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PubMed1986

Morphological changes of sensory CGRP-immunoreactive and sympathetic nerves in peripheral tissues following chronic denervation.

The morphological relationship between sensory and sympathetic nerves was studied in tissues of the eye and the oral cavity following chronic sympathetic or sensory denervation. Immunoreactivities for calcitonin gene-related peptide (CGRP) and tyrosine hydroxylase (TH) were used as indexes to assess the changes of the two nerve populations after denervation. Following surgical sympathectomy, a marked increase of CGRP-containing fibres was seen in all tissues studied, while TH-imunoreactive fibres were totally depleated. Conversely, after capsaicin treatment, an increase of TH-immunoreactive nerves was found in the same tissues, concomitant with a sharp decrease of CGRP-immunoreactive nerves. These changes were particularly evident in iridial stroma and around blood vessels in all tissue, where sensory and sympathetic nerves have a closely overlapping distribution pattern. The altered proportion of sensory peptide- and catecholamine-containing nerves following sympathetic and sensory denervation suggest that there is a reciprocal trophic influence between the two nerve subsets, possibly with the intervention of neurotrophic substances such as nerve growth factor. These results indicate a close interaction between sensory peptidergic and sympathetic nervous systems in peripheral organs.

Animals↗
PubMed1988

Effect of neonatal denervation on the distribution of fiber types in a mouse fast-twitch skeletal muscle.

This study was designed to assess the changes in fiber-type distribution of the extensor digitorum longus (EDL) muscle of the mouse during the first 21 days of age following neonatal sciatic neurectomy. Denervated and normal muscles were compared at 7, 14, and 21 days of age and the normal EDL was also studied at 1 day of age. Frozen sections of the EDL were treated histochemically to detect NADH-tetrazolium reductase and myosin ATPase reactions. Quantitative assessment included measurements of cross-sectional areas and fiber counting. Denervation resulted in muscle atrophy which was due primarily to a decrease in individual fiber area as opposed to fiber loss. Histochemical maturation of the EDL was severely affected by neonatal denervation during the first three postnatal weeks. By 21 days, two extrafusal fiber types which were both oxidative could be distinguished. One type was highly atrophied and resembled an immature fiber exhibiting myosin ATPase staining at both acid and alkaline preincubation conditions, whereas another type was less atrophied and showed myosin ATPase staining resembling fast-twitch (type IIA) fibers. These findings emphasize the importance of an intact nerve supply in determining the phenotypic expression of skeletal muscle, and point to the early postnatal period as a critical stage in fiber type differentiation.

Adenosine Triphosphatases↗
PubMed1985

The role of nerve lysosomal enzymes in the pathogenesis of denervation atrophy. Electromyographic and histochemical study in rats.

Section of sciatic nerves of rats produced fibrillations within 3 days. Foci of hyalination leading to necrosis corresponded to segments of muscles containing end plates. The electrolyte content, mainly Ca, was increased, NADH2-TR activity was decreased and membrane ATP-ase was increased. The known increase in hydrolytic enzyme activities in denervated muscles was due to spilling of lysosomal enzymes from degenerating axons at the myoneural junction. This explains the discrepancy between morphological studies indicating paucity of lysosomes in normal muscles and the high hydrolytic enzyme activities in denervation. We propose that denervation changes are at least partly due to the effect of lysosomal spillage from degenerating axons.

Adenosine Triphosphatases↗
PubMed1988

Effect of sino-aortic denervation in comparison to cardiopulmonary deafferentiation on long-term blood pressure in conscious dogs.

