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PubMed1988

Influence of renal denervation on vascular responsiveness of isolated rat intrarenal arteries.

Microsurgical renal denervation of the rat has been reported to increase blood loss and bleeding time after a standardized kidney resection. To investigate the vascular effects of denervation, isolated intrarenal arteries were studied using sensitive 'isometric' recording equipment. Four pieces of evidence were obtained to indicate an effective functional denervation I week after renal nerve transection: (i) Phentolamine reduced the K+-induced contraction in controls but not in denervated arteries. (ii) The K+-induced contraction was significantly smaller in denervated than in control arteries. (iii) Noradrenaline (NA) was a significantly more potent vasoconstrictor (4 x) in denervated than in control arteries. (iv) Cocaine increased the NA sensitivity in control arteries (3 x), whereas it failed to do so in denervated vessels. Vasopressin, 5-hydroxytryptamine (5-HT), NA (in the presence of cocaine), prostaglandin F2 alpha (PGF2 alpha) and dopamine (DA) produced concentration-dependent contractions in the mentioned order of potency. Denervated arteries were found to be about two to three times more sensitive to the vasoconstrictors than control arteries. Angiotensin I and II had no contractile effect in any of the vessel segments examined. Indomethacin-pretreated arteries also failed to respond to angiotensin II. Neuropeptide Y produced only weak contractions and failed to influence the NA concentration-response relationship in either control or denervated arteries. In conclusion, renal denervation caused a general supersensitivity of the vascular smooth muscle cells to both circulating and non-circulating vasoconstrictors. Our results cannot explain the increased blood loss and bleeding time seen after denervation, but rather support the view that the enhanced bleeding was caused by an interrupted vasoconstrictor influence of the sympathetic nerves.

Angiotensins↗
PubMed1989

Reorganization of sympathetic preganglionic connections in cat bladder ganglia following parasympathetic denervation.

1. Experiments were undertaken to examine the mechanisms involved in the reorganization of sympathetic efferent pathways to the urinary bladder of the cat following chronic unilateral, parasympathetic preganglionic denervation of the bladder. 2. Electrical stimulation (10-30 Hz) of the hypogastric nerve in cats with an intact bladder innervation or on the normally innervated side of the bladder in unilaterally denervated preparations elicited low-amplitude (10-25 cmH2O) transient (10-30 s) bladder contractions and non-synaptic axonal volleys on bladder postganglionic nerves. However, after chronic (3-22 months) sacral preganglionic denervation, hypogastric nerve stimulation on the side of the denervation elicited large (60-80 cmH2O) and more sustained (4-5 min) bladder contractions as well as synaptically mediated firing on bladder postganglionic nerves. 3. The vesicoexcitatory effects of hypogastric nerve stimulation on the chronically denervated side were not altered selectively by the adrenergic blocking agent, phenoxybenzamine, but were blocked by atropine and hexamethonium suggesting that the responses were mediated by muscarinic and nicotinic cholinergic synapses. These drugs did not influence the responses elicited by hypogastric nerve stimulation on the normally innervated side of the bladder. 4. Following more extensive chronic unilateral denervation (transection of the pelvic and hypogastric nerves on one side of the bladder) stimulation of the contralateral intact pelvic nerve elicited postganglionic firing in vesical postganglionic nerves on the denervated side. This crossed excitatory pathway was not observed in normal animals or following sacral preganglionic denervation. 5. It is concluded that parasympathetic preganglionic denervation of the bladder ganglia leads to a reinnervation of the denervated cholinergic ganglion cells by sympathetic preganglionic pathways in the ipsilateral hypogastric nerve. This reinnervation results in the conversion of sympathetic inhibitory pathways to excitatory pathways in the denervated bladder. This change may contribute to the development of the autonomous hyperactive bladder seen under conditions of peripheral nerve or conus medullaris lesions of the spinal cord.

Action Potentials↗
PubMed1984

Effects of renal denervation on the renal responses of anesthetized rats to cyclohexyladenosine.

