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Ontogeny of calcitonin gene-related peptide in the organ of Corti of the rat.

The ontogeny of calcitonin gene-related peptide (CGRP)-like immunoreactive (CGRPI) fibers in the rat cochlea was examined using immunocytochemistry. It was found that the CGRPI cochlear system developed markedly in the postnatal period; CGRPI fibers first appeared in the inner spiral bundle at postnatal day 8, then at the base of the outer hair cells, tunnel spiral bundle and tunnel radial fibers at postnatal day 19. The ontogenetical profile elucidated by this study suggests that CGRP has a role as a neuromodulator or neurotransmitter in this system.

Animals↗

Localization and fine structure of calcitonin gene-related peptide (CGRP)-like immunoreactive nerve fibres in the organ of Corti of guinea pigs by immunohistochemistry.

The localization and fine structure of calcitonin gene-related peptide (CGRP)-like immunoreactive (CGRPI) fibres in the guinea pig cochlea were examined using immunohistochemistry. Numerous CGRPI fibres were located in the inner spiral bundle corresponding to the lateral system of the olivocochlear bundle. Immunoelectron microscopic analysis demonstrated that the CGRPI fibres belonged to the efferent terminals and some of them made synaptic contacts with peripheral neurites of the auditory nerve. These findings suggested that the olivocochlear CGRP neuron system influenced the neural activity of the auditory nerve, which conveys auditory information from the cochlea to the central nervous system.

Animals↗

[Morphological evaluation of the organ of Corti of guinea pigs submitted to acoustic trauma. II. Correlations of depth and surface lesions].

Adult guinea pigs (250-500 g) were exposed to a chronic wide-band noise, at intensities ranging from 117 to 133 dB(A) at different times. While the first part of this paper concentrated on the surface study of the lesions produced by noise, this second part describes to correlating deep structural damage, based on the study of semi-thin and ultra-thin sections in the same specimen. Finally, a general discussion is presented with respect to the lesions described, both in so far as their specific characteristics as well as the possible mechanisms of damage which determine their formation.

Animals↗

Neuronal sprouting and synapse formation in response to injury in the mouse organ of Corti in culture.

The effect of mechanical injury on induction of regenerative phenomena within the neurosensory epithelium was investigated in cultures of neonatal mouse cochlea. The oldest examined culture in which new neuronal growth followed insult, was injured at 13 days in vitro and fixed 24 h later. By far, the most vigorous regenerative reaction was observed in a 3-day culture 4 h post-injury. The reaction included sprouting of nerve fibers injured directly, synapse formation between the surviving hair cells and sprouting neuronal growth cones, wrapping of growing nerve fibers by extending processes of hair cell cytoplasm, and collateral sprouting of synaptically-engaged nerve endings and of nerve fibers in passage.

Animals↗

Amikacin intoxication induces apoptosis and cell proliferation in rat organ of Corti.

Recently, an attempt at cochlear hair cell neodifferentiation has been reported in amikacin-treated rats. In the present study, we aimed to ascertain whether hair cell losses are mediated by apoptosis and whether cell proliferation occurs in damaged intoxicated cochleas. The results show that apoptosis is responsible for hair cell losses and that cell proliferation occurs in the region of the outer spiral sulcus but not in the region of Deiters cells and pre-existing hair cells. We suggest that cell proliferation maintains a certain homeostasis in the number of non-sensory cells and participates in epithelial scar formation. Neodifferentiated cells therefore probably arise from direct transdifferentiation, which could be triggered by phagocytosis of apoptotic bodies.

Amikacin↗

Incorporation of glycerol in the organ of Corti: predominance in hair cells and effects of kanamycin.

A biochemical study revealed that [3H]glycerol was incorporated into various kinds of phospholipids in the guinea pig cochlea. The sites of incorporation of [3H]glycerol injected into the scala tympani were localized autoradiographically. The most active incorporation occurred in the hair cells, especially in the outer ones, followed by the inner ones and the nerve endings attached to hair cells. Glycerol incorporation into hair cells appeared to increase as the apex was approached. Chronic intoxication with kanamycin selectively suppressed glycerol incorporation in the hair cells. The site of glycerol incorporation shown by the present autoradiographic study is likely to reflect the site of phospholipid synthesis. Autoradiographic studies could constitute a new approach to understanding the possible involvement of phospholipid metabolism in the function and pathology of the cochlea.

Animals↗

[Susceptibility of organ of Corti with or without melanin to acoustic overstimulation].

