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PubMed1993

Changes in mitochondrial calmitine and calcium in rat denervated skeletal muscle after injection of a myotoxic drug, chlorpromazine.

1. Calmitine and mitochondrial calcium were studied after injection of chlorpromazine into control and denervated gastrocnemius muscle in rat. 2. Calmitine decreased under the effect of chlorpromazine and then increased again. Regenerative capacity was more marked for denervated than control muscle. Calcium increased and then returned to its normal level in control muscle while remaining elevated in denervated muscle. 3. Thus, it would appear that calmitine synthesis can occur in the absence of innervation and that denervation, which probably causes disturbances in mitochondrial calcium regulation systems, may prevent total regeneration of muscle after an injury.

Animals↗
PubMed1989

Spatial and temporal expression of acetylcholine receptor RNAs in innervated and denervated rat soleus muscle.

In adult vertebrate skeletal muscle acetylcholine receptors are localized to the neuromuscular junction. Upon denervation, this distribution changes, with new receptors appearing in extrajunctional regions of the muscle fiber. The location of acetylcholine receptors in innervated or denervated muscle may result, in part, from the distribution of their RNAs. This was tested by assaying for receptor RNAs in junctional and extrajunctional regions of innervated and denervated rat soleus muscle using in situ hybridization and RNAase protection assays. These experiments showed alpha, beta, and delta subunit RNAs concentrated beneath the endplates of innervated muscle fibers. Following denervation, there was an unequal distribution of receptor RNAs along the muscle fiber, with highest levels occurring in extrajunctional regions near the endplate. These data are consistent with a nonuniform pattern of gene expression in adult skeletal muscle fibers.

Animals↗
PubMed1995

Motor activity patterns in rat soleus muscle after neonatal partial denervation.

In normal rats the development of organized patterns of hind limb movements takes place during the first three weeks of life. After removal of a part of the rat soleus muscle's innervation in 5-day-old animals, the remaining motoneurones occupy a large peripheral field. The possibility that the development of the normal activity patterns of these motor units may be altered was studied. The EMG activity of the soleus muscles partially denervated at five days was compared to that of the contralateral unoperated muscles during spontaneous locomotion and induced reflex activity in animals at various ages. Like a normal soleus the partially denervated soleus developed with age a tonic activity pattern but the aggregate activity recorded from the partially denervated soleus was less than that in the control muscle. However, the amount of activity per motor unit was higher in the operated than in the control muscles, since these had only one-third to half of their normal complement of motor units. During locomotion both soleus muscles were activated like typical ankle extensors during the stance phase of the step cycle, but the burst duration of the operated muscle was significantly shorter. We conclude that partial denervation shortly after birth leads to an overall increase in activity of the remaining soleus motor units but does not drastically alter their temporal pattern of use during locomotion.

Animals↗
PubMed2005

Evaluation of ventral cardiac denervation as a prophylaxis against atrial fibrillation after coronary artery bypass grafting.

BACKGROUND: To evaluate the efficacy of ventral cardiac denervation as a prophylaxis against post-coronary artery bypass grafting (CABG) atrial fibrillation (AF). METHODS: Seventy consecutive patients who underwent CABG (group A) were compared to 70 consecutive subsequent patients who underwent CABG + ventral cardiac denervation (group B). Both groups were well-matched for age, gender, disease severity, LV function, Euro scores, Parsonnet scores, preoperative beta-blockers, Ca-channel blockers, digoxin, and angiotensin converting enzyme inhibitors. The same cardioplegia, bypass, and operation techniques were used in all cases. Denervation before initiating bypass increased operation time by approximately 5 minutes. Heart rate and rhythm were monitored by continuous telemetry until postoperative day 5 and then 4- hourly until discharge. RESULTS: The cross-clamp time (p = 0.6), bypass time (p = 0.1), number of grafts (p = 0.9), inotrope usage (p = 0.4), reexploration rate (p = 1), postoperative myocardial infarction (none in either group), blood loss (p = 0.7), and length of stay (p = 0.8) were comparable in both groups. There was no significant difference in the incidence of AF; 34% in group A versus 29% in group B (p = 0.3). CONCLUSIONS: Ventral cardiac denervation failed to significantly reduce the incidence of AF following coronary revascularization in our study.

