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PubMed1988

Spinal cord TRH deficiency is associated with incomplete recovery of denervated muscle in the rat.

The raphe-spinal pathway, which contains co-localized serotonin (5-HT), thyrotropin-releasing hormone (TRH), and several TRH-prohormone-derived non-TRH peptides, projects to the ventral horn of the spinal cord. Pharmacologic ablation of this pathway with the 5-HT neurotoxin, 5,7-dihydroxytryptamine, in neonatal rats resulted in deficient recovery of plantar foot muscles, functionally denervated with botulinum toxin type A. Failure of reinnervation was suggested by slower and incomplete recovery of the plantar foot compound muscle action potential amplitude and by a reduced mean diameter of plantar foot muscle fibers in ablated rats. These findings indicate that deprivation of alpha motor neurons from descending raphe-spinal input interferes with their ability to respond to muscle-derived signals for reinnervation.

5,7-Dihydroxytryptamine↗
PubMed1989

Fibrillatory activity and other membrane changes in partially denervated muscles.

Rat soleus muscles were partially or totally denervated by sectioning the radicular nerve L5 or the radicular nerves L3 through L6, respectively. Three days after these procedures, fibrillation potentials were not observed in the case of partial denervation, whereas they were clearly detectable after total denervation. At later times, spontaneous spike activity also developed in the partially denervated muscles. The difference in time of onset of fibrillation between partially and totally denervated muscles was confirmed by a more gradual increase in the number of acetylcholine receptors and a greater sensitivity to tetrodotoxin of the former muscles. These differences between partially and totally denervated muscles are interpreted on the basis of the different amounts of nerve breakdown products generated in the two situations.

Acetylcholine↗
PubMedDate not supplied

Insulin binding in denervated muscle.

Insulin binding was measured in rat muscle following denervation. There was a 40% reduction in the number of high-affinity insulin receptors, with no change in the insulin binding Kd. Selected muscles showed a 40%-60% reduction in weight during this period. The down-regulation in the number of insulin receptors may contribute to the mechanism of muscle atrophy following denervation.

Animals↗
PubMed1968

Sodium movements in denervated muscle and the effects of antimycin A.

1. Fibre sodium in rat diaphragm exchanged at a faster rate in muscles which had been denervated 8 days previously. The half-time was 3.7 min for outward movement in denervated muscles and 5.1 min in controls.2. The inward movement of sodium was also faster in denervated muscle as compared with controls, and the calculated permeability to sodium was approximately doubled.3. In the presence of antimycin A (1.8 x 10(-5)M), the outward movement of sodium in denervated diaphragm was slowed and the fibres gained sodium and lost potassium.4. Antimycin markedly reduced the twitch produced by stimulation of denervated diaphragm, and also the response to acetylcholine. Similar effects were found in denervated tibialis anterior of the cat.

Acetylcholine↗
PubMedDate not supplied

Muscle biopsies show that FES of denervated muscles reverses human muscle degeneration from permanent spinal motoneuron lesion.

This paper presents biopsy analyses in support of the clinical evidence of muscle recovery induced by a new system of life-long functional-electrical-stimulation (FES) training in permanent spinal-motoneuron-denervated human muscle. Not earlier than 1 year after subjects experienced complete conus cauda lesion, their thigh muscles were electrically stimulated at home for several years with large skin surface electrodes and an expressly designed stimulator that delivered much longer impulses than those presently available for clinical use. The poor excitability of long-term denervated muscles was first improved by several months of twitch-contraction training. Then, the muscles were tetanically stimulated against progressively increased loads. Needle biopsies of vastus lateralis from long-term denervated subjects showed severe myofiber atrophy or lipodystrophy beginning 2 years after spinal cord injury (SCI). Muscle biopsies from a group of 3.6- to 13.5-year denervated subjects, who underwent 2.4 to 9.3 years of FES, show that this progressive training almost reverted long-term muscle atrophy/degeneration.

Adult↗
PubMed1996

Reciprocal GLUT-1 and GLUT-4 expression and glucose transport in denervated muscles.

We investigated in 3-day-denervated muscles 1) the expression of GLUT-1 in perineurial sheaths (PNS) and muscle, 2) the muscle fiber-specific changes in GLUT-1 and GLUT-4, and 3) changes in basal and insulin-stimulated 3-O-methylglucose transport. GLUT-1 was increased in both the PNS (P < 0.05) and in the muscle membranes (P < 0.05). GLUT-1 and GLUT-4 concentrations were changed reciprocally, in a fiber-dependent fashion [GLUT-1: red gastrocnemius (RG), +31%; white gastrocnemius (WG), +10%; GLUT-4: RG, -53%; WG, -16%]. Basal glucose transport was increased (P < 0.05), and this increase was correlated with the oxidative nature of the muscles (r = 0.97). Insulin-stimulated glucose transport was decreased in denervated muscles (P < 0.05). This was also related to the oxidative nature of the muscles (r = -0.88). The increase in basal glucose transport was correlated with the loss of insulin-stimulated transport (r = 0.95). Thus the increase in GLUT-1 compensates for the loss of GLUT-4, resulting in a 56% regain of the reduced insulin-stimulated glucose transport.