Albino and pigmented guinea pigs were compared in terms of susceptibility to acoustic trauma. The animals were exposed to a 4 kHz pure tone of 120 dB for 60 min. N1 thresholds of CAP were measured before and after the acoustic exposure. Changes in the outer hair cell and stria vascularis were studied using SEM and TEM. After acoustic trauma, N1 thresholds were more elevated in the albino than in the pigmented guinea pigs. Also, pathological changes in the outer hair cell and stria vascularis were more severe in the albino animals. A noteworthy finding in the stria vascularis was that the melanin in intermediate cells had moved into marginal cells. This melanin migration may be possibly involved in mechanisms underlying prevention of acoustic trauma.

Acoustic Stimulation↗

Serotonergic innervation of the organ of Corti of the cat cochlea.

The presence and distribution of serotonin-containing fibers within the adult cat cochlea is reported here for the first time. The 5-HT-like immunoreactive fibers were mainly found in the middle coils of the cat cochlea, following a peripheral distribution similar to that of the olivocochlear lateral efferent system (OLES). Thus, 5-HT-like immunoreactive varicose fibers were found within the intraganglionic spiral bundle, the inner and the tunnel bundles, although, some variation with the distribution of other neuroactive substances of the OLES were observed. In particular, some isolated fibers from the tunnel bundle branched towards the first row of the outer hair cells. Cochlear serotonergic fibers might be involved in the auditory processing within the cochlea as efferent modulating fibers.

Animals↗

Loss of stereocilia in the human organ of Corti.

The process of disappearance of the stereocilia at the top of the outer hair cell was described by observing aged human cochlea under scanning electron microscope. After loss of hair, remnants of hair could be recognized at the top of outer hair cells. As the process continued, the remnants of the stereocilia increase in percentage, while the remaining abnormal hair decrease. As remnants gradually disappear, the W-configuration faded away. At the same time, the diameter of the hair cell top decreased by shrinking. Before the supporting cells made a complete cover, there may be a depression in the reticular lamina due to shrinking of the top of the hair cell. However, if the depression persists, there is the potential danger of reticular lamina rupture. Existence of a breaking point in the stereocilia of the outer hair cell was proposed.

Age Factors↗

Innervation densities of inner and outer hair cells of the human organ of Corti. Evidence for auditory neural degeneration in a case of Usher's syndrome.

The innervation densities, i.e. the number of afferent endings per inner and outer hair cell, number of synaptic specializations per inner hair cell and the number of efferent endings per outer hair cell, were evaluated by serial section electron microscopy in the normal human inner ear and a case of Usher's syndrome (retinitis pigmentosa and sensorineural hearing loss). There was a significant decrease in the innervation density in Usher's syndrome as compared to normative controls, which could not be explained by the decrease in density of spiral ganglion cells. This was interpreted as suggesting a decrease in the number of neural processes and endings within the dendritic arborization of remaining spiral ganglion cells in this disorder.

Aged↗

[Regenerative potential of the sensory epithelium of the mammalian organ of Corti after poisoning with ototoxic antibiotics].

Cochlear sensory hair cells are very sensitive to noxious influences such as ageing, noise and ototoxic drugs. Whereas lost auditory hair cells are replaced by new hair cells in the avian and lower vertebrates, cochlear sensory hair cells do not regenerate in mammals. Recently, we have observed transient atypical cells in the cochlea of amikacin intoxicated rats. We have related their presence to an attempt at sensory hair cell neodifferentiation. The aim of the present study was to i) investigate the mechanisms responsible for sensory hair cell losses during the intoxication and the subsequent appearance of atypical cells, ii) characterise the phenotype of these atypical cells and iii) evaluate the influence of cochlear immaturity in such an attempt at sensory hair cells neo-differentiation.

Amikacin↗

Postnatal changes in the reticular lamina of the guinea pig organ of Corti.

The dimensions of the apical surfaces of hair cells were measured in guinea pigs, aged from 3 weeks before term to 25 weeks after birth. In the basal two-thirds of the cochlea, the apical surfaces of the outer hair cells and their supporting cells changed with age, shrinking in a direction radial across the cochlear duct. There was an associated widening of the angle of the 'V' of the rows of stereocilia. Further apically, between 12 and 16 mm from the base of the cochlea, the outer hair cells and their supporting cells underwent the opposite change, becoming wider in a radial direction with age. The changes were seen before birth and continued for more than 3 weeks after birth. The results suggest that the guinea pig cochlea continues certain developmental processes for a considerable time after birth.

Aging↗

Neuron-specific enolase-like immunoreactivity in inner hair cells but not outer hair cells in the guinea pig organ of Corti.

Neuron-specific enolase (NSE) has been localized only in neurons and cells with characteristics of neurons. The immunocytochemical localization of NSE was examined in guinea pig cochleae to determine if hair cells, which have some neuronal characteristics, would show NSE-like immunoreactive labeling. NSE-like immunoreactivity was seen in inner hair cells but not in outer hair cells. This is the first report of NSE-like immunoreactivity in a receptor cell. NSE-like immunoreactivity was also seen in efferent fibers and terminals and in both type I and type II spiral ganglion cells. The finding of NSE-like immunoreactivity in inner but not outer cells adds to the number of differences found between them and may be related to differences in function and action.

