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.

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

PubMed1981

Effect of denervation on the levels and rates of synthesis of specific enzymes in "fast-twitch" (breast) muscle fibers of the chicken.

It has been well documented that neural information, or the consequences of it, is required for the full phenotypic expression of different skeletal muscle fiber types. In the present work, we investigate the effect of removal of neural information, via surgical denervation, on the levels and rates of synthesis of several enzyme in mature breast ("fast-twitch") "white" muscle fibers of the chicken. Denervation of these muscles resulted in reductions in the concentrations of several glycolytic enzymes to new steady state levels which were only about 50% of normal, and these decreases in enzyme levels were completed within 2 weeks after severing the nerves. In contrast, denervation for as long as 6 weeks did not have a significant effect on the levels of creatine-P kinase molecules in this muscle type. The decreased level of the skeletal muscle-specific aldolase A4 isoenzyme in denervated breast muscle fibers was associated with a 2- to 3-fold reduction in the relative rate of synthesis of this enzyme following denervation. As expected, denervation had no appreciable effect on the relative rate of synthesis of the muscle-specific MM isoenzyme of creatine-P kinase in this muscle. Our results show that neural information, or the consequences of it, is required to maintain the levels and rates of synthesis of glycolytic enzymes but not of creatine-P kinase in mature fast-twitch muscle fibers. We suggest that denervation results in a partial "dedifferentiation" of these fibers.

Animals↗

PubMed1981

Denervation supersensitivity to norepinephrine in the guinea-pig vas deferens in vivo and in vitro: influence of the bathing solution.

After seven days of denervation there was a 10.7-fold increase in sensitivity without a significant alteration of the maximum response to norepinephrine (NE) in the guinea-pig vas deferens, in vivo. On the second postoperative day there was a significant increase in sensitivity and a decrease of the maximum response to NE in experiments performed in vivo. In the isolated guinea-pig vas deferens, immersed in Kreb's-Henseleit solution, an increased sensitivity to NE was demonstrable after two and seven days of denervation. However, an increased maximum response to NE was demonstrable only after seven days of denervation. Using McEwen solution there was no significant increase in the maximum response to NE in the seven-days denervated guinea-pig vas deferens. Slight alterations of the ionic composition of the physiological salt solutions prevented the demonstration of denervation-induced augmentation of the maximum response to NE in the isolated guinea-pig vas deferens. The characteristics of cocaine-induced supersensitivity to NE in the isolated guinea-pig vas deferens did not differ in vivo and were not affected by small changes in the ionic composition of the bathing solution. The absence of a postjunctional component of denervation supersensitivity to NE in the guinea-pig vas deferens, in vivo, is suggested. Furthermore, the demonstration of the postjunctional component of denervation supersensitivity to NE in the isolated guinea-pig vas deferens appears to be dependent of the composition of the bathing solution used.

Animals↗

PubMed1994

Pancreatic denervation does not influence glucose-induced insulin response.

BACKGROUND: Pancreatic transplantation results in denervation and loss of splanchnic venous drainage and inflicts numerous metabolic abnormalities. However, it is unclear whether denervation or loss of splanchnic venous drainage is responsible for the observed metabolic abnormalities. METHODS: To discern denervation's role in these abnormalities, four mongrel dogs underwent extrinsic pancreatic denervation with preservation of splanchnic venous drainage. These animals, as well as four innervated control subjects, underwent standardized enteral and intravenous glucose tolerance testing. In addition, hyperglycemic clamps that maintained stable serum glucose elevations at either 2.8 or 8.3 mmol/L above basal were also performed. RESULTS: Prestimulated glucose (90.4 +/- 2.7 vs 92.6 +/- 4.9 mg/dl) and insulin levels (6.8 +/- 1.7 vs 8.5 +/- 1.4 muU/ml) did not differ between innervated and denervated groups. Integrated incremental enteral glucose (5320 +/- 1900 vs 7790 +/- 2000 mg/dl) and insulin (2565 +/- 350 vs 2836 +/- 598 muU/ml) levels did not differ between groups. Integrated incremental intravenous glucose (3680 +/- 400 vs 3950 +/- 1000 mg/dl) and insulin (741 +/- 70 vs 1053 +/- 326 muU/ml) levels also did not differ. During glucose clamp studies, time-weighted 60 to 120-minute insulin levels (2.8 mmol/L, 30 +/- 5.0 vs 24 +/- 4.8 muU/ml; 8.3 mmol/L, 57 +/- 5.9 vs 50 +/- 9.8 muU/ml) did not differ between groups. In addition, glucose disposal, cyclic insulin release, and insulin sensitivity indexes were unchanged by denervation. CONCLUSIONS: Extrinsic pancreatic neural elements are not necessary for cyclic insulin release in response to enteral or parenteral glucose challenge or physiologic and pharmacologic hyperglycemia. These findings suggest that the previously described posttransplantation glucose and insulin abnormalities are not attributable to denervation.

