Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “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.

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

At least 1,585 records · Page 88Linked to original sources
PubMed2000

Cloning and neuronal expression of a type III newt neuregulin and rescue of denervated, nerve-dependent newt limb blastemas by rhGGF2.

Urodele amphibians are the only vertebrates that can regenerate their limbs throughout their life. The critical feature of limb regeneration is the formation of a blastema, a process that requires an intact nerve supply. Nerves appear to provide an unidentified factor, known as the neurotrophic factor (NTF), which stimulates cycling of blastema cells. One candidate NTF is glial growth factor (GGF), a member of the neuregulin (NRG) growth factor family. NRGs are both survival factors and mitogens to glial cells, including Schwann cells. All forms of NRGs contain an EGF-like domain that is sufficient to activate NRG receptors erbB2, erbB3, and erbB4. To investigate the involvement of neuregulin in newt limb regeneration, we cloned and characterized one neuregulin isoform, a neuregulin with a cysteine-rich domain (CRD-NRG), from newt (Notophthalmus viridescens) spinal cord. Results of in situ hybridization showed that the newt CRD-NRG is highly expressed in dorsal root ganglia and spinal cord neurons that innervate the limbs. We also demonstrated the biological activity of recombinant human GGF2 (rhGGF2) in urodele limb regeneration. When rhGGF2 was injected into denervated, nerve-dependent axolotl blastemas, the labeling index (LI) of blastema cells was maintained at a level near to that of control, innervated blastemas, whereas without rhGGF2 the LI decreased significantly. In another experiment, rhGGF2 was delivered into denervated, nerve-dependent blastemas either by direct infusion into blastemas or by injection into the intraperitoneal cavity. The denervated blastemas were rescued into a regeneration response.

Ambystoma mexicanum↗
PubMed1996

Functional and histologic effects of a free nonvascularised muscle graft implanted into a reinnervated muscle after prolonged denervation.

Striated muscle atrophy and degeneration, which increase with the delay of denervation, represent two of the main causes for poor recovery following delayed nerve repair. The present study, using a rat model, tests the hypothesis that an adjunction of small, free, nonvascularised muscle grafts of contralateral healthy triceps into a chronically denervated triceps improves muscle regeneration and recovery following sciatic nerve repair delayed for 3 months. Our experiments seem to show a relative increase in mechanical properties in animals in which free muscle graft into the triceps was performed 3 weeks following nerve repair. The improvement of the regenerative process of muscles which have suffered a long period of denervation should be considered as an additional therapeutic procedure in the case of late nerve repair.

Animals↗
PubMed2000

Bcl-2 and bax immunohistochemistry in denervation-reinnervation and necrosis-regeneration of rat skeletal muscles.

Bcl-2 and Bax immunohistochemistry was examined in the skeletal muscle of rats after cutting the sciatic nerve, as a model of denervation and reinnervation, and in the anterior tibialis muscle of rats after an intramuscular injection of metoclopramide, as a model of necrosis and regeneration of muscle fibers, to better understand the role of these proteins in muscle disorders. An increase in Bax immunoreactivity was seen in long-standing denervated and reinnervated muscle fibers. Bcl-2 and Bax immunoreactivity was limited to macrophages in necrotic muscle fibers at 24 h after the intramuscular injection of metoclopramide. However, increased Bax immunoreactivity was observed in regenerating muscle fibers by the fourth day after the injection. Muscle fiber nuclei with the morphological features of apoptosis were not observed in rat muscles after the intramuscular injection of metoclopramide or after the severing of the sciatic nerve. Furthermore, using the Tunel method, no stained nuclei were observed in the two groups of animals. Our observations in the experimental models of skeletal muscle denervation-reinnervation and necrosis-regeneration here described suggest that modification in the intensity of the Bax protein is not related to the process of cell death but rather that increased Bax expression is associated with muscle fiber regeneration.

Animals↗
PubMed1981

Scanning electron microscopy of the normal and denervated limb regenerate in the newt, Notophthalmus, including observations on embryonic amphibia limb-bud mesenchyme and blastemas of fish-fin regenerates.

The present work deals with the morphology of normal and denervated early limb regenerates in the newt and compares them with early limb-bud mesenchyme and blastemas of fish-fin regenerates using the three-dimensional properties of the SEM. It shows that blastemal cells are polymorphic, in contrast to those of the stump-cell population, which are fairly homogeneous and from which blastema cells are said to arise by "dedifferentiation." The appearance of cells had not changed by two days following denervation even though previous biochemical studies have detected many changes in metabolism. Longterm denervation (7 days) did result in morphological changes. A comparison between well-known cell types-myoblasts, Schwann cells, osteoblasts observed in vitro, limb-bud mesenchyme and mesenchymatous fin blastema-was carried out in order to suggest explanations for the blastema-cell polymorphism.

