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PubMed1977

In vitro studies of skeletal muscle membranes. Adenylate cyclase of fast and slow twitch muscle and the effects of denervation.

Sarcolemmal membranes were prepared from slow-twitch (red) and fast-twitch (white) skeletal muscle of the rat. A sensitive adenylate cyclase assay was used and basal, fluoride- and catecholamine-stimulated activities measured. The greater in vivo sensitivity of red muscle to the effects of catecholamines correlates, in the present study, with approximately a twofold stimulation of its sarcolemmal adenylate cyclase with isoproterenol (10 micronm). The white muscle enzyme, on the other hand, is only minimally stimulated (20%) at the same concentration of beta-adrenergic agonist. Fast-twitch muscle is known to be physiologically insensitive to catecholamine in vivo. A course of sciatic nerve denervation was followed to further distinguish these two metabolic types of skeletal muscle and their respective adenylate cyclases. The slow-twitch muscle enzyme activities were completely and permanently lost on denervation. The white muscle enzyme, however, recovered almost completely after an initial reduction in specific activity the first week. Interestingly, the NaF-stimulated activity lagged behind both the basal and hormone-stimulated activities of the white muscle enzyme, in returning to control levels. The activities of cyclic nucleotide phosphodiesterase were evaluated in homogenates of the two muscle types in innervated rats and following denervation, in order to further define the neural influence on skeletal muscle cyclic nucleotide metabolism. The results suggest that the motor nerve may regulate some of the metabolic properties of slow-twitch muscle (which may involve cyclic AMP) by controlling the responsiveness of its sarcolemmal-bound adenylate cyclase system.

Adenylyl Cyclases↗
PubMed1979

Satellite cells in denervated muscles.

It is known that, in a denervated striated muscle, the satellite cells multiply by mitotic division. A liaison between these satellite cells and the Schwann cell in front of the post-synaptic membrane in denervated frog muscle has been observed. It is probable that such cell connections help in the subsistence of the Schwann cell in a denervated muscle.

Animals↗
PubMed1996

Chronic sensory denervation reduces thrombin-stimulated endothelin release from aortic endothelial cells.

The long-term (trophic) influence of perivascular nerves on the endothelium was investigated by measuring changes in thrombin-stimulated release of the potent vasoconstrictor, endothelin, after selective chronic denervation. Rat pups were treated with either guanethidine or capsaicin to destroy sympathetic or sensory nerves, respectively. The abdominal aortas from the rats at three months of age (5 pooled per experiment) were incubated with 4U thrombin/ml in medium for 24 h at 37 degrees C, and the amount of endothelin released from the preparation determined by immunoassay. After neonatal sensory denervation there was a significant reduction in the thrombin-stimulated release of endothelin compared to the controls (0.012 +/ -0.012 (4) compared to 0.063 +/- 0.012 (6), pmol/cm2/24 h, p < 0.02). There was no change in endothelin release after sympathetic denervation. In summary, sensory nerves play a trophic role in the expression of endothelin in endothelial cells of the intima.

Animals↗
PubMed1979

A histochemical study of denervated marsupial hemidiaphragm.

The marsupial (quokka) hemidiaphragm showed postdenervation hypertrophy and subsequent atrophy. The type II muscle fibres hypertrophied up to 20 days postoperation and then regressed. However, the type I fibres hypertrophied throughout the experimental period (100 days) studied. Unlike denervated eutherian hemidiaphragm, fibre-splitting was absent in the denervated marsupial muscle. An enhancement of the ATPase reaction in the denervated type I fibres may be due to dedifferentiation. Presumably innervation exerts a 'negative control' and prevents increase of type I fibre size in the normal hemidiaphragm.

Adenosine Triphosphatases↗
PubMed1977

Differential effects of disuse preceding denervation on the onset and development of fibrillation in fast and slow muscles.

Section of the sciatic nerve, performed after a week of muscular disuse, is followed by fibrillation earlier in the soleus (S) than in the anterior tibialis (AT) muscle of the rat. The subsequent development of fibrillation, which is different in the control denervated S as compared with the control denervated AT, tends to become similar in the disused-denervated muscles.

Animals↗
PubMed1996

Effect of chronic sciatic nerve lesion on the neurogenic inflammatory response in intact and acutely injured denervated rat skin.

