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PubMed2001

Improved functional recovery of denervated skeletal muscle after temporary sensory nerve innervation.

Prolonged muscle denervation results in poor functional recovery after nerve repair. The possible protective effect of temporary sensory innervation of denervated muscle, prior to motor nerve repair, has been examined in the rat. Soleus and gastrocnemius muscles were denervated by cutting the tibial nerve, and the peroneal nerve was then sutured to the transected distal tibial nerve stump either immediately or after two, four or six months. In half of the animals with delayed repair, the saphenous (sensory) nerve was temporarily attached to the distal nerve stump. Muscles were evaluated three months after the peroneal-to-tibial union, and were compared with each other, with unoperated control muscles and with untreated denervated muscles. After four to six months of sensory "protection", gastrocnemius muscles weighed significantly more than unprotected muscles, and both gastrocnemius and soleus muscles exhibited better preservation of their structure, with less fiber atrophy and connective tissue hyperplasia. The maximum compound action potentials were significantly larger in gastrocnemius and soleus muscles following sensory protection, irrespective of the delay in motor nerve union. Isometric force, although less than in control animals and in those with immediate nerve repair, remained reasonably constant after sensory protection, while in unprotected muscles there was a progressive and significant decline as the period of denervation lengthened. We interpret these results as showing that, although incapable of forming excitable neuromuscular junctions, sensory nerves can nevertheless exert powerful trophic effects on denervated muscle fibers. We propose that these findings indicate a useful strategy for improving the outcome of peripheral nerve surgery.

Animals↗
PubMed2001

Mechanisms of the effects of exogenous levodopa on the dopamine-denervated striatum.

The efficacy of exogenous levodopa (L-DOPA) is attributed to its conversion to dopamine by the enzyme aromatic L-amino-acid decarboxylase in striatal dopaminergic terminals. However, there is controversy about the mechanisms underlying the therapeutic and adverse effects of L-DOPA after almost all striatal dopaminergic afferents have disappeared (i.e. in the later stages of Parkinson's disease). After administration of 30mg/kg or 100mg/kg of L-DOPA, rats subjected to unilateral dopaminergic denervation showed intense contraversive rotation and a high density of Fos-immunoreactive nuclei throughout the denervated striatum, with no significant induction of Fos in the intact striatum. Injection of the central aromatic L-amino-acid decarboxylase inhibitor NSD-1015 30min before and 15min after the injection of L-DOPA suppressed the rotational behavior and the striatal induction of Fos. Comparison of results obtained in rats subjected to unilateral and bilateral dopaminergic denervation indicated that the presence of contralateral dopaminergic innervation does not significantly modulate the effects of L-DOPA on the denervated striatum. Serotonergic denervation led to slight and statistically non-significant decrease in the rotational behavior and Fos expression induced by high doses of L-DOPA (100mg/kg) in the dopamine-denervated striatum, but totally suppressed the rotational behavior and Fos expression induced by low doses of L-DOPA (30mg/kg). The present data indicate that the major effects observed after administration of exogenous L-DOPA are not due to a direct action of L-DOPA on dopamine receptors, or to extrastriatal release of dopamine, but to conversion of L-DOPA to dopamine by serotonergic terminals and probably some intrastriatal cells. Given that serotonergic neurons appear to play an important role in the action of L-DOPA in the later stages of Parkinson's disease, strategies targeting the serotonergic system should be considered for the treatment of Parkinson's disease and for combating undesirable side effects of L-DOPA therapy.

Animals↗
PubMed1998

Neural cell adhesion molecule, neuron-specific enolase and calcitonin gene-related peptide immunoreactivity in hamster taste buds after chorda tympani/lingual nerve denervation.

