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PubMed1984

Cellular ions in intact and denervated muscles of the rat.

Tissue composition, membrane potentials and cellular activity of potassium, sodium and chloride have been measured in innervated and denervated rat skeletal muscles incubated in vitro. After denervation for 3 days, tissue water, sodium and chloride were increased but cellular potassium content and measured activity were little affected, despite a decrease of 16 mV in resting membrane potential which would have necessitated a decrease in cellular potassium activity of almost 50% were potassium distributed at electrochemical equilibrium. These findings, therefore, preclude a decreased electrochemical potential gradient for potassium as the cause of the membrane depolarization characteristic of denervated muscle fibers. Analysis of the data excludes an important contribution of rheogenic sodium transport to the resting potential of innervated muscles. These results strongly support the hypothesis that the decreased membrane potential in denervated fibers reflects a relative increase in the membrane permeability to sodium.

Animals↗
PubMed1977

In vitro studies of skeletal muscle membranes. Effects of denervation on the macromolecular components of cation transport in red and white skeletal muscle.

The effects of denervation on the macromolecular components of active monovalent cation transport in skeletal muscle have been studied using purified sarcolemma membranes. A comparison of membrane activities of fast-twitch, slow-twitch, and mixed-fiber muscles was made to determine what role, if any, the motor nerve has in regulating this important aspect of muscle metabolism. A dramatic increase in the basal sarcolemmal Mg++ ATPase activity (three- to fourfold) was found for both major muscle types. An increase in the ouabain-inhibitable (Na+ + K+)-stimulated enzyme was also found, but the effect was substantially less (1.5- to twofold). [3H]-ouabain binding, as an index of glycoside receptor sites, also increased (two- to threefold) midway in the course of denervation. On the other hand, the phosphorylated intermediate activity, a functional component of the transport system, clearly decreased over the same time course and remained below control values for the remainder of the course. This resulted in a two- to threefold increase in the turnover number, suggesting that active transport of cations should increase dramatically with denervation. The membrane protein patterns on SDS gels were less obvious than the changes observed in the functional components. The major effects appeared after only one week and seemed to be restricted to high molecular weight membrane proteins, especially in the 100,000 to 250,000 daltons range. This effect was more prominent in slow-twitch membranes with an apparent semiquantitative decrease in stain at 240,000 daltons. In gels of membranes from fast-twitch muscles a decreased stain in the range of 100,000 to 110,000 daltons occurred, and this became more obvious with longer periods of denervation. The results suggest that considerable influence on the macromolecular components of active cation transport in skeletal muscle is exerted by the motor nerve. No appreciable difference was found in this effect when the two major types of skeletal muscle, fast-twitch and slow-twitch, were compared, suggesting that motor nerve regulation of this membrane property is qualitatively the same.

Adenosine Triphosphatases↗
PubMed1998

Pudendal denervation affects the structure and function of the striated, urethral sphincter in female rats.

Our aim was to examine the effects of denervation on urethral anatomy and urine voiding pattern. Rats usually void at one end of their cage, which gives a behavioral index of continence. The voiding preference for denervated rats was decreased to 88.8 + 4.7%, n = 32, P < 0.001, compared to improvements with time for unoperated (117 +/- 10%, n = 16) or sham-operated rats (105 +/- 8%, n = 5). The volume of urine or the frequency of voidings between denervated, unoperated or sham-operated rats did not differ significantly. Urethral sections were analyzed immunochemically and quantified morphometrically. Smooth muscle volume remained constant but skeletal muscle volume decreased after denervation, from 43 +/- 2% to 36 +/- 3% (P < 0.05, n = 5). Fiber diameter decreased from 14.3 +/- 1.4 microm to 8.5 +/- 0.7 microm (P < 0.005). We concluded that pudendal nerve transection in female rats causes behavioral alterations in voiding and muscular atrophy of the striated sphincter.

Animals↗
PubMed1978

Effects of disuse and nerve stump length on the development of fibrillation in denervated soleus muscle.

Both in normal (control) and in cordotomized (disused) rats, the soleus muscle was denervated either by cutting the sciatic nerve near the trochanter (proximal denervation) or by cutting the soleus nerve near the insertion into the muscle (distal denervation). In the control muscles, the development of fibrillation was not dependent on the level of nerve section. In disused muscles, the development of fibrillation was greater following distal denervation that following the proximal one.

