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Descent of the bladder neck: a urographic finding in denervation of the urethral sphincter in children with myelodysplasia.

The urographic position of the neck of the bladder in relation to the pubic symphysis was correlated with lower motor neuron (LMN) denervation of the urethral sphincter as detected with electromyography in 65 infants and children with myelodysplasia. Descent (prolapse) of the bladder (bladder neck below the upper margin of the pubic symphysis) was present in 30 (46.2%) patients. Prolapse was both more frequent and tended to be more severe in girls. Complete LMN denervation of the urethral sphincter was present in 25 (83.3%) of the 30 patients with prolapse and in only four (11.4%) of 35 with a normally positioned bladder. Conversely, 25 (86.2%) of the 29 patients with complete LMN denervation of the sphincter had prolapse as compared with only five (13.9%) of 36 patients with partial or no LMN denervation of the sphincter. Although not as precise as urodynamic testing, significant descent of the bladder neck is a reliable urographic finding of complete LMN denervation of the external urethral sphincter in infants and children with myelodysplasia.

Child↗

Splanchnic and vagal denervation attenuate central Fos but not AVP responses to intragastric salt in rats.

We have recently reported that an acute intragastric hypertonic saline load increases plasma arginine vasopressin (PAVP) and Fos immunoreactivity in several central nuclei, including the supraoptic nucleus (SON), paraventricular nucleus (PVN), nucleus of the solitary tract (NTS), area postrema (AP), and lateral parabrachial nucleus (LPBN). We hypothesized that these responses are mediated by stimulation of peripheral osmoreceptors with splanchnic and/or vagal afferent projections. To test this hypothesis, we examined the effect of bilateral subdiaphragmatic vagotomy and bilateral splanchnic denervation on the PAVP and Fos immunoreactivity responses to intragastric hypertonic saline infusion in awake rats. Compared with responses in sham rats, Fos immunoreactivity responses were significantly reduced in vagotomized rats in the AP, SON, and PVN, whereas normal Fos levels were observed in the LPBN. However, vagotomized rats exhibited a normal increase in PAVP. Splanchnic-denervated rats also exhibited similar changes in PAVP in response to intragastric hypertonic saline compared with sham-denervated rats, and no differences were observed in Fos immunoreactivity in the LPBN, SON, and PVN compared with sham rats. However, splanchnic-denervated rats were observed to have significantly lower Fos staining in the NTS and AP compared with sham rats. The inability of splanchnic or vagal denervation alone to block the PAVP response to intragastric hypertonic saline suggests that either peripheral osmoreceptors project via both splanchnic and vagal afferents to mediate AVP release or that the observed response of PAVP is due to the activation of central osmoreceptors in the absence of measurable changes in plasma osmolality.

Animals↗

Blood flow in the ovary and oviduct of rats after sympathetic denervation.

The effect of sympathetic denervation on blood flow in the ovary and oviduct was studied in rats undergoing oestrous cycles or at Day 14 of pregnancy. The ovary and oviduct on one side were denervated by briefly freezing the ovarian vascular pedicle and the ovarian suspensory ligament. Blood flow was measured using 15 microns 57Co-labelled microspheres while the rats were under barbiturate anaesthesia. In cyclic rats denervation raised blood flow to the oviduct by 90% the next day (P less than 0.01) and 39% at 4-10 days (0.05 less than P less than 0.1). Blood flow to the ovary was not affected. Denervation on Day 13 of pregnancy raised blood flow in the oviduct 5-fold at Day 14 (P less than 0.01) and denervation on Day 7 raised blood flow 3-fold on Day 14 (P less than 0.05). Blood flow to the luteal and non-luteal components of the ovary was not affected. Sham-operation did not affect blood flow in the oviduct or ovary. It is concluded that sympathetic nerves exert tonic vasoconstrictor control on the vasculature of the oviduct but not on that of the ovary, and that these nerves do not regulate the major changes in blood flow that occur in ovaries in various physiological states.

