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PubMed2005

Differentiation of activated satellite cells in denervated muscle following single fusions in situ and in cell culture.

Satellite cells represent a cellular source of regeneration in adult skeletal muscle. It remains unclear why a large pool of stem myoblasts in denervated muscle does not compensate for the loss of muscle mass during post-denervation atrophy. In this study, we present evidence that satellite cells in long-term denervated rat muscle are able to activate synthesis of contractile proteins after single fusions in situ. This process of early differentiation leads to formation of abnormally diminutive myotubes. The localization of such dwarf myotubes beneath the intact basal lamina on the surface of differentiated muscle fibers shows that they form by fusion of neighboring satellites or by the progeny of a single satellite cell following one or two mitotic divisions. We demonstrated single fusions of myoblasts using electron microscopy, immunocytochemical labeling and high resolution confocal digital imaging. Sequestration of nascent myotubes by the rapidly forming basal laminae creates a barrier that limits further fusions. The recruitment of satellite cells in the formation of new muscle fibers results in a progressive decrease in their local densities, spatial separation and ultimate exhaustion of the myogenic cell pool. To determine whether the accumulation of aberrant dwarf myotubes is explained by the intrinsic decline of myogenic properties of satellite cells, or depends on their spatial separation and the environment in the tissue, we studied the fusion of myoblasts isolated from normal and denervated muscle in cell culture. The experiments with a culture system demonstrated that the capacity of myoblasts to synthesize contractile proteins without serial fusions depended on cell density and the availability of partners for fusion. Satellite cells isolated from denervated muscle and plated at fusion-permissive densities progressed through the myogenic program and actively formed myotubes, which shows that their myogenic potential is not considerably impaired. The results of this study suggest that under conditions of denervation, progressive spatial separation and confinement of many satellite cells within the endomysial tubes of atrophic muscle fibers and progressive interstitial fibrosis are the important factors that prevent their normal differentiation. Our findings also provide an explanation of why denervated muscle partially and temporarily is able to restore its functional capacity following injury and regeneration: the release of satellite cells from their sublaminal location provides the necessary space for a more active regenerative process.

Animals↗

PubMed1999

Passive stretch modulates denervation induced alterations in skeletal muscle myosin heavy chain mRNA levels.

The effect of denervation and denervation combined with immobilisation in either the shortened or lengthened position (passive stretch) upon myosin heavy chain (MyHC) mRNA levels was examined in three rat hind-limb muscles with differing phenotypes. Denervation alone caused a reduction in type I and type IIa MyHC transcripts in all three muscles. In contrast denervation caused a 72% increase in type IIb in the slow postural soleus muscle only which was prevented by immobilisation in the lengthened position. In the same muscle passive stretch also significantly retarded the effects of denervation upon the type I transcript (from 38% below control levels to 24% below) and type IIa transcript (from 59% to 32% below control levels). The levels of both type I and IIa transcripts, in the fast phasic plantaris muscle, were both unaffected by stretch combined with denervation when compared to denervation alone. In the mixed gastrocnemius muscle stretch affected the level of the type I but not the type IIa transcript. These data suggest that passive stretch can modulate MyHC gene expression independently of innervation but that it does so in a muscle-specific manner.

Animals↗

PubMed2005

Corticotropin releasing factor 2 receptor agonists reduce the denervation-induced loss of rat skeletal muscle mass and force and increase non-atrophying skeletal muscle mass and force.

Of the two corticotropin releasing factor receptors known, corticotrophin releasing factor 2 receptor (CRF2R) is expressed in skeletal muscle. The function of this receptor in skeletal muscle is at present unknown. In order to better understand the role of the CRF2R in skeletal muscle, we treated rats with CRF2R agonists and evaluated the effect of these agents on normal and denervated muscle mass. Rats treated with the non-selective CRFR agonist, sauvagine, did not demonstrate any significant and consistent change in non-denervated and denervated fast twitch [tibialis anterior (TA) or extensor digitorum longus (EDL)] or slow/mixed twitch [medial gastrocnemius (MG) or soleus] fiber muscle mass. In adrenalectomized rats, sauvagine treatment resulted in no significant and consistent change in non-denervated fast or slow/mixed twitch fiber muscles but did cause a significant and consistent increase in denervated fast twitch (TA and EDL) but not slow/mixed twitch muscle mass. Interestingly adrenalectomy had no effect on the degree of muscle atrophy. Rats treated with the CRF2R selective agonist urocortin 2 demonstrated an increase in non-denervated and denervated fast and slow/mix twitch fiber muscle mass. The urocortin 2 induced increase in muscle mass was accompanied by an increase in muscle fiber cross-sectional area and muscle absolute force. These studies demonstrated that activation of the CRF2R decreased the level of skeletal muscle mass, force, and myocyte cross-sectional area loss resulting from sciatic nerve damage and increased the mass, force and myocyte cross-sectional area of normal (non-atrophying) skeletal muscle. In addition, we also observed that removal of the adrenals increased the effectiveness of the non-selective CRFR agonists sauvagine, presumably via the removal of the pro-atrophy influence of adrenal produced corticosteroids. These results demonstrate that pharmacological modulation of the CRF2R may be a viable method to treat skeletal muscle atrophy.