In the present experiments, we tested the hypothesis that renal denervation would attenuate or abolish some of the renal effects of cyclohexyladenosine, a nonmetabolized adenosine receptor agonist. A paired design (left kidney sham-denervated or denervated versus the innervated right kidney) was used in anesthetized rats. Intravenous cyclohexyladenosine (2.3 nmol/min) reduced para-aminohippurate and inulin clearances in both denervated and sham-denervated kidneys; these effects were increased rather than decreased in denervated kidneys. Similarly, cyclohexyladenosine decreased the excretion of Na+ and K+ more in denervated than in innervated kidneys. Renal plasma flow was decreased by cyclohexyladenosine, without a corresponding increase in the arteriorenal venous difference in plasma renin concentrations, and arterial plasma renin concentration decreased in all rats given cyclohexyladenosine, suggesting inhibition of renin secretion. No differences in the latter variables were noted in denervated versus sham-denervated kidneys. Since cyclohexyladenosine produced effects in denervated kidneys which were equal to or greater than the effects in sham-denervated kidneys, it is concluded that these effects are mediated by direct actions, rather than by inhibition of transmitter release from the renal nerves.

Adenosine↗
PubMed2001

Effects of vagal denervation on cardiorespiratory and behavioral responses in the newborn lamb.

Recently, Wong et al. (Wong KA, Bano A, Rigaux A, Wang B, Bharadwaj B, Schurch S, Green F, Remmers JE, and Hasan SU, J Appl Physiol 85: 849-859, 1998) demonstrated that fetal lambs that have undergone vagal denervation prenatally do not establish adequate alveolar ventilation shortly after birth. In their study, however, vagal denervation was performed prenatally and the deleterious effects of vagal denervation on breathing patterns and gas exchange could have resulted from the prenatal actions of the neurotomy. To quantify the relative roles of pre- vs. postnatal vagal denervation on control of breathing, we studied 14 newborn lambs; 6 were sham operated, and 8 were vagally denervated below the origin of the recurrent laryngeal nerve. Postoperatively, all denervated animals became hypoxemic and seven of eight succumbed to respiratory failure. In vagally denervated lambs, expiratory time increased, whereas respiratory rate, minute ventilation, and lung compliance decreased compared with the sham-operated animals. In the early postoperative period, the frequency of augmented breaths was lower but gradually increased over time in the denervated vs. sham-operated group. The dynamic functional residual capacity was significantly higher than the passive functional residual capacity among the sham-operated group compared with the denervated group. No significant differences were observed in the prevalence of various sleep states and in the amount of total phospholipids or large- and small-aggregate surfactants between the two groups. We provide new evidence indicating that intrauterine actions of denervation are not required to explain the effects of vagal denervation on postnatal survival. Our data suggest that vagal input is critical in the maintenance of normal breathing patterns, end-expiratory lung volume, and gas exchange during the early neonatal period.

Animals↗
PubMed2006

Effect of denervation on mitochondrially mediated apoptosis in skeletal muscle.