Animals↗
PubMed1988

Effects of autonomic denervation on canine exocrine pancreatic secretion and blood flow.

The effect of autonomic denervation on the exocrine pancreatic secretion and blood flow was studied in a group of dogs. Pancreatic secretion was collected and analyzed for volume and bicarbonate by direct cannulation of the main papilla through a duodenotomy prior to and following truncal vagotomy and celiac plexus denervation. Pancreatic blood flow was determined by the radioisotope distribution method (141Ce). Truncal vagotomy causes a reduction in pancreatic secretion of volume and bicarbonate by 25-30%, while celiac denervation caused a reduction of 70% in the secretion. The mean baseline pancreatic blood flow was 0.5 ml/g pancreas/min. Truncal vagotomy did not cause any significant flow changes, while celiac denervation caused a significant increase in blood flow of 350% (to 1.75 ml/g/min). These results suggest that both the parasympathetic and the sympathetic system affect pancreatic secretion independently of their effect upon pancreatic blood flow.

Animals↗
PubMed2000

Suppressive effects of remifentanil on hemodynamics in baro-denervated rabbits.

PURPOSE: To elucidate mechanisms by which remifentanil, an ultra-short-acting mu-opioid receptor agonist, causes hypotension and bradycardia. METHODS: Mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were measured and recorded after bolus injections of 1, 2 or 5 microg x kg(-1) of remifentanil in neuraxis intact (n=6 for each dose) and baro-denervated rabbits (n=6 for each dose). Arterial baroreflex sensitivity was assessed by depressor tests. An additional six baro-denervated animals received remifentanil, 5 microg x kg(-1) after pretreatment with naloxone, 40 microg x kg(-1). RESULTS: All values were expressed in % change from baseline. In the neuraxis intact animals, MAP and HR were decreased briefly immediately after remifentanil injection. RSNA was increased dose-dependently: 137 +/- 8% (mean +/- SE), 170 +/- 14% (P < 0.05) and 225 +/- 29% (P < 0.05) after 1, 2 and 5 microg x kg(-1) remifentanil, respectively. RSNA was increased even after MAP and HR had returned to baseline values. The depressor tests revealed that remifentanil did not attenuate arterial baroreflex sensitivity. In the baro-denervated animals, MAP and HR decreased gradually to 77 +/- 3% (P < 0.05) and 94 +/- 1% (P < 0.05), respectively 300 sec after 5 microg x kg(-1) remifentanil. At that time, increased RSNA (159 +/- 9%, P < 0.05) had returned to baseline. Pretreatment with naloxone in the baro-denervated animals abolished these changes. CONCLUSION: Remifentanil decreases HR and MAP by its central vagotonic effect and by stimulating peripheral mu-opioid receptors. These effects appear to be counteracted and masked by its central sympathotonic effect and by maintaining arterial baroreflex integrity.

Analgesics, Opioid↗
PubMed2005

Recruitment of gastrocnemius muscles during the swing phase of stepping following partial denervation of knee flexor muscles in the cat.

In walking cats, the biarticular medial and lateral gastrocnemius (MG-LG) muscles act to produce extension and flexion torques at the ankle and knee, respectively, and they usually display only one burst of activity beginning just before ground contact and ending near the end of the stance phase. Currently, the MG-LG muscles are considered to function primarily to control extension movements around the ankle joint during the stance phase. However, their flexion action at the knee means that they have the capacity to regulate rotations at the knee, but this role has not yet been clearly defined. Following partial denervation of the other muscles that normally act to flex the knee during swing, we observed that the MG-LG muscles, but not the Soleus muscle (a pure ankle extensor), often generated strong bursts of activity during early swing. These bursts were enhanced following mechanical stimulation of the paw, and they were especially prominent when the leg trailed over an object. They were absent when the leg led over an object. During treadmill walking the swing-related bursts in MG and LG had little influence on ankle flexion at the beginning of swing, but they were associated with slowing of ankle flexion when the leg trailed over an object. We hypothesized that the recruitment of these bursts functions to partially compensate for the reduction in knee torque resulting from the denervation of other knee flexors. Consistent with this hypothesis was our finding that the magnitude of the swing-related activity in the MG-LG muscles was linearly correlated to the extent of the knee flexion and to the peak angular velocity of knee flexion, and that the timing of the bursts was similar to that in the denervated muscles prior to denervation. Our findings suggest that an excitatory pathway exists from the flexor half-center of the central pattern-generating network to MG-LG motoneurons, and that this pathway is strongly regulated by central and/or peripheral signals.