Amphibian Proteins↗

PubMed1981

A new type of lesion-induced synaptogenesis: I. Synaptic turnover in non-denervated zones of the dentate gyrus in young adult rats.

It is well established that partial denervation causes the formation of new synapses within denervated areas. It is also possible that synapse formation and remodeling occurs outside denervated zones. In this study we evaluate this possibility by examining the effect of a unilateral entorhinal lesion on the number and characteristics of synapses in non-denervated zones of the dentate gyrus within the hippocampal formation. A unilateral entorhinal lesion massively denervates the outer two-thirds of the ipsilateral dentate molecular layer and also causes a minor loss of synapses in the outer two-thirds of the contralateral dentate molecular layer. The inner one-third of the molecular layer is not denervated on either side. In the ipsilateral inner molecular layer the number of synapses rapidly decreases by about 20% and recovers by 10 days post-lesion. Similarly, in the contralateral inner molecular layer, synapses are lost and replaced, but the time course is slower. Loss is maximal at 60 days post-lesion and this recovers by 180 days post-lesion. Thus, a complete cycle of turnover occurs in both of the inner molecular layers. No degenerating terminals of any type were seen throughout the time course in these layers. Small synapses with non-complex synaptic junctions appear to account for most of the changes. Also the outer two-thirds of the contralateral molecular layer, which has lost less than 5% of its input, loses about 37% of its synapses and replaces the majority of them over time. However, the total number of synapses in the contralateral molecular layer never fully attains the value of unoperated animals. The total synaptic population reaches a value such that the ipsilateral and contralateral molecular layers are nearly equivalent. These changes, achieved through synaptic turnover, may represent a homeostatic response to nearby denervation which may facilitate restoration of bilateral function in the dentate gyrus.

Afferent Pathways↗

PubMed1984

Denervation disperses acetylcholine receptor clusters at the neuromuscular junction in Xenopus cultures.

The effect of denervation on acetylcholine receptor (AChR) cluster distribution on cultured Xenopus muscle cells has been examined in order to study the role of intact nerve in the maintenance of clusters at the nerve-muscle junction during development. AChRs on the muscle cell were labeled with tetramethyl rhodamine-conjugated alpha-bungarotoxin and sequential changes in AChR cluster distribution were examined with a fluorescence microscope using an image intensifier. Denervation was carried out by exposing the nerve cell body to a focused laser light of a high intensity. After this procedure the neurites originating from the cell quickly disintegrated and large AChR clusters associated with nerve divided into smaller clusters. Individual clusters subsequently decreased in size and finally disappeared. In about 30% of the cases new AChR clusters appeared at the extrajunctional region after denervation. These observations indicate that intact nerves are necessary for the maintenance of receptor localization at the nerve-muscle junction and that nerve-induced accumulation is seemingly reversible during the early period of synapse formation. We tested the idea that receptor clusters were lost due to diffusion of receptors in the muscle membrane after denervation. However, the rate of receptor cluster dispersal after denervation was much slower than that predicted by the diffusion model, suggesting that diffusion of receptors is not a rate-limiting step. Furthermore, we found that receptor clusters at the junction stabilize during days in culture. Thus, 80-90% of receptor clusters at the nerve-muscle junction disappeared at 7 hr after denervation in 1-day cocultures, while about 50% of receptor clusters remained after denervation in 3-day cocultures.

Animals↗

PubMed1985

Organ culture of young rat vas deferens as an in vitro model for the study of denervation supersensitivity.