Hamster fungiform papilla taste buds persist in an atrophic form following sensory denervation. While atrophic and innervated taste buds are morphologically similar, it is not known whether their gemmal cells have similar molecular characteristics. Three neurochemicals, neural cell adhesion molecule, neuron-specific enolase, and calcitonin gene-related peptide have been implicated in trophic phenomena, synaptogenesis and cell recognition in neurons and sensory neuroepithelia. The present study uses immunocytochemical localization of these molecular markers to characterize normal and denervated fungiform taste buds following unilateral chorda tympani/lingual nerve denervation in hamsters. In normal taste buds, immunoreactivity to neural cell adhesion molecule, neuron-specific enolase, and calcitonin gene-related peptide was present in a group of cells located centrally in the bud as well as in fungiform nerve fibres and endings. After denervation, gemmal cell immunoreactivity to all three markers was reduced and often confined to a single or a few bud cell(s). Also, fibre staining was absent except for sparse calcitonin gene-related peptide-immunoreactive fibres associated with blood vessels and within the fungiform papillae. These remaining fibres may be autonomic or somatomotor in origin. These results indicate that sensory denervation of hamster taste buds reduces, but does not wholly eliminate the immunoreactivity of surviving gemmal cells to neural cell adhesion molecule, neuron-specific enolase, and calcitonin gene-related peptide. While the number of taste bud cells expressing the markers appears to be nerve-dependent, immunoreactivity in sensory-denervated bud cells of hamster may reflect the influence of local tissue factors.

Animals↗
PubMedDate not supplied

Ileal absorptive adaptation to jejunal resection and extrinsic denervation: implications for living-related small bowel transplantation.

Net absorption of water, electrolytes, and simple nutrients decreases early after jejunoileal autotransplantation (extrinsic denervation) in a canine model but recovers toward normal by 8 weeks. However, the ability of the extrinsically denervated ileum to adapt after total jejunectomy, which would be relevant as a model of segmental small bowel transplantation, remains unknown. Two groups of five dogs each were studied before and 2 weeks and 12 weeks after 50% proximal enterectomy. A control group remained neurally intact, whereas the other group underwent extrinsic denervation (Ext Den) of the remaining ileum. Using a perfusion technique, net absorption of water, electrolytes, and five simple nutrients (glucose, arginine, glutamine, and oleic and taurocholic acids) was measured at the three time points. Ileal morphometry was also evaluated. All dogs developed diarrhea, which resolved by 12 weeks in all but two of the Ext Den dogs. Weight in both groups was decreased at 2 weeks (P <0.05), returned to normal at 12 weeks in control dogs, but remained low in Ext Den dogs (P <0.05). Maximal weight loss was greater in the Ext Den group (P <0.05). No consistent or important differences in net absorptive fluxes of water, electrolytes, or simple nutrients were noted either within or between groups at any time point. Villous height, crypt depth, and longitudinal muscle width increased significantly at 12 weeks after jejunectomy in the Ext Den dogs, but not in the control dogs (P <0.05). Extrinsic denervation of the ileum results in persistent weight loss after proximal 50% enterectomy. Despite diarrhea, only minor changes in electrolyte absorption occur, and ileal net absorption of simple nutrients remains unaffected. The ileum of extrinsically denervated dogs undergoes a more prominent morphometric adaptation after jejunectomy. Extrinsic denervation necessitated by small bowel transplantation, independent of immune effects, does not appear to suppress the ileal adaptive response to maintain net absorption of water, electrolytes, and simple nutrients.

Adaptation, Physiological↗
PubMed2002

Denervation of vagal cardiopulmonary receptors by injection of kainic acid into the nodose ganglia in dogs.