Animals↗

Effect of cold and hot ambient temperatures on plasma progesterone concentrations in ewes with intact and denervated ovaries containing experimentally maintained corpora lutea.

Twenty ewes in which maintained corpora lutea had been established were subject to 1 of 3 treatments: denervation of the ovaries by freezing, denervation of the ovaries using the chemical 6-hydroxydopamine, or control. The animals were exposed sequentially to normal (24.5 degrees C), cold (10.7 degrees C), normal (23.8 degrees C), hot (39.4 degrees C) and normal (24.6 degrees C) temperatures, each for 1 week. On the final 3 days of exposure rectal temperatures and heart rates were measured, and on the final day the body weights, respiratory rates, and blood glucose concentrations were measured and a series of 5 blood samples was collected from each ewe for determination of the progesterone concentrations. The progesterone concentration was greatest during the hot period in 8 of the 12 animals, particularly in the ewes with denervated ovaries (6 of the 7 animals). This suggests that high ambient temperatures increase progesterone concentrations non-specifically, and that denervated ovaries are more sensitive to the circulating catecholamines that presumably mediate this effect. The progesterone concentrations were lower (P less than 0.001) in the groups with freezing or chemically denervated ovaries (2.86 and 2.73 ng/ml respectively) than in the control group (3.38 ng/ml), suggesting that the ovarian innervation plays a physiological role in regulating progesterone secretion.

Animals↗

Crossover study on effects of duct obliteration, celiac denervation, and autotransplantation on glucose- and meal-stimulated insulin, glucagon, and pancreatic polypeptide levels.

In segmental-pancreas transplantation the body and tail of the pancreas are used. In an experimental study in dogs, the effects of sequentially conducted removal of the right pancreatic lobe (pancreatic head), duct obliteration, celiac denervation, and autotransplantation were studied according to a crossover design. Two groups of dogs were studied. In both groups the right lobe of the pancreas was removed at primary operation, and the duct of the transected left lobe (body and tail) was injected with fibrin sealant. The left lobe was completely freed from surrounding tissue (celiac denervation) in group 1 (n = 9), and the innervation of the left lobe was left intact in group 2 (n = 8). At 12 wk, two dogs in group 1 and four dogs in group 2 underwent successful autotransplantation of the left lobe. Pancreatic hormone secretion was stimulated by intravenous glucose injection and test-meal administration before primary operation and at 11 and 18 wk thereafter. The combination of removal of the right lobe and duct obliteration led to a decrease in glucose tolerance at both stimulation tests and a decrease in peripheral insulin release after intravenous glucose injection. At test-meal administration, no change in insulin and glucagon levels was demonstrated. If celiac denervation was added, similar results were obtained based on the understanding that the peripheral insulin release after the test meal was significantly elevated. Meal-stimulated pancreatic polypeptide response was abolished in both groups. Removal of the right lobe leads to parasympathic denervation of the left lobe, and celiac denervation mainly interferes with alpha-adrenergic innervation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Influence of nonselective ET(A)/ET(B) receptor blockade on renal function in conscious rats: effects of renal denervation.

The effects of nonselective ET(A)/ET(B) receptor blockade with intravenous bolus injection of bosentan (10 mg/kg) on renal excretory function and blood pressure were investigated in conscious, male, normotensive Wistar rats before and one week after bilateral renal denervation. Renal denervation was followed by an increase in urine flow rate from 4.54+/-0.38 to 5.72+/-0.36 microl/min x 100 g b.w. (p<0.05) and a decrease in urine osmolality from 855.5+/-44.6 to 707.4+/-47.5 mosm/kg H(2)O (p<0.05). Bosentan administration in sham-operated rats resulted in decrease in urine flow rate from 4.54+/-0.38 to 3.49+/-0.34 microl/min x 100 g b.w. (p<0.05), and increase in urine osmolality from 855.5+/-44.6 to 1075.0+/-76.1 mosm/kg H(2)O (p<0.05). Sodium excretion decreased from 226.9+/-20.0 to 155.1+/-11.0 nmol/min x 100 g b.w. (p<0.01). Bosentan administration in renal denervated rats did not produce any changes in renal water or electrolyte excrections. Blood pressure, heart rate, clearance of Inulin or clearance of paraaminohippuric acid (PAH) did not change in sham-operated or renal denervated rats during nonselective ET(A)/ET(B) receptor blockade. Bosentan did not alter the baroreflex sensitivity or sympatho-vagal balance in sham-operated or renal denervated rats. In conclusion, an interaction between renal nerves and endothelins appears to be involved in the regulation of the renal excretory function.