Aged↗
PubMed2004

Opposite morphological responses of partially denervated cortical serotonergic and noradrenergic axons to repeated stress in adult rats.

We examined plastic changes in serotonin (5-HT) axons following repeated stress in the adult rat brain, and compared stress-induced changes between 5-HT and noradrenaline (NA) axons. We locally injected the specific neurotoxin to 5-HT axons or to NA axons into the frontal cortex to cause partial denervation. The animals were mildly restrained from 1 day after the neurotoxin injection and this stress was repeated daily for 20 min during the first 2 days and for 40 min during the next 11 days. On the fourteenth day after injection, the brains were removed to visualize 5-HT and NA axons by immunohistochemistry. Repeated stress did not significantly alter the denervation area of 5-HT or NA axons, but the density of 5-HT axons was increased whereas that of NA axons was decreased in cortical regions outside the denervation site. In addition, the expression of brain-derived neurotrophic factor (BDNF) was increased in cortical regions where the 5-HT axon density was increased in response to stress. These results suggest that repeated stress causes opposite changes in the morphology of partially denervated 5-HT and NA axons in the cerebral cortex. The stress-induced increase in BDNF expression may contribute to 5-HT axon sprouting following repeated stress.

5,6-Dihydroxytryptamine↗
PubMed2004

Muscle magnetic resonance imaging of denervation and reinnervation: correlation with electrophysiology and histology.

A signal increase in denervated muscle on magnetic resonance imaging (MRI) has been described in several clinical and experimental studies. Here, we studied the time course of T2-relaxation time changes in denervation and subsequent reinnervation in a rat model and correlated the findings with electrophysiology and quantitative histology. A prolongation of the T2 relaxation time in muscles was present 48 h after denervation, which was paralleled by spontaneous activity on electromyography (EMG). Histologically, there was a marked enlargement of the capillaries at that time point, indicating increased blood volume. The relaxation time changes peaked 3 weeks after beginning of nerve regeneration identified by EMG. Subsequently, the T2 prolongation normalized until 10 weeks after beginning of regeneration which was associated with a histological regression of the capillary enlargement. MRI closely mirrors the electrophysiological changes following denervation and reinnervation and may thus be used as adjunct to electrophysiology. The pathophysiological basis for the MR relaxation time changes is predominantly the enlargement of the capillary bed.

Animals↗
PubMed2005

Denervation-induced spatiotemporal upregulation of ephrin-A2 in the mouse hippocampus after transections of the perforant path.

Transections of the entorhinal afferent fibers to hippocampus, perforant path (PP), result in the denervation in specific hippocampal subregions, which is followed by a series of plastic events including axon sprouting and reactive synaptogenesis. Many growth-associated molecules are thought to participate in these events. In the present study, we proved the upregulation of ephrin-A2 in the denervated areas of the ipsilateral hippocampus following PP transections. Interestingly, when the elevation of ephrin-A2 reached the maximum axon sprouting in the denervated areas almost finished, implying the possible inhibitory effect of ephrin-A2 on sprouting. In addition, ephrin-A2 expression was observed in synapses during reactive synaptogenesis, suggesting that this molecule might also be implicated in the formation and maturation of synapses in the denervated areas.

Animals↗
PubMed2006

Ventral cardiac denervation increased right coronary arterial blood flow.

BACKGROUND: Cardiac denervation accompanied with coronary artery bypass surgery has been widely performed for the treatment of vasospastic angina associated with atherosclerotic coronary artery disease. However, the effect of cardiac denervation on phasic coronary blood flow patterns of the left anterior descending coronary artery (LAD), left circumflex coronary artery (LCX) and right coronary artery (RCA) remains unknown. This study aimed to investigate the effect of cardiac denervation on phasic coronary blood flow patterns of the LAD, LCX and RCA. METHODS: Phasic coronary blood flow patterns were analyzed using three flow probes placed around the LAD, LCX and RCA with and without LAD stenosis. Ventral cardiac denervation (VCD) was performed in 8 pigs, and 16 pigs were used as control subjects. Autonomic activities before and after the VCD were quantified by wavelet analysis of heart rate variability. RESULTS: The mean LAD flow (34.4+/-9.4 to 32.6+/-7.1 ml/min, p=0.638) and mean LCX flow (26.3+/-10.2 to 27.2+/-6.0 ml/min, p=0.825) showed no significant change after VCD, while the mean RCA flow (31.3+/-9.0 to 38.2+/-11.2 ml/min, p=0.003) significantly increased. The hemodynamic variables in the VCD group were well maintained after creation of LAD stenosis, while they deteriorated in the control group. The low-frequency components, high-frequency components and their ratio did not change after VCD. CONCLUSIONS: VCD prevented the deterioration of cardiac function after creation of an LAD stenosis and resulted in an increase of the mean RCA flow. VCD did not affect autonomic nervous system activity.

