and extensor digitorum longus. Phosphofructokinase, lactate dehydrogenase, malate dehydrogenase and 3-hydroxyacyl-CoA-dehydrogenase showed decreased activities. These results suggest that enzyme which represents glucose uptake increased its activity in fast muscles and that enzymes for anaerobic glycolysis, lactate fermentation, citric acid cycle and beta-oxidation had a decreased activity in slow and fast muscles.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1992

Androgen locally regulates rat bulbocavernosus and levator ani size.

Adult male rats were gonadectomized, and small Silastic capsules filled with hormone were sutured to each bulbocavernosus and levator ani muscle complex (BC/LA). In the first experiment, one capsule contained testosterone (T), while the capsule on the contralateral muscles contained the antiandrogen hydroxyflutamide (hFl). The intent of this treatment was to provide a focus of androgenic stimulation to the muscles on one side. After 30 days, animals were sacrificed, and the BC/LA muscle pairs were removed, weighed, and compared. BC/LAs receiving T treatment were heavier than those receiving hFl treatment (p less than 0.0001), with an average weight difference of 12%. Muscle fibers from T-treated BCs were significantly larger in diameter than those from contralateral, hFl-treated BCs. These results indicate that androgen exerts its anabolic effect by acting locally upon a cell population within or near the BC/LA. When hFl and blank capsules were implanted in castrated males, the hFl-treated muscles were significantly heavier (by 9%), demonstrating an anabolic effect of hFl in the absence of androgen, and refuting the idea that hFl may have caused local toxic effects in the first experiment. Gonadectomized animals given T versus blank capsules had T-treated muscles that were 8% heavier than the blank-treated side. Muscle weights were also compared in animals receiving bilateral denervation of the BC/LA at the time of T and hFl capsule implantation and gonadectomy; local testosterone treatment failed to affect BC/LA weights in these denervated muscles.

Animals↗
PubMed2003

MyoD and myogenin protein expression in skeletal muscles of senile rats.

We analyzed the level of protein expression of two myogenic regulatory factors (MRFs), MyoD and myogenin, in senile skeletal muscles and determined the cellular source of their production in young adult (4 months old), old (24, 26, and 28 months old), and senile (32 months old) male rats. Immunoblotting demonstrated levels of myogenin approximately 3.2, approximately 4.0, and approximately 5.5 times higher in gastrocnemius muscles of 24-, 26-, and 32-month-old animals, respectively, than in those of young adult rats. Anti-MyoD antibody recognized two major areas of immunoreactivity in Western blots: a single MyoD-specific band (approximately 43-45 kDa) and a double (or triple) MyoD-like band (approximately 55-65 kDa). Whereas the level of MyoD-specific protein in the 43- to 45-kDa band remained relatively unchanged during aging compared with that of young adult rats, the total level of MyoD-like immunoreactivity within the 55- to 65-kDa bands was approximately 3.4, approximately 4.7, approximately 9.1, and approximately 11.7 times higher in muscles of 24-, 26-, 28-, and 32-month-old rats, respectively. The pattern of MRF protein expression in intact senile muscles was similar to that recorded in young adult denervated muscles. Ultrastructural analysis of extensor digitorum longus muscle from senile rats showed that, occasionally, the area of the nerve-muscle junction was partially or completely devoid of axons, and satellite cells with the features of activated cells were found on the surface of living fibers. Immunohistochemistry detected accumulated MyoD and myogenin proteins in the nuclei of both fibers and satellite cells in 32-month-old muscles. We suggest that the up-regulated production of MyoD and myogenin proteins in the nuclei of both fibers and satellite cells could account for the high level of MRF expression in muscles of senile rats.

Aging↗
PubMed2002

Control of muscle degeneration following autotomy of a hindleg in the grasshopper, Barytettix humphreysii.

When the grasshopper, Barrytettix humphreysii, sheds a hindlimb during autotomy, certain thoracic muscles degenerate although they are neither directly damaged nor denervated. Muscle degeneration is induced when a leg nerve (N5) that does not innervate the thoracic muscles is severed. Together these results suggest that transneuronal mechanisms influence muscle survival. To further characterize this autotomy-induced process, we studied the degeneration of a thoracic tergotrochanteral muscle (M#133b,c) following autotomy or experimental manipulation in adult animals. Its degeneration is correlated with reduced activity of its neural input and occurs by programmed cell death (PCD). PCD onset is variable between individual muscle fibers, indicating that the trigger of degeneration is fiber specific. Muscle degeneration appears to be triggered by the loss of proprioceptive input from the autotomized limb, since severing of axons from proprioceptive organs, but not exteroceptive chemo- or mechanoreceptors, leads to muscle degeneration. Muscle disuse, neuronal degeneration, or changes in juvenile hormone titer do not appear to play a role in autotomy-induced degeneration. We propose that the loss of proprioceptive input from proximal campaniform sensilla on the tibia deafferents the thoracic muscle motor neurons and leads to a decrease in their activity. Muscle degeneration is ultimately triggered by the loss of normal neural activity.