Animals↗

Effect of temperature on the maximum rate of rise of tension in denervated rat diaphragm muscle.

Effects of chronic denervation and temperature were studied on the maximum rate of rise of tension in isometric twitch and tetanus of rat diaphragm muscles. The muscles were denervated for 15-20 days and the maximum rate of rise of tension was measured according to Hill (1951). The results showed that the maximum rate of rise of tension in twitch and tetanus was temperature dependent, exponentially increasing with increasing temperatures in both the normal and denervated muscles. A further observation was that the maximum rate of rise of tension in denervated muscle was always smaller than normal controls. It is suggested that probable changes in the series elasticity and duration of active state in the denervated muscle are responsible for the observed changes.

Journal Article↗

[Inhibitor of nitric oxide synthase on the denervated muscle atrophy].

OBJECTIVE: To study the effect of the competitive inhibitor of nitric oxide synthase N(G)-nitro-L-arginine methyl ester (L-NAME) on the denervated muscle atrophy. METHODS: A model of the denervated gastrocnemius at the right lower limb was established in 36 SD adult rats. The rats were randomly divided into two groups: the L-NAME group (Group A) and the control group (Group B). L-NAME 10 mg/kg daily was injected into the denervated gastrocnemius in Group A, and normal saline was injected into the denervated gastrocnemius in Group B. At 2, 4 and 8 weeks after operation, the rate of the muscle wet weight preservation, the cross section area of the myocyte, the protein amount, and the percentage of the apoptotic muscle cells were measured respectively and the ultramicrostructure of the myocyte was observed. RESULTS: At 2 and 4 weeks after operation, the rate of the muscle wet weight preservation, the cross section area of the myocyte, and the protein amount were significantly greater in Group A than in Group B; however, the percentage of the apoptotic muscle cells was significantly smaller in Group A than in Group B. The observation of the ultramicrostructure of the myocyte showed that an injection of L-NAME could protect the ultramicrostructure of the myocyte. At 8 weeks after operation, there was no significant difference between the two groups in the above-mentioned parameters. CONCLUSION: The nitric oxide synthase inhibition can delay the denervated muscle atrophy.

Animals↗

Dopamine agonist-induced elevation of striatal acetylcholine: relationship between receptor occupancy and response in normal and denervated rat striatum.

Unilateral denervation of the nigrostriatal dopamine (DA) pathway with 6-hydroxydopamine resulted in a supersensitive response for elevation of striatal acetylcholine concentrations by the full DA agonist (R)-(-)-N-n-propylnorapomorphine (NPA), reflected in a parallel 4-fold leftward shift in the dose-response curve (ED50, intact, 8.8 micrograms/kg; denervated, 2.2 micrograms/kg). The maximal response, however, was not changed. In the intact striatum, irreversible DA receptor inactivation with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) (6 mg/kg) produced a depression in the maximal acetylcholine increase elicited by NPA (control, 52.4%; EEDQ, 25.0%), without altering the ED50 for the agonist. In contrast, in the denervated striatum, EEDQ treatment produced a much smaller reduction in the maximal response (to 39.6%), as well as a small rightward shift in the ED50 (from 2.2 to 3.5 micrograms/kg). Double-reciprocal analysis of equieffective doses of NPA necessary to elicit response yielded similar values for the pseudo-dissociation constant (pseudo-KA, in units of dose) in intact and denervated striatum (8.3 and 7.0 micrograms/kg, respectively). A plot of receptor occupancy versus response was linear for the intact striatum, indicating the absence of a receptor reserve. In contrast, a nonlinear relationship was obtained for the denervated side, and a small apparent receptor reserve for NPA of 25-30% was estimated to be present. The results suggest that 6-hydroxydopamine-induced supersensitivity reflects the generation of a postsynaptic D2 DA receptor reserve, which may account for the observation that weak partial agonist elicit measurable response in supersensitive animals (and at presynaptic DA receptors, which normally exhibit a receptor reserve for agonists) but not at normosensitive receptors devoid of spare receptors.