Animals↗

PubMed1994

Embryonic neural cell adhesion molecule (N-CAM) is elevated in the denervated rat dentate gyrus.

We evaluated the immunohistological changes in neural cell adhesion molecule (N-CAM) expression in the adult rat dentate gyrus during the period of synaptic degeneration, axonal sprouting, and synaptogenesis following ipsilateral entorhinal cortex (ERC) lesion. This lesion denervates the outer two-thirds of the dentate granule cells dendrites and induces compensatory sprouting from the subjacent inner one-third into the denervated zone, as well as reactive synaptogenesis in the denervated outer molecular layer. In unlesioned adult hippocampus, antibodies to total N-CAM stained the inner molecular layer intensely, and the outer molecular layer (ML) more lightly. After ERC lesion the intense staining of the inner layer widened, the expansion following the known temporal sequence of commissural and associational (C/A) axon sprouting into the denervated zone. In normal unlesioned controls there was very light, uniform staining of the ML with antibodies directed against embryonic N-CAM (eN-CAM). By 2 d post-ERC lesion, the outer two-thirds of the ML stained robustly with antibody to eN-CAM. This area of intense staining receded as the C/A axon collaterals from the inner one-third entered the denervated zone, so that by 30 d the intense eN-CAM staining only occupied the outer half of the ML. The increased expression of eN-CAM remained present at 60 d post-ERC lesion, past the point that synaptic volume density has returned to normal levels in the denervated zone. Ultrastructural studies showed that the newly expressed eN-CAM was located on the surface of dendrites in the denervated zone, but was not found at the synaptic contacts.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

PubMed1993

Electrophysiology of dopamine-denervated striatal neurons. Implications for Parkinson's disease.

Unilateral 6-hydroxydopamine-induced lesions of the substantia nigra have been used as an experimental model for Parkinson's disease. Although the biochemical and the behavioural effects of striatal denervation have been widely characterized, the physiological and pharmacological changes caused by dopamine depletion at the cellular level are still unknown. We studied the electrical activity of single rat striatal neurons recorded intracellularly in vitro from a brain slice preparation. Recordings were obtained at different periods after the denervation (4, 6, 8 months). In dopamine-denervated slices, unlike naive slices, most of the neurons showed spontaneous depolarizing postsynaptic potentials. The percentage of cells showing spontaneous depolarizing postsynaptic potentials was maximal 4 months after the denervation. In most of the dopamine-denervated neurons (60%) spontaneous depolarizing postsynaptic potentials were reversibly blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM), an antagonist of non-N-methyl-D-aspartate glutamate receptors. In some neurons, however, the amplitude of spontaneous depolarizing postsynaptic potentials was reduced by bicuculline (30 microM) suggesting that they were mediated by the release of endogenous gamma-aminobutyric acid (GABA). Intrinsic membrane properties (membrane potential, input resistance and firing pattern) and postsynaptic responses to different agonists of excitatory amino acid receptors were not altered in neurons recorded from dopamine-depleted slices. In dopamine-depleted slices, unlike in naive slices, LY 171555 (0.1-10 microM), a D2 dopamine receptor agonist, reduced the frequency and the amplitude of CNQX-sensitive spontaneous depolarizing postsynaptic potentials and reduced the amplitude of glutamate-mediated synaptic potentials evoked by cortical stimulation. LY 171555 did not affect the membrane responses to exogenous glutamate. SKF 38393 (3 microM), a D1 dopamine receptor agonist, decreased postsynaptic excitability of striatal neurons recorded from naive animals. On the contrary, this agonist was ineffective in most of the cells obtained from dopamine-depleted slices. These results suggest that dopamine-denervation augments neuronal excitability in the striatum. Abnormal excitability of striatal neurons is not caused by changes of the intrinsic membrane properties of these cells, but is the result of increased glutamatergic cortical inputs to the striatum. Dopamine-denervation also alters the physiological responses to dopamine receptor stimulation. Nigral lesions induce supersensitivity of D2 dopamine receptors controlling the release of glutamate and reduce the inhibitory influence of D1 receptors at postsynaptic level. These functional changes of the striatal neurons may alter the output signals from the striatum to the other structures of the basal ganglia and then produce most of the physiopathological changes observed in Parkinson's disease.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