Journal Article↗
PubMed1982

The effect of low-frequency electrical stimulation on the denervated extensor digitorum longus muscle of the rabbit.

Both extensores digitorum longi (EDL) muscles of rabbits were denervated by crushing the common peroneal nerves. The EDL muscle on one side was directly stimulated at 10-12 Hz via implanted electrodes. This treatment reduced the changes of twitch/tetanus ratios produced by denervation and prevented the slowing of contraction and relaxation that follows denervation. It is concluded that the stimulation reduced the duration of the active state of denervated muscles. These effects of stimulation were reduced after 5 weeks, probably because by that time the slowing effect of low-frequency activity on the fast muscles became apparent.

Animals↗
PubMed1982

[Role of the sympathetic nervous system in neurotrophic control of the muscle fiber membrane in frogs].

Surgical desympathization of skeletal muscle fibre does not change the resting membrane potential or input resistance of muscle fibre membrane, but induces extrajunctional sensitivity to acetylcholine though lesser by half than that after anatomical muscle denervation. Raucedil injection and nerve stump transplantation on the muscle do not cause any changes in muscle membrane. The data obtained suggest the sympathetic nervous system participation in neurotropic control of muscle membrane sensitivity to acetylcholine.

Acetylcholine↗
PubMed1998

[Change of cell proliferation after the denervation laryngeal adducent muscles in dogs].

OBJECTIVE: To investigate the changes of cell proliferation state after denervation of laryngeal adducent muscles in dog. METHODS: The muscles were obtained from 8 dogs with recurrent lanyrgeal nerves injured. The cross sectional areas of muscle cells were measured by VIDS Image Analysis System in HE stained sections. A quantitative collagen/muscle ratio was measured by TJTY-300 image analysis system in Van Gieson stained sections. The percentages of S phase cell nucleus were calculated by image cytometry/DNA quantitative analysis with CAS 200 System. RESULTS: It showed that the cross sectional area of muscle cells decreased gradually after denervation (out-standing in 6 months after denervation) and collagen/muscle ratio increased significantly with time. The percentage of S phase nucleus was high at 5 months and then decreased. CONCLUSION: The proliferation of thyroarytenoid muscle and lateral cricoarytenoid muscle cell of dog remained at high level in 5 months after denervation and then slowed down and atrophy of muscles occurred 6 months after denervation. This suggests that nerve repair should be performed early. Examination of cell proliferation might indicate if the denervation of cells irreversible. It is helpful in choosing proper surgery and estimating the effect of nerve repair.

Animals↗
PubMedDate not supplied

A prospective study of shoulder disability resulting from radical and modified neck dissections.

A prospective longitudinal study of shoulder function after 103 neck dissections involving either preservation or sacrifice of the spinal accessory nerve is presented. The postoperative evolution and course of trapezius muscle denervation and resultant shoulder dysfunction were objectively determined for both radical and modified nerve sparing neck dissections. All patients were enrolled in a program of physical therapy aimed at maintaining range of motion at the shoulder joint. Shoulder function was examined preoperatively and for 12 months postoperatively with manual muscle strength testing, range of motion measurements, and electrodiagnostic testing. Results indicate that modified nerve sparing dissections are followed on the average by a significant, but temporary and reversible phase of shoulder dysfunction. By comparison, radical neck dissection is followed by profound and permanent trapezius muscle weakness and denervation.

Accessory Nerve↗
PubMedDate not supplied

[Changes in structural and functional properties of actin in denervated rabbit skeletal muscles].

Amino acid composition of actin from white skeletal muscles of the rabbit was studied 14 and 50 days after denervation. The content of valine, histidine and tyrosine was shown to decrease and that of lysine and leucine to increase on the 14th day following denervation. The content of these amino acids was almost normalised on the 50th day. In case of actin obtained from the contralateral leg similar but less pronounced changes were revealed. The results obtained are discussed as to the role played by some of amino acids in actin polymerization.

Actins↗
PubMed1995

Small-signal sensitivity of muscle spindles reinnervated after long-term denervation.

After long periods of denervation regenerated muscle spindle afferents show functional recovery despite gross histological abnormalities in their ending structure. This study prevents results examining the responses of such afferents to small amplitude stimuli, within the linear range of the spindle. The majority of regenerated afferents responded to the stimuli with a sensitivity similar to that of normal afferents.

Animals↗
PubMed1985

Stimulation of denervated rat soleus muscle with fast and slow activity patterns induces different expression of acetylcholinesterase molecular forms.