Chronic muscle disuse induced by denervation reduces mitochondrial content and produces muscle atrophy. To investigate the molecular mechanisms responsible for these adaptations, we assessed 1) mitochondrial biogenesis- and apoptosis-related proteins and 2) apoptotic susceptibility and cell death following denervation. Rats were subjected to 5, 7, 14, 21, or 42 days of unilateral denervation of the sciatic or peroneal nerve. Muscle mass and mitochondrial content were reduced by 40-65% after 21 and 42 days of denervation. Denervation-induced decrements in mitochondrial content occurred along with 60% and 70% reductions in transcription factor A (Tfam) and peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha, respectively. After 42 days of denervation, Bax was elevated by 115% and Bcl-2 was decreased by 89%, producing a 16-fold increase in the Bax-to-Bcl-2 ratio. Mitochondrial reactive oxygen species production was markedly elevated by 5- to 7.5-fold in subsarcolemmal mitochondria after 7, 14, and 21 days of denervation, whereas reactive oxygen species production in intermyofibrillar (IMF) mitochondria was reduced by 40-50%. Subsarcolemmal and IMF mitochondrial levels of MnSOD were also reduced by 40-50% after 14-21 days of denervation. The maximal rate of IMF mitochondrial pore opening (V(max)) was elevated by 25-35%, and time to V(max) was reduced by 20-25% after 14 and 21 days, indicating increased apoptotic susceptibility. Myonuclear decay, assessed by DNA fragmentation, was elevated at 7-21 days of denervation. Our data indicate that PGC-1alpha and Tfam are important factors that likely contribute to the reduced mitochondrial content after chronic disuse. In addition, our results illustrate that, despite the reduced mitochondrial content, denervated muscle has greater mitochondrial apoptotic susceptibility, which coincided with elevated apoptosis, and these processes may contribute to denervation-induced muscle atrophy.

Adaptation, Physiological↗
PubMed1990

Selective denervation of the Musculus pectoralis muscle in the chicken.

A surgical method for selective denervation was developed to facilitate investigations about the postmortem characteristics of denervated pectoralis muscles in chickens, Musculus (M.) pectoralis. The M. pectoralis was denervated in anesthetized chickens unilaterally or bilaterally by excising a 1-cm section of the nervus pectoralis as it branched from the N. medianoulnaris in the brachial plexus. Denervation resulted in significant (P less than .01) and consistent depression in the relative weight of M. pectoralis from the wk 2 through 17 postoperative. The relative weight of the functionally antagonistic M. supracoracoideus was unaffected by ipsilateral denervation of the M. pectoralis. The M. coracobrachialis acts in synergism with the M. pectoralis and displayed significant muscle atrophy at 4, 6, 8 and 17 wk postoperative in treatment groups where the ipsilateral M. pectoralis was denervated. Only the M. pectoralis displayed histological signs of denervation in transverse cryostat sections. Denervated tissue was characterized by atrophic and rounded muscle-fiber profiles, an increase in the endomysial and perimysial connective-tissue spaces, and leucocytes within degenerative perimysial nerves from 2 through 17 wk postoperative. Signs of denervation were distributed throughout seven zones sampled from the M. pectoralis. This study indicated that selective denervation of the M. pectoralis was achieved and that postoperative histology was necessary to accurately assess denervation.

Animals↗
PubMed1999

Neonatal partial denervation results in nodal but not terminal sprouting and a decrease in efficacy of remaining neuromuscular junctions in rat soleus muscle.

Mature motoneurons respond to partial denervation of their target muscle by sprouting to reinnervate denervated fibers, thus maintaining muscle strength in the face of motoneuronal loss caused by injury or disease. Neonatal motoneurons, however, do not expand to innervate more muscle fibers. The present work seeks to understand this developmental change in motoneuron response to partial denervation. It has been suggested that neonatal motor units cannot increase in size because they are already at their maximum size (approximately five times larger than in adulthood). We ruled out this explanation by showing that after partial denervation on postnatal day 14 (P14), when motor units have decreased to their adult size, motoneurons still did not sprout to reinnervate as many fibers as in adulthood. Instead, we found evidence supporting an alternative explanation involving terminal Schwann cells. After partial denervation of neonatal (but not adult) muscles, terminal Schwann cells at denervated endplates undergo apoptosis. We found that terminal (but not nodal) sprouting was absent in partially denervated neonatal muscles. This finding suggests that terminal Schwann cells, previously reported to guide terminal sprouts to denervated endplates in adult muscles, are necessary for the formation and growth of terminal sprouts. Moreover, partial denervation on P14 severely weakened the remaining, uninjured synapses, suggesting that neonatal motoneurons may withdraw terminals after the denervation of nearby fibers. These findings have implications for the interpretation of previous studies on synapse elimination and offer insight into the failure of young motor units to expand after partial denervation.