Animals↗
PubMed2003

Subacute mandibular and hypoglossal nerve denervation causing oedema of the masticator space and tongue.

We report the MRI of five patients with denervation oedema in the head and neck. Four had denervation oedema in one masticator space caused by a skull-base tumour invading the ipsilateral foramen ovale. Another case had denervation oedema confined to the half of the tongue ipsilateral to oral reconstruction surgery which involved mandibulectomy, free flap repair and wide excision of a buccal mucosal carcinoma. Inversion-recovery and/or T2-weighted spin-echo images showed increased signal in the affected areas. Contrast-enhanced T1-weighted images revealed enhancement of the muscles. There was no evidence of tumour or infection in the masticator space or tongue. It is important to differentiate denervation oedema from other disease processes causing high signal on T2-weighted images, such as tumour infiltration and soft-tissue infection.

Adult↗
PubMed1997

Denervation-induced changes in perineuronal plexuses in the major pelvic ganglion of the rat: immunohistochemistry for vasoactive intestinal polypeptide and tyrosine hydroxylase and histochemistry for NADPH-diaphorase.

To characterize further the injury response of autonomic ganglia, we have examined the effect of chronic denervation on perineuronal plexuses that are immunoreactive for vasoactive intestinal polypeptide (VIP) and tyrosine hydroxylase (TH) or that stain for nicotinamide adenine dinucleotide phosphate (NADPH) in the rat major pelvic ganglion, and their relationship to an identified sub-population of neurons in the ganglion (the penile neurons). Penile neurons contain VIP and NADPH diaphorase (NADPH-D) but lack TH. VIP-immunoreactive (VIP-IR) and TH-IR perineuronal plexuses (baskets) are rare in the rat major pelvic ganglion and those present are not associated with penile neurons. A small increase in VIP-IR baskets occurs 2 weeks after proximal interruption of the pelvic nerve, but TH-IR baskets increase five-fold. The emergent VIP-IR and TH-IR baskets enclose TH-negative neurons, none of which are penile ganglion cells. These changes remain up to 4 weeks after denervation. Interrupting the pelvic nerve nearer the margin of the major pelvic ganglion results in a rapid, more dramatic increase in VIP-IR, in cell bodies and beaded fibers, than that seen with the more proximal lesion. About 27% of neurons in the ventral pole of the ganglion are enveloped by NADPH-D perineuronal baskets. The incidence of NADPH-D baskets falls to less than 1% after acute interruption of the pelvic and hypogastric nerves, but their frequency returns to control levels in chronically denervated ganglia. The rapid, vigorous changes in peptide (VIP) fibers after the pelvic nerve is cut close to the major pelvic ganglion may be attributable to the interruption of axons of postganglionic neurons and to preganglionic nerve fibers, whereas the slowly developing changes in VIP-IR and TH-IR fibers after more proximal lesions may represent the more modest effects of true decentralization. The source and significance of the VIP-IR, TH-IR, and NADPH-D baskets that appear in chronically denervated ganglia remain unclear.

Animals↗
PubMed1991

Denervation of transplanted porcine lung causes airway obstruction.

Lung transplantation can be complicated by a form of small airway obstruction known as bronchiolitis obliterans. We tested the hypothesis that lung denervation causes small airway obstruction in young pigs (10 +/- 1 weeks). Control pigs had an innervated native lobe, and study pigs had either a denervated native lobe or a denervated transplant lobe. Transplanted pigs received standard immunosuppression. At 10 weeks we measured isolated left lobe pulmonary mechanics. Dynamic resistance in both study groups was significantly higher than in the lobectomy group, whereas dynamic compliance in both study groups was significantly lower than in the lobectomy group. No significant difference in resistance or compliance was noted between the transplant and reimplant groups. Histologic changes consistent with rejection were noted in the transplant lobes. We conclude that the small airway obstruction noted in this model is due to operative denervation rather than to immunosuppression or rejection.