The relative amount and distribution of acetylcholinesterase (AChE) molecular forms were studied in slow soleus and (less extensively) in fast extensor digitorum longus (EDL) muscles of the rat before and after denervation and direct stimulation. Normal EDL muscles showed higher total and specific AChE activity than normal soleus muscles and contained essentially three different molecular AChE forms (G1, G4, and A12) as opposed to six forms (G1, G2, G4, A4, A8, and A12) in the soleus. Denervation reduced AChE activity in both muscles. In the soleus direct stimulation starting 2 to 3 weeks after denervation increased the specific AChE activity markedly. The increase started 12 to 24 hr after the onset of stimulation, reached 3 to 5 times normal values after 2 to 7 days, and then declined gradually toward normal values over the next 2 weeks. Furthermore, the effect on the different molecular forms depended strongly on the stimulus pattern. Thus, intermittent 100 Hz stimulation (fast pattern) induced essentially the three forms typical of the normal EDL, whereas continuous 10 Hz stimulation induced the six forms characteristic of normal soleus muscles but with some differences in their relative proportions. In the EDL, 2 days of continuous 10 Hz stimulation (the only duration and pattern examined) failed to induce a similar increase in AChE activity.

Acetylcholinesterase↗
PubMed1992

Clinical and morphological study of calf enlargement following S-1 radiculopathy.

Calf enlargement following sciatica is a rare condition. It is reported the case of a 28-year-old woman who complained of repeated episodes of lower back pain radiating into the left buttock and foot. One year after the beginning of her symptoms, she noticed enlargement of her left calf. X-ray studies disclosed L5-S1 disk degeneration. EMG showed muscle denervation with normal motor conduction velocity. Open biopsies of the gastrocnemius muscles were performed. The left gastrocnemius muscle showed hypertrophic type 2 fibers in comparison with the right gastrocnemius. Electron microscopy showed mildly increased number of mitochondria in these fibers. A satisfactory explanation for denervation hypertrophy has yet to be provided.

Adult↗
PubMed1990

Acetylcholinesterase histochemistry in the non-endplate region of skeletal muscles and effect of denervation.

We measured acetylcholinesterase (AChE) in the non-endplate region of rat muscle, documenting its intrinsic activity within muscle fibers, as well as the extrinsic level in the capillaries and endomysium. When each muscle was considered as a whole, intrinsic AChE activity detected within the fibers was stronger in the fast-twitch extensor digitorum longus than in the slow-twitch soleus. Analysis of individual muscle fibers also showed the same tendency with a higher value in the fast-twitch type II fibers than in the slow-twitch type I fibers. On the average, 73% of the fibers showed intermediate or strong enzymatic activity in the fast-twitch muscle, whereas 56% of the slow-twitch muscle had only low activity. Sectioning or ligation of the sciatic nerve resulted in nearly complete abolition of the enzyme in the non-endplate region of the denervated muscles within 7 days, suggesting that nerve transmission regulates AChE activity not only in the endplate, as is well known, but also outside this region. Human skeletal muscles showed the same pattern of AChE activity in the non-endplate region as seen in rat muscles.

Acetylcholinesterase↗
PubMed1992

Scanning electron microscopic study of denervated and reinnervated intrafusal muscle fibers in rats.

Isolated muscle spindles from lower lumbrical muscles of rats were used to study the 3-dimensional organization of intrafusal structures by scanning electron microscopy following (a) complete denervation, (b) reinnervation after a single crush lesion of the sciatic nerve, or (c) reinnervation after transection and immediate suture of this nerve. One week after complete denervation, previous sites of intrafusal motor endplates were transformed into sarcolemmal ovoid bulges. These bulges persisted in denervated muscle spindles up to 12 weeks. Regenerated motor nerve endings were detected on intrafusal muscle fibers 1 month, and thereafter following sciatic nerve crush injuries, and 3 months and later following transection and suture of the nerve. Furthermore, 3 different types of subsynaptic areas of motor nerve terminals were observed. The scanning electron microscopic technique also allowed visualization of splitting and fusion of intrafusal muscle fibers. The findings are discussed in view of their possible functional implications.

Animals↗
PubMedDate not supplied

Preservation of bulk and strength in muscles affected by neurogenic lesions.

Mechanisms involved in maintaining bulk and strength in partially denervated muscles of patients with neurogenic lesions are discussed. Estimation of muscle fiber hypertrophy by electrophysiological examination is possible, but it depends on the construction of sampling electrodes with precise geometry. The arrangement of muscle fibers of motor units within the muscle is discussed by analogy with the four-color map problem. An experiment to measure the twitch tensions of individual motor units in man is devised; it requires the use of microprocessor control of the stimulus and recurrent measurements of the twitch forces.

Animals↗