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Response of spiral ganglion neurones to cochlear hair cell destruction in the guinea pig.

Loss of ganglion cells after hair cell destruction in the mammalian cochlea continues to occur over a long period of time, with the possibility of more than one factor contributing to this process. Despite the absence of hair cells, some ganglion cells are, however, able to survive for considerable periods of time. Because functional ganglion cells are crucial to the successful use of cochlear implants, a better understanding of the response of these cells to injury is required so that their loss can be prevented or ameliorated. Quantitative light microscopy, electron microscopy and immunocytochemical techniques were used to examine the response of type I spiral ganglion neurones to hair cell destruction, in guinea pigs at 1, 3, 6 and 30 weeks survival following intracochlear injection with gentamicin. The time course of ganglion cell loss was determined, while a closer examination of those cells able to survive was carried out. A significant early loss of large numbers of ganglion cells was followed by a further significant loss of these cells by 30-week survival. At the same time a decrease in the numbers of central fibres was also observed. Surviving ganglion cells have little or no perikaryal myelin, an appearance resembling that of type I ganglion cells at 55 days gestation. Ganglion cells surviving the initial loss were also found to have a significantly larger soma size than controls although this was not maintained and at 30 weeks survival the few remaining cells were similar in size to that of controls. The growth associated protein GAP 43 was upregulated in surviving ganglion cells at 3 weeks survival, but appeared diminished by 6 weeks survival. These features may indicate a survival response in ganglion cells and may provide a basis on which to develop appropriate means to prevent their loss.

Animals↗

Loss and survival of spiral ganglion neurons in the guinea pig after intracochlear perfusion with aminoglycosides.

Loss of cochlear hair cells results in a loss of ganglion cells and further neurodegenerative changes throughout the auditory pathway. Understanding more about the early stages of ganglion cell loss in vivo may lead to ways of ameliorating or preventing the loss of these neurons. To examine these stages, the effects of intracochlear perfusion with aminoglycoside antibiotics on the organ of Corti and spiral ganglion cells were evaluated in young adult guinea pigs at survival periods ranging from 1 hour to 12 weeks, using immunocytochemical and ultrastructural techniques. At 1 hour survival a base-to-apex gradient of damage was indicated in the cochlea by the appearance of severely damaged hair cells and injured ganglion cells in the basal coil while in the apical coil, hair cells were damaged but intact and ganglion cells appeared normal. By 4 hours the appearance of severely disrupted hair cells and damaged ganglion cells had extended throughout the cochlea. The ultrastructural appearance of many injured ganglion cells demonstrated features characteristic of cell death including condensed cytoplasm, non-marginal clumping of nuclear chromatin, and wrinkled nuclear membrane. Despite the loss of many ganglion cells, a population of these cells remained at 12 weeks survival. These contained large amounts of rough endoplasmic reticulum, were unmyelinated apart from the central process and were surrounded by satellite cells. These features are typical of ganglion cells during development, before the onset of hearing. Immunolabelling of cochlear whole mounts after hair cell destruction with protein gene product 9.5 (PGP 9.5) revealed the presence of neural elements in the organ of Corti at up to 12 weeks survival. These may be associated with the remaining ganglion cells. In these surviving ganglion cells, the intense labelling with PGP 9.5 together with the increase in rough endoplasmic reticulum, indicates the presence of active protein synthesis which may be connected with their survival.

Aminoglycosides↗

Brain-derived neurotrophic factor inhibits changes in soma-size of retinal ganglion cells following optic nerve axotomy in rats.

To determine if optic nerve axotomy affects the cell soma size of retinal ganglion cells and to establish whether such quantitative analysis is useful as a new way of evaluating retinal ganglion cell damage, we measured the changes in both the number and soma size of retinal ganglion cells after optic nerve axotomy in rats. Retinal ganglion cells were retrogradely labeled by fluoro-gold injection into the superior colliculus, and the soma size was measured using image-analysis software. We detected a decrease in the proportion of large-sized retinal ganglion cells that was significant at 3, 5 and 7 days after the axotomy, and an increased proportion of small-sized ones that was significant at 5 and 7 days after the axotomy, indicating that retinal ganglion cells shrank following axotomy, that there was a shift away from the largest category of retinal ganglion cells towards the smallest category. On days 3 and 5 post-axotomy, there was no significant change in the proportion of medium-sized retinal ganglion cells. Intravitreal injection of brain-derived neurotrophic factor one hour before the axotomy significant inhibited the increase in the proportion of small-sized retinal ganglion cells otherwise seen at 3 days after the axotomy. These results may suggest that larger retinal ganglion cells are more sensitive to optic nerve axotomy than small- and medium-sized ones, and that a quantitative analysis of soma size is a useful way of detecting retinal ganglion cell damage in the early phase after axotomy.