The isolated and combined influence of cardiopulmonary and sinoaortic denervation on long-term blood pressure (MAP), heart rate (HR), plasma renin activity (PRA) and plasma volume (PV) was studied in 11 conscious, chronically instrumented foxhounds receiving a normal sodium diet. MAP, HR, PV and PRA remained unchanged in the 5 dogs after bilateral thoracic vagal stripping, which eliminates the cardiopulmonary afferents. After sino-aortic denervation in another 5 dogs there was equally little change when compared to the control group. Only total baroreceptor and cardiopulmonary denervation (7 dogs) revealed significantly higher levels of MAP (119.6 +/- 4.6 vs. 100.4 +/- 1.5, P less than 0.01), HR (118.2 +/- 3.7; vs. 84.1 +/- 3.5; P less than 0.0001), and PRA (3.6 +/- 0.9 vs. 0.9 +/- 0.2; P less than 0.05). In conclusion, the function of either arterial baroreceptors or cardiopulmonary receptors is sufficient for normal circulatory control. When both groups of receptor afferents are interrupted, MAP, HR, and PRA rise to significantly higher levels. Thus, both systems interact in a sense of a non-additive attenuation on "cardiovascular centres". This may clarify previous disputes concerning neurogenic hypertension, and supplies information for the role of the renin-angiotensin system in blood pressure control.

Afferent Pathways↗
PubMed1985

Changes of energy metabolism, myosin light chain composition, lactate dehydrogenase isozyme pattern and fibre type distribution of denervated fast-twitch muscle from rabbit after low frequency stimulation.

The influence of low frequency (8-10 Hz) electrical stimulation on denervated fast-twitch muscle from rabbit was investigated. Prolonged direct stimulation of denervated muscle resulted in higher oxidative enzyme activities. Furthermore, single fibre analyses for succinate dehydrogenase showed a more uniform distribution of activity in stimulated-denervated muscle when compared to normal muscle. As was also the case following stimulation of innervated muscle, glycolytic enzymes were decreased in activity and the LDH-isozyme pattern was also shifted towards heart type. No change of the myosin light chain pattern could be observed after 56 days of stimulation.

Animals↗
PubMed1988

Characteristics of Schwann-cell miniature end-plate currents in denervated frog muscle.

End-plates in denervated frog sartorius muscles were investigated, under voltage clamp, to determine the characteristics of miniature endplate currents (mepc) caused by the release of acetylcholine (ACh)-quanta from Schwann-cells. Staining for acetylcholinesterase ascertained that in most cases Schwann-cell mepc had been recorded focally from the end-plate. The mean amplitude of Schwann-cell mepc (about 1 nA) was smaller than the amplitude (3-4nA) of normal nerve evoked mepc. The amplitude distribution of Schwann-cell mepc was skewed, as were also the distributions of decay time constants and of rise times. Some Schwann-cell mepc appeared to be of composite nature, as shown by an inflexion on either the rising of falling phase. The decay time constant tau of both fast and slowly decaying Schwann-cell mepc increased with membrane hyperpolarization suggesting an exponential correlation. The potential dependence was 118 +/- 37 mV (means +/- SD from 6 experiments) for an e-fold change of tau, which does not differ significantly from that for neural mepc (98 mV). The cholinesterase inhibitor neostigmine increased the amplitude and prolonged the time course of Schwann-cell mepc to a similar degree after short and long term denervation, which indicates that cholinesterase was still functional after 3-4 months of denervation. The results show that the characteristics of Schwann-cell mepc resemble in many respects those of neural mepc but are more variable in shape and amplitude.

Acetylcholine↗
PubMed1980

The hepatic arterial blood flow response to portal vein occlusion in the dog: the effect of hepatic denervation.

The acute effect of portal vein occlusion on hepatic arterial blood flow was studied in a group of nine anaesthetised dogs. The influence of hepatic artery denervation and total liver denervation on the hepatic arterial flow response was determined subsequently. Blood flows in the hepatic artery and portal vein were measured with electromagnetic flowmeters, and hepatic tissue perfusion with 85Krypton clearance. A side-to-side mesocaval shunt was constructed to provide a drainage channel for the mesenteric venous blood during the periods of portal vein occlusion. Occlusion of the portal vein produced an immediate and significant increase in hepatic arterial flow which was sustained at approximately 80% above control for the 6 min period of observation. Total liver blood flow and hepatic tissue perfusion were both significantly reduced by about 40%. Denervation either of the hepatic artery alone or the entire liver produced no change in the response, and it is concluded that there is no neurogenic component either initiating or modifying the early changes in hepatic arterial flow.

Animals↗
PubMed1975

Regeneration in grafts of normal and denervated rat muscles. Contractile properties.

