SEARCH · Search PubMed

Results for “Muscle Denervation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 487 records · Page 27Linked to original sources

PubMed2001

Testosterone mediates satellite cell activation in denervated rat levator ani muscle.

Denervation stimulates quiescent satellite cells in skeletal muscle to reenter the cell cycle. In the androgen-sensitive rat levator ani muscle (LA), this mitotic response to loss of neural input fails to occur in castrated animals. To elucidate the role of androgens in denervation-induced satellite cell proliferation, the denervated LA of castrated rats (Group A) was compared with that of animals infixed with testosterone implants after castration (Group B). Mean myofiber cross-sectional areas (Group A: 362.95 microm(2) +/- 27.74; Group B: 403.13 microm(2) +/- 53.87) and linear nuclear densities (Group A: 74.07 mm(-1) +/- 17.58; Group B: 104.13 mm(-1) +/- 4.06) were similar (P > 0.05) in both groups. The androgen-deprived myofibers of Group A, however, had a significantly lower nuclear content (271.0 +/- 74.91 vs. 1,285.80 +/- 81.74 in Group B; P < 0.05) on account of their considerably shorter mean length (3.44 mm +/- 0.29 vs. 12.31 mm +/- 0.92 in Group B; P < 0.05). The proportional representation of satellite cells in hormone-replaced, denervated muscle was more than twice that in the untreated group (Group B: 5.15 +/- 0.83% vs. Group A: 2.28 +/- 0.23%; P < 0.05). In absolute terms, the satellite cell number in Group B was approximately an order of magnitude greater than in Group A (408.4 x 10(3) vs. 38.08 x 10(3)). The results confirm the absence of testosterone as the factor responsible for the inability of satellite cells in the LA of castrated rats to respond mitotically to the withdrawal of neural input after denervation.

Anal Canal↗

PubMed1987

Reinnervation of muscle fiber types in the newborn rat soleus.

We have examined the selectivity of reinnervation of fiber types in rat soleus muscle denervated by crush of the soleus nerve 2 d after birth. The fibers innervated by single, regenerated motor axons were identified by use of glycogen depletion approximately 2 weeks following denervation. The types of fibers were determined by immunohistochemistry employing anti-myosin antibodies and, in some cases, by myofibrillar ATPase staining. Two distinct types of fibers are present in soleus at 2 d and through the next 16 d of normal postnatal development. These fiber types are retained in a denervated muscle for the period of time required for reinnervation. Although 40% of the fibers are lost from the muscle during reinnervation, we find no evidence for interconversion of muscle fiber types. Nonetheless, 10 of the 12 single motor units examined had fiber type compositions that were markedly biased toward one or the other of these 2 types; the bias in these units could not be explained by chance reinnervation. On the basis of the topographical distribution of the muscle fibers in each of these units, the motor axons reinnervated a novel set of fibers. We interpret these findings to mean that neonatal soleus motor neurons reinnervate fiber types in a selective manner. This selective innervation may explain the bias in the fiber type composition of normal motor units during early postnatal development.

Animals↗

PubMed1987

New muscle growth in denervated extraocular muscle.

Current therapies for paralytic ocular motility disorders often provide less than satisfactory results. Promising new techniques of nerve grafting and muscle transplantation used to treat muscle paralysis elsewhere in the body may have application to the ocular motor system. In studying a procedure designed to reinnervate paretic extraocular muscle (e.o.m.), we produced not only the expected nerve growth but also abundant new muscle growth. A considerable amount of this muscle growth occurred within the axon depleted nerve fascicles of the paretic muscle, suggesting that this structure was a particularly good matrix for muscle fiber growth. These observations suggest that new, entire neuromuscular units may be induced to grow in the plane of a paretic muscle if appropriate surface characteristics can be established.

Animals↗

PubMed2002

Resistance vessel remodeling and reparative angiogenesis in the microcirculatory bed of long-term denervated skeletal muscles.