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↗

PubMed1989

Non-additivity of D2 receptor proliferation induced by dopamine denervation and chronic selective antagonist administration: evidence from quantitative autoradiography indicates a single mechanism of action.

Experiments were conducted to investigate whether chronic dopamine (DA) D2 receptor blockade and DA denervation exert additive effects on striatal D2 receptor density. We employed for the first time chronic treatment with a pure D2 antagonist, metoclopramide, and measured regional striatal DA receptor binding with quantitative receptor autoradiography. Rats with extensive unilateral DA denervation induced by intracerebral 6-hydroxydopamine (6-OHDA) were injected daily for 21 days with either metoclopramide (30 mg/kg i.p.) or saline. Following a 72-h drug wash-out period, rats were sacrificed and brain sections through the caudate-putamen and nucleus accumbens were incubated with [3H]spiroperidol or [3H]SCH 23390 to assay D2 and D1 receptors, respectively. Autoradiographic analysis revealed that chronic metoclopramide treatment increased the density of D2 sites in the intact hemisphere for all regions examined without further augmenting the already increased density of D2 receptors seen in the 6-OHDA-treated hemisphere. In addition, chronic metoclopramide and 6-OHDA treatment by themselves exhibited remarkably parallel anterior-posterior gradients in their effects on D2 receptor density. D1 receptor density was not affected by metoclopramide treatment but was slightly reduced in the DA-denervated hemisphere. [3H]Mazindol labelling of high-affinity DA uptake sites indicated that the extent of DA denervation was greater than 98% in both saline- and metoclopramide-treated rats. These findings are consistent with the view that chronic D2 receptor blockade and DA denervation act via a single, common mechanism to increase D2 receptor density. Work from other laboratories, in which additive effects of denervation and chronic neuroleptic treatment have been purported, may have resulted from incomplete denervation. Experimental discrepancies may also be due to differing means by which the mesotelencephalic dopaminergic neurons are injured.

Animals↗

PubMed1988

The effect of liver denervation on the consumption of various diets by rats.

Liver afferents have been proposed to influence food intake control, however, previous studies have shown that chow (pellet) intake is apparently not altered in total liver denervated rats. The present study explored whether total liver denervation could alter the rats' intake of various diets other than chow pellets. Total liver denervations were verified using staining histological and monoamine histofluorescence techniques. The denervated and sham operated rats were given short-term (4-6 days) exposure to four diets: (diet 1, chow plus a 32% w/v sucrose-water solution; diet 2, 1:1 mixture of powdered chow and granular glucose; diet 3, 33% w/w Crisco and powdered chow mixture and diet 4, a 5% w/v glucose-water solution plus chow. Body weight gains were not affected-by either surgery or diet exposure. Daily consumptions of the diets were similar in both groups, nevertheless, there was a trend for the denervated rats to consume slightly more of a high fat diet, which lends support for one hypothesized liver satiety mechanism. Also, the denervated rats consumed less (an average 5 kcal/day) of the 5% glucose solution (one hypothesis tested would predict an increase consumption of glucose by the denervated rats). Thus the liver may play a role, albeit small, through several ill defined mechanism(s) in the regulation of feeding.

Afferent Pathways↗

PubMed1993

The effects of chronic administration of chloroquine and quinacrine on the response of normal and denervated smooth muscle to agonist drugs.