Acetylcholine↗

Portrayal of adrenergic denervation in the presence of myocardial infarction: a feasibility study.

Myocardial infarction interrupts adrenergic neurons beyond the region of necrosis to give peri-infarct denervation. A method to define the regions of denervation would be a valuable aid in determining the role that loss of adrenergic neurons plays in myocardial infarction and particularly in causing arrhythmias. [123I] meta-iodobenzylguanidine (MIBG) was used to portray scintigraphically the intact neurons in dog hearts. Occlusion of the left circumflex (LCX) or the left anterior descending coronary artery (LAD) produced defects that appeared to be regularly larger in the [123I]MIBG images than in the [201T1]images of the same heart; the differences were considered to be the regions of denervation which were relatively larger after LCX than LAD infarcts. Ex vivo measurements of endogenous norepinephrine and residual [125I]MIBG concentrations gave confirmation of neuronal injury. A computer program to quantify the regions of denervation appeared imprecise, but gave some promise. Scintigraphy of [123I]MIBG offers a method to define patterns of denervation in the living animal and man.

3-Iodobenzylguanidine↗

Parietal cell structure and acid secretion in the vagally innervated stomach and the vagally denervated fundic pouch in cats.

In seven cats provided with gastric fistula (GF) of the main stomach and a denervated Heidenhain pouch (HP) the structure of the innervated and denervated mucosa was examined by light and electron microscopy. In four of these cats dose-response curves for acid output to pentagastrin were determined before and after vagal denervation of the fundic pouch. Vagal denervation reduced the acid response to pentagastrin by decreasing both the secretory capacity and the sensitivity of the oxyntic glands. Accordingly, in the same cat the parietal cells of the HP were less sensitive to pentagastrin than the cells of the innervated main stomach. Light and electron microscopic investigations revealed that the fundic mucosa was thinner, and the size and proportion of the parietal cells was smaller in the HP than in the GF. It is likely that the morphological changes in the pouch were caused by the vagal denervation rather than by the loss of mucosal contact with food. The secretory and morphological changes produced by the vagotomy are not necessarily related.

Animals↗

Reinnervation of denervated Pacinian corpuscles: ultrastructural observations in rats following free nerve grafts.

Nerve transection and immediate free nerve grafts using rat sciatic nerves were employed to observe the morphologic changes in periodical denervation and reinnervation of Pacinian corpuscles located on the interosseous membrane between the fibula and tibia. During periods of from 2 weeks to 20 months after the surgery, a total of 28 corpuscles were obtained under an operating microscope and processed for morphologic analysis using light and electron microscopes. Based on our morphologic findings, normal corpuscles were composed of an axon terminal and inner and outer cores. The axon terminal disappeared within 2 weeks after the nerve grafts, but the original inner and outer core cells remained for up to 20 months. In addition, a small number of collagen fibrils was observed between the inner and outer core cells. After 4 months, multiple axon terminals began to regenerate in the inner core. From 7 to 20 months, these axon terminals in some corpuscles developed a structure resembling that of normal terminals. Some of these terminals were located in the center of the inner core, but a few were in contact with the outside of the inner core. The production of collagen fibrils in denervated corpuscles was periodically activated in the intercellular spaces. These findings suggest that the morphologic changes in denervated corpuscles correspond to those in denervated nerves. Inner core cells, which are continuous with Schwann cells, remain in their original condition in denervated corpuscles until regenerating nerves enter the inner core and are essential for corpuscle regeneration, because they may produce some trophic substances that induce the regeneration of multiple axon terminals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Tuberous electroreceptor organs form in denervated regenerating skin of a weakly electric fish.