In denervated skeletal muscles, atrophy of muscle fibers and interstitial fibrosis are associated with alterations within the vascular bed. Our study has placed particular emphasis on changes occurring in resistance vessels and the microcirculatory bed of rat hindlimb skeletal muscles that had been denervated for 25 months. We found that the tunica media of the majority of long-term denervated resistance vessels undergoes deterioration. In small intramuscular arteries and arterioles, atrophic vascular smooth muscle cells (vSMCs) enclosed in a thick basal lamina are separated by expanded extracellular space. The remodeling and sclerotic changes in the arterial wall occasionally result in deformation of the lumen. It was also found that the microcirculatory bed undergoes significant alterations. In 25-month denervated extensor digitorum longus muscle, the capillary-to-fiber ratio is only 0.13 +/- 0.01 and the mean number of capillaries per fascicle decreases almost ninefold compared to contralateral control muscle. Ultrastructural findings demonstrate that 24.67 +/- 0.48% of capillaries examined in the chronically denervated fascicles show structural features typical for capillary regeneration. In addition, long cytoplasmic extensions of pericytes might develop a layer completely encircling the capillary endothelium. In pre- and postcapillary segments of the microcirculatory bed, some perivascular cells possess a phenotype that is intermediate between that of pericytes and atrophic vSMCs. RT-PCR and/or Western blot analyses showed that molecules participating in angiogenesis are detected in 25-month denervated skeletal muscle. We hypothesize that despite the fact that the microcirculatory bed of chronically denervated muscle undergoes significant reduction it still sustains the capacity for reparative capillary growth.

Animals↗

PubMed2005

Proteomic analysis of rat laryngeal muscle following denervation.

Laryngeal muscle atrophy induced by nerve injury is a major factor contributing to the disabling symptoms associated with laryngeal paralysis. Alterations of global proteins in rat laryngeal muscle following denervation were, therefore, studied using proteomic techniques. Twenty-eight adult Sprague-Dawley rats were divided into normal control and denervated groups. The thyroarytenoid (TA) muscle was excised 60 days after right recurrent laryngeal nerve was resected. Protein separation and identification were preformed using 2-DE and MALDI-MS with database search. Forty-four proteins were found to have significant alteration in expression level after denervation. The majority of these proteins (57%), most of them associated with energy metabolism, cellular proliferation and differentiation, signal transduction and stress reaction, were decreased levels of expression in denervated TA muscle. The remaining 43% of the proteins, most of them involved with protein degradation, immunoreactivity, injury repair, contraction, and microtubular formation, were found to have increased levels of expression. The protein modification sites by phosphorylation were detected in 22% of the identified proteins that presented multiple-spot patterns on 2-D gel. Significant changes in protein expression in denervated laryngeal muscle may provide potential therapeutic strategies for the treatment of laryngeal paralysis.

Animals↗

PubMed1981

Desensitization in denervated mouse muscles.

In denervated mouse soleus (DSOL) muscle preparations washed in Na methanesulfonate solutions containing 30 mmol X 1(-1) K+, bath-applied ACh (55 mumol X 1(-1) ) caused the resting potential to decrease from about -36 to -3.2 mV within 2-4 s; the potential remained stable or became slightly more negative when ACh was applied for 1- 2 min. Two components of the membrane current change (ACh current) were found in DSOL when using a point voltage clamp, an initial current component declining to 1/2 the initial amplitude in 11-15 s (desensitization) and a steady late current comprising 16-47% of the maximum ACh current. Membrane conductance (in microseconds X cm-2) was 0.35 in the absence of ACh, 20.3 at the peak of the initial current, and 1.57 during late current. The late current saturated at 0.55 to 5.5 mumol X 1(-1) ACh, whereas the initial current required 55 or more mumol X 1(-1) ACh to saturate. The null (reversal) potential was 6-13 mV more positive for the late current than for the initial current. The late current was masked when Na+ was replaced by Tris+, sucrose, or K+. An initial and a late current could also be distinguished in non-denervated endplates. The late current was more sensitive to ACh than the initial current, but the null potential was more negative than that for the initial current in endplates. In denervated membrane, the half time of desensitization was increased when Mg2+ was replaced by Ca2+ but the changes were on the average less than 15% the control values. It was concluded that desensitizing and non-desensitizing receptors may exist in extrajunctional membranes of denervated muscles and in endplates, the two being attached to different ionic channels.

Animals↗

PubMed2001

Interrelations of myogenic response, progressive atrophy of muscle fibers, and cell death in denervated skeletal muscle.