Aging↗
PubMed1993

[Effect of endurance running training on the structural and metabolic properties of partially denervated soleus muscle in rats].

To estimate the influence of partial denervation on the skeletal muscle, a histochemical and biochemical study was performed on the soleus muscle. Partial denervation was carried out by cutting the proximal root of the nerve innervating the soleus muscle. Further, the effect of endurance running training on the recovery of the partially denervated muscle was examined. Partial denervation did not cause apparent diminution of the number of muscle fibers, nor the muscle weight. Four weeks after denervation, histological changes such as grouping atrophy, fiber splittings, and invasive phagocytes were observed in the denervated portion of the muscle. In the non-running group, mean cross-sectional fiber area of each muscle fiber type increased significantly at 4 weeks after denervation. On the other hand, mean cross sectional fiber area of type II fibers increased at 8 weeks after denervation in the running group. The oxidative enzyme activities were significantly increased in the partially denervated muscle by endurance running training after 4 weeks of denervation. The results indicate that the influence of partial denervation gradually extends over the whole muscle. Furthermore, the running exercise appears to add a good effect to a recovery of the function and the maintenance of muscle structures.

Animals↗
PubMedDate not supplied

Partial sympathetic denervation of the rat epididymis permits fertilization but inhibits embryo development.

The rat cauda epididymidis receives sympathetic innervation from the inferior mesenteric ganglion (IMG). We have previously demonstrated that surgical removal of the IMG and proximal hypogastric nerves (IMG denervation) results in significant and cauda-specific changes in epididymal sperm transport, sperm motility, luminal fluid protein composition, and tissue histology. In the present study we used natural mating trials and intrauterine insemination (IUI) techniques to determine whether or not IMG denervation affects male fertility and reproductive capacity. For the initial studies, adult male Sprague Dawley rats were mated with estrous females 1 and 4 weeks following IMG denervation. Nine days after mating, uterine implantation sites and corpora lutea (CL) were counted. In females mated with sham-operated control males, 85.8% of ovulated oocytes were fertilized and subsequently implanted. In contrast, females mated with IMG-denervated males 1 or 4 weeks following surgery had 0% and 3.5%, respectively, of ovulated oocytes fertilized and implanted. For rats maintained 21 days after mating, an average of 13 +/- 1 pups were delivered by each of nine females mated with sham-operated control male rats; whereas, only seven morphologically normal pups were delivered by one of 14 females mated with IMG-denervated male rats. Additional experiments demonstrated that the decrement in offspring was, in part, due to a significant decrease in the number of spermatozoa in the female uterus following mating with IMG-denervated males. To determine whether IMG denervation exerted an additional effect directly on the fertilizing ability of spermatozoa, IUI experiments were performed. Six million cauda epididymal spermatozoa from 1- or 4-week IMG-denervated males were inseminated into the uterine horns of luteinzing hormone-releasing hormone (LHRH)-synchronized females and 9 days later implantation sites and CL were counted. Implantations were observed for 78%, 28%, and 25% of ovulated oocytes following IUI with spermatozoa from sham-operated controls and from 1- and 4-week IMG-denervated rats, respectively. To determine whether the reduction in implantation sites following IUI with spermatozoa from IMG-denervated rats resulted from impaired oocyte fertilization, studies were performed in which oocytes were retrieved and stained 24 hours after IUI. Comparable fertilization rates of 76.5% and 89.0% were observed using cauda epididymal spermatozoa from IMG-denervated and sham-operated control males, respectively, indicating that oocyte fertilization was not affected by the loss of innervation. These studies establish the importance of innervation from the IMG for ejaculatory competence and sperm reproductive capacity in the male rat. These data further suggest that sympathetic innervation in the epididymis critically influences paternal factors associated with embryonic development.

Animals↗
PubMed1985

Sympathetic denervation does not alter the density or properties of alpha-1 adrenergic receptors in rat vas deferens.