A supersensitivity to the neuropeptide substance P (SP) has been shown to develop in post-terminal membranes of many denervated tissues. This study examined changes in the sensitivity of post-terminal vascular receptors to SP and calcitonin gene-related peptide (CGRP) in rat skin microvasculature following sciatic nerve section. In anaesthetised rats, 0.5 cm of sciatic nerve in the right mid-thigh region was removed. Two weeks later, SP (100 microM) and sodium nitroprusside (SNP, 1 mM), a direct smooth muscle vasodilator, were introduced into denervated intact footpad skin, via the electrophoresis technique. Laser doppler flowmeter was used to record changes in relative blood flow in the rat hind footpad. The results showed a significant increase in SP response over controls and slight increase in smooth muscle reactivity as determined by an increase in the vascular response to SNP. In another set of experiments, the sensitivity of post-terminal receptors was examined over a 4 weeks period in an acutely injured footpad skin of sciatic nerve lesioned rats. A vacuum-induced blister was raised on the hind footpad and SP, CGRP (each at 1 microM) or SNP (100 microM) were superfused over the blister base. In nerve lesioned rats, using the acutely injured footpad skin model, the results showed a reduction in the vascular responses to SP, CGRP and SNP. The response to SP continued to decrease over time reaching 22% of control values by 4 weeks. Responses to SNP and CGRP were reduced to 53% and 45% respectively by 2 weeks and then improved to 75% of control values by 4 weeks. Possible contributions of sympathetic efferents and the saphenous nerve to these reduced responses in acutely injured skin of nerve lesioned rats were examined using guanethidine (50 mg/kg i.p.) or sectioned saphenous nerve respectively. These procedures did not significantly modify the reduced vascular responses in the blister base of lesioned rats. Possible activation of endogenous opioids and/or the release of endothelin due to blister induction in nerve lesioned rats was examined using naloxone and the endothelin receptor antagonist, BQ-123, respectively. Treatment with naloxone increased SP response in lesioned rats to 41% of control value with no change in smooth muscle reactivity. BQ-123 significantly increased the responses to SP and SNP to 51% and 100% of their own control values respectively. It is concluded that supersensitivity of post-terminal vascular receptors develops in intact skin following chronic nerve lesion. On the other hand, acute injury of the denervated skin area induces activation of endogenous inhibitory modulatory mechanisms that masks this supersensitivity.

Anesthesia↗
PubMed1996

Epidermal denervation and its effects on keratinocytes and Langerhans cells.

Skin innervation has been considered to subserve sensory perception only, but several lines of evidence suggest that there are "effector' influences of skin innervation on the immune system and keratotinocytes. In this study, we transected the sciatic nerves of rats and examined the effects of denervation on the epidermis. In normal skin, the epidermis was densely innervated by fine axons that were immunostained with several axonal markers, including neuronal ubiquitin carboxyl terminal hydrolase (protein gene product 9.5). All of the epidermal axons in the regions innervated by sciatic nerve disappeared within 24-48 h after transection of sciatic nerve, and remained absent as long as subsequent reinnervation by regenerating axonal sprouts was prevented. Denervation produced changes in both the keratinocytes and the Langerhans cells, the bone marrow-derived antigen-presenting cells of the epidermis. The thickness of epidermis decreased within 7 days. By 48 h after transection, the Langerhans cells and their dendritic processes became intensely immunoreactive for protein gene product. Protein gene product 9.5 expression on Langerhans cells remained prominent as long as skin was denervated, but disappeared with reinnervation. By reverse transcription-polymerase chain reaction, we demonstrated the presence of the transcripts for protein gene product 9.5 in epidermis, consistent with the synthesis of the protein by the Langerhans cells. We conclude that epidermal sensory fibres have novel influences on both keratinocytes and Langerhans cells of the epidermis.

Animals↗
PubMed1996

Reinnervation of frog sympathetic ganglia after selective denervation of B or C neurons.