Animals↗

On the duality of the facial nerve ganglion.

OBJECTIVES: Describe quantitatively the number of ganglion cells in the geniculate (G) and meatal (M) segments of the human facial nerve. STUDY DESIGN: One hundred human temporal bone specimens that were sectioned horizontally and stained with hematoxylin and eosin were selected from a temporal bone collection on the basis of minimal artifact and absence of pathology involving the facial nerve. METHODS: Cells with a nucleolus in all sections through the facial nerve were projected on tracing paper with a camera lucida and counted manually. A modified Abercrombie technique was employed to compute total cells in the G and M segments. RESULTS: Ages of patients ranged from 1 month to 92 years; the male-to-female ratio was 56:44. The total number of cells in individual temporal bones ranged from 589 to 4183 (mean, 2162 cells). The range of cells in the G ganglion was from 66 to 4017 (mean, 1713 cells); in the M ganglion the number ranged from 0 to 2764 (mean, 448 cells). There was no correlation of total ganglion cell number to age or sex. The majority of cells were found in the G ganglion in 88% of temporal bones. In 8% temporal bones the majority of cells were in the M ganglion and in 4% the M and G ganglions contained an equal number of cells. CONCLUSIONS: The facial nerve sensory ganglion consists of two components: G and M. The G ganglion outnumbers the M component in the majority of temporal bones (88%). The M ganglion was equal to or greater in number than the G ganglion in 12% of temporal bones.

Adolescent↗

Neuroprotective effects of nipradilol on purified cultured retinal ganglion cells.

PURPOSE: To investigate effects of nipradilol, a nonselective beta- andbgr;-and selective alpha1-receptor antagonist and a potential nitric oxide releaser, on retinal ganglion cells purified and cultured in a serum-free medium. METHODS: Retinal ganglion cells were isolated from 2-day-old Sprague-Dawley rats by means of two-step panning. A series of nipradilol (10(-5), 10(-6), 10(-7), 10(-8), 10(-9), and 10(-10)-mol/L) or vehicle solutions were administered to the culture medium for 48 hours, and the survival rate of retinal ganglion cells was evaluated using a newly developed system that evaluates the survival rate in small and large retinal ganglion cells separately. The effects of timolol maleate or bunazosin (10(-5), 10(-6), 10(-7), and 10(-8) -mol/L) solutions on retinal ganglion cells survival were also evaluated. The survival rate was evaluated after 10(-5)-mol/L c-PTIO (2-[4-carboxyphenyl]-4,4,5,5 tetramethylimidazoline-1-oxyl-3-oxide potassium salt), a nitric oxide scavenger, was administered to retinal ganglion cells with 10(-5)-mol/L nipradilol. RESULTS: Nipradilol significantly increased the survival rate of both small and large retinal ganglion cells in a concentration-dependent manner compared with the controls. The maximum survival rate improvement of small and large retinal ganglion cells was 29.1% and 14.5%, respectively. Although timolol maleate and bunazosin did not affect the survival rate, 10(-5)-mol/L c-PTIO significantly inhibited the nipradilol-induced survival rate improvement by 69.9% in small retinal ganglion cells and by 91.6% in large retinal ganglion cells. CONCLUSION: Nipradilol improves the survival rate of cultured postnatal rat retinal ganglion cells, and the nitric oxide generated from nipradilol may contribute to this effect.

Adrenergic alpha-Antagonists↗

Strategies to preserve or regenerate spiral ganglion neurons.