To investigate whether organ culture is a suitable in vitro model for studying the mechanisms of denervation-induced supersensitivity, we cultured 1-week-old rat vas deferens for 3 days with a basic applied tension of 20 mg. Cultured muscles showed supersensitivity to norepinephrine and methacholine with concomitant elevation of the maximal response. To compare these changes with those caused by denervation, young rats were chemically denervated by injecting 6-hydroxydopamine, and consequent sensitivity changes were investigated. Denervated muscles showed non-specific supersensitivity to norepinephrine and methacholine but the maximal response did not increase. When these denervated muscles were organ-cultured, they showed no or only a slight increase in sensitivity to norepinephrine and methacholine, but the maximal response increased greatly. These observations led to the suggestion that the increase in sensitivity may be mediated through the same mechanisms as those for denervation supersensitivity. The elevation of the maximal response was suggested to be produced by the improvement of cell-to-cell conduction as well as some other unknown factor(s) probably specific to organ culture. Thus, it was concluded that organ-cultured 1-week-old rat vas deferens is a useful model to study the mechanisms of denervation supersensitivity.

Animals↗

PubMed1992

Cardiovascular responses of sinoaortic-denervated rats to intracerebroventricular injection of alpha 1- and alpha 2-adrenoceptor agonists.

The aim of the present work was to analyse the cardiovascular responses induced by i.c.v. administration of the alpha 1- and alpha 2-adrenoceptor agonists, phenylephrine and clonidine, respectively, in conscious normal and sinoaortic-denervated rats. Sinoaortic denervation involves changes in central and peripheral catecholaminergic pathways. Clonidine (1-10 micrograms) produced a dose-dependent rise in blood pressure and a bradycardiac response in sham-operated animals, whereas in sinoaortic-denervated rats it provoked a brief rise in blood pressure followed by a marked fall as well as bradycardia. The responses involved mostly activation of central alpha 2-adrenoceptors, but the blood pressure responses induced by clonidine in sinoaortic-denervated rats may also have involved alpha 1-adrenoceptors. The bradycardia induced by the alpha 2-agonist in both groups of rats involved preferentially central alpha 2-adrenoceptors but also partially stimulated alpha 1-adrenoceptors. Phenylephrine, at a dose of 10-60 micrograms, induced a rise in blood pressure and a bradycardiac response while 90 micrograms produced a biphasic pressure response (early transient rise followed by a fall) as well as bradycardia in both sham-operated and sinoaortic-denervated animals. Phenylephrine activated alpha 1-adrenoceptors in every case, but the fall in blood pressure and the bradycardia also involved alpha 2-adrenoceptors. The responses were significantly higher in the sinoaortic-denervated rats than in the sham-operated. Our findings suggest that arterial baroreceptor reflexes can modify the effects of alpha-agonists initiated in the central nervous system. Sinoaortic denervation preparations enable one to unmask the depressor response to clonidine and also demonstrate the true magnitude of the phenylephrine response.

Adrenergic alpha-Agonists↗

PubMed1986

Repetitive action potentials induced in chloride-free solution: effect of denervation.

Isometric mechanical activity and action potentials registered with intracellular microelectrodes were studied in innervated and denervated fibers of the soleus muscle of the rat in normal and chloride-free solutions. The chloride-free solution promoted in both innervated and denervated fibers an increment in the resting membrane potential. The innervated muscles showed long mechanical relaxation and repetitive action potentials after a single depolarizing pulse. On the contrary, denervated muscles were resistant to show mechanical and electrical changes in the chloride-free medium. Spontaneous and evoked action potentials from innervated muscle fibers were abolished by tetrodotoxin. The evoked action potentials generated in denervated fibers had a slower time course and were resistant to tetrodotoxin. After 7 to 10 days of denervation the input resistance was increased by about 30%. Substitution of chloride with sulfate resulted in a 150% increase in input resistance of innervated muscle fibers and 80% in denervated preparations. Alterations in the ionic conductances, a decrease in the maximum rate of rise of the action potentials, and changes in the sodium current kinetics could be the main factors for the absence of repetitive action potentials in denervated fibers exposed to the chloride-free medium.

Action Potentials↗

PubMed1988

Effect of neonatal denervation-reinnervation on the functional capacity of a 129ReJ dy/dy murine dystrophic muscle.