We determined if kainic acid, a neuroexcitotoxin, could be used to denervate the cell bodies of cardiopulmonary vagal sensory neurons. Kainic acid (5 microg) was injected into the nodose ganglion of five dogs. Ten to fourteen days following this procedure, these kainic acid-injected dogs were anesthetized and tested for the extent of the deafferentation. Five additional dogs were used as the control group. Heart rate and mean arterial pressure were measured, and a Swan-Ganz catheter was advanced into a branch of the pulmonary artery to measure pulmonary capillary wedge pressure. We recorded renal sympathetic nerve activity from branches of the left renal nerves. Bilateral carotid occlusion increased heart rate and mean arterial pressure in only the denervated group, but sympathetic nerve activity increased significantly in both groups. This demonstrates that the carotid baroreflex is preserved after kainic acid is injected into the nodose ganglia. Volume expansion by use of warmed saline (15 ml kg(-1)) increased pulmonary capillary wedge pressure 5 mm Hg in control and 14 mm Hg in denervated dogs. In control dogs, sympathetic nerve activity decreased by 10% per mm Hg increase in pulmonary capillary wedge pressure while in denervated dogs, it decreased by 2% per mm Hg. This demonstrates that the vagal cardiopulmonary baroreflex is essentially abolished after injection of kainic acid into the nodose ganglia. After opening the chest, acetylstrophanthidin 100 microg was applied directly to the epicardial surface of the left ventricle to activate cardiac vagal afferents. Epicardial acetylstrophanthidin decreased sympathetic nerve activity by 28% in the control group, but resulted in no change in the kainic-acid-injected dogs. This demonstrates that vagal cardiac chemosensitive reflexes are abolished after bilateral injection of kainic acid into the nodose ganglia. At the end of these experiments, we removed the nodose ganglia for histological evaluation. The vast majority of cell bodies in the ganglia from the denervated group appeared injured compared to cell bodies in ganglia that had not been injected, suggesting that the destruction of cell bodies of vagal afferents was responsible for the functional denervation. Our findings are consistent with the interpretation that kainic acid treatment interrupts vagal afferents that meditate reflex responses to epicardial acetylstrophanthidin and to volume expansion.

Adrenergic Fibers↗
PubMed1999

Differential response of the membrane systems involved in excitation-contraction coupling to early and later postnatal denervation in rat skeletal muscle.

We compared the morphological features of the membrane systems involved in excitation-contraction (E-C) coupling during early postnatal development stages in rat skeletal muscles (tibialis anterior) denervated either at birth or 7 days after birth. Four obvious structural changes are observed in the arrangement of the transverse (T) tubule network and the disposition of triads following early postnatal denervation: (1) an increase in the longitudinal segments of the T tubule network, (2) changes in the direction and disposition of triads, (3) the appearance of caveolae clusters, (4) the appearance of pentads and heptads (i.e. a close apposition of two or three T tubule elements with three or four elements of terminal cisternae of sarcoplasmic reticulum). The increased presence of longitudinal T tubules parallels the loss of cross striations, and this in turn is due to misalignment of the myofibrils. The clusters of caveolae appear almost exclusively in muscle fibres denervated at birth, and pentads and heptads are more frequently observed in muscles denervated at 7 days. The differential growth of muscle fibres in response to denervation leads to the formation of abnormal membrane systems involved in the E-C coupling with very unique morphological features, which differ from the case of denervation in adult muscle fibres.

Age Factors↗
PubMed1984

Effects of interscapular brown adipose tissue denervation on body weight and energy metabolism in ovariectomized and estradiol-treated rats.

Ovariectomy-induced increases and estradiol-induced decreased in body weight cannot be fully accounted for by changes in energy intake and appear to reflect alterations in thermogenesis. Because changes in energy expenditure have been linked to altered sympathetic nervous system (SNS) activity in brown adipose tissue (BAT), the role of estradiol in thermogenesis and body weight, as mediated by the SNS innervation of interscapular BAT (IBAT), was examined. The IBAT of ovariectomized rats was bilaterally or unilaterally surgically denervated. The chow-fed, bilaterally denervated group gained more weight than the unilaterally denervated or sham-operated group, an effect that was exaggerated by sucrose feeding. Food intake did not differ among the groups within each dietary condition. Estradiol benzoate (EB) injections decreased body weight in all groups. Bilateral, and to a lesser extent, unilateral IBAT denervation blocked the EB-induced increase in thermogenesis. Treatment with EB increased IBAT wet weight regardless of surgical treatment. Because IBAT denervation markedly decreased lipoprotein lipase activity and fatty acid synthesis/uptake, the estradiol-induced increase in denervated IBAT wet weight is most likely due to decreased lipolysis produced by the surgical sympathectomy. These results are discussed in terms of the role of the SNS and IBAT in the mediation of estradiol-induced changes in body weight and energy metabolism.