The soleus or extensor digitorum longus muscles of young rats were freely garfted into the bed of the corresponding contralateral muscle. The grafts were of normal muscle or muscles which had been denervated for 14 days. Grafts of normal muscle were characterized by little or no contractile activity for the first 2-4 days after transplantation. In contrast, denervated grafts contracted weakly, but consistently, throughout this early period. The patterns of contraction were complex. In early transplants, the contractions were due entirely to surviving muscle fibers in the graft, and the contractile characteristics were those of denervated muscle fibers. After the first week, contractions of newly regenerating muscle fibers within the grafts were superimposed upon and later took over those from the fibers that survived the original transplantation. The contraction times approached those of the normal soleus or extensor muscles during the second month after grafting, and the grafts contracted like fast or slow muscles.

Animals↗
PubMed1986

A comparison of miniature end-plate potentials at normal, denervated, and long-term botulinum toxin type A poisoned frog neuromuscular junctions.

The effects of denervation and long-term botulinum toxin type A (BoTx) poisoning on miniature end-plate potentials (m.e.p.p.s) in the frog were studied with intracellular microelectrode recording. BoTx reduced the frequency of m.e.p.p.s to less than 1% of the level seen in untreated frogs, leaving a large percentage of tiny m.e.p.p.s and slow-rising m.e.p.p.s (slow m.e.p.p.s). Unlike what is observed in the rat, the frequency of slow m.e.p.p.s never increased above the low rate measured in the untreated controls, and in fact slightly but significantly decreased after BoTx. A comparison of the m.e.p.p.s seen after BoTx poisoning (BoTx m.e.p.p.s) and m.e.p.p.s seen after denervation (Schwann m.e.p.p.s) revealed many similarities between the two including amplitude and time-to-peak distributions, temperature Q10 values and responses to several drugs and procedures. However, it was concluded that BoTx m.e.p.p.s do not originate from the Schwann cells because denervation of BoTx-paralysed frogs abolishes all m.e.p.p.s and the drug 4-aminoquinoline affects BoTx m.e.p.p.s and Schwann m.e.p.p.s in opposite ways, increasing the frequency of the former while almost eliminating the latter. BoTx m.e.p.p.s and Schwann m.e.p.p.s probably represent similar processes of secretion which are non-specific in nature, having a lower energy barrier than for normal release and not originating from specialized areas of transmitter release.

Aminoquinolines↗
PubMed1984

Muscle fiber type differentiation and satellite cell populations in normally grown and neonatally denervated muscles in the rat.

To examine the neural influence upon fiber type differentiation in developing muscles, newborn rats were subjected to sciatic nerve dissection, and the denervated extensor digitorum longus (EDL) (white) and soleus (red) muscles were examined in chronologic sequence by means of histochemistry and electron microscopy. The skeletal muscles in the newborn rats were undifferentiated (type 2C fibers seen on ATPase staining) and contained numerous myotubes. In the controls, the type 2C fibers started to differentiate at around 5 days and had almost completed type differentiation by 30 days in EDL and by 90 days in soleus muscles. On the other hand, none of the fibers in the neonatally denervated muscles developed into well differentiated type 1 and 2 A fibers, but both the EDL and soleus showed long-lasting type 2C and 2B populations. The satellite cells in the denervated EDL and soleus muscles decreased in number at the same rate as in the control muscles with maturation. The absence of a neural supply in the developing muscles induced a delay in muscle fiber type differentiation but did not influence the satellite cell populations in either EDL or soleus muscles.

Animals↗
PubMed1988

Caffeine produces contralateral rotation in rats with unilateral dopamine denervation: comparisons with apomorphine-induced responses.