Weakly electric fish use tuberous electroreceptor organs to detect their own electric fields. We investigated the role of innervation upon regeneration and differentiation of tuberous electroreceptor organs. The left, infraorbital, anterior lateral line nerve of brown ghosts (Apteronotus leptorhynchus) was sectioned, and the proximal stump was dipped in ricin to prevent regrowth. Immediately after denervation, a piece of cheek skin (approximately 0.5 cm2) was removed bilaterally to induce skin regeneration. After survival periods of 3, 4, or 5 weeks, regenerated skin from the left (denervated) and the right (reinnervated) sides was removed and processed for immunocytochemistry or electron microscopy. Tuberous electroreceptor organs were present in regenerated reinnervated, as well as regenerated denervated skin patches at all survival times. With increased time after skin removal, the number of fully differentiated organs increased in the reinnervated regenerated skin while the number of organs with degenerating receptor cells or entirely devoid of receptor cells increased in the denervated regenerated skin. These results suggest that innervation is not essential for tuberous electroreceptor organ development, but that it is necessary for complete sensory cell differentiation and long-term survival.

Animals↗

Focal denervation alters cellular phenotypes and survival in the developing rat olfactory bulb.

Several studies have demonstrated that contact between the olfactory nerve and the forebrain is critical for normal olfactory bulb development. Removal of the embryonic olfactory placode results in a failure of the olfactory bulb to form, as well as causing other forebrain malformations. The current study introduces a technique that permits removal of contact between specific regions of the olfactory nerve and the bulb early in development, without causing damage to other brain regions, and without removing the peripheral olfactory organ. The manipulation, which involves insertion of a small Teflon chip between the cribriform plate and the bulb, prohibits growth of new axons into the "shadow" region behind the implant. Focal denervation of the olfactory bulb causes a decrease in bulb and layer sizes, a reduction in mitral cell number, and changes to bulb architecture. Using a battery of antibodies (OMP, MAP2, TuJ1, calretinin, calbindin, parvalbumin, TH, and GAD), we further demonstrated that 1) focal denervation alters the relationship between the olfactory nerve and the bulb, 2) the fine structure of cells in denervated regions is disrupted, and 3) cellular phenotypes change in response to loss of afferent contact. These results suggest that contact between the olfactory nerve and the bulb is important for maintaining bulb architecture and cell survival, structure, and phenotype. They also point to focal denervation as a useful technique for examining the role of neural contact in olfactory development and maintenance of the central nervous system.

Animals↗

Scanning electron microscopy of denervated taste buds in hamster: morphology of fungiform taste pores.

BACKGROUND: Taste pores of fungiform papillae are critical for taste function. Taste nerve injury affects the pore, rendering it refractory to staining with vital dyes. Whether pores of denervated fungiform papillae disappear or undergo more modest structural changes to account for diminished staining was the subject of the present study. METHODS: The chorda tympani in the hamster was served unilaterally and the anterior tongue prepared for scanning electron microscopy after 31 days of survival. RESULTS: Taste pores were found on 92% of control fungiform papillae. They were round openings formed by the free margins of keratinocytes, and centered in hillock-shaped elevations of the papillary surface. Hillocks were encircled by an indentation which, in turn, was surrounded by a circular epithelial rim. These structures associated with fungiform pores distinguish pores on the anterior tongue from those on the posterior tongue. The pores led to a channel that penetrated into the papilla. The experimental side of the tongue had markedly fewer pores. Definitive pores were present on only 53% of denervated papillae. The papillae that lacked pores either exhibited a small hillock and a subtle depression in place of the pore, or had entirely flat apical surfaces. The denervated papillae that retained pores exhibited structural changes. The pores had smaller diameters and led to shallower channels than control pores. Moreover, these persistent pores were associated with hillocks, indentations and rims that were more variable and less distinct than those of control papillae. CONCLUSIONS: Pores of fungiform papillae in hamster are associated with specialized surfaces features of the papillary epithelium. Denervation results in changes that range from disappearance of the pores to their shrinkage and the atrophy of pore-associated epithelial structures.