Adipose Tissue, Brown↗
PubMed1979

A central role for denervated tissues in causing nerve sprouting.

One of the oldest known forms of neuronal plasticity is the ability of peripheral nerves to grow and form functional connections after damage to neighbouring axons. Yet the source of the signal which elicits this "sprouting" remains unknown. In mammalian muscles, paralysis-which gives rise to many of the changes which occur in denervated muscles-causes motor nerve terminals to sprout. Could the inactive muscle fibres (rather than nerve degeneration products, another likely source) be responsible for some of the sprouting found in partial denervation? We confirm in this paper that direct stimulation of a partially denervated muscle inhibits sprouting and show that stimulation does so by activating the denervated fibres. Consequently after partial denervation the same signal as that which causes terminal sprouting in a paralysed muscle is able to spread from the denervated muscle fibres to the nerves on the innervated fibres and initiate terminal sprouting.

Animals↗
PubMed1995

Increase in levels of polyubiquitin and proteasome mRNA in skeletal muscle during starvation and denervation atrophy.

Most of the increased protein degradation in muscle atrophy caused by starvation and denervation is due to activation of a non-lysosomal ATP-dependent proteolytic process. To determine whether expression of the ubiquitin-proteasome-dependent pathway is activated in atrophying muscles, we measured the levels of mRNA for ubiquitin (Ub) and proteasome subunits, and Ub content. After rats had been deprived of food for 1 or 2 days, the concentration of the two polyubiquitin (polyUb) transcripts increased 2-4-fold in the pale extensor digitorum longus muscle and 1-2.5-fold in the red soleus, whereas total muscle RNA and total mRNA content fell by 50%. After denervation of the soleus, there was a progressive 2-3-fold increase in polyUb mRNA for 1-3 days, whereas total RNA content fell. On starvation or denervation, Ub concentration in the muscles also rose by 60-90%. During starvation, polyUb mRNA levels also increased in heart, but not in liver, kidney, spleen, fat, brain or testes. Although the polyUb gene is a heat-shock gene that is induced in muscles under certain stressful conditions, the muscles of starving rats or after denervation did not express other heat-shock genes. On starvation or denervation, mRNA for several proteasome subunits (C-1, C-3, C-5, C-8 and C-9) also increased 2-4-fold in the atrophying muscles. When the food-deprived animals were re-fed, levels of Ub and proteasome mRNA in their muscles returned to control values within 1 day. In contrast, no change occurred in the levels of muscle mRNAs encoding cathepsin L, cathepsin D and calpain 1 on denervation or food deprivation. Thus polyUb and proteasome mRNAs increased in atrophying muscles in co-ordination with activation of the ATP-dependent proteolytic process.

Adenosine Triphosphate↗
PubMed2003

Effect of extrinsic denervation on muscarinic neurotransmission in the canine ileocolonic region.