The functional effects of chronic administration of 60 mg kg-1 chloroquine or quinacrine given as daily intraperitoneal injections for 84 days on normal and denervated expansor secundariorum muscles, a smooth muscle from the wing of chicks wholly innervated by noradrenergic nerves, have been investigated. Administration of quinacrine, but not chloroquine, blocked responses to noradrenergic nerve stimulation. Surgical denervation abolished responses to nerve stimulation. Contraction of the expansor muscle induced by noradrenaline was not changed by chronic administration of chloroquine or quinacrine, and both drugs did not influence denervation supersensitivity of expansor muscles to noradrenaline. Expansor muscles were unresponsive to acetylcholine (ACh) and histamine, but muscles from chicks chronically treated with chloroquine and quinacrine were responsive to ACh and histamine. Denervation also restored the response of expansor muscles to ACh and histamine and the responses were greater for denervated muscles from chronically treated chicks; these changes were more marked with quinacrine. Expansor muscles were contracted by potassium chloride (KCl) and 5-hydroxytryptamine (5-HT), and chronic treatment increased the responsiveness of expansor muscles to KCl. Denervation increased the responsiveness of expansor muscles to KCl and 5-HT; this effect was more pronounced in denervated muscles from quinacrine-treated chicks. The findings indicate that chronic administration of quinacrine sensitizes smooth muscles to agonist drugs by blocking noradrenergic transmission to induce postjunctional changes and exerting a direct action on the smooth muscle; these actions are less pronounced with chloroquine administration.

Acetylcholine↗

PubMed1989

Ventricular arrhythmias and local electrograms after chronic regional denervation of the ischemic area in the pig heart.

Cardiac denervation has been proved to reduce the incidence of coronary occlusion arrhythmias in digs, but the effect of limiting the extent of sympathectomy to the ischemic area, particularly in hearts with sparse coronary collateral circulation, as in the human heart, needs further investigation. Ventricular arrhythmias and changes in epicardial direct current electrograms induced during acute left anterior descending coronary artery occlusion were recorded in 14 pigs subjected to regional denervation of the ischemic area 2 weeks before; these were compared with findings in 14 sham-operated control pigs. Regional denervation was induced by pericoronary application of phenol above the occlusion site and it was confirmed by the loss of myocardial catecholamine histofluorescence. During 35 min of ischemia, significant differences in occurrence of ventricular premature beats, ventricular tachycardia, ST segment elevation, TQ segment depression and epicardial activation delays were observed between the two groups of experiments, with lower values of each variable in the denervated hearts. Ventricular fibrillation occurred 32 times in 11 control pigs and only 15 times in eight denervated hearts. In contrast, programmed ventricular extrastimuli delivered during 35 to 50 min of ischemia induced 39 fibrillatory episodes in 13 denervated hearts and only 14 episodes in seven control pigs. Thus, denervation limited to the ischemic area in hearts with a human-like coronary artery pattern was associated with a decrease in the magnitude of early ischemic arrhythmias and electrocardiographic alterations, but the procedure was unable to prevent early induction of ventricular fibrillation.

Animals↗

PubMed1993

Regional cardiac sympathetic denervation in patients with ventricular tachycardia in the absence of coronary artery disease.

OBJECTIVES: The aim of this study was to determine whether patients with ventricular arrhythmias in the absence of coronary artery disease also have abnormalities in sympathetic innervation. BACKGROUND: We have previously shown by cardiac sympathetic scintigraphy using iodine-123-metaiodobenzylguanidine (I-123-MIBG) that patients with ventricular tachycardia after myocardial infarction have regional cardiac sympathetic denervation. It is not known whether patients with ventricular tachycardia in the absence of coronary artery disease also have regional cardiac sympathetic denervation. METHODS: We performed cardiac I-123-MIBG and thallium-201 single-photon emission computed tomographic (SPECT) scans at rest in 18 patients (mean age 47 +/- 18 years) with cardiomyopathy (n = 6), left ventricular hypertrophy (n = 1), valvular disease (n = 2) or a structurally normal heart (n = 9) who presented with monomorphic (n = 15) or polymorphic (n = 3) ventricular tachycardia. These scans were compared with scans in 12 control patients without ventricular tachycardia (mean age 30 +/- 17 years) who had cardiomyopathy (n = 3) or a structurally normal heart (n = 9). Cardiac sympathetic denervation was defined as myocardial areas having thallium uptake with reduced or absent I-123-MIBG uptake. RESULTS: Twelve (67%) of 18 patients with ventricular tachycardia had regional cardiac sympathetic denervation compared with 1 (8%) of 12 patients who did not have ventricular tachycardia (p = 0.002). In the nine patients with a structurally normal heart and ventricular tachycardia, five (55%) patients had regional cardiac sympathetic denervation compared with zero of nine control patients with a structurally normal heart (p = 0.029). Five patients underwent right ventricular radiofrequency ablation for ventricular tachycardia, and sympathetic denervation was adjacent to the ablation site in one of these patients. CONCLUSIONS: Patients with ventricular tachycardia in the absence of coronary artery disease have abnormal cardiac sympathetic innervation detectable by cardiac sympathetic scintigraphy. The role of regional cardiac sympathetic denervation in arrhythmogenesis remains to be determined.