The sciatic nerves of 14-day-old 129 ReJ normal (++) and dystrophic (dy/dy) mice were transected in the mid-thigh region. The cut ends of the nerves were approximated to facilitate regeneration. One hundred days after denervation, contractile properties of denervated-reinnervated, normal and dystrophic extensor digitorum longus (EDL) muscles were compared to age-matched normal and dystrophic muscles. In dystrophic muscle, in vitro twitch and tetanic tensions were reduced, compared to those of normal muscle. The denervation-reinnervation procedure resulted in an increase in these parameters as compared to unoperated dy muscle. These data correlated with increases in total myofiber cross-sectional areas. Twitch contraction time was not significantly affected by the dystrophic condition or by the denervation-reinnervation protocol. Whereas dystrophic muscle had a longer half-relaxation time than normal muscle, denervation-reinnervation of the dystrophic EDL resulted in a significantly faster half-relaxation time. While fatigue resistance was greater in dystrophic muscles than in normal muscle, there was a significant decrease in fatigue resistance in the denervated-reinnervated dystrophic muscle. Transient neonatal denervation results in modification of both the morphological and physiological characteristics of murine dystrophy.

Animals↗

PubMed1988

Cordotomy-denervation interactions on contractile and myofibrillar properties of fast and slow muscles in the rat.

Cordotomy-denervation interactions were studied on contractile and myofibrillar properties of slow (soleus) and fast (extensor digitorum longus) muscles of the rat. The spinal cord was transected midthoracically in neonatal (2-day-old) animals. Two months after birth, a unilateral transection of the sciatic nerve was carried out in both cordotomized and control animals. Five weeks after denervation, contractile properties were tested isometrically in vitro; myofibrillar properties were assessed by histochemical staining of the muscle fibers and by electrophoretic analysis of the myosin heavy chain composition. The following results were obtained: (i) In cordotomized animals the contraction time of the soleus was significantly shorter (-23.3% on average) than that in the control animals and this shortening was accompanied by a proportional slow-to-fast shift in myofibrillar properties. (ii) The extensor digitorum longus properties were not significantly different in the control and cordotomized animals. (iii) Denervation in control animals was followed by a marked increase of contraction and half-relaxation times in the extensor digitorum longus, whereas in the soleus only the half-relaxation time was significantly increased; myofibrillar properties in the soleus showed an appreciable slow-to-fast shift, whereas in the fast muscle the main change was an increase in type 2A fibers to the detriment of type 2B. (iv) In cordotomized animals, denervation caused the soleus contraction time to increase to control values, whereas myofibrillar properties shifted to an even faster pattern; in the extensor digitorum longus denervation caused the same changes seen in the control animals. The results showed that cordotomy at birth caused the soleus to develop as a faster muscle than in the control animals. The concurrent effects of cordotomy and denervation on the myofibrillar properties of the soleus suggest that the slow-to-fast change in these properties is a common consequence of the reduction in the level of motor activity. The opposite effects of the two experimental conditions in the soleus contraction time support the view that the contractile alterations that follow denervation mainly reflect alterations in the muscle activation process.

Animals↗

PubMed1992

Reinnervation of denervated skeletal muscles by grafted dorsal root ganglion.

We examined whether or not the cervical dorsal root ganglion (DRG) of the rat, when isografted and connected to the distal stump of the severed common peroneal nerve, could survive, project axons to the denervated leg muscles, and exert beneficial influences to delay the degeneration of the denervated muscles. Rats in which the muscles were similarly denervated but no DRG was grafted served as the control. After a postoperative period of 72 to 286 days, histological study showed that nerve cells at the superficial part of the grafted DRG survived. Indirect electrical stimulation via the distal stump of the common peroneal nerve produced no contraction of the muscles, indicating that no functional neuromuscular contacts had been reestablished. Direct stimulation of the denervated muscles did elicit contraction, and the isometric twitch and tetanic tensions were significantly much higher in the experimental rats with a grafted DRG than in the control rats. Cholinesterase-silver staining indicated the presence of axons in the denervated muscles, but the axons did not terminate on endplates. Compared with the control muscles, the experimental muscles had significantly more axons, and had atrophied less as indicated by muscle wet weight and histological appearance. These results indicate that the sensory axons can delay the weakening and atrophy of muscles after denervation. We suggest that the sensory axons may exert certain trophic influence on the denervated muscle fibers, though the actual mechanism is unknown.

Animals↗

PubMedDate not supplied

Uptake of horseradish peroxidase in denervated skeletal muscle occurs primarily at the endplate region.