Amphibians↗
PubMed1986

Proliferation of arteriovenous anastomoses in the developing rabbit ear is enhanced after denervation.

The innervation of the rabbit ear vasculature by noradrenergic and substance P-immunoreactive (SP-IR) nerves was investigated in both young and adult animals. All vascular segments were supplied by both noradrenergic and SP-IR nerves. In the ear margins, the arteriovenous anastomoses (AVAs) were more densely innervated than other vessels. In general, the density of both noradrenergic and SP-IR nerves increased with age until 10-12 weeks postnatum. The ear vasculature was denervated in young rabbits to test whether the normal proliferation of AVAs in the growing ear was altered in the absence of nerves. Surgical resection of all auricular nerve trunks except the auricular branch of the auriculo-temporal nerve, and removal of the ipsilateral superior cervical ganglion in 10- to 12-day-old rabbits left the ear devoid of both noradrenergic and SP-IR nerves for at least four weeks. Repeated administration of 6-hydroxydopamine (6-OHDA) to young rabbits produced degeneration of noradrenergic terminal axons, but preterminal nerve trunks survived. SP-IR nerves did not appear to be affected by 6-OHDA. These denervation regimes resulted in a 1.5- to 2-fold increase in the number of AVAs formed in the growing ear. Surgical denervation and 6-OHDA treatment also led to retarded growth of the media of the central ear artery, but this effect of 6-OHDA was probably not due to a specific action on vascular smooth muscle. Surgical resection of most of the dorsal auricular nerves in adult rabbits did not affect AVA density. Large differences in AVA density were apparent between groups of control animals from different parts of the country, or groups examined at different times of the year. These results demonstrate that the labile nature of AVAs in the rabbit ear can result in considerable variability in the absolute number of AVAs and suggest that both intrinsic and extrinsic factors may influence development of the microvasculature.

Animals↗
PubMed1994

Expression pattern of M-cadherin in normal, denervated, and regenerating mouse muscles.

Following muscle damage in adult vertebrates, myofibers can be regenerated from muscle precursor cells (satellite cells). During this process, prenatal myogenesis is recapitulated to a large extent, both morphologically and molecularly. A putative morphoregulatory molecule involved in myogenesis is M-cadherin (Mcad), a calcium-dependent cell adhesion protein. The expression of Mcad was studied by immunofluorescence in regenerating, denervated, and normal mouse muscles. Our results demonstrate that Mcad is present in satellite cells in normal muscle. Enhanced staining at sites of contact between satellite cells and the parent muscle fiber suggests an additional, spatially restricted expression of Mcad in muscle fibers. Mcad positive cells in normal and denervated muscles did not incorporate bromodeoxyuridine within 24 hr after injection in vivo, indicating that Mcad is expressed on mitotically quiescent satellite cells. Neural cell adhesion molecule (NCAM) co-localized with Mcad in nearly all satellite cells in denervated muscles but rarely in intact muscles. At early stages of regeneration, Mcad was exclusively and strongly expressed in myoblasts. After fusion of myoblasts into myotubes, Mcad was down-regulated and was barely detectable on more mature myotubes surrounded by distinct basal lamina sheaths. These observations are in line with the idea that Mcad plays a crucial role in myogenesis. In intact muscle, Mcad might function as a molecular link between satellite cell and muscle fiber.

Animals↗
PubMed2005

Natural history of denervation in SMA: relation to age, SMN2 copy number, and function.

Denervation was assessed in 89 spinal muscular atrophy (SMA) 1, 2, and 3 subjects via motor unit number estimation (MUNE) and maximum compound motor action potential amplitude (CMAP) studies, and results correlated with SMN2 copy, age, and function. MUNE and maximum CMAP values were distinct among SMA subtypes (p < 0.05). Changes in MUNE and maximum CMAP values over time were dependent on age, SMA type, and SMN2 copy number. SMN2 copy number less than 3 correlated with lower MUNE and maximum CMAP values (p < 0.0001) and worse functional outcomes. As SMN2 copy number increases, so does functional status (p < 0.0001). Change in MUNE longitudinally over the time intervals examined in this study was not statistically significant for any SMA cohort. However, a decline in maximum CMAP over time was apparent in SMA2 subjects (p = 0.049). Age-dependent decline in MUNE and maximum CMAP was apparent in both SMA 1 (p < 0.0001) and SMA 2 (p < 0.0001) subjects, with age as an independent factor regardless of type. Maximum CMAP at the time of the initial assessment was most predictive of functional outcome (p < 0.0001). Prospective longitudinal studies in four prenatally diagnosed infants demonstrated significant progressive denervation in association with symptomatic onset or functional decline. These data highlight the potential value of such measures in increasing our understanding of pathophysiological factors involved in denervation in SMA.