3-Iodobenzylguanidine↗

PubMed2001

Denervation alters protein-lipid interactions in membrane fractions from electrocytes of Electrophorus electricus (L.).

Protein-lipid interactions are studied in normal and denervated electrocytes from Electrophorus electricus (L.). Structural modifications of the lipid micro-environment encircling integral membrane proteins in membrane fractions presenting Na(+),K(+)-ATPase activity are investigated using ESR spectroscopy of stearic acid spin labeled at the 14th carbon (14-SASL). The microsomal fraction derived from the innervated electric organ exhibits, on a discontinuous sucrose gradient, a bimodal distribution of the Na(+),K(+)-ATPase activity, bands a and b. Band b is almost absent in microsomes from the denervated organ, and band a', with the same density as band a has lower Na(+),K(+)-ATPase activity. Band a' presents a larger ratio of protein-interacting lipids than band a. Analysis of the lipid stoichiometry at the protein interface indicates that denervation causes at least a twofold average decrease on protein oligomerization. Physical inactivity and denervation have similar effects on protein-lipid interactions. Denervation also influences the selectivity of proteins for fatty acids. Experiments in decreasing pH conditions performed to verify the influence of stearic acid negative charge on protein interaction revealed that denervation produces loss of charge selectivity. The observed modifications on molecular interactions induced by denervation may have importance to explain modulation of enzyme activity.

Animals↗

PubMed2000

Effect of phospholipase C and protein kinase C following cholinergic denervation and hippocampal sympathetic ingrowth in rat hippocampus.

Following cholinergic denervation of the hippocampus by medial septal lesions, an unusual neuronal reorganization occurs in which peripheral adrenergic fibers arising from the superior cervical ganglia grow into the hippocampus (hippocampal sympathetic ingrowth). We have reported previously that cholinergic denervation and hippocampal sympathetic ingrowth differentially affected cholinergically stimulated phosphoinositide hydrolysis, concentration and affinity of muscarinic receptors, Go-protein level and protein kinase C activity. To complete these studies, we determined whether cholinergic denervation and hippocampal sympathetic ingrowth influenced phospholipase C and protein kinase C expression in dorsal hippocampal membranes and cytosol. Using immunoblotting methods, the results showed that the 100,000 mol. wt subunit of phospholipase Cbeta was increased in the membrane fraction in the hippocampal sympathetic ingrowth group by 45% compared to controls and the 150,000 mol.wt subunit was increased by 75% and 59% compared to controls and cholinergic denervation, respectively. For protein kinase C detection, immunoblots were prepared using antibodies selective for "classical" protein kinase C members (alpha, beta, gamma) and for the "novel" protein kinase C subfamily members (delta, θ). Membrane protein kinase Cbeta was decreased in hippocampal sympathetic ingrowth by 35% compared to controls and by 41% compared to cytosolic hippocampal sympathetic ingrowth. Membrane protein kinase Cbeta was decreased in cholinergic denervation by 28% compared to controls. When compared to membranes from controls and the cholinergic denervation group, and to cytosolic fractions from the hippocampal sympathetic ingrowth groups, respectively, the following membrane protein kinase isoforms were found to be decreased by hippocampal sympathetic ingrowth: gamma by 55%, 40% and 57%; delta by 91.5%, 70% and 120%; theta; by 95%, 100% and 86%.In conclusion, our results may indicate the connection between the previously reported differential influence of hippocampal sympathetic ingrowth and cholinergic denervation on cholinergically stimulated phosphoinositol hydrolysis. The "normalization" of phosphoinositol hydrolysis found in hippocampal sympathetic ingrowth may be due to the increase in phospholipase Cbeta expression in hippocampal sympathetic ingrowth membrane fractions. Since the activation of protein kinase C is known to block phosphoinositol hydrolysis, hippocampal sympathetic ingrowth "normalization" of phosphoinositol hydrolysis may result from a reduction in protein kinase expression in hippocampal sympathetic ingrowth membranes.