The spatial distribution of horseradish peroxidase (HRP) uptake has been studied by light- and electron microscopy in the denervated hemidiaphragm of the mouse. Segments with high HRP uptake were observed in a band centrally located in the denervated muscle. This distribution is similar to the well-known innervation pattern of the diaphragm. Ultrastructural studies demonstrated a high incidence of postsynaptic folds in close proximity of fibre areas with high intracellular content of HRP. 8-12 days after denervation a large number of fibres showed segments of high HRP uptake. 2-4 days after denervation very few such segments were observed. Biochemical studies also demonstrated an increase in HRP uptake after denervation occurring primarily in the endplate region. The activities of the lysosomal enzymes N-acetyl-beta-D-glucosaminidase, acid phosphatase and cathepsin D all increased after denervation, most prominently in the endplate region. It is suggested that the observed segmental uptake of HRP and lysosomal activation reflects a process for rapid membrane turnover in denervated muscle.

Acetylglucosaminidase↗

PubMed1994

Endocytotic activity of mouse skeletal muscle fibres after long-term denervation.

The endocytotic activity of skeletal muscle fibres and its relation to the denervated endplate region has been studied using horseradish peroxidase (HRP) as marker for endocytosis. In muscles denervated for a short time period (10-20 days) HRP-uptake occurred in small segments of the muscle fibres near the centre of the muscle (endplate region). After long-term denervation (6-12 months) similar segments with high endocytotic activity were seen preferentially in more peripheral parts of the muscle fibres. Ultrastructural characteristics of segments with high endocytotic activity from long-term denervated muscle fibres include a proliferating transverse tubular system, HRP-containing bodies of different sizes with some very large vacuoles extending over several sarcomeres. These characteristics are similar to those described previously for HRP-uptake in the endplate region of short-term denervated muscle (Tågerud et al., J. Neurol. Sci., 75 (1986) 141) except that no recognizable endplate structures were observed in the present study. The results are discussed in relation to the fate of the denervated endplate and the receptive capacity for synapse formation in long-term denervated muscle.

Animals↗

PubMed1995

Barium resistant potassium current in mammalian skeletal muscle following denervation.

Inward rectifier potassium channels are thought to be related to resting membrane potential and in innervated skeletal muscle they are specially sensitive to the blocking action of Ba2+ ions. After denervation other channels are known to become resistant to their blockers. We study the effect of Ba2+ upon the inward rectifier potassium channels after denervation. Rat extensor digitorum longus fibers were equilibrated for 150 minutes in 150 mM KCl; when they were returned to 5 mM KCl the resting potential went back to its original level with a half time of 35 minutes. This repolarization was blocked by 5 mM BaCl2 in innervated muscles and in muscles denervated for 7 days, but failed to do so after 14 days of denervation. Voltage-clamp experiments performed in lumbricalis denervated muscle showed a lack of effect of Ba2+ upon potassium current after 18 days of denervation. This results suggest that the inward rectifier potassium channels become resistant to Ba2+ ions after denervation, indicating a neural influence.

Animals↗

PubMed1976

Analysis of fiber types in the pigeon's metapatagialis muscle. II. Effects of denervation.

The pigeon's metapatagialis muscle consists of three slips, two twitch and one tonic, and these slips are distinguishable at the gross anatomical level. Comparative studies of denervation are facilitated because the two fiber types are under the same mechanical forces, can be denervated as one muscle, and can be distinguished after denervation. Both fiber types atrophied after denervation, with the twitch fibers having a more variable response. Pathological alterations observed by light microscopy suggested that the twitch fibers were more affected by denervation than the tonus fibers. Ultrastructurally, both fiber types showed the same changes, with the twitch fibers again being more consistently altered. Proliferation of the transverse tubular system and sarcoplasmic reticulum were more marked in the tonus than twitch fibers, and the sarcoplasmic reticulum proliferated prior to the transverse tubules. Filament and fibril degeneration, peripheral and central degeneration, lysosomes and their derivatives, and satellite cell proliferation were common to both fiber types. Contracture knots were common to the denervated fibers, and were suggested to be characteristic of degenerating fibers. Degenerating motor end plates were observed, and most neurons in the fibers were naked, lacking myelin sheaths. The results are discussed in relation to the function of the neuron in maintaining the muscle, and the possibility of denervation inducing a transformation of tonic to twitch fibers.

Animals↗

PubMed1992

Influence of denervation on the molecular forms of junctional and extrajunctional acetylcholinesterase in fast and slow muscles of the rat.