Alpha-1 adrenergic receptors in surgically denervated rat vas deferens were studied using radioligand binding assays of [125I] BE 2254 ([125I]BE) and contraction measurements. Scatchard analysis of saturation isotherms of specific [125I]BE binding showed no change in the affinity or density of binding sites 4, 7 or 14 days after denervation of rat vas deferens. The potency of norepinephrine in inhibiting specific [125I]BE binding was also unchanged 7 days after denervation of vas deferens. The potency of phenylephrine in causing contraction in vitro did not change 4, 7 or 14 days after denervation of vas deferens; however, there was a significant increase in the maximum contractile response to phenylephrine at all time points. After partial inactivation of alpha-1 adrenergic receptors in vitro with phenoxybenzamine, there was an equivalent reduction in the number of [125I]BE binding sites in the control and 14-day denervated vas deferens. The equilibrium dissociation constants calculated from contractile measurements for norepinephrine were the same in the control and denervated tissues. However, there was a 2.2-fold increase in contractile sensitivity to norepinephrine 14 days after denervation and a 3.6-fold increase in contractile sensitivity to methacholine 7 days after denervation. These results show that surgical denervation of the rat vas deferens results in an increase in contractile sensitivity to norepinephrine and methacholine and an increase in maximum contraction. However, there is no change in alpha-1 adrenergic receptor density or properties at any time after denervation. Thus, alterations in alpha-1 adrenergic receptors do not contribute to contractile supersensitivity of denervated rat vas deferens.

Animals↗
PubMed2000

Effects of short- and long-term Schwann cell denervation on peripheral nerve regeneration, myelination, and size.

Poor functional recovery after peripheral nerve injury has been generally attributed to inability of denervated muscles to accept reinnervation and recover from denervation atrophy. However, deterioration of the Schwann cell environment may play a more vital role. This study was undertaken to evaluate the effects of chronic denervation on the capacity of Schwann cells in the distal nerve stump to support axonal regeneration and to remyelinate regenerated axons. We used a delayed cross-suture anastomosis technique in which the common peroneal (CP) nerve in the rat was denervated for 0-24 weeks before cross-suture of the freshly axotomized tibial (TIB) and chronically denervated CP nerve stumps. Motor neurons were backlabeled with either fluoro-ruby or fluorogold 12 months later, to identify and count TIB motor neurons that regenerated axons into chronically denervated CP nerve stumps. Number, size, and myelination of regenerated sensory and motor axons were determined using light and electron microscopy. We found that short-term denervation of < or =4 weeks did not affect axonal regeneration but more prolonged denervation profoundly reduced the numbers of backlabeled motor neurons and axons in the distal nerve stump. Yet, atrophic Schwann cells retained their capacity to remyelinate regenerated axons. In fact, the axons were larger and well myelinated by long-term chronically denervated Schwann cells. These findings demonstrate a progressive inability of chronically denervated Schwann cells to support axonal regeneration and yet a sustained capacity to remyelinate the axons which do regenerate. Thus, axonal interaction can effectively switch the nonmyelinating phenotype of atrophic Schwann cells back into the myelinating phenotype.

Animals↗
PubMed2001

Expression of Leu-19 (CD56, N-CAM) and nitric oxide synthase (NOS) I in denervated and reinnervated human skeletal muscle.

