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PubMed1996

Distinct structure-activity relations for stimulation of 45Ca uptake and for high affinity binding in cultured rat dorsal root ganglion neurons and dorsal root ganglion membranes.

The [3H]resiniferatoxin (RTX) binding assay using membrane preparations has been used to identify and characterize the vanilloid receptors in the central and peripheral nervous system of different species. In the present study, using cultured adult rat dorsal root ganglion neurons either in suspension or attached to the tissue culture plates, we developed an assay to measure specific [3H]RTX binding by the intact cells. We were able to characterize the vanilloid binding characteristics of the neurons and compared those to the properties of vanilloid binding sites present in rat dorsal root ganglia membrane preparations. We found that [3H]RTX bound with similar affinity and positive cooperativity to attached neurons (cultured for 5 days before being assayed), neurons in suspension (using a filtration assay) and dorsal root ganglion membrane preparations. Dissociation constants obtained in the three assays were 47.6 +/- 3.5 pM, 38.4 +/- 3.1 pM and 42.6 +/- 3.1 pM, respectively. The cooperativity indexes determined by fitting the data to the Hill equation were 1.73 +/- 0.11, 1.78 +/- 0.12 and 1.78 +/- 0.09, respectively. The maximal binding capacity was 0.218 +/- 0.026 fmol/10(3) cells and 0.196 +/- 0.021 fmol/10(3) cells in the case of the attached cells and cells in suspension, respectively. Nonradioactive RTX, capsaicin, capsazepine and resiniferonol 20-homovanillylamide fully displaced specifically bound [3H]RTX from cells in suspension with Ki and Hill coefficient values of 42.5 +/- 5.3 pM, 2.06 +/- 0.16 microM, 3.16 +/- 0.21 microM and 32.4 +/- 4.1 nM and 1.79 +/- 0.17, 1.68 +/- 0.06, 1.72 +/- 0.11 and 1.81 +/- 0.12, respectively. Structure-activity analysis of different vanilloid derivatives revealed that the various compounds have distinct potencies for receptor binding and inducing 45Ca uptake in rat dorsal root ganglion neurons. Affinities for receptor binding and stimulation of 45Ca uptake of RTX, resiniferonol 20-homovanillylamide, RTX-thiourea, tinyatoxin, phorbol 12,13-dibenzoate 20-homovanillylamide and capsaicin were 38.5 +/- 2.9 pM, 25.7 +/- 3.0 nM, 68.5 +/- 3.8 nM, 173 +/- 25 pM, 7.98 +/- 0.83 microM and 4.93 +/- 0.35 microM as compared to 0.94 +/- 0.12 nM, 26.5 +/- 3.5 nM, 149 +/- 30 nM, 1.46 +/- 0.25 nM, 1.41 +/- 0.48 microM and 340 +/- 57 nM. Computer fitting of the data yielded Hill coefficient values indicating positive cooperativity of receptor binding; however, stimulation of 45Ca uptake appeared to follow a non-cooperative mechanism of action. The competitive capsaicin antagonist capsazepine inhibited specific binding of [3H]RTX by rat dorsal root ganglion membrane preparations with Ki and Hill coefficient values of 3.89 +/- 0.38 microM and 1.74 +/- 0.11. On the other hand it inhibited the induction of 45Ca uptake into the cells induced by capsaicin and RTX in a non-cooperative fashion with Ki values of 271 +/- 29 nM and 325 +/- 47 nM. Our results show that the membrane binding assay relates to the reality of receptor function in the intact, cultured neurons, both in terms of affinity and positive cooperativity. However the different vanilloid derivatives displayed markedly distinct structure-activity relations for high affinity receptor binding and stimulation of 45Ca uptake into rat dorsal root ganglion neurons. Among various explanations for this discrepancy, we favor the possibility that the two assays detect distinct classes of the vanilloid (capsaicin) receptor present in primary sensory neurons.