To explore the hypothesis that denervation hypersensitivity increases ileocolonic motor activity after extrinsic denervation, we compared muscarinic neurotransmission in canine ileocolonic loops that were isolated and either extrinsically innervated or extrinsically denervated. We recorded ileal, ileocolonic sphincter (ICS) and colonic pressures, and colonic tone, compliance and relaxation during ileal distention. Muscarinic effects were probed by neostigmine, and minimally effective doses of muscarinic receptor antagonists. Denervation augmented ileal, ICS and colonic contractile activity; colonic high-amplitude propagating contractions (HAPCs) were also augmented; colonic relaxation during ileal distention was abolished. Neostigmine induced HAPCs in both loop preparations. Pirenzipine (M1 antagonist) reduced ileal contractile activity in all loops and reduced colonic relaxation during ileal distention in innervated loops. Pirenzipine also reduced colonic tone and colonic HAPCs, more in denervated loops. Darifenacin (M3 antagonist) reduced ileocolonic contractile activity and tone more than did AF-DX 116 (M2 antagonist) in all loops. Cholinergic receptor subtypes modulate different facets of ileocolonic motor activity in the canine ileocolonic region. Increased sensitivity at M1 muscarinic receptors may partly account for the effects of extrinsic denervation.

Animals↗
PubMed1999

Kidney denervation combined with elimination of adrenal-renal portal circulation prevents the development of hypertension in spontaneously hypertensive rats.

1. Kidney denervation in spontaneously hypertensive rats (SHR) during the prehypertensive stage delays and attenuates the development of hypertension. The same results have been obtained after elimination of the adrenal-renal portal circulation (ARPC). The aim of the present study was to investigate the influence of concomitant kidney denervation and elimination of ARPC on hypertension in SHR. 2. Experiments were performed on 6-week-old male SHR and Wistar-Kyoto (WKY) rats. In the first group of animals (group I), the ARPC was eliminated by removing the left adrenal gland and the right kidney. In the second group of rats (group II), the right kidney and the right adrenal gland were removed and the left kidney was denervated. In the third group of rats (group III), the right adrenal gland and the left kidney were removed and the right kidney was denervated. In the fourth group of rats (group IV), the right adrenal gland and the right kidney were removed. Group IV served as the control group. Denervations were repeated every 3 weeks. Systolic blood pressure was measured indirectly. 3. Elimination of ARPC (group I) and kidney denervation (group II) delayed and attenuated hypertension to the same degree (163 +/- 5 and 157 +/- 4 mmHg, respectively). Application of the these two methods concomitantly (group III) prevented the development of hypertension (130 +/- 6 mmHg). 4. We conclude that both intact efferent sympathetic renal nerves and adrenal hormones reaching the kidney through the ARPC may be mandatory factors for the development of arterial hypertension in SHR.

Adrenal Glands↗
PubMed1999

1H NMR investigation of changes in the metabolic profile of synovial fluid in bilateral canine osteoarthritis with unilateral joint denervation.

OBJECTIVE: High resolution 1H-nuclear magnetic resonance (NMR) techniques have been used to compare the effects of unilateral knee-joint denervation on the biochemical profiles of synovial fluid in a bilateral canine model of osteoarthritis. METHOD: Paired synovial fluid samples were obtained from seven dogs all of which had previously undergone bilateral anterior cruciate ligament transection, unilateral knee denervation and contralateral sham nerve exposure. All synovial fluid samples were then analyzed using 500 MHz 1H-CPMG spin-echo NMR Spectroscopy to assess differences in endogenous metabolite levels between the paired fluids. RESULTS: The results indicate statistically significant increases in glycerol, hydroxybutyrate, glutamine/glutamate, creatinine/creatine, acetate and N-acetyl-glycoprotein concentrations in synovial fluids from denervated with respect to control knees. Furthermore, significant trends towards elevated lactate, alanine and pyruvate levels in the denervated knee fluids are consistent with our previous findings comparing NMR spectroscopy metabolic profiles of normal and osteoarthritic canine synovial fluids. CONCLUSION: This study lends support to the principle of neurogenic acceleration of OA in that the observed differences in metabolite concentrations found in the denervated knee fluids seem to correlate with metabolic changes resulting from aggravation of the OA process caused by joint denervation.

Animals↗
PubMed1985

Neural cell adhesion molecule (N-CAM) accumulates in denervated and paralyzed skeletal muscles.