Animals↗

Remodeling of the cytoskeletal lattice in denervated skeletal muscle.

The effect of denervation-induced atrophy on the cytoskeletal lattice in rat fast- and slow-twitch skeletal muscle has been investigated. Immunochemical analyses and immunofluorescence microscopy experiments employing monospecific antibodies to dystrophin, desmin, and alpha-tubulin were carried out on intact and denervated muscles. The relative cellular content of dystrophin and desmin were reduced in the soleus muscle (slow-twitch), while significant increases were shown in the gastrocnemius muscle (fast-twitch). In both muscles, alpha-tubulin levels increased up to 12-fold as a function of time compared to control values. Immunofluorescence microscopy revealed a distinct rearrangement of the microtubule network toward a predominantly longitudinal alignment, which was accompanied by an increase in the density of the fluorescence. It is concluded that the relative increase of the three structural proteins in the fast-twitch gastrocnemius muscle may be related to the apparent resistance of this muscle type to denervation-induced atrophy. The increased alpha-tubulin content in denervated slow- and fast-twitch muscles could be indicative of an adaptive mechanism designed to maintain the integrity of the muscle fiber in view of eventual regenerative activities.

Animals↗

Effects of denervation and muscle inactivity on the organization of F-actin.

To discriminate between the influences of a motoneuron and muscle activity on the conformation of actin filaments, the extrinsic polarized fluorescence [of rhodamine-phalloidin and N-(iodoacetylamine)-1-naphthylamine-5-sulfonic acid attached to F-actin] was measured in "ghost" fibers from intact rat soleus muscles and atrophying muscles after denervation, immobilization, or tenotomy. The results show that the conformation of F-actin changed in all the atrophying muscles, but differently. In the denervated muscle, the flexibility of the actin filaments decreased, whereas in the other experimental muscles it remained as in the intact muscle. In the denervated muscle, the mobility of the C-terminus of the actin polypeptide increased. Attachment of myosin subfragment-1 influenced the F-actin conformation differently in the denervated muscle than in the other muscles studied. These results suggest that changes in the conformation of the actin filament are induced by the lack of connection with the motoneuron rather than by muscle inactivity.

Actins↗

Membrane skeleton of innervated and denervated fast- and slow-twitch muscle.

We used confocal microscopy and immunoblotting to study membrane skeletal proteins of fast-twitch (extensor digitorum longus) and slow-twitch (soleus) muscles of the adult rat. In the extensor digitorum longus (EDL), beta-spectrin concentrates in costameres, whereas dystrophin is enriched at costameres but is also present in intercostameric regions. In the soleus, beta-spectrin and dystrophin underlie much of the sarcolemma, and intercostameric regions are difficult to detect. The EDL sarcolemma reorganizes following denervation to resemble soleus sarcolemma, but denervation does not significantly affect the latter. Consistent with these observations, soleus contains similar amounts of dystrophin but more beta-spectrin than EDL. Denervation increases beta-spectrin levels only in the EDL and dystrophin levels in both muscles. Denervation does not affect beta-fodrin, a beta-spectrin homolog expressed in embryonic myofibers. Thus, neuromuscular activity controls sarcolemmal organization and the levels of beta-spectrin and dystrophin, but not postnatal downregulation of beta-fodrin. The differences in organization of the sarcolemma may underlie the differential susceptibility of fast and slow myofibers to dystrophinopathies.

Animals↗