Animals↗
PubMed1976

Fate of ganglionic synapses and ganglion cell axons during normal and induced cell death.

In order to understand the significance of cell death in the formation of neural circuits, it is necessary to determine whether before cell death neurons have (a) sent axons to the periphery; (b) reached the proper target organs; and (c) have established synaptic connections with them. Axon counts demonstrated that, after sending out initial axons, ciliary cells sprouted numerous collaterals at the time of peripheral synapse formation. Subsequently, large numbers of axons were lost from the nerves, slightly later than the onset of ganglion cell death. A secondary loss of collaterals later occurred unaccompanied by cell death. Measurements of conduction velocity and axon diameters indicated that all ganglion cell axons grew down the proper pathways from the start, but it was not possible to determine whether all axons had actually formed proper synapses. This was ascertained, however, in the ganglion itself where preganglionic fibres were shown to synapse selectively with all ganglion cells before cell death. During this period, degenerating preganglionic synapses were observed on normal cells. It can therefore be inferred that at least some preganglionics established proper synapses before dying and that a single synapse is not sufficient to prevent cell death. In this system neither preganglionic nor ganglionic cell death seems designed to remove improper connections but rather to remove cells that have not competed effectively for a sufficient number of synapses, resulting in a quantitative matching up of neuron numbers.

Animals↗
PubMed1989

Opioid receptor modulation of neural transmission in the rabbit coeliac ganglion and ganglionic opioid receptor activation by bunitrolol.

1. We examined the preganglionic splanchnic nerve activity and postganglionic renal nerve activity before and after a local injection of naloxone (20 micrograms/kg) into the coeliac ganglion of anaesthetized rabbits. This was done during graded hypertension, induced by the administration of phenylephrine (0.5-10 micrograms/kg, i.v.) and with selective intraganglionic injection of methionine-enkephalin (ME) and bunitrolol, which is a beta-blocker. 2. During hypertension both pre- and postganglionic discharge decreased, but only postganglionic discharge was inhibited by naloxone treatment into the ganglion. 3. Local injection of ME (0.1-10 micrograms/kg) into the coeliac ganglion decreased postganglionic activity by 9.0 +/- 1.0 to 41.2 +/- 4.7% from control, and this decrease was inhibited by naloxone. 4. Administration of bunitrolol (1-300 micrograms/kg) decreased postganglionic discharge by 3.9 +/- 1.4 to 39.7 +/- 2.4% of the control and this decrease was also inhibited by naloxone. 5. These results suggest that opioid receptors in the coeliac ganglion play an inhibitory role in neural ganglionic transmission and that this inhibitory action reduces postganglionic sympathetic discharge.

Adrenergic beta-Antagonists↗
PubMed2005

Thermocoagulation of the ganglion impar or ganglion of Walther: description of a modified approach. Preliminary results in chronic, nononcological pain.

The ganglion impar, a single structure usually found at the anterior aspect of the sacrococcygeal joint, is the lowest ganglion of the paravertebral sympathetic chain. Its blockade is indicated in visceral pain syndromes and/or sympathetic pain syndromes of the perineal region. Several approaches to this block have been described, mainly through the anococcygeal or sacrococcygeal ligaments. We propose a modified approach to thermocoagulation of the ganglion impar, using a two-needle technique, the first one, placed through the sacrococcygeal ligament, the transsacrococcygeal needle, and the second one through a coccygeal disc, the transdiscal needle. The thermocoagulation technique that we employ uses a conventional radiofrequency application of 80 degrees C for 80 seconds through each needle. In this prospective study, 13 patients with chronic perineal, noncancer-related pain were followed for a maximum of 6 months. All of these patients underwent diagnostic ganglion impar block with local anesthetic prior to inducing neurodestruction with conventional radiofrequency application, as a positive result to the diagnostic local anesthetic block was a requisite for radiofrequency neurodestruction. We measured pain using a visual analog scale (VAS) before and after treatment. Statistical significance was assessed using the Mann-Whitney U-test and Wilcoxon range summation test. Initially the VAS was equal to or greater than 7. After therapy the VAS decreased by an average of 50% in the whole group. There were no adverse events. Our result show that this proposed modified approach to the block and use of radiofrequency for the ganglion impar is useful for the treatment of perineal noncancer-related pain.