Animals↗

PubMed2002

Asymmetrical changes of excitatory synaptic transmission in dopamine-denervated striatum after transient forebrain ischemia.

Spiny neurons in the neostriatum are highly vulnerable to cerebral ischemia. Recent studies have shown that the postischemic cell death in the right striatum was reduced after ipsilateral dopamine denervation whereas no protection was observed in the left striatum after dopamine denervation in the left side. In order to reveal the mechanisms of such asymmetrical protection, electrophysiological changes of dopamine-denervated striatal neurons were compared after ischemia between the left and right striatum using intracellular recording and staining techniques in vivo. No difference in cortically evoked initial excitatory postsynaptic potentials was found between the left and right striatum in intact animals after ipsilateral dopamine denervation. The initial excitatory postsynaptic potentials in the dopamine-denervated right striatum were suppressed after transient forebrain ischemia while no significant changes were found in the dopamine-denervated left striatum. Paired-pulse tests suggested that these changes involved presynaptic mechanisms. Although the incidence of a late depolarizing postsynaptic potential elicited by cortical stimulation increased after ischemia in both sides, the increase was greater in the left side. The analysis of current-voltage relationship of spiny neurons indicated that inward rectification in the left striatum transiently disappeared shortly after ischemia whereas that in the right side remained unchanged. The intrinsic excitability of spiny neurons in both sides were suppressed after ischemia, however, the suppression in the right side was stronger than in the left side. The above results demonstrate that after ipsilateral dopamine denervation, the depression of excitatory synaptic transmission and neuronal excitability in the right striatum is more severe than that in the left striatum following ischemia. The depression of excitatory synaptic transmission and neuronal excitability, therefore, might play an important role in neural protection after ischemic insult.

Animals↗

PubMed1983

Sympathetic denervation impairs agonist-stimulated phosphatidylinositol metabolism in rat parotid glands.

Substance P, muscarinic and alpha-adrenoceptor agonists stimulated the incorporation of [3H]inositol into phosphatidylinositol in rat parotid gland slices. Surgical denervation of the sympathetic input to the rat parotid gland by superior cervical ganglionectomy produced marked reductions in these responses. The stimulated incorporation of radiolabelled precursors into phosphatidylinositol is a measure of its resynthesis after receptor-mediated breakdown of inositol phospholipids. We therefore examined the enzymic site of the lesion induced by sympathetic denervation using parotid gland slices labelled with either [3H]inositol or [32P]phosphate and stimulated with substance P. Receptor-activated phospholipase C attack upon [3H]inositol phospholipids was assayed by measuring the formation of [3H]inositol 1-phosphate in the presence of 10 mM-Li+ to inhibit further breakdown. It was not affected by denervation. Substance P elicited a rapid breakdown of phosphatidylinositol 4,5-bisphosphate and this response was reduced in the denervated gland. The second step in stimulated phosphatidylinositol turnover, phosphorylation of diacylglycerol to phosphatidate was not affected by denervation. Sympathetic denervation appears to induce a specific enzymic lesion in the parotid gland that impairs receptor-stimulated resynthesis of phosphatidylinositol from phosphatidate. This change in membrane lipid metabolism may be related to a number of the effects of sympathetic denervation, such as agonist supersensitivity, reduced gland cell proliferation and induction of new surface receptors.

Animals↗

PubMed2004

Effects of vitamin E and electrical stimulation on the denervated rat gastrocnemius muscle malondialdehyde and glutathione levels.