Angina Pectoris↗
PubMed2005

Insulin-like growth factor I slows the rate of denervation induced skeletal muscle atrophy.

Loss of the nerve supply to skeletal muscle results in a relentless loss of muscle mass (atrophy) over time. The ability of insulin-like growth factor-1 to reduce atrophy resulting from denervation was examined after transection of the sciatic nerve in transgenic MLC/mIGF-1 mice that over-express mIGF-1 specifically in differentiated myofibres. The cross sectional area (CSA) of all types of myofibres and specifically type IIB myofibres was measured in tibialis anterior muscles from transgenic and wild-type mice at 28 days after denervation. There was a marked myofibre atrophy ( approximately 60%) in the muscles of wild-type mice over this time with increased numbers of myofibres with small CSA. In the muscles of MLC/mIGF-1 mice, over-expression of mIGF-1 reduced the rate of denervation induced myofibre atrophy by approximately 30% and preserved myofibres with larger CSA, compared to wild-type muscles. It is proposed that the protective effect of mIGF-1 on denervated myofibres might be due to reduced protein breakdown.

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↗
PubMed1994

Early L-dopa treatment initially retards but later enhances dopamine receptor supersensitivity following unilateral dopamine denervation.

Rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of nigrostriatal dopamine neurons were administered 25 mg/kg L-DOPA methyl ester/2 mg/kg carbidopa once or twice per day or saline in separate treatment groups for 13 days. Treatment was initiated within 18-20 h postoperative, well-before the onset of denervation supersensitivity. Contralateral rotation emerged as a response to L-DOPA on day 7 postoperative first in the L-DOPA once/day group and then on day 9 for the L-DOPA twice/day group. Thus, early postoperative L-DOPA treatment retarded but did not prevent the development of dopamine receptor supersensitivity. Following a 14-day withdrawal period, these same L-DOPA treated groups exhibited substantially higher rates of contralateral rotation to an L-DOPA challenge as compared to a drug-naive group with comparable 6-OHDA lesions. HPLC-EC measurements of L-DOPA in striatal and cortical tissue samples showed no differences in concentration across the L-DOPA treatment groups. There were several differences, however, in the neurochemical impact of L-DOPA on frontal cortex vs. striatum. In the striatum but not the cortex, L-DOPA concentrations were higher in the 6-OHDA than the intact hemisphere and, L-DOPA increased dopamine concentrations in cortex but not in the striatum. Behaviorally, L-DOPA exerted two diametrically opposite effects linked to the state of dopamine receptors. Prior to the onset of dopamine receptor supersensitivity L-DOPA suppressed locomotor behavior and delayed the emergence of denervation supersensitivity. Once denervation supersensitivity developed, however, the L-DOPA engaged sensitization mechanisms and enhanced locomotor behavior and dopamine receptor supersensitivity. These findings suggest that the initiation of antiparkinsonian treatment prior to the onset of denervated dopamine receptor supersensitivity in the 6-OHDA model is a valuable strategy to determine if a drug treatment retards or facilitates the development of dopamine receptor supersensitivity.

Animals↗
PubMed1999

Morphometric characteristics of myonuclear distribution in the normal and denervated fast rat muscle fiber.