Journal Article↗
PubMed1991

Presynaptic facilitation by the new nootropic drug nebracetam, of ganglionic muscarinic transmission in the dog cardiac sympathetic ganglion.

Effects of nebracetam (4-aminomethyl-1-benzylpyrrolidine-2-one hemifumarate, WEB 1881 FU, CAS 118607-07-1), a new nootropic drug, on impulse transmission in the cardiac sympathetic ganglia were studied in spinal dogs by monitoring heart rate as an indicator of the ganglionic function. The ganglionic stimulants were given directly into the cardiac sympathetic ganglia through the right subclavian artery (i.a.). Nebracetam, 5 mg/kg, i.v. caused a slight and temporal increase in heart rate. After nebracetam, the frequency-response curves of heart rate for preganglionic stellate stimulation (0.25-4 Hz) were not altered in the untreated and atropine-pretreated animals, but the curves (2.5-40 Hz) were shifted to the left in the hexamethonium-pretreated animals. The enhancement of ganglionic muscarinic transmission was dose-dependent on nebracetam i.v. at doses ranging from 0.5 to 15 mg/kg, with a maximal effect at 5 mg/kg. This enhanced muscarinic transmission by nebracetam was almost abolished after subsequent administration of pirenzepine 0.5 mg/kg i.v. The enhancement in the muscarinic transmission by nebracetam was also eliminated after depletion of acetylcholine at preganglionic sites caused by treatment with hemicholinium-3 in combination with preganglionic stimulation. Furthermore, nebracetam failed to affect dose-dependent post-ganglionic stimulation by McN-A-343 (1-32 micrograms), 1,1-dimethyl-4-phenylpiperazinium (1-32 micrograms) and angiotensin II (0.1 and 0.2 micrograms) administered i.a. directly to the ganglia. These results suggest that nebracetam facilitates the ganglionic muscarinic transmission through acting on presynaptic sites.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1982

Facilitation of ganglionic transmission by sulpiride: evidence for an inhibitory role of dopamine in the canine sympathetic ganglion.

Effects of the (R) and (S) enantiomers of sulpiride, a potent dopamine (DA) antagonist, on ganglionic transmission were studied in anesthetized dogs. The pre- and postganglionic nerves of cardiac sympathetic ganglia were stimulated electrically, and heart rate was monitored as a measure of ganglionic transmission and sympathetic nerve activity. The heart rate was free from influence of the central nervous system. (R)- And (S)-sulpiride injected i.a. close to the blood supply of the ganglia did not alter basal heart rate, but facilitated ganglionic transmission as demonstrated by an increase in the tachycardia induced by preganglionic nerve stimulation. The (R) enantiomer was 4 times more active than the (S) enantiomer in this respect. Neither enantiomer affected the tachycardia induced by postganglionic nerve stimulation. Norepinephrine and DA injected i.a. caused inhibition of the tachycardia induced by preganglionic nerve stimulation. The inhibitory effect of both catecholamines was antagonized by the sulpiride enantiomers (R)-sulpiride was about 4-fold more potent than (S)-sulpiride in antagonizing DA, whereas (S)-sulpiride was more active against norepinephrine. The sulpiride enantiomers affected neither the tachycardia induced by i.a. administration of acetylcholine nor the bradycardia induced by vagal nerve stimulation. Thus, cholinesterase inhibition and ganglionic stimulation were excluded. These data are, therefore, consistent with the hypothesis that the facilitatory action of the sulpiride enantiomers is related to the antagonism of catecholamines. Positive correlation between the activity of the (R) enantiomer to facilitate ganglionic transmission and to antagonize DA suggests that DA is a physiologically released catecholamine modulating transmission in the cardiac sympathetic ganglia of the dog.