Selective transection of the B or C preganglionic nerve fibres respectively innervating the B and C sympathetic neurons was carried out on the last two ganglia of the sympathetic chain of the frog Rana esculenta. At different times thereafter, the cross-reinnervation of one type of denervated neuron by nerve endings sprouting within the ganglia from intact fibres innervating the other type was investigated by both the quantitative morphology of the synaptic contacts and related structures and electrophysiological recordings of ganglionic transmission. As there are no fine ultrastructural criteria for distinguishing B from C neurons, the overall density of synapse, simple contact, and 'vacated' postsynaptic differentiation profiles was measured in the two cases of selective section and compared with the values for normal ganglia, therefore permitting the progress of cross-reinnervation with time for each type of neuron to be followed. At ten days after section of the C preganglionic fibres, immunocytochemistry showed that there were no anti-LH-RH-like peptide containing fibres within the ganglia. The B myelinated preganglionic fibres were able to reinnervate the denervated C neurons, with return to normal values of synaptic density and fully efficient transmission at two months in all tested C neurons. However, the latency of orthodromic action potentials was close to that of normally innervated B neurons. In contrast, the C non-myelinated preganglionic fibres reinnervated the denervated B neurons with limited efficiency, the synaptic density being two-thirds the normal value after five months, while subthreshold excitatory postsynaptic potentials or action potentials were only recorded in 44% of the tested B neurons. The latency of these orthodromic responses was close to that of normally innervated C neurons. It is postulated that the poor cross-reinnervation of B neurons could be due to insufficient sprouting of C fibres and/or lack of 'affinity' between C fibres and B neurons. In addition, these experiments demonstrated that the subsynaptic apparatus, fairly characteristic of frog ganglionic synapses, is present in both types of sympathetic neurons, although predominantly in B neurons.

Animals↗
PubMed1998

Bipolar implantable stimulator for long-term denervated-muscle experiments.

A micropower bipolar implantable stimulator has been developed and tested for long-term (four weeks-six months) use in experiments involving the stimulation of denervated skeletal muscle. Implantable stimulators are typically operated from a single lithium battery at 3 V. After the first week of denervation, stimulation of denervated muscles of rats requires voltages in the range of 6-12 V. The stimulator described can deliver voltages up to 15 V, with variable pulsewidth, frequency and duty cycle. All stimulation parameters are set prior to implantation by selection of appropriate resistors and capacitors. Each primary failure mode for implantable stimulators is addressed. Long-term reliability rates in excess of 95% are achievable if the construction details are followed closely. Methods for battery power management, circuit component selection, electrode construction and encapsulation are described in detail. This device is not intended for use in humans.

Electric Stimulation↗
PubMed1992

Endocrine response to intragastric and intravenous glucose challenge in the denervated dog pancreas.

The functional connection between the gut and the islet cells comprises nerves and gastrointestinal hormones. In this study, we quantified the incretin effect and the glucose tolerance (KG value) before and after denervation of the pancreas in dogs in order to find out whether the incretin effect is mediated by nerves. The participation of nerves was estimated by comparing metabolic tests before and after total extrinsic pancreatic denervation in 10 dogs. Fifty-nine percent of the insulin response after intragastric glucose was calculated preoperatively to be the result of incretin factors, a value similar to the 62% found in the postoperative series (with denervated pancreas). The response of GIP to intragastric glucose was not significantly different between pre- and postoperative tests. The KG values pre- and postoperative were in the same range. From our data, we conclude that extrinsic nerves of the pancreas do not seem to play an important role in mediating glucose homeostasis in dogs.

Animals↗
PubMed2002

[Microsurgical testicular spermatic cord denervation as therapy of chronic testicular pain].

Diagnosis and treatment of chronic testicular pain (CTP) has been a difficult and often unrewarding clinical situation. Success rates of conservative and surgical measures rarely exceed 55% to 73% and 10% to 40%, respectively. We report on our experience with microsurgical testicular denervation as therapeutic option in CTP. Following an extensive preoperative work-up and a positive response to spermatic cord block, 25 patients underwent microsurgical testicular denervation. After a mean follow-up of 31.5 months 24/25 patients are painfree; no intra- or postoperative complications were encountered. In none of the cases testicular atrophy or testicular hydrocele was observed during postoperative follow-up. Microsurgical testicular denervation produces reliable and reproducible excellent therapeutic success rates and should be integrated in the management of CTP at an early stage. High success rates, however, require adequate and meticulous diagnostic workup of the patients with the spermatic cord block using saline and different local anaesthetics being an initial diagnostic armentarium predicting postoperative outcome.