Activities of Daily Living↗
PubMed1986

Dopamine denervation does not alter in vivo 3H-spiperone binding in rat striatum: implications for external imaging of dopamine receptors in Parkinson's disease.

Striatal particulate preparations, both from rats with lesion-induced striatal dopamine (DA) loss and from some striatal dopamine (DA) loss and from some patients with Parkinson's disease, exhibit increased 3H-neuroleptic binding, which is interpreted to be the mechanism of denervation-induced behavioral supersensitivity to dopaminergic compounds. After intravenous 3H-spiperone (3H-SP) administration to rats with unilateral nigral lesions, we found no differences in accumulation of total or particulate-bound 3H-SP in dopamine-denervated compared with intact striata. 3H-SP in vivo binds to less than 10% of striatal sites labeled by 3H-SP incubated with striatal particulate preparations in vitro. Quantitative autoradiography of 3H-SP binding to striatal sections in vitro also failed to reveal any effects of dopamine denervation. 3H-SP bound to striatal sites in vivo dissociates more slowly than that bound to striatal particulate preparations labeled in vitro. Striatal binding properties of 3H-SP administered in vivo are quite different from the same kinetic binding parameters estimated in vitro using crude membrane preparations of striatum. In addition, striatal binding of in vivo-administered 3H-SP is not affected by prior lesion of the substantia nigra, which results in profound ipsilateral striatal dopamine depletion. Thus, behavioral supersensitivity to dopaminergic compounds may not be associated with altered striatal binding properties for dopamine receptor ligands in vivo.

Animals↗
PubMed1977

Effects of denervation and tenotomy on the gastrocnemius muscle in the frog: a histologic and histochemical study.

The effects of denervation on the gastrocnemius muscle of the frog were studied by histologic and histochemical methods. Thirteen Rana pipiens underwent unilateral sciatic neurotomy and were sacrificed weekly as long as 46 days. Of the three normal populations of muscle fibers, the small fibers underwent atrophy, the intermediate sized fibers remained unchanged in size, and the large fibers either did not change or underwent hypertrophy between 21 and 46 days. Necrosis of muscle fibers did not occur. Histochemical stains showed persistence of the normal pattern after denervation. The small fibers continued to have a high concentration of both oxidative and glycolytic enzyme activity (NADH-TR, SDH, phosphorylase), and the large fibers continued to have a low concentration of these enzymes. Depletion of glycogen stores was seen with PAS. Hypertrophic muscle fibers had mostly subsarcolemmal nuclei and few internal nuclei, suggesting that they may be physiologically tonic rather than twitch fibers. Achilles tenotomy at the time of denervation prevented the hypertrophy of large fibers. Abnormal inclusions have been demonstrated in mammalian muscle following tenotomy alone, but were not seen in the frog.

Achilles Tendon↗
PubMed1978

Changes in the satellite cells of growing muscle following denervation.

Satellite cells exhibit a number of distinct morphological changes after denervation which appear to be a direct response to nerve section or altered functional state of the muscle fibers. These changes appear generally related to increased movement and overall activation of the cells. After longer periods of denervation many satellite cells appear to separate from their fibers and become free cells in the interstitial space. It is proposed that this mechanism provides a cellular source for the small-diameter, immature fibers dispersed throughout the muscle after two to three weeks. Although neo-formation of myofibers appears to be a feature of denervated growing muscle, an increase in total fiber population was not observed. It is suggested that in the absence of a viable nerve supply the new fibers degenerate.

Animals↗
PubMed1992

Localization of the Ca(2+)-dependent proteinases and their inhibitor in normal, fasted, and denervated rat skeletal muscle.