Animals↗
PubMedDate not supplied

[Influence of the subesophageal ganglion on the electrical activity of neurons of the metathoracic ganglion of the cockroach Periplaneta americana].

Studies have been made of non-specific effect of suboesophageal gnaglion on excitability of the segmental centers in the cockroach P. americana. It was shown that the electrical stimulation of the ganglion increases the frequency of the spontaneous activity and decreases the threshold of the evoked reactions in neurons of the metathoracic ganglion. The level of activation depends on the intensity of stimulation. Application of GABA (0.1 M) to the suboesophageal ganglion decreases the frequency of the background activity in the segmental neurons, this effect being presumably due to activation of the inhibitory structures. The descending influences from the suboesophageal ganglion may spread to centers of the metathoracic ganglion along monosynaptic pathways.

Animals↗
PubMed1998

Urografin injection demonstrated soft tissue ganglion communication with an intraosseous ganglion cyst.

Intraosseous ganglion cysts rarely occur in the hand or wrist. We present a case of a soft tissue ganglion cyst that communicated with the intraosseous ganglion of the scaphoid. Typical diagnostic studies include radiography, computed tomography, and magnetic resonance imaging. The diagnosis was made in this case by injection of Urografin into the soft tissue ganglion. The patient underwent excision of both ganglion cysts, resulting in a satisfactory outcome.

Adult↗
PubMed1996

Fibroblast growth factor receptor function is required for the orderly projection of ganglion cell axons in the developing mammalian retina.

During the early stages of development various cell adhesion molecules (CAMs) and fibroblast growth factor receptors (FGFR) are expressed throughout the retinal neuroepithelium. The ability of retinal ganglion cells to project their axons to the optic fissure depends, in part, on cell-cell interactions mediated by cell adhesion molecules. In the present study we show that the ability of the firstborn rat retinal ganglion cells to extend axons in vitro can be stimulated by NCAM and L1, but not N-cadherin. Both CAM responses can be fully inhibited by antibodies that block neuronal fibroblast growth factor receptor function and by agents that block defined steps in the FGFR signal transduction cascade. When added to living E13.5 rat retinal whole-mount preparations the same agents induced errors in the orderly establishment of young axon patterns in the retinal periphery and caused axons in the retinal center to defasciculate. These results suggest that the activation of the fibroblast growth factor receptor signal cascade not only promotes survival and proliferation of various cell types but can also mediate intraretinal axon guidance.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1983

Evidence that the early postnatal reduction in the number of rat retinal ganglion cells is due to a wave of ganglion cell death.

Horseradish peroxidase (HRP) was injected into the retino-recipient nuclei of each hemisphere in newborn rats. The animals were perfused 3--9 days after the injections; the number of retinal ganglion cells in retinal wholemounts was estimated by counting cells containing granules of HRP reaction product. The mean number (150,500) of labelled cells in 3-day-old rats was significantly higher than those in older animals (117,000, 121,000, 113,000 respectively on 6th, 8th and 9th postnatal days). However, in animals of any of the ages studied, the estimated numbers of ganglion cells were virtually the same as those in the animals of the same age but injected with HRP only 15--20 h before the perfusion. Thus, the reduction in the number of retinal cells projecting to the central visual nuclei observed during the first few postnatal days is due to a wave of retinal ganglion cell death; ganglion cell death induced by the neonatal removal of the contralateral superior colliculus has a similar time course.

Animals↗
PubMed1997

Nerve fibre interaction with large ganglion cells in the human spiral ganglion. A TEM study.