Neural cell adhesion molecule (N-CAM, Leu-19, CD 56) expression appears during muscle fiber regeneration and after denervation. Sarcolemma-associated nitric oxide synthase (NOS) I, however, disappears from denervated myofibers. The dynamics of expression of both proteins were studied in 5 cases of acute/subacute denervation, 28 cases of chronic denervation with and without collateral reinnervation, 5 cases of the intermediate type spinal muscular atrophy (SMA 2), and in 2 normal biopsies. NOS I and its NADPH diaphorase (NADPHd) activity disappeared from the sarcolemma region shortly after denervation, and before the appearance of denervation atrophy. N-CAM was found diffusely distributed in the sarcoplasm at the most severe phase of denervation atrophy in the majority of highly atrophic fibers. During reinnervation, NOS I expression remained absent and in part of the cases the target/targetoid phenomenon appeared. In parallel with the increase in volume of the reinnervated muscle fibers, the intensity of N-CAM immunoreactivity decreased progressively. After full restitution of muscle fiber caliber, the target/targetoid phenomenon and N-CAM immunostaining disappeared completely, and, finally, NOS I reappeared in the sarcolemma region. The sarcolemmal expression of dystrophin and dystrophin-associated proteins was unchanged during denervation. NOS I was completely absent in children with SMA 2, since the protein does not appear before 5 years of age in skeletal muscle, while N-CAM was very intensely expressed in the sarcoplasm of highly atrophic denervated muscle fibers. In conclusion, this study suggests that innervation is an important factor for selective gene expression and positioning of NOS I and N-CAM in skeletal muscle and gives practical information for the assessment of the phase and developmental stage of the denervation and reinnervation process.

CD56 Antigen↗
PubMed2001

Sodium influx during action potential in innervated and denervated rat skeletal muscles.

Resting Na(+) influx (J(i)(Na)) was measured in innervated and denervated (1-6 days) rat extensor digitorum longus muscle in the absence and presence of 2 micromol/L tetrodotoxin (TTX). The mean value of Na(+) permeability (P(Na)) in innervated muscles was 49.6 +/- 2.6 pm.s(-1). At the second day postdenervation, it decreased by about 45%. This was followed, between the second and fourth days, by a sharp rise, which by the sixth day reached a steady value approximately 2.5 times greater than that of innervated muscles. This, most likely, generated the 30% increase in internal [Na(+)] concentration ([Na(+)](I)) observed at this time. Tetrodotoxin reduced P(Na) of both innervated and denervated muscles by about 25%. In 6-day denervated muscles, virtually all the TTX effect on P(Na) represents the blockage of TTX-resistant Na(+) channels. Denervation produced a depolarization of about 20 mV by the sixth day. The extra J(i)(Na) per action potential (AP) decreased monotonically with time after denervation from 20.0 +/- 3.8 in innervated to 11.1 +/- 1.0 nmol.g(-1).AP(-1) in 6-day denervated muscles. The overshoot of the AP decreased from 15 +/- 1 in innervated to 7 +/- 1 mV in 6-day denervated muscles. Likewise, the maximum rate of rise (+dV/dt), an expression of the inward Na(+) current, fell from 305 +/- 14 in innervated to 188 +/- 18 V.s(-1) in 6-day denervated muscles. The estimated 6-day denervated/innervated ratio of peak Na(+) conductance (g(Na)) was 0.67. The changes in AP parameters promoted by denervation were substantially reduced when both innervated and denervated fibers were hyperpolarized to -90 mV. These results suggest that the depolarization, mainly due to the increase in P(Na) /P(K) ratio, increases Na(+) inactivation and consequently reduces peak g(Na), in spite of the absolute increment in resting TTX-sensitive P(Na). This, in addition to the moderate reduction in the inward driving force on Na(+), decreases the inward Na(+) current and the extra J(i)(Na) per AP.

Action Potentials↗
PubMed1988

Denervation-induced proliferative changes of triads in rabbit skeletal muscle.