Adult↗
PubMed1998

Time course of changes in EMG activity of fast muscles after partial denervation.

After partial denervation, the remaining motor units (MUs) of adult fast extensor digitorum longus muscle (EDL) expand their peripheral field. The time course of this event was studied using tension measurement and recordings of electromyographic (EMG) activity. The results show that after section of the L4 spinal nerve, when only 5.3 +/- 0.63 of the 40 MUs normally supplying EDL muscle remain, the force of individual motor units starts to increase between the 1st and 2nd week after the operation and continues to do so for a further week. The drastic reduction of the number of motoneurones supplying the fast EDL leads to an increase in activity of the remaining MUs. In the 1st week after partial denervation, there was a sharp increase in the EMG activity of remaining motor units. During the next 12 days, this increase became less marked, but EMG activity remained nevertheless significantly higher than that of the unoperated EDL muscle. Many MUs became tonically active during posture. The EMG activity pattern during locomotion was also altered, so that the burst duration was positively correlated with the step cycle duration. Moreover, shortly after partial denervation, the interlimb coordination was disturbed but returned to its original symmetrical use 1-2 weeks later.

Animals↗
PubMed1999

Cardiac sympathetic denervation in familial amyloid polyneuropathy assessed by iodine-123 metaiodobenzylguanidine scintigraphy and heart rate variability.

Familial amyloid polyneuropathy (FAP) is a rare and severe hereditary form of amyloidosis, due to nervous deposits of a genetic variant transthyretin produced by the liver and characterized by both sensorimotor and autonomic neuropathy. Left ventricular systolic dysfunction is rare, but conduction disturbances and sudden deaths can occur. The neurological status of the heart has not been elucidated, and an alteration of the sympathetic nerves may be involved. We studied 17 patients (42+/-12 years) before liver transplantation by iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy, heart rate variability analysis, coronary angiography, radionuclide ventriculography, rest thallium single-photon emission tomography (SPET) and echocardiography. Coronary arteries, left ventricular systolic function and rest thallium SPET were normal in all patients. Only mild evidence of amyloid infiltration was found at echocardiographic examination. Cardiac MIBG uptake was dramatically decreased in patients compared with age-matched control subjects (heart-to-mediastinum activity ratio at 4 h: 1.36+/-0.26 versus 1.98+/-0.35, P<0.001), while there was no difference in MIBG washout rate. Heart rate variability analysis showed a considerable scatter of values, with high values in four patients despite cardiac sympathetic denervation as assessed by MIBG imaging. The clinical severity of the polyneuropathy correlated with MIBG uptake at 4 h but not with the heart rate variability indices. Cardiac MIBG uptake and the heart rate variability indices did not differ according to the presence or absence of conduction disturbances. Patients with FAP have sympathetic cardiac denervation as assessed by MIBG imaging despite a preserved left ventricular systolic function and cardiac perfusion, without correlation with conduction disturbances. Results of the heart rate variability analysis were more variable and this technique does not seem to be the best way to evaluate the extent of cardiac sympathetic denervation in FAP patients.

3-Iodobenzylguanidine↗
PubMed2002

CT-guided percutaneous radiofrequency denervation of the sacroiliac joint.

Defining the origin of low back pain is a challenging task. Among a variety of factors the sacroiliac joint (SIJ) is a possible pain generator, although precise diagnosis is difficult. Joint blocks may reduce pain, but are, in cases, of only temporary effect. This study was conducted to evaluate CT-guided percutaneous radiofrequency denervation of the sacroiliac joint in patients with low back pain. The procedure was performed on 38 patients who only temporarily responded to CT-guided SIJ blocks. The denervation was carried out in the posterior interosseous sacroiliac ligaments and on the dorsal rami of the fifth spinal nerve. All interventions were carried out under CT guidance as out-patient therapies. Three months after the therapy, 13 patients (34.2%) were completely free of pain. Twelve patients (31.6%) reported on a substantial pain reduction, 7 patients (18.4%) had obtained a slight and 3 patients (7.9%) no pain reduction. The data of 3 patients (7.9%) was missing. There were no intra- or postoperative complications. Computed tomography-guided percutaneous radiofrequency denervation of the sacroiliac joint appears safe and effective. The procedure may be a useful therapeutic modality, especially in patients with chronic low back pain, who only temporarily respond to therapeutic blocks.

