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PubMed1998

The significance of endothelin for generation of endocochlear potential.

The role of intermediate cells (ICs) in the stria vascularis (SV) of the cochlear ducts in the generation of endocochlear potential (EP) is clear because certain mutants cannot generate EP. Recent reports have shown that endothelin (ET) stimulates or inhibits the function of Na+, K(+)-ATPase in various organs. This study was designed to examine the immunocytochemical localization of ET and its receptor in the SV. The cochlear ducts of WBB6F1 (+/+) mice and mutants (W/Wv) devoid of the ICs were used for light and electron microscopic immunocytochemistry using rabbit anti-ET-1, ET-3, and ETA receptor antisera. The location of Na+, K(+)-ATPase using rabbit anti-rat Na+, K(+)-ATPase was also examined. Immunoreactivity to Na+, K(+)-ATPase was seen in the marginal cells (MCs) in both species. Immunoreactivity to ET-1 and ET-3 was preferentially localized in the rough endoplasmic reticulum and cytoplasmic vesicles of the ICs and along the plasma membrane of the ICs and in the MCs apposed to the ICs. Immunoreactive sites for ETA were almost identical to those of ET-1 and ET-3. Because Na+, K(+)-ATPase activities also exist in the MCs of the mutants, it appears likely that ET, synthesized and released by the ICs, may participate in generation of EP by regulating the function of Na+, K(+)-ATPase for production of the endolymph of the MCs.

Animals↗
PubMedDate not supplied

Frozen-section autoradiography of the cochlea: evidence for differential distribution of amino acids.

A histological method is described for embedding the whole cochlea in an egg yolk medium that permits frozen sectioning in the mid-modiolar plane. Resulting tissues can be processed using standard autoradiographic techniques and stained with Nissl or silver impregnation methods. Following identical intracochlear injections of tritiated proline or leucine and frozen sectioning of embedded cochleae, differential uptake patterns within the cochlea were revealed for these amino acids. Frozen sectioning of the cochlea promises to provide an efficient means to examine specific labeling patterns within the cochlear duct for compounds suspected of contributing to cochlear function by permitting the application of multiple histological techniques including routine stains and anterograde and retrograde tracers.

Animals↗
PubMed1997

Fluid-structure interaction of the stereocilia bundle in relation to mechanotransduction.

Current hypotheses regarding mechanotransduction rely upon motion of the stereocilia relative to the apical surface of the hair cell. The viscosity of the surrounding endolymphatic fluid will, however, attenuate stereocilia motion at higher frequencies of excitation. To investigate stereocilia motion for physiologically reasonable deflections and frequencies of excitation, the fluid-structure interaction of the stereocilia bundle is considered analytically. Solutions in the frequency domain are determined for stereocilia bundle dimensions at several locations along the cochlear duct of the chinchilla. Results indicate that motion of the stereocilia is analogous to that of a low-pass filter. Comparison of these solutions with Greenwood's frequency-place map demonstrates that motion of the stereocilia bundle exists without substantial attenuation at least up to frequencies appropriate for the location of the corresponding hair cell along the cochlear duct. The variation in stereocilia morphology within the mammalian cochlea thus appears to provide a collection of low-pass mechanoreceptors, arranged in order of increasing corner frequency across the auditory spectrum.

Animals↗
PubMed1989

Role of perilymphatic fistula in sudden hearing loss: an animal model.

The electrophysiologic response of the guinea pig cochlea was monitored after sequential lesions to Reissner's membrane and the round window (RW). Action potential (AP) responses to click stimuli were recorded from the RW before and after discrete puncture-type lesions were created in the cochlear partition of the second turn. Observed decrements were typically minor, comparable to no greater than 10 dB attenuation of stimulus intensity. The RW membranes then were perforated to create perilymphatic fistulas. Further monitoring demonstrated a rapid (within 5 to 10 minutes), severe decrement in AP amplitude and latency, with complete loss of the AP within 1 hour. Control animals with RW perforations alone did not show these decrements. Correct placement of the second turn lesions was documented by histology. We conclude that discrete lesions in the cochlear duct are not reflected in the AP input-output functions unless there is a fluid leak from the RW, and thus present a possible model for idiopathic sudden hearing loss.

Action Potentials↗
PubMed1996

Distribution of beta-tectorin mRNA in the early posthatch and developing avian inner ear.