Protein compositional and functional differences exist between longitudinal and junctional sarcoplasmic reticulum (SR) in relation to Ca transport and to Ca release. In light of this knowledge, we have reinvestigated the effects of denervation on SR of rabbit gastrocnemius, a predominantly fast muscle. Electron microscopy of 2-weeks denervated muscle showed proliferation of transverse tubules (TT), forming junctional contacts with SR terminal cisternae (TC). At coincident periods, the yield of muscle microsomes was increased, and their fractionation by sucrose-density centrifugation demonstrated a relative increase of heavy vesicles. Thin-section electron microscopy of heavy SR from denervated muscle showed an increased number of vesicles containing calsequestrin (CS) as compared with control muscle. Electrophoretic analysis confirmed the relative decrease of Ca-ATPase protein and the striking increase of CS both in total microsomes and in heavy SR vesicles. Calcium loading and Ca-ATPase activity as well as the density of Ca-ATPase protein were decreased to a similar extent (20-30%) in denervated muscle microsomes. Stimulation of Ca-ATPase activity by Ca-ionophore A23187 showed that the vesicles were tightly sealed. When probed by competitive ELISA with antibody to SR Ca-ATPase from pure fast muscle, the Ca-ATPase of denervated microsomes was found to be highly cross reactive. Cleveland's peptide maps of the Ca-ATPase protein after partial digestion with S. aureus V8 protease also showed no significant change after denervation. Changes in cholesterol content and in the ratio of Mg-ATPase to Ca-ATPase activity of denervated muscle microsomes indicated a 4-fold increase of TT protein, i.e., from about 3% to not more than 12% of total protein, at 2 weeks after denervation. All these changes were totally reversed upon reinnervation of muscle fibers, and the consequent muscle recovery, as obtained by nerve crushing instead of nerve sectioning. From these results, we conclude that denervated adult fast muscle, similarly to immature fast muscle, contains more junctional SR. However, the molecular and catalytic properties of the Ca-ATPase are unaffected by denervation.

Animals↗
PubMed1999

Altered gene expression in steroid-treated denervated muscle.

In rats treated with high-dose corticosteroids, skeletal muscle that is denervated in vivo (steroid-denervated) develops electrical inexcitability similar to that seen in patients with acute quadriplegic myopathy. To determine whether changes in muscle gene transcription might underlie inexcitability of steroid-denervated muscle we performed RNase protection assays to quantitate adult (SkM1) and embryonic (SkM2) sodium channel isoforms and chloride channel (CLC-1) mRNA levels in control, denervated, steroid-innervated, and steroid-denervated skeletal muscle. While SkM1 mRNA levels were relatively unaffected by denervation or steroid treatment, SkM2 mRNA levels were increased by both. These effects were synergistic and high levels of SkM2 mRNA were expressed in denervated muscle exposed to corticosteroids. Skeletal muscle CLC-1 mRNA levels were decreased by denervation. To better understand the marked upregulation of SkM2 in steroid-denervated muscle we examined changes in myogenin and glucocorticoid receptor mRNA levels. However, changes in these mRNA levels cannot account for the upregulation of SkM2 in steroid-denervated muscle.

Adolescent↗
PubMed2005

Denervation of the neorectum as a potential cause of defecatory disorder following low anterior resection for rectal cancer.

PURPOSE: The aim of this study was to determine whether denervation of the sigmoid colon during low anterior resection contributes to the postoperative motility characteristics of the neorectum and to the defecatory function of patients. METHODS: Sixty-seven patients who underwent either low or ultralow anterior resection for rectal cancer were evaluated. In accordance with the length of denervated neorectum, each patient was assigned to either the short-denervation or long-denervation group, determined by whether the inferior mesenteric artery was divided. Colonic propagated contraction was then measured by means of intraluminal pressure monitoring. Transit time was calculated with orally administered radiopaque markers. RESULTS: Propagated contraction down to the neorectum was significantly less common in the long-denervation group (14/36) than in the short group (12/15, P < 0.05), whereas spastic minor contraction at the neorectum was significantly more common in the long-denervation group (21/36) than the in short group (3/15, P < 0.05). Colonic transit time below the sigmoid colon was significantly longer in long group (6.4 hours) than in the short group (3.4 hours, P < 0.01). Although motility disorder of the neorectum was correlated with clinical defecatory malfunctions, including multiple evacuations, urgency, and soiling, no significant correlation was noted between the length of the denervated neorectum and the defecatory disorders. CONCLUSIONS: Motility of the neorectum following low anterior resection appears degraded by intraoperative maneuvers that cause denervation of the remnant sigmoid colon. Motility disorder of the neorectum, but not the length of the denervated neorectum causing the disorder, correlates well with several defecatory malfunctions. This finding suggests that postoperative defecatory disorder as a result of low anterior resection is caused by many factors in addition to denervation of the neorectum.