PURPOSE OF REVIEW: Degeneration of spiral ganglion neurons following hair cell loss carries critical implications for efforts to rehabilitate severe cases of hearing loss with cochlear implants or hair cell regeneration. This review considers recently identified neurotrophic factors and therapeutic strategies which promote spiral ganglion neuron survival and neurite growth. Replacement of these factors may help preserve or regenerate the auditory nerve in patients with extensive hair cell loss. RECENT FINDINGS: Spiral ganglion neurons depend on neurotrophic factors supplied by hair cells and other targets for their development and continued survival. Loss of this trophic support leads to spiral ganglion neuron death via apoptosis. Hair cells support spiral ganglion neuron survival by producing several peptide neurotrophic factors such as neurotrophin-3 and glial derived neurotrophic factor. In addition, neurotransmitter release from the hair cells drives membrane electrical activity in spiral ganglion neurons which also supports their survival. In animal models, replacement of peptide neurotrophic factors or electrical stimulation with an implanted electrode attenuates spiral ganglion neuron degeneration following deafferentation. Cell death inhibitors can also preserve spiral ganglion neuron populations. Preliminary studies show that transfer of stem cells or neurons from other ganglia are two potential strategies to replace lost spiral ganglion neurons. Inducing the regrowth of spiral ganglion neuron peripheral processes to approximate or contact cochlear implant electrodes may help optimize signaling from a diminished population of neurons. SUMMARY: Recent studies of spiral ganglion neuron development and survival have identified several trophic and neuritogenic factors which protect these specialized cells from degeneration following hair cell loss. While still preliminary, such strategies show promise for future clinical applications.

Animals↗

Parallel processing in retinal ganglion cells: how integration of space-time patterns of excitation and inhibition form the spiking output.

Our goal was to understand how patterns of excitation and inhibition, interacting across arrays of ganglion cells in space and time, generate the spiking output pattern for each ganglion cell type. We presented the retina with a 1-s flashed square, 600 microm on a side, and measured patterns of excitation and inhibition over an 1,800-microm-wide region encompassing many ganglion cells. Excitatory patterns of on ganglion cells resembled rectified versions of the voltage patterns of on bipolar cells. Inhibitory patterns in on ganglion cells resembled the rectified versions of voltage patterns of off bipolar cells. off ganglion cells received off excitation and on inhibition. Many ganglion cells also received an additional wide field transient inhibition derived from the activity of both on and off bipolar cells. Ganglion cell spiking was suppressed in those space-time regions dominated by inhibition. We classified each ganglion cell type by correlating its space-time patterns with its dendritic morphology. These studies suggest the bipolar and amacrine cell circuitry underlying the interplay between on and off signals that generate spiking patterns in ganglion cells. They reveal a surprising synergistic interaction between excitation and inhibition in most ganglion cells.

Action Potentials↗

Survival of Scarpa's ganglion in the profoundly deaf human.

The electrically evoked auditory brain stem response in some cochlear implant patients may be confounded by evoked potentials generated by vestibular neurons. The magnitude of this contribution to the response from the vestibular system is unknown, in part because the survival of cells within Scarpa's ganglion in profoundly deaf humans is unknown. Therefore, we undertook a quantitative study of Scarpa's ganglion in 48 deaf subjects who in life would have been candidates for cochlear implantation and in 5 subjects with normal hearing. The numbers of residual cells in both Scarpa's ganglion and the spiral ganglion in deaf subjects were significantly less than in individuals with normal hearing. Bivariate analysis demonstrated a highly significant positive correlation between cell counts of Scarpa's ganglion and the spiral ganglion. The durations of hearing loss and of profound deafness were negatively correlated with Scarpa's ganglion cell counts. However, in contrast to spiral ganglion cell survival, the cause of profound deafness did not predict the number of Scarpa's ganglion cells. Multiple linear regression analysis using a variety of clinical parameters demonstrated that the best predictor of the number of Scarpa's ganglion cells in profoundly deaf humans was the number of remaining spiral ganglion cells.

Adult↗

The development of the pattern of retinal ganglion cells in the chick retina: mechanisms that control differentiation.

Neurons in both vertebrate and invertebrate eyes are organized in regular arrays. Although much is known about the mechanisms involved in the formation of the regular arrays of neurons found in invertebrate eyes, much less is known about the mechanisms of formation of neuronal mosaics in the vertebrate eye. The purpose of these studies was to determine the cellular mechanisms that pattern the first neurons in vertebrate retina, the retinal ganglion cells. We have found that the ganglion cells in the chick retina develop as a patterned array that spreads from the central to peripheral retina as a wave front of differentiation. The onset of ganglion cell differentiation keeps pace with overall retinal growth; however, there is no clear cell cycle synchronization at the front of differentiation of the first ganglion cells. The differentiation of ganglion cells is not dependent on signals from previously formed ganglion cells, since isolation of the peripheral retina by as much as 400 microm from the front of ganglion cell differentiation does not prevent new ganglion cells from developing. Consistent with previous studies, blocking FGF receptor activation with a specific inhibitor to the FGFRs retards the movement of the front of ganglion cell differentiation, while application of exogenous FGF1 causes the precocious development of ganglion cells in peripheral retina. Our observations, taken together with those of previous studies, support a role for FGFs and FGF receptor activation in the initial development of retinal ganglion cells from the undifferentiated neuroepithelium peripheral to the expanding wave front of differentiation.