Effects of vitamin E treatment and local electrical stimulation on progression of atrophy in the denervated rat gastrocnemius muscle were studied. Denervation was performed by right leg sciatic nerve axotomy. Electrical stimulation (3-10 mA ms(-1), 10 min per day for 7 days) was applied to the right gastrocnemius muscle starting from day 1 of denervation. The muscle samples were assayed for malondialdehyde (MDA) and glutathione levels, as well as the histological appearance after 8 days of denervation. MDA levels were markedly increased following denervation. However, electrical stimulation, vitamin E treatment (30 mg kg(-1), i.m., everyday for 7 days), and combination of electrical stimulation and vitamin E treatment markedly reduced MDA levels. Glutathione levels were significantly decreased in the denervation group. Electrical stimulation, vitamin E treatment, and electrical stimulation plus vitamin E treatment prevented these reductions in glutathione levels. In the vitamin E treatment group, glutathione levels were markedly higher than in the control group. These results indicate that electrical stimulation and vitamin E treatment alone, or in combination, were able to prevent the effects of denervation on muscle atrophy.

Analysis of Variance↗

PubMed1991

Induced ventricular arrhythmias in regionally denervated porcine heart with healed myocardial infarction.

STUDY OBJECTIVE: The aim was to test the hypothesis that chronic sympathetic denervation of the boundaries of a healed myocardial infarction may modify the arrhythmogenic response to programmed electrical stimulation. DESIGN: Electrical induction of ventricular arrhythmias and infarct size were evaluated in a control group of pigs with a one month old myocardial infarction induced by ligature of the left anterior descending coronary artery below the first diagonal branch. These were compared with a group of similarly infarcted pigs subjected to regional denervation of the peri-infarction area induced by topical pericoronary application of phenol. Denervation was verified by the absence of adrenergic histofluorescent reaction to glyoxylic acid in myocardial samples. EXPERIMENTAL MATERIAL: 24 pigs (weight 15-20 kg) with myocardial infarction were studied, 13 of which were subjected to regional peri-infarction denervation, and 11 acted as controls. MEASUREMENTS AND MAIN RESULTS: Programmed ventricular stimulation with one to four extrastimuli at 500 and 400 ms basic cycle length at the left and right ventricles induced fewer episodes of ventricular fibrillation in the denervated than in the non-denervated group (five episodes in three pigs v 14 in nine pigs, p less than 0.005), but more episodes of sustained ventricular tachycardia (79 in eight pigs v 23 in two, p less than 0.001). Unlike fibrillation, induction of ventricular tachycardia increased with multiple extrastimuli and with short basic cycle length. The denervated preparations tended to develop smaller infarcts but this difference was not statistically significant: infarct weight (g) relative to total ventricular mass (g) = 7.2 (SD 2.4)% v 10.5(4.5)%. CONCLUSIONS: Neural integrity of the non-ischaemic myocardium bordering a healed infarction modulates inducibility of ventricular tachycardia and fibrillation during programmed ventricular stimulation.

Animals↗

PubMedDate not supplied

Denervation hypertrophy of muscle: MR features.

OBJECTIVE: Denervation hypertrophy is an entity well recognized in the neurology literature, but with little mention in the radiology literature. Denervation hypertrophy occurs when a muscle paradoxically enlarges rather than atrophies in response to loss of innervation. The purpose of this report is to describe the MR appearance of true hypertrophy and pseudohypertrophy of muscle following denervation. MATERIALS AND METHODS: The clinical data and MRI findings in three patients with muscle enlargement due to denervation hypertrophy are reviewed retrospectively. Two women and one man aged 19-80 years were included. Denervation resulted from spinal stenosis in one patient, a herniated thoracic disc in another, and spina bifida with a tethered cord in the third. RESULTS: True hypertrophy of a single muscle was seen in one patient and pseudohypertrophy of two muscles was present in one patient. One patient had one muscle with true hypertrophy and one muscle with pseudohypertrophy. Electromyographic examination was performed and was consistent with denervation in two patients. Biopsy confirmation of denervation was obtained in two patients. All five abnormal muscles exhibited increased volume, well defined margins, and normal contour. In true hypertrophy the enlarged muscle was isointense with normal muscle on all MRI sequences. In pseudohypertrophy the MRI appearance was consistent with an excessive amount of fat interspersed throughout normal muscle. CONCLUSION: Magnetic resonance in these cases established muscle hypertrophy rather than neoplasm as the cause of a palpable mass. If muscle hypertrophy or pseudohypertrophy is seen on an MR examination of an enlarged extremity, the possibility of an underlying neurologic process should be considered.

Adult↗