Unlike the majority of mammalian tissues, which have mononuclear cells as a basic unit of the tissue composition, skeletal muscle fiber is a polynuclear syncytium. Polynuclear organization offers an additional possibility for the regulation of protein expression: it can also be controlled at the level of myonuclear distribution and specialization. Distribution of myonuclei can be considered as the distribution of genes. Variability in gene concentration may have important impact on the regional differentiation of the muscle fiber, since it leads to different regional concentrations of various gene products including factors controlling their expression. The aim of the present study was: 1) to provide morphometrical data on the myonuclear distribution in the junctional and extrajunctional regions of the normal fast rat muscle fiber, and 2) to analyze, whether morphometrical parameters of nuclear distribution change after mechanical denervation of this muscle. Single muscle fibers were isolated from the normal and denervated fast rat m. sternomastoideus. Their neuromuscular junctions were stained by thiocholine histochemical procedure and myonuclei were fluorescently labeled by Hoechst 33342. Myonuclear distribution in each individual muscle fiber was morphometrically analyzed on the image analyzer. Synaptic concentrations of myonuclei were found to exceed extrasynaptic concentrations by a factor of 17. The number of myonuclei accumulated at the endplates did not change after one or two weeks of denervation, neither did the morphometric parameters of these nuclei. A higher concentration of myonuclei due to muscle atrophy was observed in the extrasynaptic region and the longitudinal axis of these nuclei also became significantly shorter. Unchanged morphometric parameters of the junctional myonuclei after denervation are indicative of either irreversibility of the nerve-induced formation of nuclear clusters in this region or persistence of the factors responsible for their formation and maintenance.

Animals↗
PubMed1997

Dopamine D2-like receptors in the rat kidney: effect of denervation.

The effects of monolateral denervation induced by renal artery occlusion on dopamine D2-like receptors were assessed in rat kidney using radioligand binding assay and autoradiographic techniques. [3H]spiperone was used as a ligand. [3H]spiperone was bound specifically to sections of control innervated kidneys with a dissociation constant (Kd) value of 0.07 +/- 0.003 nM and a maximum density of binding sites (Bmax) value of 35.4 +/- 0.16 fmol/mg tissue. Light microscope autoradiography showed the accumulation of silver grains both in the arterial tree and in cortical tubules. At the vascular level, [3H]spiperone binding sites were accumulated primarily in the adventitia and in adventitia-media transitional zone. In cortical tubules, the higher density of [3H]spiperone binding sites was noticeable in proximal convoluted tubules. A few binding sites were also found in the glomerular tuft. In denervated kidneys, noradrenaline and dopamine levels were reduced by about 90% and 60% respectively in comparison with control innervated kidneys. Denervation reduced the density of [3H]spiperone binding sites by more than 85%. In denervated kidneys, light microscope autoradiography showed the disappearance of specific vascular binding sites and a remarkable reduction of tubular [3H]spiperone binding sites. The above results indicate that the largest majority of renal dopamine D2-like receptors labelled by [3H]spiperone is prejunctional in location.

Animals↗
PubMed2003

Denervation-activated inward rectifier in frog slow skeletal muscle fibers.

We tested whether the absence of an inward rectifier channel in slow skeletal muscle fibers of the frog is regulated by innervation. Normal and denervated slow fibers were identified according to their passive electrical properties. In current-clamp experiments, anomalous rectification was quantified as the ratio of effective resistances for hyperpolarizing and depolarizing pulses. In isotonic potassium solution, this ratio was 0.45 +/- 0.1 (n = 14) for twitch fibers, whereas slow fibers displayed linear behavior [ratio = 1.0 +/- 0.05 (n = 15)]. However, denervated slow fibers showed anomalous rectification (ratio, 0.48 +/- 0.07; n = 5). This finding was supported by voltage-clamp experiments in which denervated slow fibers displayed (1) an inward rectifier current during hyperpolarizing pulses, (2) an increase in this current when [K(+)](o) was increased, and (3) a current inhibition after application of Ba(2+). These results suggest that frog slow fibers, which normally do not possess inward rectifier channels, can express them after denervation.

Animals↗
PubMed1990

Partial denervation of amphibian skeletal muscle does not induce neuronal growth at the node of Ranvier.

Following partial denervation of a striated muscle sprouting occurs at the nodes of Ranvier and terminal arborizations of the intact motor neurons. We studied the sprouting response of intact frog (Rana pipiens) motor neurons to partial denervation of the cutaneous pectoris muscle (CP). In the 5-19 days following partial denervation of the CP muscle, tetranitroblue tetrazolium-stained motor neurons exhibited sprouting. However, the mixed response of both nodal and terminal sprouting characteristic to mammalian muscle was replaced by a preferential response of only terminal sprouting. Histological examination showed that in many cases these terminal sprouts appeared to reinnervate abandoned junctional sites on adjacent denervated fibers. Given that nodal sprouting failed to occur for the duration of the experiment, these preliminary results suggest that the cues responsible for nodal sprout formation in the amphibian may differ from those in the mammal.