3T3 Cells↗

Effects of unilateral stellate ganglion block on the spectral characteristics of heart rate variability.

The effect of unilateral stellate ganglion block on cardiovascular regulation remains controversial, so the present study used power spectral analysis of heart rate variability to investigate its effect on the autonomic neural control of the heart. In 20 young healthy volunteers (mean age: 25 years), heart rate variability was determined before and after unilateral stellate ganglion block (right side 11, left side 9) using 8 ml of 1% mepivacaine during supine rest. Using autoregressive spectrum analysis, power spectra were quantified by measuring the area in 3 frequency bands: high-frequency power (lnHF, parasympathetic influence) from 0.15 to 0.40 Hz, low-frequency power (lnLF, predominantly sympathetic influence) from 0.04 to 0.15 Hz, and total-frequency power (lnTF) less than 0.40 Hz. Right stellate ganglion block decreased not only the lnLF component from 6.55+/-0.84 to 5.77+/-0.47 but also the lnHF component from 4.40+/-0.95 to 3.42+/-1.12 (p<0.05). In contrast, left stellate ganglion block changed neither the lnLF nor the lnHF component. The lnTF component was also decreased significantly by right stellate ganglion block from 7.80+/-0.95 to 7.01+/-0.36 (p<0.05), but was unchanged following left stellate ganglion block. Neither right nor left stellate ganglion block induced any significant change in both the RR and corrected QT intervals. However, changes in the RR interval induced by right stellate ganglion block showed significant positive correlation with changes in lnHF (p<0.005) and lnTF (p<0.05). These results suggest that (1) autonomic innervation to the sinus node is mainly through the right-sided stellate ganglion, (2) pharmacological right-sided stellate ganglion block may attenuate not only sympathetic but also parasympathetic activity and (3) following right stellate ganglion block the decrease in both the sympathetic and parasympathetic influence on the sinus node may inconsistently counterbalance and change the RR interval.

Adult↗

Scaling the hill of vision: the physiological relationship between light sensitivity and ganglion cell numbers.

PURPOSE: Differential light sensitivity (DLS) in white-on-white perimetry is used as a measure of ganglion cell function to estimate the amount of neuronal damage in glaucoma. The physiological relationship between DLS and ganglion cell numbers is poorly understood. Within small retinal areas, brightness information is summated, so that A * L = C, or A = C/L, where A is target area, L is threshold luminance, and C is a constant. In larger illuminated areas, as with a Goldmann size III target in perimetry, summation is incomplete, so that A(k) = C/L, where k is the coefficient of summation, and 0 < k < 1. This study tests the hypothesis that the target area (A) can be represented by the number of underlying ganglion cells (G) to give G(k) = C/L. METHODS: Normative human data for ganglion cell density within 30 degrees of retinal eccentricity were taken from the literature and corrected for lateral displacement of ganglion cells from the fovea to estimate ganglion cell receptive field density (g). The number of ganglion cell receptive fields within a Goldmann size III target (G) was calculated from target area (A) and receptive field density (g) [G = A (g)]. Normative data for DLS in the central 30 degrees (Humphrey 30-2) were taken from the literature. The coefficient summation (k) was measured empirically at each Humphrey 30-2 test point in 8 normal subjects. The relationship between DLS and G was investigated by plotting DLS as decibels (dB) against G and DLS as 1/L (1/Lamberts) against G(k). The physiological relationship was extrapolated to glaucomatous ganglion cell loss by calculating hypothetical cell losses for 3 and 6 dB sensitivity defects at each test point. RESULTS: Spatial summation increased with eccentricity. The relationship between DLS (dB) and G was curvilinear. The relationship between DLS (1/L) and G(k) was linear (r2 = 0.73). The extrapolation to glaucomatous ganglion cell loss indicated that a proportionally greater loss of ganglion cells is required in the central compared with peripheral visual field for equal losses in dB sensitivity. CONCLUSIONS: The number of underlying ganglion cells, adjusted for local spatial summation, is better reflected by the DLS scale of 1/L than by dB. If spatial summation is unchanged in glaucoma, this scale more accurately reflects the amount of neuronal damage.