Immunofluorescence and immunogold localization studies show that the two Ca(2+)-dependent proteinases (mu-calpain for the micromolar Ca(2+)-requiring proteinase and m-calpain for the millimolar Ca(2+)-requiring proteinase) and their protein inhibitor (calpastatin) are located exclusively intracellularly in normal rat soleus muscle. Quantitative immunogold studies indicate that binding of antibodies to both calpains and to calpastatin is approximately two times greater at the Z-disk of myofibrils than it is at the I-band or A-band regions. Mitochondria and nuclei in muscle cells contain both calpains and calpastatin at concentrations approximately one-tenth and one-fifth, respectively, of the concentration at the Z-disk, as estimated by antibody binding. Very little calpain or calpastatin was seen in the cytoplasmic intermyofibrillar spaces, and most of the calpain and calpastatin in muscle cells is associated with intracellular structures. Immunofluorescence results suggest that concentration of m-calpain but not mu-calpain or calpastatin is, in some instances, slightly higher near the intracellular surface of the plasma membrane than elsewhere in the muscle cell. Most m-calpain, however, is distributed throughout the interior of mature rat skeletal muscle cells. Denervation, or fasting and refeeding increases the concentration of the calpains and calpastatin in the muscle cell but does not change their distribution. Some mu- and m-calpain and calpastatin is found extracellularly in denervated soleus muscle or soleus muscle from fasting rats, but the extracellular calpains and calpastatin seem to originate from "leakage" of these proteins out of the cell because serum creatine kinase levels are much higher than normal in denervated or fasting rats.

Animals↗
PubMed1977

The ultrastructure of cutaneous type I mechanoreceptors (Haarscheiben) in cats following denervation.

Denervation of specialized cutaneous mechanoreceptors (Haarscheiben or domes) in cats was followed after 20 and 25 days by the following alterations in receptor structure: (1) reduced numbers of Merkel cells, (2) Merkel cells degenerating in situ, (3) fewer dense-core granules in the cytoplasm of Merkel cells, (4) an increased number of agranular dendritic cells and Langerhans cells in the dome, (5) the apparent phagocytosis of Merkel cells by Schwann and Langerhans cells, (6) fewer epithelial cell layers over the dome, and (7) a decrease in the number of transitional cells. Skin excised between the domes in the denervated nerve field appeared normal when compared to innervated skin, and it was considered unlikely that the alterations in dome structure were due to generalized nutritional changes in the skin caused by transection of sympathetic axons or to some other side effect of denervation. Since domes are formed in new locations on the skin after nerves have regenerated (Burgess et al., '74), changes in dome structure following nerve transection are probably due to loss of the "trophic" influence of the nerves supplying the dome.

Animals↗
PubMed1978

The effects of denervation and stimulation upon synaptic ultrastructure.

Quantitative studies of synaptic ultrastructure were made in the upper layers of cat cerebral cortex. Tissues were from intact cortex and from long-term (chronic) undercut cortex with or without electrical stimulation. The synaptic effects of chronic electrical stimulation of denervated cortex are most readily understood as growth and remodeling of synaptic elements. Associated with chronic stimulation were increases in: symmetric membrane contacts; areas of round and flat vesicle containing terminals; dendritic shaft contacts; and synaptic contact lengths. Even without stimulation there were indications of synaptic plasticity in denervated cortex; compared with intact cortex, synapses having symmetric membrane contacts showed an increase in bouton area and an increase in synaptic contacts on dendritic shafts. These data are consistent with the observations of others in which axonal terminal growth occurred after differentation. But it appears that chronic electrical stimulation in the adult nervous system promotes significantly more plasticity than occurs without stimulation. In a functional sense stimulation in the present experiments produced effective inhibition which did not occur with denervation alone. Thus the plasticity observed with stimulation had both structural and functional components.

Animals↗
PubMed1989

Regeneration of muscle axons in the frog is directed by diffusible factors from denervated muscle and nerve tubes.

In the frog, peripheral muscle axons regenerate after a lesion to reinnervate the original synaptic sites on muscle fibers. Previous experiments in the frog have shown that satellite cells of the nerve tube direct the outgrowth of regenerating muscle axons over distances of many millimeters. In the present experiments, denervated muscle was used as a target for regenerating muscle axons. Muscle and satellite cells of the nerve tube also were placed in filters to determine if their influence on axonal outgrowth was exerted by diffusible factors. Filters were used with a pore size of 0.22 micron. With this pore size, target cells were isolated from physical contact with the surrounding cells; yet an exchange of fluids--and therefore of molecules released by the target cells--could occur across the filter. In the presence of denervated muscle or satellite cells of the nerve tube in filters, regenerating axons turn and grow toward the target cells. This influence on the direction of axonal outgrowth was produced over distances of 6 mm by muscles and 4 mm by cells of the nerve tubes. This directed outgrowth is in marked contrast to the random pattern of outgrowth in the absence of the targets. The present findings set the stage for tissue culture experiments in which the phenomena observed in vivo can be analyzed in terms of mechanisms. The present finding that denervated muscle attracts regenerating axons means that sufficient material may be available for the characterization and isolation of the relevant molecules.