Little is known concerning the time-course and structural dynamics of reactivation of compensatory myogenesis in denervated muscle, its initiating cellular mechanisms, and the relationship between this process and the progression of postdenervation atrophy. The purpose of this study was to investigate the interrelations between temporal and spatial patterns of the myogenic response in denervated muscle and progressive atrophy of muscle fibers. Another objective was to study whether reactivation of myogenesis correlates with destabilization of the differentiated state and death of denervated muscle cells. It has remained unclear whether muscle fiber atrophy was the primary factor activating the myogenic response, what levels of cellular atrophy were associated with its activation, and whether the initiation and intensity of myogenesis depended on the local and individual heterogeneity of atrophic changes among fibers. For this reason, our objective was also to identify the levels of atrophic and degenerative changes in denervated muscle fibers that are correlated with activation of the myogenic response. We found that the reactivation of myogenesis in the tibialis anterior and extensor digitorum longus muscles of the rat starts between days 10-21 following nerve transection, before atrophy has attained advanced level, long before dead cells are found in the tissue. Formation of new muscle fibers reaches its maximum between 2 and 4 months following denervation and gradually decreases with progressive postdenervation atrophy. The myogenic response is biphasic and includes two distinct processes. The first process resembles the formation of secondary and tertiary generations of myotubes during normal muscle development and dominates during the first 2 months of denervation. During this period, activated satellite cells form new myotubes on live differentiated muscle fibers. Most of the daughter myotubes in 1- and 2-month denervated muscle develop on the surface of fast type parent muscle fibers, and some of the newly formed muscle fibers express slow myosin. Some fast type parent fibers are weakly or, more rarely, moderately immunopositive for embryonic isomyosin. This indicates that reactivation of myogenesis may also depend on the fiber type. The level of atrophy, destabilization of the differentiated myofiber phenotype, and degenerative changes of individual fibers in denervated muscle are very heterogeneous. The myogenic response of the first type is associated predominantly with fibers of average and higher than average levels of atrophy. Muscle cells that undergo a lesser degree of atrophy also form daughter fibers, although with a lower incidence. We did not find any correlation between the size of newly formed fibers and the level of atrophy of parent fibers. The topographical distribution of new myotubes both in the peripheral and central areas of the mid-belly equatorial sections at the early stages following nerve transection indicates that myogenesis of the first type represents a systemic reaction of muscle to the loss of neural control. These data indicate that activation of the myogenic response does not depend on cell death and degenerative processes per se. The second type of myogenesis is a typical regenerative reaction that occurs mainly within the spaces surrounded by the basal laminae of dead muscle fibers. Myocytes of different sizes are susceptible to degeneration and death, which indicates that cell death in denervated muscle does not correlate with levels of muscle cell atrophy. The regenerative process frequently results in development of abnormal muscle cells that branch or form small clusters. Replacement of lost fibers becomes activated between 2 and 4 months following nerve transection, i.e., mainly at advanced stages of postdenervation atrophy, when cell death becomes a contributing factor of the atrophic process. In long-term denervated muscle, the first and second types of myogenesisoccur concurrently, and the topographical distribution of the myogenic response becomes more heterogeneous than during the first weeks following denervation. Thus, our data demonstrate differential temporal and spatial expression of two patterns of myogenesis in denervated muscle that appear to be controlled by different regulatory mechanisms during the postdenervation period. (c) 2001 Wiley-Liss, Inc.

Animals↗

PubMed2005

Participation of bone marrow-derived cells in fibrotic changes in denervated skeletal muscle.

In denervated skeletal muscle, mononuclear interstitial cells accumulate in the perisynaptic regions before fibrotic change occurs. These cells are currently considered to be fibroblasts that originate from muscle tissue. However, when we denervated hind limbs of GFP-bone marrow chimeric mice by excising the sciatic nerve unilaterally, many bone marrow-derived cells (BM-DCs) infiltrated the interstitial spaces and accumulated in the perisynaptic regions, peaking 14 days after denervation. They accounted for nearly one-half of the increase in mononuclear interstitial cells. Although BM-DCs did not incorporate into satellite cells, immunohistochemical and FACS analyses revealed that BM-DCs were both CD45 and CD11b positive, indicating that they were of macrophage/monocyte lineage. BrdU staining showed inactive proliferation of BM-DCs. Reverse transcriptase-polymerase chain reaction of mononuclear cells isolated by FACS revealed that BM-DCs did not express type I collagen or tenascin-C; however, they did express transforming growth factor-beta1, suggesting that they regulate the fibrotic process. In contrast, muscle tissue-derived interstitial cells expressed type I collagen and tenascin-C, suggesting that these populations were the final effectors of fibrosis. These findings identify elementary targets that may regulate the migration, homing, differentiation, and function of BM-DCs, leading to amelioration of the excessive fibrosis of denervated skeletal muscle.

Animals↗

PubMed1998

GDNF expression is increased in denervated human skeletal muscle.