3-O-Methylglucose↗
PubMed1984

Motor neuron survival and neuritic extension from spinal cord explants induced by factors released from denervated muscle.

Extracts prepared from denervated adult skeletal muscle contain increased amounts of neurotrophic activity which promotes both survival of dissociated motor neurons and the outgrowth of neurites from explants of spinal cord maintained in serum-free defined media. The trophic activity is specific for motor neurons and reaches a peak within the first week post-denervation. In these most potent extracts the neurite outgrowth enhancement is a linearly increasing function of protein concentration at low concentrations; at higher concentrations the neurite activity-concentration relationship saturates and in the milligram range the relationship becomes inhibitory. When media containing active denervated muscle extract was preincubated over polycationic substrata, it lost the ability to promote neuritic growth; this could be restored if fresh extract was added to the cultures. Thus it was demonstrated that within the denervated muscle extract there are physically separable agents responsible for neuron survival and neurite expression. It is possible that the release of neurotrophic factors may be in part responsible for the in vivo phenomenon of nerve sprouting.

Animals↗
PubMed2000

The expression kinetics of myogenin in facial muscle denervation.

OBJECTIVE: To study the expression kinetics of myogenin in long-term denervated facial muscle and to explore the possibility of gene therapy for facial muscle paralysis with myogenin gene. MATERIALS AND METHODS: In 48 New Zealand rabbits, buccal muscle paralysis of one side was produced by excision of 1 cm segment buccal branch of the facial nerve. The opposite side served as controls. The animals were sacrificed and the buccal muscles of both sides were removed for examination at 1 day, 3 days, 1 week, 2 weeks, 1 month, 2 months, 4 months, and 6 months after the initial operation. The myogenin expression in denervated and innervated buccal muscles was analyzed by Western blot. Satellite cell proliferation was detected with proliferating cell nuclear antigen (PCNA) analysis. Muscle nucleic acid concentration was determined through acridine orange (AO) staining method. RESULTS: Myogenin expression increased to the highest level at 3 days after denervation, thereafter it gradually decreased. The Western blotting signal for myogenin intensified again after 1 month and at 4 months. In contrast, the highest expression of the controls (innervated muscles) were observed at 1 month. These changes in myogenin expression in denervated buccal muscles were consistent with the change in satellite cell proliferation and in muscle nucleic acid concentration. CONCLUSION: Myogenin protein expression in longterm facial muscle denervation is closely associated with satellite cell regeneration. Myogenin may promote satellite cell differentiation, and therefore may improve the treatment of facial paralysis.

Acridine Orange↗
PubMed1993

Protein secretion from mouse skeletal muscle: coupling of increased exocytotic and endocytotic activities in denervated muscle.

The secretion of proteins labelled by incorporation of radioactive amino acids was studied in innervated and 10 to 13-day-denervated mouse skeletal muscle. The secretion of 3H-leucine-labelled proteins, expressed per mg muscle wet weight, increased after denervation, and the kinetics of the secretory process was also altered in denervated muscle. Separation of secreted 35S-methionine-labelled proteins by sodium dodecyl sulphate polyacrylamide gel electrophoresis followed by autoradiography revealed some denervation-induced alterations in the pattern of secreted proteins. The secretion from both innervated and denervated muscle was highly temperature sensitive and was reversibly inhibited by brefeldin A, a drug that blocks forward membrane transport from the endoplasmic reticulum/Golgi apparatus. This drug was also found to inhibit the uptake of fluorescein isothiocyanate-labelled dextran in denervated muscle but had no effect on the endocytotic activity of innervated muscle. This lends support to the hypothesis that the increased endocytotic activity in denervated muscle is coupled to a high secretory activity.

Animals↗
PubMed1999

Ulnar nerve injuries of the hand producing intrinsic muscle denervation on magnetic resonance imaging.

Muscle and nerve injuries in the hand may be difficult to detect and diagnose clinically. Two cases are reported in which magnetic resonance imaging showed ulnar nerve injury and intrinsic hand muscle denervation. The clinical, anatomical and radiological features of injury to the deep motor branch of the ulnar nerve and associated muscle denervation are discussed and illustrated.