Animals↗
PubMed2004

Laser microdissection reveals regional and cellular differences in GFAP mRNA upregulation following brain injury, axonal denervation, and amyloid plaque deposition.

Astrocytes are one of the major cell types responding to central nervous system injury. Upregulation of the astrocytic intermediate filament molecule glial fibrillary acidic protein (GFAP) is a key event associated with this reaction. To study the response of astrocytes to different types of brain lesions, GFAP mRNA expression was analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in mouse brain following injury, axonal denervation (entorhinal cortex lesion), and amyloid plaque deposition (APP23 transgenic mice). Analysis of tissue areas surrounding a lesion revealed a 21-fold increase of GFAP mRNA in tissue surrounding an injury site, a 6-fold increase in denervated tissue areas, and a 5-fold increase in plaque containing tissue. To this GFAP mRNA increase, astrocytic proliferation and migration as well as an increase of cellular GFAP mRNA expression within astrocytes could have contributed. To determine the degree of GFAP mRNA upregulation in individual astrocytes, an immunofluorescence protocol was developed to harvest astrocytes selectively by laser microdissection and preserve intact RNA. qRT-PCR analysis of GFAP mRNA in microdissected astrocytes revealed an 82-fold increase in astrocytes surrounding an injury site, a 30-fold increase in astrocytes located in a denervation zone, and an 18-fold increase in astrocytes surrounding an amyloid plaque. These data demonstrate that GFAP mRNA is strongly upregulated within individual reactive astrocytes in response to a lesion. Because astrocytic GFAP mRNA upregulation differs among the three lesioning paradigms, we conclude that the lesion type is an important determinant of postlesional astrocytic reactivity.

Animals↗
PubMed1995

Secretion of plasminogen activator and lysosomal enzymes from mouse skeletal muscle: effect of denervation.

Levels of hydrolytic enzymes increase in skeletal muscle after denervation and their activities in the extracellular matrix appear to be important for interaction between muscle and nerve. Using enzymatic assays for beta-glucuronidase, beta-galactosidase, and plasminogen activator, we show that secretion of these enzymes from mouse skeletal muscle increases after denervation and that drugs interfering with the secretory pathway or the reuptake of enzymes modulate this release. Thus, brefeldin A inhibited secretion of plasminogen activator activity and mannan increased secreted amounts of beta-glucuronidase, but not of beta-galactosidase, in denervated muscle. In innervated muscle, brefeldin A decreased secreted activity of plasminogen activator, but mannan had no effect on secretion of either beta-glucuronidase or beta-galactosidase. Furthermore, secretion of plasminogen activator was temperature dependent. These observations, together with previous studies, suggest that secretion of hydrolytic enzymes from adult skeletal muscle may be of physiological significance in nerve-muscle communication.

Animals↗
PubMed1989

Lack of proliferative response in denervated, reamputated limb regenerates of larval Ambystoma.

This paper describes the response of early four-digit regenerates of axolotls to reamputation and denervation. Reamputation of innervated regenerates led to sharp increases in 3H-thymidine labeling index (LI) and mitotic index (MI) on days 2-5 post-reamputation. This resembles the response of innervated limbs following initial amputation. Regenerates that were denervated at the time of reamputation exhibited no proliferative response through day 5. This is in marked contrast to denervated, original amputation limb stumps, in which LI and MI rise for several days (as in innervated stumps) before falling to background levels. Although myelin was scarce near the level of reamputation, the lack of proliferation cannot be explained solely on that basis. The results are consistent with the possibility that the "neurotrophic factor" that causes stump and blastema cell mitosis is not present in unamputated limbs but is made in response to amputation.

Ambystoma mexicanum↗
PubMed1983

Increased phosphorylation of nuclear protein in myonuclei isolated from denervated skeletal muscle.

The slow-twitch soleus muscle of the rat hindlimb was denervated by cutting the sciatic nerve in the midthigh on one side. A sham operation was performed on the contralateral side to provide a control soleus muscle. At 24, 48, 72, and 120 hours after these surgical procedures, the animals were sacrificed and the nuclei which were isolated from these muscles incubated in a phosphorylating medium containing [gamma-32P]ATP. At the 48 hour denervation period only, the in vitro phosphorylation of TCA-precipitable nuclear proteins was significantly increased compared to control values. Resolution of the SDS-solubilized nuclear proteins by polyacrylamide gel electrophoresis revealed that the increased phosphorylation was more marked in some phosphoproteins than others. The significance of these early denervation changes are discussed with respect to increases in the activities of the nuclear RNA polymerases and changes in the phosphorylation of cytosolic protein.

Animals↗