Animals↗
PubMed1987

Chemically induced bowel denervation improves survival in short bowel syndrome.

This study evaluates the effect of chemically induced bowel denervation on survival, weight gain or loss, transit time, and d-xylose absorption in rats following 80% small bowel resection. Forty-three male Sprague-Dawley rats (150 g) underwent 80% midsmall bowel resection and anastomosis. Twenty rats were short bowel controls (group I). In 23 rats (group II), a 2.0 cm segment of jejunum proximal to the anastomosis was denervated by application of 0.1% benzalkonium chloride (BK) for 30 minutes. Ten additional rats underwent sham laparotomy without bowel resection. Five remained untreated (group III) and in 5 (BK) denervation was added (group IV). Bowel denervation was confirmed by histologic study in all (BK) rats. Weight and daily food and water intake were measured for 30 days and the groups compared. Weight in group I was 43.8 +/- 52.9 g, group II 95.0 +/- 50.1, (P less than .005), group III 177 g, and group IV 175 g. Food intake was greater in group I than II (P less than .05) and was similar to groups III and IV. Water intake calculated as animal weight (g)/mL H2O ingested was lowest in group I (P less than .05). Mortality was 30% in group I (6/20) and only 8.6% in group II (2/23). No deaths were observed in unresected controls (III and IV). Twenty-four additional rats were evaluated for d-xylose absorption and transit time by bringing out a loop enterostomy 10.0 cm from the Ligament of Treitz. Twelve rats were ostomy controls (group V).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2000

Fertility ratio in male rats: effects after denervation of two pelvic floor muscles.

Fertility ratio is defined here as the proportion of females that a male can impregnate after a constant period of in-polygyny living. This ratio was investigated in male rats after denervation of two pelvic floor muscles, the pubococcygeus and iliococcygeus. Denervation was carried out by transecting the somatomotor branch of the pelvic nerve. The lesion did not modify the sexual behavior of males or their overall fertility, but decreased the weight of the ejaculated seminal plug. Consequently, the number of days living in cohabitation to induce pregnancy was increased in lesioned males (approximately 13 days) compared with intact and sham animals (approximately 5 days). These results showed that the fertility ratio was optimal when intact/sham males cohabited with females for two consecutive estrous cycles, but that lesioned males needed up to four cycles to induce most pregnancies. Two hypotheses are raised by our results. The first is that pelvic floor denervation decreases the forceful tension required to expel the semen from the prostatic urethra to the vagina, then an incomplete seminal plug is expelled. The second is that denervation cut afferent fibers that reflexively promote the continence of the semen deposited in the prostatic urethra during seminal emission, allowing some to leak out before ejaculation. The latter hypothesis can also explain the recovery of the fertility ratio in lesioned males. It could be a compensatory mechanism mediated by the pudendal nerve supply to the coccygeus muscle, the other pelvic floor muscle.

Abdominal Muscles↗
PubMed2003

Chronic extrinsic denervation of the small bowel: effect on adrenergic and cholinergic contractile mechanisms in canine ileal circular muscle.

BACKGROUND: Small bowel transplantation necessitates chronic extrinsic denervation and is often followed by enteric dysfunction. Our aim was to study canine ileal contractile activity after extrinsic denervation. METHODS: In vitro dose responses to cholinergic and adrenergic agonists were evaluated in canine ileal muscle strips in control subjects and after jejunoileal extrinsic denervation (EX DEN) at 0, 2, and 8 weeks after operative preparation. RESULTS: Spontaneous activity and the increased activity after tetrodotoxin (enteric nerve blockade) did not differ between groups. Response to acetylcholine and bethanechol did not differ at any time in the control or EX DEN group. In contrast, the EX DEN group demonstrated a procontractile hypersensitivity to norepinephrine at 2 and 8 weeks that was not seen in the control group. This adrenergic hypersensitivity in the EX DEN group was insensitive to intramural neural blockade with tetrodotoxin. CONCLUSIONS: Extrinsic denervation does not affect basal contractile activity, augmented contractile activity to intramural neural blockade, nor response to cholinergic agonists. However, it induces a procontractile adrenergic hypersensitivity in canine ileal circular muscle mediated at the level of the smooth muscle and not at the enteric nervous system.

Acetylcholine↗