We have used immunofluorescence and immunoblotting methods to study the amount and distribution of the neural cell adhesion molecule (N-CAM) in rat skeletal muscle; this molecule is thought to mediate adhesion of neurons to cultured myotubes. N-CAM is present on the surface of embryonic myotubes, but it is lost as development proceeds and is nearly absent from adult muscle. However, denervation of adult muscle results in the reappearance of N-CAM. In denervated muscle, N-CAM is associated both with muscle fibers and with cells in interstitial spaces between fibers. The N-CAM in interstitial spaces is concentrated near denervated endplates, which are known to be preferential sites for reinnervation. Paralysis of innervated muscle, known to mimic denervation in many respects, also induces the accumulation of N-CAM. Axons that regenerate to reinnervate muscle bear N-CAM on their terminals, and reinnervation results in the disappearance of N-CAM from muscle. Denervation induces accumulation of N-CAM in mouse and chicken, as well as in rat muscles. Thus, the expression of N-CAM in muscle is regulated by the muscle's state of innervation. In that N-CAM-rich muscles (embryonic, denervated, and paralyzed) are known to be competent to accept synapses, while N-CAM-poor muscles (normal adult and reinnervated) are refractory to hyperinnervation, N-CAM might, in turn, participate in regulating muscle's susceptibility to innervation.

Animals↗
PubMed2001

Effect of denervation on healing after tooth replantation in the ferret.

Studies have shown that the sensory nerves participate in inflammation and immune responses and possess trophic-facilitating wound healing in general. Tooth avulsion represents a pulpal and periodontal injury, and the mechanisms involved in the healing responses subsequent to replantation of teeth are still unclear. The objective of this study was to investigate the healing responses after denervation and replantation of teeth. Unilateral denervation was performed in 15 ferrets by axotomy of the inferior alveolar nerve, 5 days before extraction of the first lower premolars. Six weeks later the mandibles were excised and processed for histological evaluation. Immunohistochemistry was performed using antibodies against the sensory neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP), and measurements of root resorption and ankylosis were performed in four sections from each replanted tooth. After 6 weeks substantial reinnervation was observed in the jaws. Immunoreactivity in the pulp was observed in only two replanted teeth on the denervated side, compared with four on the innervated side. Total pulp necrosis appeared in 10 replanted teeth on the denervated side and in 5 on the innervated, indicating that sensory nerves promote survival of the pulp after replantation. SP-immunoreactive (IR) fibers were more frequently observed in the resorptive lacunae than CGRP-IR fibers. However, resorptive areas lacking IR fibers were frequently found along the root surface. Root resorption averaged 0.062 +/- 0.029 mm2 on the innervated side compared to 0.016 +/- 0.0043 mm2 on the denervated (P< 0.02). Ankylosis was observed in four of the replanted teeth on the innervated side (169.3 +/- 49.7 microm) and in six on the denervated side (332.56 +/- 193.2 microm) (P = 1). It is concluded that the sensory nerves promote root resorption after pulpoperiodontal injuries but have less influence on the osteoblastic activity expressed by ankylosis.

Animals↗
PubMed1984

Impulse activity evokes precocious sprouting of nociceptive nerves into denervated skin.