Adult↗
PubMed2002

Sequential MR imaging of denervated muscle: experimental study.

BACKGROUND AND PURPOSE: MR changes in denervated muscles have been reported to occur within days up to several weeks after peripheral nerve damage. The purpose of this experimental study was to investigate the longitudinal changes in denervated muscles by using MR imaging. METHODS: In 12 Lewis rats, the left sciatic nerve was transected at the level of the proximal thigh. MR imaging of both legs was performed before and 1 hour, 24 hours, 48 hours, 7 days, 14 days, 28 days, and 2 months after the procedure. The MR protocol included T1-weighted spin-echo, T2-weighted double turbo spin-echo, and turbo inversion recovery magnitude (TIRM) sequences obtained in the axial plane. Signal intensities (T2-weighted double turbo spin-echo and TIRM sequences) and the T2 TR (T2-weighted double turbo spin-echo sequence) were recorded for the soleus, peroneal, and gracilis muscles of both sides. Moreover, the circumferences of both lower legs were determined on the basis of T1-weighted images. RESULTS: Twenty-four hours after denervation, a signal intensity increase in the denervated peroneal and soleus muscles was present on TIRM images. On T2-weighted images, only the peroneal muscle exhibited slightly increased signal intensities and T2 TR. Forty-eight hours after nerve transection, the denervated soleus and peroneal muscles revealed prolonged T2 TR and marked increased signal intensities on T2-weighted and TIRM images when compared with the contralateral side, which further increased at or less than 2 months after denervation. Muscle atrophy of the denervated muscles was present as early as 7 days after denervation and was also increased at follow-up examinations. CONCLUSION: The TIRM sequence is more sensitive than is T2-weighted imaging in the detection of signal intensity changes in denervated muscle. These changes occur as early as 24 (TIRM sequence) and 48 (T2-weighted sequence) hours, respectively, after complete transection of the sciatic nerve in rats and precede muscle atrophy. The sensitivity to early signal intensity changes in denervated muscles may support the use of MR imaging in the diagnosis of peripheral nerve lesions.

Animals↗
PubMed1999

Standing up with denervated muscles in humans using functional electrical stimulation.

The use of electrical stimulation for denervated muscles is still considered to be a controversial issue by many rehabilitation facilities and medical professionals because prior clinical experience has shown that treating denervated muscle tissue using exponential current over a long time period constitutes an impossible task. Despite this fact, we managed to evoke tetanic contractions in denervated muscle using a long duration stimulation with anatomically shaped electrodes and sufficiently high amplitudes. The pulse amplitudes, which were being used for this purpose, exceeded by far the MED-GV and EC regulations (300 mJ/impulse). For this reason, an application has recently been submitted to have the EC regulations changed accordingly. It takes a tetanic contraction to achieve the desired muscle fiber tension, constituting a hypertrophic stimulus. It is also an appropriate means of exercise, which is capable of creating the metabolic and structural conditions needed (e.g, increased mitochondrial volume and capillary density) to obtain satisfactory muscle performance. With patients suffering from a complete spinal cord injury at level D12/L1, having motor and sensory loss in both lower extremities, we were able to train denervated muscle using long-duration stimulation, evoking single muscle contractions at first, soon followed by tetanic contractions against gravity. To increase the efficacy of this functional electrical stimulation (FES) strengthening program, we used ankle weights. With daily FES training over a period of 1-2 years, denervated muscle was exercised until it produced torques between 16 and 38 Nm in the m. quadriceps. With that muscle force, it is possible to stand up from a sitting position in parallel bars. Our results show that denervated muscle in humans is indeed trainable and can perform functional activities with FES. Furthermore, this method of stimulation can assist in decubitus prevention and significantly improve the mobility of paraplegics.

Capillaries↗
PubMed2005

Distribution of rest periods between electrically generated contractions in denervated muscles of rats.

Stimulation protocols for denervated muscles distribute the generated contractions either within treatment sessions followed by hours of rest, or repeated 24 h per day with each contraction followed by a constant interval of rest. Our purpose was to directly compare the effects of the same number of identically generated contractions having different temporal daily distributions. For 5 weeks in denervated extensor digitorum longus muscles of rats, between 100 and 800 contractions were generated daily, distributed either within worksets that alternated periods of activity and rest, or separated by constant intervals of rest. Most of the tested protocols maintained muscle mass and maximum force near values of innervated controls. Although 100 contractions daily generated at constant intervals were sufficient to maintain mass and force, 100 contractions during a 4-h treatment session followed by 20 h of rest were not sufficient, and mass and force were not different from values of denervated muscles.

Analysis of Variance↗