Adult↗

Immunocytochemical localisation of substance P in vagal ganglion cells and pericellular arborisations in the monkey.

The quantitative cell count showed the presence of about 20,000 ganglion cells with associated satellite elements in the nodose ganglion in the monkey. Among these closely packed cells, at least one-third were substance P (SP) immunoreactive, ranging from faint or moderate to intense staining. Substance P immunoreactivity (SP-IR) was localised in the cell bodies and their long extending neurites. Ultrastructural study showed that SP-IR was not associated with any particular organelles or inclusions. A striking feature of the nodose ganglion was the occurrence of SP-positive pericellular arborisations associated with about 0.5% of the ganglion cells which were almost exclusively SP-negative. The pericellular arborisation displayed diverse morphological forms from a simple tortuous fibre to complex glomerular networks or plexuses encircling the soma of SP-negative ganglion cells. The varicose nerve fibres forming the pericellular arborisations appeared to terminate as 'boutons' contacting the soma of the ganglion cells. Electron microscopic study demonstrated the close spatial relation between the SP-IR profiles and the ganglion cell but there was no direct synaptic contact. In some instances, the SP-IR profiles containing agranular and dense-cored vesicles penetrated the cytoplasm of satellite cells, almost reaching the surface of the soma of the ganglion cell. The sources of origin of the nerve plexuses in the pericellular arborisation were either from the small and sparsely distributed jugular ganglion cells which were intensely SP-IR or from the intrinsic SP-IR nodose ganglion cells. The possibility that the efferent neurons in the dorsal motor nucleus of the vagus could also contribute to the pericellular arborisation was also considered. The function of the pericellular arborisations may be related to the modulation of the SP-deficient ganglion cells with which they associate through the release of SP and probably by way of the satellite cells.

Animals↗

Ganglion cells in the turtle retina contain the neuropeptide LANT-6.

This study investigated the presence of the neurotensin-related hexapeptide, LANT-6, in retinal ganglion cells and their central projections in the turtle Pseudemys scripta elegans. Immunocytochemical techniques demonstrated that many of the cells in the ganglion cell layer of the turtle retina could be labeled with an antiserum specific for LANT-6. Radioimmunoassay and chromatographic analysis confirmed the presence of LANT-6-related peptides in retina, as well as brain. Several molecular forms of LANT-6 were observed, some larger than LANT-6. Characterization of the cells labeled in the ganglion cell layer in terms of their cell body size and their dendritic arborization patterns revealed that at least 6 specific LANT-6-positive cell types were present in the ganglion cell layer. Morphologically, the LANT-6-positive cells strongly resembled turtle ganglion cells, as previously described. In addition, two other lines of evidence supported this interpretation. First, double-label studies were performed in which retinal ganglion cells projecting to the tectum were retrogradely labeled by HRP injected into the tectum (using a cobalt chloride color-modified DAB reaction product) and immunocytochemically labeled with DAB using the antiserum against LANT-6. These double-label studies revealed that many of the LANT-6-positive cells in the ganglion cell layer in the portion of the retina labeled retrogradely by the HRP injection did project to the tectum. Within the retrogradely labeled portion of the retina, LANT-6-positive cells that were not labeled retrogradely, as well as neurons labeled retrogradely that did not contain LANT-6 were also observed. Second, the central projections of LANT-6-positive cells of the ganglion cell layer were examined by studying the effects of monocular enucleation on the distribution of LANT-6-positive fibers in the central projection targets of the turtle retina. Two to 8 weeks after enucleation, a substantial reduction in LANT-6-positive fibers was observed in all retinal target areas contralateral to the enucleated eye. Radioimmunoassay and chromatographic studies confirmed the presence of LANT-6-related peptides in the turtle brain and corroborated the reduction of LANT-6 observed in the contralateral tectum following monocular enucleation. Previous studies have demonstrated that LANT-6-related material is present in cells of the ganglion cell layer in a variety of vertebrates. The present results indicate that LANT-6 is in ganglion cells and that it may play a role in neurotransmission between retinal ganglion cells and their central target areas.

Animals↗

The distribution and size of ganglion cells in the regina of the pigmented rabbit: a quantitative analysis.