Glial cell line derived neurotrophic factor (GDNF) is a potent trophic factor for several subpopulations of neurons including motor neurons. Two different transcripts of the GDNF gene (GDNF633 and GDNF555) have been detected in various tissues, including skeletal muscle. Denervation leads to an upregulation of GDNF633 in rat skeletal muscle, indicating that GDNF is involved in the response of skeletal muscle to denervation and possibly in reinnervation. To determine the role of GDNF in human neuromuscular disease, we investigated the expression of both transcripts in normal and denervated muscle and in muscle biopsies from Duchenne muscular dystrophy patients. GDNF expression levels were analyzed by competitive RT-PCR in 38 muscle specimens. Levels of both transcripts were significantly elevated in denervated muscle compared to normal and dystrophic muscle. Morphometric analysis of muscle-fiber calibers and its correlation to GDNF expression revealed that higher levels of GDNF were expressed in rapidly-progressive neurogenic atrophy, including four amyotrophic lateral sclerosis (ALS) cases, compared to cases of chronic atrophy. In dystrophic muscle, transcript levels were not significantly altered compared to normal controls. These data indicate that denervation, but not dystrophy, enhances GDNF expression in human skeletal muscle. Thus, the increase of GDNF expression is part of the reaction of human skeletal muscle to denervation caused by motor nerve lesion. GDNF might act on regenerating nerve fibers during muscle fiber reinnervation.

Cells, Cultured↗

PubMed2002

Rescue of motoneurones by MK-801 innervating partially denervated rat muscles.

Partial denervation of the extensor digitorum longus muscle by cutting the L4 spinal nerve in 3-day-old rats causes some of the remaining uninjured motoneurones to die. A previous study has shown that of the 12 motor units usually present in the remaining uninjured L5 spinal nerve, a significantly smaller number of motor units to extensor digitorum longus muscle is found in animals operated on at 3 days. This reduction can be caused by a greater sensitivity of neonatal motoneurones with axons in a partially denervated muscle, to excitotoxic effects of glutamate. Therefore an N-methyl- D-aspartic acid (NMDA) receptor antagonist, MK-801, was injected daily for 12 days after partial denervation at 3 days. Two months after the operation contractile properties, motor unit numbers and sizes were studied. Following MK-801 treatment, the reduction in muscle weight and force output of the partially denervated muscle was less than that in the untreated group. Moreover there were more motor units in MK-801 treated animals. After partial denervation only, 15% of the total number of motor units was present whereas when the same operation was followed by treatment with MK-801, 29% remained. The mean motor unit size in the untreated group was 69% while after treatment with MK-801 it was 152% of the control. Thus treatment with MK-801 after partial denervation of neonatal animals rescued some of the motoneurones destined to die, and allowed expansion of motor unit territory of most of the surviving motoneurones.

Animals↗

PubMed1979

[Functional reinnervation of the larynx. Experimental study (author's transl)].

This study of reinnervation of the larynx results from the research for a functional method of treatment for laryngeal paralysis of peripheral origin. The physiological reality of reinnervation of a denervated muscle by a nerve other than that anatomically destined for it, or "neurotisation", is now an established fact. This experimental study in 12 dogs consisted of neurotisation of a posterior crico-thyroid muscle, denervated by section of the recurrent laryngeal nerve, by implantation of a graft of sub-hyoid muscle with a nerve pedicle. Only one positive result at six months was seen. 8 failures could be explained by the absence of ventilatory difficulty necessary for the sub-hyoid muscles to be brought into action, and the other 3 failures two months after the operation by muscular fibrosis of the graft before neurotisation could occur. Physiology and the experience of other teams justify the continuation of this study.

Animals↗

PubMed1997

Exercise training of moderate intensity does not abate the effects of denervation on muscle morphology.

Denervation elicits profound alterations in the morphometry of skeletal muscle. These alterations include changes in fiber type composition as well as reductions in fiber size. There is evidence that the increased mechanical load placed upon muscle via rhythmic stretching attenuates denervation induced alterations in muscle morphology. The purpose of the present study was to determine whether the mechanical stimuli associated with exercise training, i.e. rhythmic stretching and mechanical loading, would effectively moderate the changes in muscle morphometry observed following denervation. Unilateral denervation of the soleus muscle of eight male Sprague-Dawley rats was performed under aseptic conditions. The animals were then randomly assigned to two groups: sedentary controls and exercise trained. The exercise training protocol featured treadmill running five days per week for six weeks. At the conclusion of the experimental period, animals from both groups were sacrificed and soleus muscles were histochemically analyzed for muscle morphometry. Results demonstrated that denervation caused marked alterations in fiber type profile and in fiber cross-sectional areas. Interestingly, the degree of denervation induced atrophy appeared to be fiber type specific. However, the data presented here indicate that in denervated soleus muscles there were no significant differences in fiber type composition or fiber size between the sedentary and exercise trained groups. Hence, it appears that the mechanical stimuli provided by treadmill running of moderate intensity and duration are not sufficiently potent to ameliorate muscle morphometric responses to denervation.