Animals↗

Cross-links between stereocilia in the human organ of Corti.

Human cochleae were fixed in glutaraldehyde, without the use of osmium. Cross-links were seen between the stereocilia, similar to those we have previously reported for the guinea pig: first, stereocilia of the same row on each hair cell were joined by horizontally-running links; secondly, the shorter stereocilia had pointed tips, each giving rise to a single, vertically-pointing link, which ran upwards to join the adjacent taller stereocilium of the next row. We suggest that distortion of this link is involved in sensory transduction. The links were sparser than had been seen in the guinea pig which may be a reflection of the vulnerability of the links to non-optimal fixation, and the greater difficulty in producing good fixation in human specimens.

Adult↗

A study of postmortem autolysis in the human organ of Corti.

Forty-six human temporal bones from 24 individuals were removed at autopsy and prepared for electron microscopy. The adequacy of histologic preservation was evaluated by light and electron microscopy. Characteristic autolytic changes included vacuolization of afferent neurons and neural poles of inner and outer hair cells, lysis of limiting membranes of hair and supporting cells, swelling of endoplasmic reticulum, and dissolution of mitochondrial cristae. The rate of autolysis varied significantly within cellular components of the inner ear. The neural poles of hair cells demonstrated more rapid autolysis than apical poles and nerve terminals showed more autolysis than myelinated nerve fibers. Postmortem time and the cause of death affected the adequacy of histologic preservation. Fixation in patients dying of pneumonia, hypoxia, head injury, or malignancy tended to be poor, whereas the fixation achieved in patients dying of cardiac disease with postmortem time of under 140 minutes was generally good.

Autolysis↗

Confocal microscopic analysis of the chinchilla organ of Corti following exposure to high-level impact noise.

To better understand the nature of mechanical changes following exposure to high-level impact noise, normal cochleas and cochleas from chinchillas exposed to either 125 or 131 dB SPL noise were stained with phalloidin for F-actin and examined using confocal microscopy. As seen in previous experiments, 125 dB exposures produced much more variable results than 131 dB exposures. Some cochleas were relatively unscathed by the exposure, whereas others showed damage to outer hair cells (OHCs) immediately after the exposure that included gross distortions of cell bodies and reduced F-actin in cuticular plates. Twenty-four hours later, there was also disorientation of actin filaments in supporting cells. After 30 days, Deiters cells were disarrayed and cups were separated from OHC neural poles. Exposure to noise at a level of 131 dB SPL produced less variable results than 125 dB exposure, and damage was generally more widespread and severe.

Animals↗

Predicting mechanical damage to the organ of Corti.

The potential for pharmacological intervention to ameliorate the effects of exposure to intense auditory stimulation is a truly exciting possibility. In theory, the effects of intense stimulation could be primarily a function of mechanical stress and its sequelae or possibly metabolic exhaustion. Conceivably, specific pharmacological therapies might be more effective following different types of insult, depending on the loss mechanism(s) involved. The Auditory Hazard Assessment Algorithm for the Human (AHAAH), a first-principles mathematical model for the ear, has been developed specifically to predict hazard at high intensities based on basilar membrane displacement. Validation studies have proven it to be accurate in rating risk for the human ear. AHAAH is available for download on the Internet. In the present context it was used to propose analytic stimuli that would help to elucidate the loss mechanisms and also to identify exposures for the clinician that should be considered as sufficiently hazardous to warrant potential pharmacological intervention either before or after the exposure.

Algorithms↗

Purinergic signalling and intercellular Ca2+ wave propagation in the organ of Corti.

Extracellular ATP is a key neuromodulator of visual and auditory sensory epithelia. In the rat cochlea, pharmacological dissection indicates that ATP, acting through a highly sensitive purinergic/IP(3)-mediated signaling pathway with (little or) no involvement of ryanodine receptors, is the principal paracrine mediator implicated in the propagation of calcium waves through supporting and epithelial cells. Measurement of sensitivity to UTP and other purinergic agonists implicate P2Y(2) and P2Y(4) as the main P2Y receptor isoforms involved in these responses. Ca2+ waves, elicited under highly reproducible conditions by carefully controlling dose (1 microM) and timing of focal agonist application (0.2s), extended over radial distance greater than 160 microm from the source, identical to those activated by damaging single outer hair cells. Altogether, these results indicate that intercellular calcium waves are a robust phenomenon that confers a significant ability for cell-cell communication in the mammalian cochlea. Further ongoing research will reveal the roles that such Ca2+ waves play in the inner ear.

Adenosine Triphosphate↗