Like the dopamine agonist apomorphine, the methylxanthines caffeine, theophylline and theobromine produced dose-dependent contralateral rotation in rats with unilateral 6-hydroxydopamine denervation, a response considered to be dependent upon dopamine receptors rendered supersensitive. This response was also observed after the injection of the substances into the denervated striatum. Indeed, intrastriatal administration of caffeine into the dopamine denervated striatum produced, dose-dependently (1.0-50.0 micrograms/ul), contralateral rotation. However, while apomorphine produced ipsilateral rotation in rats with unilateral striatal kainic acid lesions, a response considered to be dependent upon normosensitive dopamine receptors, neither caffeine nor theophylline produced rotational responses. As for apomorphine, the rotational behaviour elicited by caffeine (15.0 mg/kg SC) and theophylline (25.0 mg/kg SC) was inhibited by the dopamine antagonists cis-(Z)flupentixol, haloperidol and sulpiride. Nevertheless, despite the fact that cis-(Z)flupentixol was the most potent inhibitor of the caffeine response, no more than 50% inhibition was produced with doses as high as 1.0-10.0 mg/kg SC of cis-(Z)flupentixol. Pretreatment with alpha methyl-p-tyrosine inhibited the rotational response produced by caffeine in 6-OHDA-lesioned animals, but did not significantly modify the apomorphine response. Furthermore, the benzodiazepine diazepam produced a dose-dependent inhibition of the caffeine rotation, but again, the apomorphine response, although qualitatively modified, was not significantly inhibited.

Animals↗
PubMed1981

Acetylcholinesterase activity and molecular forms during denervation and reinnervation in extensor digitorum longus muscle of the rat.

The four principal molecular forms of acetylcholinesterase characteristic of the mammalian muscle (16.1 S., 12.5 S, 10.2 S, and 3.6. S) were identified by sucrose gradient sedimentation as the four activity peaks H, H1, M and L. After denervation obtained by crushing the sciatic nerve five stages of the denervation-reinnervation process were examined. Days 7, 14, 22, 30, and 60 were chosen on the basis of previous electrophysiological and histochemical studies. The AChE activity showed an initial drop followed by recovery after nerve arrival at the muscle which was completed by day 60. Marked changes in the relative proportions of the four molecular forms were observed. The 16.1 S almost disappeared during the denervation period, reappeared after nerve arrival and was completely restored at day 60. Changes were also observed in the intermediate and lower forms and were tentatively related to processes of degradation, reaggregation and de novo synthesis. A comparison of the present data with those from parallel electrophysiological and histochemical studies suggests the presence and the functional role of molecular forms other than 16S in the neuromuscular junction.

Acetylcholinesterase↗
PubMed1989

Muscle fibre loss and reinnervation after long-term denervation.

Cutaneous pectoris muscles of frog (Rana temporaria) were investigated 19.5-40 months after denervation. On whole mounts a heavy reduction in size and number of muscle fibres is noticed; in two muscles studied with semithin and ultrathin sections the number of remaining muscle fibres is 149 and around 120, while one of the contralateral muscles contains 250 and control muscles of equal sized frogs between 220 and 320 (n = 18) fibres. By electron microscopy muscle fibres undergoing degeneration or phagocytosis can be seen (3 of 20 muscle fibres present in a single ultrathin cross-section). On the other hand several profiles contained within one common basal lamina sheath are present in 14 of 20 fibres, indicating satellite cell proliferation. In one preparation 40 months after denervation not a single muscle fibre or axon is present, suggesting that eventually, without nerve supply, muscle fibres entirely disappear. Upon spontaneous reinnervation or implantation of the hypoglossal nerve 16 months after denervation, synapses are formed with the remaining muscle fibres. When studied 3.5-24 months after nerve implantation muscles innervated by few axons only (less than 10, 10-20 axons) contain a low number of muscle fibres (mean 44 +/- 41 SD, n = 6), while all muscles with a larger number of axons have more than 150 muscle fibres (n = 6). This indicates that unless large numbers of axons regenerate and/or when reinnervation is delayed muscle fibre loss continues to occur. The presence in one muscle of motor axons but only six muscle fibres 24 months after nerve implantation indicates that muscle fibre loss cannot be reversed, or recovery is extremely slow. This observation is interpreted as evidence for the exhaustibility of the satellite cell pool.

Action Potentials↗
PubMed1993

Rat jejunal absorptive function after intestinal transplantation. Effects of extrinsic denervation.