Animals↗

PubMed1991

In vitro denervation of frog skeletal muscle: expression of several conductance classes of nicotinic receptors.

The question arose as to whether the altered kinetic properties of the nicotinic acetylcholine receptor-ion channel complex (AChR) observed after muscle denervation could be due to post-translational modifications. Single AChR properties of in vitro denervated skeletal muscle were studied using the cell-attached patch-clamp technique. Patch-clamp recordings from junctional regions of fibers daily treated with cycloheximide, a protein synthesis inhibitor, and phenylmethylsulfonyl fluoride, a protease inhibitor, revealed single conductance class of acetylcholine (ACh)-activated currents after acute dissociation and several conductance classes 3-14 days after muscle denervation. alpha-Bungarotoxin blocked all conductance states induced by ACh. Biochemical assays carried out on the same experimental conditions disclosed that chronic treatment of the fibers with cycloheximide inhibited the incorporation of [3H]leucine into precipitable protein. The present findings provided evidence that the altered functional properties of nicotinic receptors after muscle denervation may occur without new transcription.

Acetylcholine↗

PubMed1993

Denervated skeletal muscle: MR imaging. Work in progress.

PURPOSE: To evaluate the change in signal intensity of skeletal muscles after denervation and to determine the clinical usefulness of magnetic resonance (MR) imaging in diagnosis of denervation. MATERIALS AND METHODS: Denervated skeletal muscles associated with various forms of peripheral neuropathy and spinal radiculopathy were studied with MR imaging in 17 patients. RESULTS: On T1-weighted images, signal intensity of denervated muscles was normal in 14 patients and high in three. On T2-weighted images, all denervated muscles showed high signal intensity on at least one MR image. High signal intensity in the denervated muscles on T2-weighted images was observed 15 or more days after onset of paralysis. In two patients, signal intensity of denervated muscles returned to normal after relief of paralysis. CONCLUSION: MR imaging is a noninvasive and accurate method for use in diagnosis of denervation and may ultimately eliminate the need for electromyography.

Adipose Tissue↗

PubMed1997

Neurocrescin: a novel neurite-outgrowth factor secreted by muscle after denervation.

Regeneration of injured axons at neuromuscular junctions has been assumed to be regulated by extracellular factors that promote neurite outgrowth. We report here the cloning of a novel neurite outgrowth factor, designated neurocrescin, from chick denervated skeletal muscle. A recombinant neurocrescin promoted neurite outgrowth from cultured neurons of spinal cord and telencephalon of chick embryo. It was expressed predominantly in neural tissue and muscle, and was secreted extracellularly after intramolecular cleavage. This truncated form was detected in denervated muscle but not in innervated muscle. Thus, neurocrescin appears to be a novel neurite outgrowth factor that is secreted in an activity-dependent fashion. A highly homologous counterpart was also cloned from mouse brain.

Amino Acid Sequence↗

PubMed1998

Lactate/H+ transport kinetics in rat skeletal muscle related to fibre type and changes in transport capacity.

Lactate/H+ transport kinetics were determined by means of the pH-sensitive probe BCECF in sarcolemmal giant vesicles, obtained from rat skeletal muscle, and related to variations in lactate/H+ transport capacity. Vesicle preparations were made from red and white muscles, mixed muscles, denervated muscles, muscles of old rats and rats that had been subjected to high-intensity training, endurance training, repeated exposure to hypoxia, and hypothyroid or hyperthyroid treatments. The lactate/H+ transport capacity of red muscles was greater than that of white muscles, and this difference was associated with a higher maximal transport rate (V max) in red muscles, whereas the K m was similar in the two muscle types. High-intensity training and hyperthyroidism increased the lactate/H+ transport capacity by enhancing V max without affecting K m. Similarly, a reduced transport capacity with old age and hypothyroidism was due to a decrease in V max. The denervation-induced decline in lactate/H+ transport capacity resulted from both an increased K m and a reduced V max. The present data show that muscle type differences and most changes in the lactate/H+ transport capacity are mediated by modifications in V max, which is expected to represent the number of membrane transporter molecules. K m is unaffected by most treatments and appears to be independent of fibre type.