Adult↗
PubMed2002

Survival of Schwann cells in chronically denervated skeletal muscles.

It is well established that over time Schwann cells disappear from the endoneurial space of the distal stump of a chronically transected sciatic nerve trunk. Nevertheless, the status of the Schwann cells within terminal branches of the transected sciatic nerve remains poorly understood. To elucidate this issue we examined the endoneurial space of the intramuscular nerves in rat hindlimb skeletal muscles, which had been denervated for a 25-month period. Based on specific ultrastructural characteristics, we identified a small population of viable Schwann cells within the intramuscular nerve trunks. The surviving Schwann cells continued to be immunopositive for both S-100 protein and neural cell adhesion molecule. In addition, reverse transcription-polymerase chain reaction and/or Western blot analyses have shown that at least two molecules, brain-derived neurotrophic factor and a non-catalytic truncated form of tyrosine protein kinase receptor B, which could potentially participate in the process of nerve repair, were detectable in chronically denervated skeletal muscle. Our results demonstrate that Schwann cells can survive inside the intramuscular nerve trunks of denervated skeletal muscle for a 25-month period without axonal contact.

Animals↗
PubMed2006

The denervated muscle: facts and hypotheses. A historical review.

Denervation changes in skeletal muscle (atrophy; alterations of myofibrillar expression, muscle membrane electrical properties, ACh sensitivity and excitation-contraction coupling process; fibrillation), and their possible causes are reviewed. All changes can be counteracted by muscle electrostimulation, while denervation-like effects can be caused by the complete conduction block in muscle nerve. These results do not support the hypothesis that the lack of neurotrophic, non-motor factors plays a role in denervation phenomena. Instead they support the view that the lack of neuromotor discharge is the only cause of the phenomena and that neuromotor activity is an essential factor in regulating muscle properties. However, some experimental results cannot apparently be explained by the lack of neuromotor impulses, and may still suggest that neurotrophic influences exist. A hypothesis is that neurotrophic factors, too feeble to maintain a role in completely differentiated, adult muscles, can concur with neuromotor activity in the differentiation of immature, developing muscles.

Animals↗
PubMed1996

Apoptosis in mouse taste buds after denervation.

Apoptotic cells in the taste buds of mouse circumvallate papillae after the sectioning of bilateral glossopharyngeal nerves were examined by the method of DNA nick-end labeling (TUNEL), together with standard electron microscopy. The taste buds decreased in number and size 3-11 days after denervation and disappeared at 11 days. The TUNEL method revealed only a few positively stained nuclei in normal taste buds but, in those of mice 1-5 days after denervation, the number of positive nuclei had increased to 3-5 times that of taste buds from normal mice. Electron-microscopic observation after denervation demonstrated taste bud cells containing condensed and fragmentary nuclei in a cytoplasm with increased density. The results show that taste bud cells under normal conditions die by apoptosis at the end of their life span, and that gustatory nerve sectioning causes apoptosis of taste bud cells with taste buds decreasing in number and ultimately disappearing.

Animals↗
PubMed2006

Myenteric denervation differentially reduces enteroendocrine serotonin cell population in rats during postnatal development.

The enteric nervous and enteroendocrine systems regulate different processes in the small intestine. Ablation of myenteric plexus with benzalkonium chloride (BAC) stimulates epithelial cell proliferation, whereas endocrine serotonin cells may inhibit the process. To evaluate the connection between the systems and the influence of myenteric plexus on serotoninergic cells in rats during postnatal development, the ileal plexus was partially removed with BAC. Rats were treated at 13 or 21 days and sacrificed after 15 days. The cell bodies of myenteric neurons were stained by beta NADH-diaphorase to detect the extension of denervation. The number of enteroendocrine cells in the ileum was estimated in crypts and villi in paraffin sections immunostained for serotonin. The number of neurons was reduced by 27.6 and 45% in rats treated on the 13th and 21st days, respectively. We tried to establish a correlation of denervation and the serotonin population according to the age of treatment. We observed a reduction of immunolabelled cells in the crypts of rats treated at 13 days, whereas this effect was seen in the villi of rats denervated at 21 days. These results suggest that the enteric nervous system might control the enteroendocrine cell population and this complex mechanism could be correlated to changes in cell proliferation.

Animals↗