We have studied the sprouting of intact high-threshold mechanosensory nerves into adjacent denervated trunk skin in adult rats behaviorally, histologically, and electrophysiologically. In the anesthetized animal, stimulation of high-threshold endings in back skin by localized pinching elicits a bilateral reflex excitation of the underlying skeletal muscle, the cutaneous trunci muscle (CTM), visible as a twitch-like puckering of the skin. The reflex was also evoked by electrical excitation of A delta and of C fibers in the dorsal cutaneous nerves (DCNs), with characteristic latencies of 7-20 msec and 40-60 msec, respectively; excitation of low-threshold (A alpha) fibers was ineffective. After cutting selected DCNs, the deprived skin became insensible, but pinch responsiveness gradually recovered over the following 2 weeks. Regeneration of cut axons was not responsible for this recovery; when neighboring intact DCNs were cut, however, all responses were abolished in the recovered skin that had been initially denervated. By 3-5 days after denervation, axons in the dermis were all histologically absent or degenerating; when pinch sensitivity was restored to such skin, silver-stainable axons reappeared in the formerly empty Schwann tubes. During the work we noticed that the periodic examination by pinching, used to follow the time course of recovery of function in individual animals, led to an earlier development of this recovery than in animals that were examined only once at a specified time after denervation. This apparent acceleration in the redevelopment of pinch sensitivity was correlated with the appearance of axons in the recovered skin, and was shown to be due to the impulse activity evoked in the remaining nerves by the periodic pinching; it did not occur when the nerves were blocked by tetrodotoxin (TTX), and it was mimicked by a brief (10-min) period of electrical excitation of the A delta fibers in a remaining nerve carried out at the time when the denervation of skin was done. The time course of the phenomenon suggested that the principal effect of the impulses was to shorten the latency to the onset of sprouting in the activated A delta axons; that is, they induced precocious sprouting. The impulses needed to be conducted centrally for the effect to occur, and precocious sprouting failed to occur if the impulses were allowed to proceed only distally toward the skin. It seems that a brief conditioning burst of impulses in A delta axons sensitizes the neurons to the influence of a sprouting stimulus that appears when skin is denervated.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1978

Quantitative studies on the localization of the cholinergic receptor protein in the normal and denervated electroplaque from Electrophorus electricus.

Electroplaques dissected from the electric organ of Electrophorus electricus are labeled by tritiated alpha1-isotoxin from Naja nigricollis, a highly selective reagent of the cholinergic (nicotinic) receptor site. Preincubation of the cell with an excess of unlabeled alpha-toxin and with a covalent affinity reagent or labeling in the presence of 10(-4) M decamethonium reduces the binding of [3H]alpha-toxin by at least 75%. Absolute surface densities of alpha-toxin sites are estimated by high-resolution autoradiography on the basis of silver grain distribution and taking into account the complex geopmetry of the cell surface. Binding of [3H]alpha-toxin on the noninnervated face does not differ from background. Labeled sites are observed on the innervated membrane both between the synapses and under the nerve terminals but the density of sites is approx. 100 times higher at the level of the synapses than in between. Analysis of the distance of silver grains from the innervated membrane shows a symmetrical distribution centered on the postsynaptic plasma membrane under the nerve terminal. In extrasynaptic areas, the barycenter of the distribution lies approximately 0.5 micrometer inside the cell, indicating that alpha-toxin sites are present on the membrane of microinvaginations, or caveolae, abundant in the extrajunctional areas. An absolute density of 49,600 +/- 16,000 sites/micrometer2 of postsynaptic membrane is calculated; it is in the range of that found at the crest of the folds at the neuromuscular junction and expected from a close packing of receptor molecules. Electric organs were denervated for periods up to 142 days. Nerve transmission fails after 2 days, and within a week all the nerve terminals disappear and are subsequently replaced by Schwann cell processes, whereas the morphology of the electroplaque remains unaffected. The denervated electroplaque develops some of the electrophysiological changes found with denervated muscles (increases of membrane resting resistance, decrease of electrical excitability) but does not become hypersensitive to cholinergic agonists. Autoradiography of electroplaques dissected from denervated electric organs reveals, after labeling with [3H]alpha-toxin, patches of silver grains with a surface density close to that found in the normal electroplaque. The density of alpha-toxin binding sites in extrasynaptic areas remains close to that observed on innervated cells, confirming that denervation does not cause an increase in the number of cholinergic receptor sites. The patches have the same distribution, shape,and dimensions as in subneural areas of the normal electroplaque, and remnants of nerve terminal or Schwann cells are often found at the level of the patches. They most likely correspond to subsynaptic areas which persist with the same density of [3H]alpha-toxin sites up to 52 days after denervation. In the adult synapse, therefore, the receptor protein exhibits little if any tendency for lateral diffusion.