Acetylcholinesterase (AChE) molecular forms in denervated rat muscles, as revealed by velocity sedimentation in sucrose gradients, were examined from three aspects: possible differences between fast and slow muscles, response of junctional vs extrajunctional AChE, and early vs late effects of denervation. In the junctional region, the response of the asymmetric AChE forms to denervation is similar in fast extensor digitorum longus (EDL) and slow soleus (SOL) muscle: (a) specific activity of the A12 form decreases rapidly but some persists throughout and even increases after a few weeks; (b) an early and transient increase of the A4 AChE form lasting for a few weeks may be due to a block in the synthetic process of the A12 form. In the extrajunctional regions, major differences with regard to AChE regulation exist already between the normal EDL and SOL muscle. The extrajunctional asymmetric AChE forms are absent in the EDL because they became completely repressed during the first month after birth, but they persist in the SOL. Differences remain also after denervation and are, therefore, not directly due to different neural stimulation patterns in both muscles: (a) an early but transient increase of the G4 AChE occurs in the denervated EDL but not in the SOL; (b) no significant extrajunctional activity of the asymmetric AChE forms reappears in the EDL up till 7 wk after denervation. In the SOL, activity of the asymmetric AChE forms is decreased early after denervation but increases thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholinesterase↗

PubMed1994

Radiofrequency lumbar facet denervation: analysis of prognostic factors.

Percutaneous radiofrequency lumbar facet denervation has been in use as a treatment for intractable, mechanical low back pain for over 2 decades. A number of case series have been reported with high rates of success in selected patients; however, there has been limited objective outcome assessment, long-term follow-up, and analysis of prognostic factors. We have reviewed our experience with diagnostic lumbar facet blocks and percutaneous radiofrequency denervation at a mean follow-up interval of 3.2 years. Long-term outcome has been assessed by disinterested third party interview. Of 82 patients selected for these procedures, 56 had undergone prior low back surgery. Following diagnostic medial branch posterior primary ramus blocks, 42 reported at least 50% relief of pain and proceeded to radiofrequency denervation. Forty-five percent of patients undergoing denervation reported at least 50% relief of pain at long-term follow-up. Among the 40 patients who only underwent temporary blocks, 13% reported relief (i.e., spontaneous improvement or placebo effect) by at least 50% at long-term follow-up). By multivariate statistical analysis, patients undergoing bilateral blocks for bilateral or axial symptoms were significantly more likely to achieve temporary relief, and to proceed to permanent denervation. There was no difference, however, between the long-term results of bilateral denervation for bilateral or axial pain and those of unilateral denervation for unilateral pain. There was no significant difference in the rate of response between the 56 patients who had undergone prior lumbosacral spine surgery and the 26 who had not. There were no complications from the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1982

The distribution of nodal sprouts in a paralysed or partly denervated mouse muscle.

The right gluteus maximus muscles of young adult mice were paralysed with botulinum toxin for up to 21 days or partly denervated by spinal root section for up to 63 days; the intramuscular and extramuscular nerves were then examined in the electron microscope in thin sections of tissue fixed conventionally or stained with zinc iodide-osmium tetroxide. Contralateral muscles were also examined as controls. The distribution of nodal sprouts in the nerves of the paralysed or partly denervated muscles was determined by calculating the mean ratios of unmyelinated to myelinated axons in nerve profiles containing different numbers of myelinated axons (intact or degenerating) and comparing these with control ratios. In paralysed muscles there was a significantly higher proportion of nerve profiles containing one or two unmyelinated axons alongside a single myelinated axon. Nerve profiles containing two or more myelinated axons did not show any increase in the proportion of unmyelinated axons. Thus, there is probably nodal sprouting in paralysed muscles which is restricted to the most distal nodes of the intramuscular nerves. In muscles partly denervated for 8 days there were significant increases in the proportion of unmyelinated axons in nerve profiles which had contained up to 5-10 myelinated axons. After 21 days of partial denervation, similar increases may have occurred in the larger intramuscular nerve profiles and after 63 days there were large increases in the proportion of unmyelinated axons in the main intramuscular nerve branches and in the extramuscular nerve. Nodal sprouting in response to partial denervation is therefore localised initially to the smaller, more distal nerve branches; at later times, some sprouts probably grow slowly in a disto-proximal direction along denervated Schwann cell pathways. The existence of nodal sprouts in paralysed muscles and their restricted distribution in paralysed and partly denervated muscles suggest that the nodal sprouting stimulus is produced by the muscle and acts only at distal nodes.

Animals↗