The distribution and soma diameters of retinal ganglion cells have been examined in whole mounted retinae of pigmented rabbits. Maps of the distribution of ganglion cells confirmed several features of earlier descriptions, but generally showed lower density values and yielded lower total ganglion cell counts (250,000-270,000). The maximum ganglion cell density encountered in each retina and its retinal location both varied between rabbits. As previously reported, the dominant feature of the rabbit's retina is a strongly developed visual streak (Hughes, '71) but some evidence of an area centralis-like specialization was found. This appears not as the area of peak gangion cell density, but as a concentration of large (greater than or equal to 20 micron in diameter) ganglion cells at the temporal end of the visual streak, 2-3 mm from the temporal margin of the retina. In one rabbit in which the optic tract was sectioned five months previously, the density distribution of large retinal ganglion cells in the retinae has been mapped. These maps indicate that the nasotemporal division for large ganglion cells in the rabbit retina is approximately centered on the area of their maximum density. It has previously been reported that in the cat the area centralis is characterized by an aggregation of smaller diameter ganglion cells of a particular functional type (Stone, '65, '78). It is possible that areas of retinal which subserve area centralis-like functions are represented not simply by localized increases in ganglion cell density, but by changes in the relative proportions of ganglion cell types, which are reflected in the changing relative densities of ganglion cell soma diameter groups.

Animals↗

A quantitative comparison between the ganglion cell populations and axonal outflows of the visual streak and periphery of the rabbit retina.

A vertical density profile of the ganglion cells 2 mm temporal of the optic nerve head in the rabbit retina has been produced by counting somata in the cresyl-violet-stained, ganglion cell layer of a flat-mounted retina. Somata classified as ganglion cells were characterized by obvious Nissl staining in an extensive cytoplasm and typically had diameters greater than 9 micrometer. The accuracy of the profile, and thus of the classification criteria, has been substantiated by electron micrographic determination of the numbers of ganglion cell axons arising within local regions of known area on the same retina. This study indicates that Vaney and Hughes' estimate ('76) of 547,100 presumed ganglion cells in the rabbit retina should be changed to 373,500 ganglion cells. The latter value is within the statistical error of their optic nerve count of 394,000 fibers. The mean diameter of ganglion cells 6 mm from the visual streak in the inferior periphery (density: 550 cells/mm2) was 28% greater than that of cells on the peak of the streak (density: 5,400 cells/mm2), although the form of the ganglion cell diameter distribution did not change markedly with eccentricity. The increase in the mean size of ganglion cells in the periphery appeared to be approximately matched by an increase in the size of their axons. Larger axons became myelinated farther from the edge of the myelinated band than did smaller axons. Within the ganglion cell layer there was another population of cells which were quite distinct from the obvious neuroglia: Their nuclei were similar to those of the larger ganglion cells and many appeared to have Nissl granules within their limited cytoplasm. About half of this heterogeneous population was classified as "coronate cells," which were characterized by the partial nuclear encapsulation of their eccentric cytoplasm.

Animals↗

Generation of new cerebral ganglion neurons in the snail Melampus: an ultrastructural study.

Reports in the literature have established that reconnection of central neural tracts occurs following commissurotomy and cerebral ganglion excision in the primitive pulmonate snail Melampus bidentatus and have suggested the possibility that long-term regeneration might result in the appearance of new neurons in the ganglion bud. We have used electron microscopy to examine the ganglion buds that form by reconnection of cerebral nerves, commissure, and connectives following cerebral ganglion excision in adult Melampus. The buds were examined from 2.5 to 12 months postoperatively. By 2.5 months, ganglion buds consist of a mixture of axon tracts that travel through the bud region and some dendritic processes; a few synaptic contacts can be identified at this stage, scattered throughout the bud. By 5--6 months, some of the most advanced ganglia have undifferentiated cells that are distinct from glia. By 7 months, differentiated neurons with clear, small dense-core or neurosecretory vesicles are present, although these cells are not all concentrated in a rind on the ganglion surface. Another cell type, the pigment-sheath cell, is present by this stage. By 11--12 months, the most advanced regenerating ganglia have neurons which form a cell rind on the ganglion surface. The gross appearance of a regenerated ganglion at this stage is similar to that of the intact contralateral cerebral ganglion, although the regenerated ganglion is smaller. One 12-month ganglion was found to possess fairly normal intraganglionic morphology, with lobes and cell types that were recognizable. Hence, nerve cell regeneration can occur in the absence of body part regeneration in adult members of one species of pulmonate snail.