Action Potentials↗
PubMed2001

Arterial baroreflex deficit induced organ damage in sinoaortic denervated rats.

To verify the independent role of the arterial baroreceptor dysfunction involved in target-organ damage in hypertension, sinoaortic denervated (SAD) rats were used as a model of arterial baroreflex (ABR) deficit. SAD, isolated aortic-denervated (AD), and isolated sinus-denervated (SD) rats were instrumented to record blood pressure (BP), heart rate (HR), BP variability (BPV), HR variability (HRV), ABR function control of heart period (ABR-HP), and BP (ABR-BP). Vascular maximum contractile/relaxant function was determined and organ damage was estimated by observation of morphologic changes. Short-term (postoperative 1 week) SAD caused hypertension and tachycardia in rats. Eighteen weeks after operation, BP and HR values in SAD and SD rats were not different from those in sham-operated rats, but AD rats were hypertensive compared with control group. Although 24-h mean BP values of long-term SAD rats were not different from those of sham-operated rats, 24-h BPV of SAD rats was significantly higher than that of sham-operated rats. Arterial baroreflex function in short-term SAD rats was significantly less than in sham-operated rats, whereas in long-term SAD rats, ABR-HP and ABR-BP were higher than those in short-term SAD rats, but were still significantly lower than those in control groups. At postoperative 18 weeks, baroreflex function in SAD and AD rats was significantly less than function in SD and control groups. SBPmax after phenylephrine and DBPmin after nitroprusside were significantly higher in SAD, AD, and SD rats than in control rats. Baroreflex function was negatively correlated to DBPmin and SBPmax in all denervated rats (n = 44). Some morphologic changes were found 18 weeks after denervation in heart, kidney, and small artery in SAD, AD, and SD rats. Baroreflex function in all denervated rats was negatively related to 24-h BPV values. In contrast, 24-h BPV values in SAD, AD, and SD rats were positively related to organ-damage score. A negative correlation between ABR function and end-organ damage score was found. Arterial baroreflex deficit played an independent and important role in organ-damage in SAD rats with significantly elevated 24-h BPV.

Animals↗
PubMed2002

The effect of two episodes of denervation and reinnervation on skeletal muscle contractile function.

Sensory or motor "baby-sitting" has been proposed as a clinical strategy to preserve muscle integrity if motion-specific axons must regenerate over a long distance to reach denervated target muscles. Denervated muscles are innervated temporarily by using axons from nearby sensory or motor nerves. After motion specific motor axons have reached the target, the baby-sitter nerve is severed and motion-specific axons are directed to the target. Although this strategy minimizes denervation time, the requisite second episode of denervation and reinnervation might be deleterious to muscle contractile function. This study was designed to test the hypothesis that two sequential episodes of skeletal muscle denervation and reinnervation result in greater force and power deficits than a single peripheral nerve injury and repair. Adult Lewis rats underwent either transection and epineurial repair or sham exposure of the left peroneal nerve. After a 4-month recovery period, the contractile properties of the extensor digitorum longus muscle of the sham exposure group (control, n = 9) and one of the nerve division and repair groups (repair group 1, n = 9) were evaluated with measurements of the maximum tetanic isometric force, peak power, and maximal sustained power. A third group of rats underwent a second cycle of nerve division and repair (repair group 2, n = 9) at this same time point. Four months postoperatively, contractile properties of the extensor digitorum longus muscles were evaluated. Maximum tetanic isometric force and peak power were significantly reduced in repair group 2 rats as compared with repair group 1 and control rats. Maximal sustained power was not significantly different between the groups. These data support our working hypothesis that skeletal muscle contractile function is adversely affected by two cycles of denervation and reinnervation as compared with a single episode of nerve division and repair.

Animals↗