Jejunal absorptive function was evaluated following small intestinal transplantation to determine the effects of extrinsic denervation. In particular, water and sodium absorption were measured following transplantation (denervated) and compared to a control group (Thiry-Vella). Water flow was initially secretory two days after transplantation (-41 +/- 27 microliters/min/g dry tissue weight) but became absorptive at day 8 (25 +/- 25). Water flow in the Thiry-Vella group was not significantly different (P > 0.05) from the transplant group at days 8 (17 +/- 7) and 10 (47 +/- 42). Sodium flows were also initially secretory in the transplant group and became absorptive. This study refutes previous claims that small bowel transplants have a deficiency of water absorption due to extrinsic denervation of the bowel and suggests normal absorptive function of water, electrolytes, and protein.

Alanine↗
PubMed1993

Percutaneous facet denervation in chronic thoracic spinal pain.

In 40 patients with chronic thoracic spinal pain of more than 12 months duration which failed to respond to conservative treatment and with a previous evaluation by specialists, mainly neurologists and orthopaedic surgeons, the diagnosis of facet syndrome was made. This diagnosis was based on clinical criteria and a transient positive response to a prognostic blockade of the medial branch of the dorsal ramus of the thoracic spinal nerve. They were selected to undergo percutaneous radiofrequency denervation of the facet joints. The short and long-term results of 51 percutaneous thoracic facet denervations in 40 patients are described. After 2 months, 19 patients (47.5%) were pain-free, 14 patients (35%) had more than 50% pain-relief, and 7 patients (17.5%) had no relief. After a follow-up of 18-54 (average 31) months in 36 cases (3 patients had died because of malignancy, and 1 had undergone a spinal fusion), 16 patients (44%) were pain-free, 14 patients (39%) had more than 50% pain-relief and in 6 cases (17%) the result was poor. Adverse effects consisted of postoperative pain in 5 patients (12.5%). When conservative treatment fails, percutaneous thoracic facet denervation can be a safe and beneficial therapy in chronic thoracic spinal pain originating from the facet joints.

Adult↗
PubMed1990

Increase of elastic fibres in muscle spindles of rats following single or repeated denervation with or without reinnervation.

Muscle spindles in the lower lumbrical muscles of rats were studied by transmission electron microscopy following denervation with or without reinnervation. The number and total area of elastic fibres per muscle spindle increased at 3-12 months following various experimental procedures: (1) denervation and reinnervation after a single crush lesion to the sciatic nerve; (2) reinnervation after four-fold repeated crush injuries; and (3) transection and suture of the nerve. The increased number of oxytalan and elaunin fibres, the precursors of mature elastic fibres, within these muscle spindles provided further evidence for their numerical and dimensional increase. An attachment site of elastic fibres at the spindle pole was identified at the inner cells of the outer spindle capsule. The processes of these cells embraced terminating elastic fibres tightly. Attachment of elastic fibres to intrafusal muscle fibres was less conspicuous since they were not similarly embraced but were rather indistinctly, though closely, associated with the basal lamina along longitudinal surface indentations of intrafusal muscle fibres. It is concluded from this series of experiments that muscle spindles, as dynamic mechanoreceptors, maintain their elastic properties even under pathological conditions. The increase of elastic fibres following denervation and reinnervation represents an obviously meaningful reaction that may compensate for loss of tonic properties of muscle spindles without causing stiffness.

Animals↗
PubMed1988

Denervation induces long-lasting changes in the distribution of microtubule proteins in hippocampal neurons.

The cellular distributions of tubulin and microtubule-associated protein 2 (MAP2) were examined in the dentate gyrus of the rat hippocampus after unilateral lesion of the entorhinal cortex, which destroys the major afferent pathway to dentate granule cells. Changes were observed in distribution of both tubulin and MAP2 in granule cell dendrites on the denervated side. After 24 h there was a noticeable increase in both anti-tubulin and anti-MAP2 staining in the outer two-thirds of the dentate molecular layer, corresponding to the area of denervation. This increased staining reached a maximum 1 week after the lesion. There was no change on the unlesioned side. During a subsequent second phase the region of increased anti-tubulin and anti-MAP2 staining became restricted, by 35 days after lesioning, to a narrow band mid-way through the molecular layer. This pattern remained the same until 6 months after the lesion, the longest time point examined. The results indicate that there is considerable plasticity in the microtubular cytoskeleton of dendrites in the adult brain and that rearrangements induced in it by axotomy can persist long after the immediate effects of denervation and subsequent re-innervation have subsided.

Animals↗