Animals↗

Ganglion cells immunoreactive for catecholamine-synthesizing enzymes, neuropeptide Y and vasoactive intestinal polypeptide in the rat adrenal gland.

Immunohistochemistry has been used to demonstrate tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), phenylethanolamine N-methyltransferase (PNMT), neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP) immunoreactivities, and acetylcholinesterase (AChE) activity was demonstrated in rat adrenal glands. The TH, DBH, NPY and VIP immunoreactivities and AChE activity were observed in both the large ganglion cells and the small chromaffin cells whereas PNMT immunoreactivity was found only in chromaffin cells, and not in ganglion cells. Most intra-adrenal ganglion cells showed NPY immunoreactivity and a few were VIP immunoreactive. Numerous NPY-immunoreactive ganglion cells were also immunoreactive for TH and DBH; these cells were localized as single cells or groups of several cells in the adrenal cortex and medulla. Use of serial sections, or double and triple staining techniques, showed that all TH- and DBH-immunoreactive ganglion cells also showed NPY immunoreactivity, whereas some NPY-immunoreactive ganglion cells were TH and DBH immunonegative. NPY-immunoreactive ganglion cells showed no VIP immunoreactivity. AChE activity was seen in VIP-immunopositive and VIP-immunonegative ganglion cells. These results suggest that ganglion cells containing noradrenaline and NPY, or NPY only, or VIP and acetylcholine occur in the rat adrenal gland; they may project within the adrenal gland or to other target organs. TH, DBH, NPY, and VIP were colocalized in numerous immunoreactive nerve fibres, which were distributed in the superficial adrenal cortex, while TH-, DBH- and NPY-immunoreactive ganglion cells and nerve fibres were different from VIP-immunoreactive ganglion cells and nerve fibres in the medulla. This suggests that the immunoreactive nerve fibres in the superficial cortex may be mainly extrinsic in origin and may be different from those in the medulla.

Adrenal Glands↗

Mast cells in the guinea pig superior cervical ganglion: a functional and histological assessment.

We have previously found that antigenic stimulation of mast cells in the guinea pig superior cervical ganglion leads to membrane depolarization of principal neurons and a long-term increase in the efficacy of ganglionic transmission. In this study experiments were conducted to discern the histological, immunological and pharmacological characteristics of the mast cells within the superior cervical ganglion. Mast cells within the superior cervical ganglion could be stained with toluidine blue or berberine sulfate, the latter indicating that heparin-like molecules were present in the granules. Stainable mast cells were distributed throughout the ganglion with no gross evidence of regional localization. The number of mast cells stained with toluidine blue was reduced significantly (P less than 0.01) in contralateral ganglia that had been exposed to the sensitizing antigen (ovalbumin), indicating antigen-induced degranulation. The superior cervical ganglion contained 208 +/- 6 picomole of histamine (mean +/- SEM, n = 66). Ovalbumin evoked the release of histamine from the superior cervical ganglion in a concentration-dependent fashion. At maximally effective concentrations, ovalbumin released 33 +/- 2% of the total histamine stores (mean +/- SEM, n = 61). Similar values were obtained with antigen-challenged stellate ganglia. A temperature of 37 degrees C and an extracellular calcium concentration of 1 mM was required to elicit optimal antigen-induced responses. In addition to releasing histamine, antigenic stimulation of the ganglion resulted in a 3- to 5-fold increase in the synthesis and release of arachidonic acid metabolites including peptidoleukotriene, thromboxane B2, prostaglandins (PG) E2, F2 alpha, D2, the PGD2 metabolite 9 alpha 11 beta-PGF2, and the prostacyclin metabolite 6-keto PGF1 alpha. Various putative mast cell secretagogues were examined for their ability to activate the superior cervical ganglion mast cell, as indicated by evoked histamine release. In contrast to rat peritoneal mast cells, high concentrations of substance P, compound 48/80, and nerve growth factor failed to stimulate the ganglion mast cells. Preganglionic nerve stimulation, electrical field stimulation of axons and cell bodies, or depolarizing concentrations of potassium chloride also failed to activate the superior cervical ganglion mast cells. These results suggest that substances released by membrane depolarization do not influence the function of the resident mast cells. The results demonstrate that the mast cells within sympathetic ganglia can be actively sensitized to respond to specific antigen. These mast cells are similar to lung parenchymal mast cells with respect to histological, immunological and pharmacological characteristics...

Animals↗