Animals↗
PubMed1979

Early changes in muscle glucose-6-phosphate dehydrogenase activity after denervation: locus and dependence on nerve stump length.

Glucose-6-phosphate dehydrogenase (G6PD) activity of rat diaphragm muscle increased significantly 12 h after intrathoracic ('distal') denervation. Since this change represented one of the earliest known events after loss of innervation, the mechanism of neuronal regulation and the nature of the muscle response were further investigated. When, instead of distal denervation, the motor nerve was cut about 3.5 cm from the diaphragm, G6PD activity slightly decreased 12 h later. Denervations in which part of the same hemidiaphragm had a short nerve stump and another part, a long nerve stump, also showed a differential increase of G6PD activity dependent on length of nerve stump. In biochemical studies of the locus of the early post-denervation elevation of G6PD, enzyme activity was increased both in endplate and non-endplate regions of the muscle. Finally, the histochemical reaction for G6PD was more intense in both muscle fibers and interstitial elements, although the former made the major contribution to the biochemical results. In sum, muscle G6PD enzyme activity is closely regulated by a neurotrophic mechanism partly independent of nerve or muscle electrical activity.

Animals↗
PubMed1980

Relationships between selective denervation of dopamine terminal fields in the anterior forebrain and behavioral responses to amphetamine and apomorphine.

To investigate the relationship between denervation of dopamine (DA) terminal fields in the anterior forebrain and the behavioral responses to amphetamine (1.5 mg/kg) and apomorphine (1 mg/kg), we injected 6-hydroxydopamine (6-OHDA) bilaterally into the anterolateral hypothalamus (ALH) or into specific mesolimbic and anterior striatal terminal fields after pretreatment with desmethylimipramine to protect noradrenergic axons and terminals from 6-OHDA toxicity. After drug testing was completed, the extent of denervation was determined by fluorescent histochemical analysis. When nearly all of the mesolimbicocortical and anteroventral striatal DA terminal fields were denervated by bilateral ALH 6-OHDA, the locomotor response to amphetamine was abolished, and the locomotor and stereotyped sniffing responses to apomorphine were increased. When fewer DA terminal fields were denervated, different results were obtained: the locomotor response to amphetamine decreased or did not change; stereotyped sniffing elicited by apomorphine did not increase or sniffing was replaced by stereotyped licking and biting. The results suggest a mass action relationship between DA terminal fields in the anterior forebrain and the locomotor response to amphetamine. The relationship between the same DA lesions and responses to apomorphine appears to be more complex.

Amphetamine↗
PubMed1981

The absence of nodal sprouts from partially denervated nerve trunks.

Nodal sprouts were absent from partially denervated, silver-stained, mouse superior gluteal (SG) nerves examined between 4 and 20 days after partial denervation. Nodal sprouts were also absent from electron micrographs of partially denervated SG nerves. We conclude that an earlier report describing profuse nodal sprouting in partially denervated nerve trunks mistakenly identified fine Schwann cell processes as nodal sprouts.

Animals↗
PubMed1983

Effects of contralateral denervation on quantal output and gross nerve terminal morphology in mouse muscles.

We have studied the effect of unilateral denervation on the quantal output and gross nerve terminal morphology of the contralateral tensor fascia latae (TEL) muscle in mice. Unilateral TFL denervation was achieved by resecting spinal nerves L4 and L5. We found no significant difference, in quantal output or in the percentage of nerve terminals with sprouts, between the contralateral muscles and muscles in unoperated, age-matched control mice, at 4 days, 11-12 days or 6.5 months after denervation. This finding is in contrast to marked differences between similar experimental and control muscles after unilateral denervation reported in frogs by others.

Animals↗
PubMed1983

Sprouting of mammalian motor neurones at nodes of Ranvier: the role of the denervated motor endplate.