A TEM study was performed on freshly fixed human spiral ganglions (HSG) biopsied during skull base surgery. Well preserved tissue specimens were obtained for ultrastructural analysis. The investigation revealed that nerve fibres frequently form contacts with the large ganglion cells (type I cells). In the areas of contact, membrane specializations occurred, consisting of symmetric or asymmetric densities often alternating from one cell to the other with a reduced intercellular distance (approximately 10 nm). High power TEM showed the intercellular cleft to contain an extra dense line resulting in a pentalaminar structure. The dense line appeared on the side of the membrane protein concentration. Protein densities jutted into the cytoplasm along the intracellular face spreading into a diffuse cytoplasmic web physically related to accumulating mitochondria. This indicated a concentration of oxygen-dependent metabolic activity in these regions. It is believed that the nerve junctions are involved in electric transmission between type I ganglion cells. The neural junctions were morphologically different from synaptic contacts between small human ganglion cells (type II cells) and nerve fibres which have been suspected of sharing the olivocochlear bundle as their origin.

Axons↗
PubMed1990

Simultaneous cell death in the trigeminal ganglion and in ganglion neurons present in the oculomotor nerve of the bovine fetus.

A well-developed ganglion and scattered ganglion cells are present in the intracranial portion of the oculomotor nerve during the first half of fetal life in the ox. In the second half of fetal life a dramatic reduction of the ganglion cells associated with the oculomotor nerve occurs because of spontaneous cell death. Concomitantly, the same phenomenon of cell death is found in the trigeminal ganglion, especially in its rostromedial portion. Free degenerating perikarya can be found in the cavernous sinus.

Animals↗
PubMed1994

Labelling of neurons in the rat superior cervical ganglion after injection of wheat-germ agglutinin-horseradish peroxidase into the contralateral ganglion: evidence of transneuronal labelling.

Recent studies have shown that injection of the tracer wheat-germ agglutinin-horseradish peroxidase (WGA-HRP) into the superior cervical ganglion (SCG) of one side results in labelling of neurons in the contralateral SCG and the stellate ganglion. This study was designed to verify whether or not bilateral projections from the superior cervical ganglion to the midline structures, particularly to the pineal gland, play a role in the transport of WGA-HRP to the contralateral SCG. One group of rats received WGA-HRP injection into the right SCG (group I). Four groups of rats underwent the following operations prior to the injection of WGA-HRP into the right superior cervical ganglion: transection of the external carotid nerve (group II), transection of the internal carotid nerve (group III), transection of the external carotid nerve combined with pinealectomy (group IV), transection of both the internal and the external carotid nerves (group V). The mean number of labelled neurons in the left SCG of each group were found as follows: group I, 1516 +/- 221 (mean +/- S.D.); group II, 861 +/- 122; group III, 543 +/- 99; group IV, 562 +/- 144; group V, 220 +/- 52. The results of this study suggest that the contralateral labelling depends on the transneuronal transport of WGA-HRP through the terminal fields of innervation of the midline structures that receive bilateral projections from both SCGs.

Animals↗
PubMed1975

Ganglion cells and paraganglionic cells in the developing superior cervical ganglion of normal and p-chlorophenylalanine treated rats.

Ganglion cells and paraganglionic (PG) cells in the developing rat superior cervical ganglion were studied following postnatal treatment with p-chlorophenylalanine (pCPA) for 5 to 8 days. Litter mates, injected with saline solution, served as controls. Ganglion cells of control animals were differentiated ultrastructurally according to L. Eränkö (1972a) into late sympathicoblasts and young sympathetic nerve cells. In both maturation stages treatment with pCPA caused marked swelling of mitochondria, concomitant with minor changes of other cell organelles. Parallel to the ultrastructural alterations, fluorescence microscopy and cytophotometry revealed a slight diminution of diffuse fluorescence intensity in sympathetic neurons as the expression of a mainly extragranular amine depletion. In distinction from ganglion blocking agents the alterations are regarded as a general toxic effect of pCPA upon maturing sympathetic neurons, which secondarily influences catecholamine storage sites. Following treatment with pCPA, in PG-cells an alteration of mitochondria was scarcely to recognize. Specific granules were distinctly decreased in number, in some cases to an almost complete degree. Concordant to ultrastructural observations a marked diminution of fluorescence intensity was demonstrable in SIF-cells. In addition in these elements the fluorescence spectrum shifted towards the green field. Fluorescence cytophotometric evaluations confirmed the optical impression. Provided, that PG-cells, demonstrated with electron microscopy, are identical with SIF-cells in fluorescence microscopy, the results are discussed on the basis of a specific decrease of primary catecholamines due to an enzyme inhibition involved in catecholamine synthesis.