Animals↗

PubMed2005

Protein abnormality in denervated skeletal muscles from patients with brachial injury.

A proteomic analysis was performed to compare protein expression between normal sternocleidomastoid muscle and denervated muscle. Two-dimensional electrophoresis (2-DE) of muscle proteins showed that 26 proteins among about 800 spots in 2-DE gel displayed a decrease and 6 proteins an increase in expression in muscles with denervation atrophy compared to normal controls; the identified proteins that were abnormally expressed could be generally grouped together as metabolic proteins, chaperone proteins, and contractile-apparatus proteins. The significance of these altered proteins is discussed. In particular, the decrease in hD54 may reduce the activity of transmembrane signaling in atrophied muscle, while the disregulation of DnaJC 1 showed a possible role of molecular chaperones in the functional recovery of atrophied muscles.

Adult↗

PubMed2000

Remodeling of the vascular bed and progressive loss of capillaries in denervated skeletal muscle.

Very little is known regarding structural and functional responses of the vascular bed of skeletal muscle to denervation and about the role of microcirculatory changes in the pathogenesis of post-denervation muscle atrophy. The purpose of the present study was to investigate the changes of the anatomical pattern of vascularization of the extensor digitorum longus muscle in WI/HicksCar rats 1, 2, 4, 7, 12, and 18 months following denervation of the limb. We found that the number of capillaries related to the number of muscle fibers, i.e. the capillary-to-fiber ratio (CFR), decreased by 88%, from 1.55 +/- 0.35 to 0.19 +/- 0.04, during the first 7 months after denervation and then slightly declined at a much lower rate during the next 11 months of observation to 10% of the CFR in normal muscle. Between months 2 and 4 after denervation, the CRF decreased by 2.4 times, from 58% to 24% of the control value. The loss of capillaries during the first 4 months following nerve transection was nearly linear and progressed with an average decrement of 4.16% per week. Electron microscopy demonstrated progressive degeneration of capillaries following nerve transection. In muscle cells close to degenerating capillaries, the loss of subsarcolemmal and intermyofibrillar mitochondria, local disassembly of myofibrils and other manifestations of progressive atrophy were frequently observed. The levels of devascularization and the degree of degenerative changes varied greatly within different topographical areas, resulting in significant heterogeneity of intercapillary distances and local capillary densities within each sample of denervated muscle. Perivascular and interstitial fibrosis that rapidly developed after denervation resulted in the spatial separation of blood vessels from muscle cells and their embedment in a dense lattice of collagen. As a result of this process, diffusion distances between capillaries and the surfaces of muscle fibers increased 10-400 times. Eighteen months after denervation most of the capillaries were heavily cushioned with collagen, and on the average 40% of the muscle cells were completely avascular. Devascularization of the tissue was accompanied by degeneration and death of muscle cells that had become embedded in a dense lattice of collagen. Immunofluorescent staining for the vascular isoform of alpha-actin revealed preservation of major blood vessels and a greater variability in thickness of their medial layer. Hyperplastic growth of the medial layer in some blood vessels resulted in narrowing of their lumens. By the end of month 7 after denervation, large deposits of collagen around arterioles often exceeded their diameters. Identification of oxidative muscle fibers after immunostaining for slow-twitch myosin, as well as using ultrastructural criteria, has shown that after 2 months of denervation oxidative muscle fibers were less susceptible to atrophy than glycolytic fibers. The lower rate of atrophy of type I muscle fibers at early stages of denervation may be explained by their initially better vascularization in normal muscle and their higher capacity to retain capillaries shortly after denervation. Thus, degeneration and loss of capillaries after denervation occurs more rapidly than the loss of muscle fibers, which results in progressive decrease of the CFR in denervated muscle. The change of capillary number in denervated muscle is biphasic: the phase of a rapid decrease of the CFR during the first 7 months after nerve transection is followed by the phase of stabilization. The presence of areas completely devoid of capillaries in denervated muscle and the virtual absence of such areas in normal muscle indicate the development of foci of regional hypoxia during long-term denervation. The anatomical pattern of muscle microvascularization changes dramatically after nerve transection. Each muscle fiber in normal muscle directly contacts on average 3-5 capillaries. (ABSTRACT TRUNCATED)

Animals↗