Treatment of the mouse gluteus maximus with the organophosphorus anticholinesterase ecothiopate, 4-aminopyridine and caffeine caused necrosis of the endplate region of the muscle fibres. When these drugs were given 12 h prior to partial denervation of the muscle there was a significant reduction in the amount of nodal sprouting seen 48 h after nerve section. No such reduction was seen if the drugs were given immediately after nerve section. In the former case both innervated and denervated fibres are necrotic; in the latter, only innervated fibres are necrotic. The amount of terminal sprouting was significantly increased in the former group, showing that the drug treatment and necrosis were not directly inhibitory to nerve growth. The reduction of nodal sprouting is therefore likely to be due to necrosis of denervated fibres; this supports the hypothesis that the denervated endplate is the source of a stimulus to nodal sprouting of motoneurones.

Animals↗
PubMed1984

Motor neuron survival and neuritic extension from spinal cord explants induced by factors released from denervated muscle.

Extracts prepared from denervated adult skeletal muscle contain increased amounts of neurotrophic activity which promotes both survival of dissociated motor neurons and the outgrowth of neurites from explants of spinal cord maintained in serum-free defined media. The trophic activity is specific for motor neurons and reaches a peak within the first week post-denervation. In these most potent extracts the neurite outgrowth enhancement is a linearly increasing function of protein concentration at low concentrations; at higher concentrations the neurite activity-concentration relationship saturates and in the milligram range the relationship becomes inhibitory. When media containing active denervated muscle extract was preincubated over polycationic substrata, it lost the ability to promote neuritic growth; this could be restored if fresh extract was added to the cultures. Thus it was demonstrated that within the denervated muscle extract there are physically separable agents responsible for neuron survival and neurite expression. It is possible that the release of neurotrophic factors may be in part responsible for the in vivo phenomenon of nerve sprouting.

Animals↗
PubMed1991

Short-term expansion of receptive fields in rat primary somatosensory cortex after hindpaw digit denervation.

The immediate effect of changing the driving cutaneous input to locations within primary somatosensory cortex (SI) was examined by denervating one or more digits of the rat hindpaw by amputation or local anesthesia. When all or part of a receptive field of a cluster of neurons was denervated, it was found that the cortical location recorded from gained responsiveness to cutaneous stimulation of hindpaw areas bordering the denervated region. In 22 of the 29 animals studied this expansion took place within 5 min of the denervation.

Amputation, Surgical↗
PubMed1993

Cat dental pulp after denervation and subsequent re-innervation: changes in blood-flow regulation and distribution of neuropeptide-, GAP-43- and low-affinity neurotrophin receptor-like immunoreactivity.

The effects of unilateral extramandibular inferior alveolar nerve injury on pulpal blood-flow responses to electrical stimulation and i.v. injections of substance P (SP) in cat mandibular canine teeth with a dentinal lesion were investigated with laser Doppler flowmetry. After blood-flow recordings, the teeth were fixed and the pulps were examined with light and electron microscopy. The distribution of pulpal SP, neurokinin A (NKA), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), growth-associated protein (GAP-43) and low-affinity neurotrophin receptor (LANR)-like immunoreactivity was examined with immunohistochemical fluorescence microscopy. Blood-flow recordings, performed at 10 days and 1 month postoperatively, showed that vasodilation, occurring in control teeth after bipolar electrical stimulation of the tooth crown, was absent in the denervated pulps, whereas at 3 months, five of six teeth had regained responsiveness, although at a low level. There was enhanced vasodilation (by 370%) to SP injections (400 fmol i.v.) at 10 days in denervated pulps. Such supersensitivity was reduced at 1 month despite the apparent lack of nerve fibers, and the response fell further towards the level in control teeth at 3 months when pulpal axons reappeared. At 10 days and 1 month postoperatively, light and electron microscopy demonstrated that surgery had resulted in total pulpal denervation. At 3 and 6 months, a large number of regenerated pulpal axons reappeared, in accordance with previous findings. At 10 days and 1 month after nerve transection immunohistochemistry showed a complete loss of pulpal immunoreactivity to all the neuropeptides that were studied. At 3 and 6 months, neuropeptide immunoreactivity reappeared but far fewer number of pulpal nerve fibers were SP-, NKA- and CGRP-immunoreactive than under normal conditions, as demonstrated by double-labeling experiments with GAP-43- or LANR-antiserum. The results indicate that pulpal hemoregulatory functions, which are lost after denervation, do not return to normal levels after nerve regeneration. This malfunction may be caused by inadequate target re-innervation and/or a deficiency of neuropeptides in the re-innervated pulp.

Animals↗