Animals↗
PubMed1984

Intercostal nerve transection and its effect on the dorsal root ganglion. A quantitative study on thoracic ganglion cell numbers and sizes in the rat.

The effect of intercostal nerve transection on the number and size distribution of thoracic spinal ganglion cells has been investigated and correlated with transganglionic degeneration (TGD) in the spinal cord dorsal horn. Unilateral transections were made of 3 or 11 consecutive intercostal nerves. Twenty to 180 days later the animals were perfused and relevant ganglia from both sides embedded in resin, serially sectioned and stained. Counts of neuronal nucleoli were made and perikaryal areas of ganglion cells measured. The number of neurons was significantly reduced on the operated side 20 days postoperatively. The cell loss increased slightly to about 35% with longer survival times. Analysis of cell size spectra showed a bilaterally symmetrical picture in normal animals. No distortions of the cell size spectrum were observed at 20 to 70 days after nerve transections. Transganglionic degeneration was found in the dorsal horn from 20 to 70 days postoperative survival, but not at 180 days. The findings indicate that TGD in the dorsal horn is related to a loss of ganglion cells in the corresponding spinal ganglion. There does not seem to be a preferential loss of any particular size class of cells.

Animals↗
PubMed1986

The presence of vasoactive intestinal polypeptide-like immunoreactive structures projecting from the myenteric ganglion of the stomach to the celiac ganglion revealed by a double-labelling technique.

The gastrofugal vasoactive intestinal polypeptide (VIP)-like immunoreactive (VIPI) structures in the rat were examined by the combined use of immunocytochemistry and retrograde tracing. Injection of biotin-wheat germ agglutinin into the celiac ganglion labeled many neurons in the myenteric ganglion of the stomach. Simultaneous staining with antiserum against VIP showed that some of these neurons are VIPI-positive. These findings indicate that VIPI neurons in the myenteric ganglion of the rat stomach project to the celiac ganglion.

Animals↗
PubMed1982

Blockade of ganglionic transmission during synaptogenesis decreases alpha-bungarotoxin binding in the chick ciliary ganglion and iris.

The role of normal synaptic activity in the biochemical development of the nervous system has been examined in the chick embryo. Chlorisondamine, a ganglionic blocking drug, was administered in ovo during the period of synaptogenesis in the parasympathetic ciliary ganglion. Following treatment with chlorisondamine, nicotinic binding sites (as measured with [125I] alpha-bungarotoxin) were significantly reduced in both the ganglion and its end organ, the striated iris muscle. While the number of [125I] alpha-bungarotoxin binding sites eventually approached control levels in the iris, binding in the ciliary ganglion remained below normal values through hatching.

Animals↗
PubMed1998

A reexamination of the synaptic connection between neuron L7 of the abdominal ganglion and neurons of the branchial ganglion in Aplysia californica, A. kurodai and A. juliana.

The presence of a synaptic connection between neuron L7 of the abdominal ganglion and branchial ganglionic neurons (BGNs) was reexamined by means of electrophysiology and fluorescent microscopy using three Aplysia species. We succeeded in recording excitatory postsynaptic potentials produced in a BGN, which followed impulses of L7 one-to-one with a constant latency, even in A. californica as well as in A. kurodai and A. juliana. Dye-injection revealed that fine collaterals extended from a major branch of L7 to the branchial ganglion and arborized in neuropil of the ganglion. The results show that L7 in the three species has a dual function as a motor neuron and as an interneuron for the gill.

Animals↗