Adult↗
PubMed1987

Mechanical and electrical properties of denervated rat skeletal muscles.

Mechanical activity (twitch and tetanus) and electrical activity (single and repetitive action potentials) were recorded in vitro (34 degrees C) in control and denervated (3 to 14 days) soleus and extensor digitorum longus muscles of the rat. After denervation tetanic tension (100 to 200 Hz, 500 ms duration) was decreased in both types of muscles. Denervation reduced significantly the rates of rise and fall and the amplitude of the action potential in both types of muscle fibers. In denervated fibers with very low resting membrane potential no action potentials could be recorded: in these fibers only a slow response without overshoot was detected. Hyperpolarization of denervated fibers to -90 mV prior to application of the depolarizing pulse increased their excitability. Action potential amplitudes were well maintained during tetanic stimulation (200 Hz, 40 to 90 ms) in innervated fibers. Depolarization of the innervated fibers with cathodic current before the tetanic pulse hindered the generation of repetitive action potentials at 200 Hz. A proportion of denervated fibers stimulated at 100 to 200 Hz generated only one action potential or gave rise to an incomplete train. Hyperpolarization of the denervated fibers resulted in an improvement in the ability to generate a train of action potentials at 100 to 200 Hz. A group of denervated fibers exhibited well maintained action potentials during tetanus. We suggest that failure in the repetitive electrical activity of denervated fibers could be the reason for the reduced tension of tetanus. Depolarization of the fibers and/or the increment in the electrical time constant of the sarcolemma are suggested for the decrease in the electrical excitability of denervated fibers.

Action Potentials↗
PubMed1994

Increase of c-fos and ras oncoproteins in the denervated neuropil of the rat dentate gyrus.

When the entorhinal cortical input to the rat dentate gyrus is destroyed, the process of sprouting and synaptogenesis begins within the denervated dendritic laminae. The present study used immunohistochemical methods to determine whether there was an increase in the oncoproteins c-fos and ras within the denervated neuropil of the dentate gyrus during this period of terminal growth and synapse formation. Animals were prepared for immunolabeling one, three, six and 30 days after unilateral lesion of the entorhinal cortex. Rats were perfused with paraformaldehyde fixative and brain sections were incubated with antibodies to either c-fos or ras oncoprotein. Qualitative light microscopic analysis showed a marked increase in both c-fos and ras proteins over the denervated zone at three days postlesion when compared to both the intact contralateral control and the naive control. At one- and six-day postlesion intervals there was also an increase in labeling over the denervated neuropil with each oncoprotein; however, the intensity of label was reduced relative to that of the three-day time interval. No increase in labeling over the denervated zone was visible for either antibody at 30 days postlesion. The high level of both c-fos and ras labeling in the denervated molecular layer was confirmed with Western blot analysis of dissected molecular layers from lesioned and contralateral control hippocampi. Controls for antibody and method specificity showed that the labeling was specific for c-fos and ras proteins. The high level of c-fos labeling over the denervated molecular layer was uniform with scattered punctate sites of reaction product interspersed in the neuropil. Glial cell bodies in the neuropil contained the highest levels of c-fos oncoprotein. The granule cell nuclei showed an apparent reduction in the level of c-fos labeling at one, three and six days postlesion when compared with the nuclear staining of naive control cases. At 30 days postlesion, high levels of labeling over the denervated zone were not visible and c-fos localization had returned to the typical predominant nuclear sites seen in controls. Ras oncoprotein localization was diffuse in the cell processes of the molecular layer, with intermittent glial labeling within the denervated zone. No cell nuclei labeling was observed with antibodies to ras protein. These results show that both c-fos and ras oncoproteins are increased within the denervated neuropil of the dentate gyrus during sprouting and synapse formation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