Expression of beta-tectorin mRNA in the inner ear of the embryonic and early posthatch (PH) chick was studied by in situ hybridisation. In the PH chick, beta-tectorin mRNA is expressed in the basilar papilla, in the clear and the cuboidal cells that lie either side of the papilla, in the striolar regions of the maculae, and in two small groups of cells lying adjacent to the midline in the cristae of the anterior and posterior ampullae. Expression of beta-tectorin is not observed in the lateral ampulla. In the sensory epithelia of the PH chick in which beta-tectorin mRNA is detected, expression is restricted to the supporting cell population. During development of the cochlear duct, beta-tectorin expression begins between embryonic (E) days 5 and 6. At E6, expression is observed throughout the length of the duct but is highest at the distal end. By E7, the pattern of expression is reversed and is highest at the proximal end of the cochlea, suggesting that a wave of high beta-tectorin expression passes disto-proximally along the papilla during E6 and E7. Expression of beta-tectorin mRNA is not detected in the homogene cells at any stage during the development of the cochlear duct, indicating that these cells do not synthesise one of the two major proteins of the avian tectorial membrane. The distribution of supporting cells expressing beta-tectorin mRNA in the different epithelia was compared with the distribution of sensory cells that have type B hair bundles, those with shaft links restricted to basal regions of their stereocilia, and sensory cells that have type A bundles, those with shaft links all over the entire surface of their stereocilia. Hair cells with type A hair bundles are never found in association with supporting cells expressing beta-tectorin. Although there is a correspondence in the basilar papilla and the maculae of the utriculus and lagena between the distribution of supporting cells expressing beta-tectorin mRNA and hair cells with type B bundles, this correlation does not generalise to the other sensory epithelia.

Animals↗
PubMed1992

Postnatal development of the rat organ of Corti. I. General morphology, basilar membrane, tectorial membrane and border cells.

The development of the rat organ of Corti was studied during the first postnatal weeks. The temporal and the spatial patterns of cochlear development were investigated between 4 and 24 days after birth by means of semi-thin sections at approx. ten equidistant positions along the entire cochlear duct. At all examined positions width, thickness and cross sectional area of basilar membrane, cross-sectional area of tectorial membrane, of cells of Hensen, Claudius and Boettcher and of the organ of Corti were quantitatively analyzed. The most conspicuous maturational changes occur between 8 and 12 days after birth. These are the detachment of the tectorial membrane, the first appearance of filaments within the basilar membrane, the formation of the tunnel of Corti and the opening of the inner spiral sulcus. Quantitative analysis revealed that structures of a given position along the cochlear duct do not develop synchronously. Width of the basilar membrane and cross-sectional area of the tectorial membrane are already mature at the onset of hearing (10-12 days after birth). Length, thickness and cross-sectional area of the basilar membrane as well as cross-sectional area of the organ of Corti and of the cells of Hensen, Claudius and Boettcher still develop after the onset of hearing (up to 20-24 days after birth). We suggest that basic cochlear function is established by structures which are mature before the onset of hearing. Cochlear structures which develop after the onset of hearing might be involved in this improvement during this period.

Animals↗
PubMed1980

Histopathology of cryosurgery for Meniere's disease.

The histopathologic findings in the temporal bones of two patients who underwent a cryo-otic-perotic shunt procedure are reported. Morphologic changes in the inner ear were limited to the area of cryoprobe application on the promontory. The hook region of the cochlear duct showed severe atrophy of the spiral ligament, stria vascularis, and sensorineural structures. The ampulla of the posterior semicircular canal showed fibrosis in the perilymphatic space and ruptured membranous walls. No changes were found in the rest of the vestibular labyrinth or in the facial nerve. The long-term improvement in these patients' symptoms, i.e., eight years in one and four years in the other, could only be explained on the basis that endolymph and perilymph mix across intact, nonfunctioning membranes of the cochlear duct or through, presumably antemortem, ruptures of the posterior semicircular canal ampulla.

Aged↗
PubMed1989

Another role for melanocytes: their importance for normal stria vascularis development in the mammalian inner ear.

The stria vascularis of the mammalian cochlea is composed primarily of three types of cells. Marginal cells line the lumen of the cochlear duct and are of epithelial origin. Basal cells also form a continuous layer and they may be mesodermal or derived from the neural crest. Intermediate cells are melanocyte-like cells, presumably derived from the neural crest, and are scattered between the marginal and basal cell layers. The marginal cells form extensive interdigitations with the basal and intermediate cells in the normal adult stria. The stria also contains a rich supply of blood vessels. We investigated the role of melanocytes in the stria vascularis by studying its development in a mouse mutant, viable dominant spotting, which is known to have a primary neural crest defect leading to an absence of recognisable melanocytes in the skin. Melanocytes were not found in the stria of most of the mutants examined, and from about 6 days of age onwards a reduced amount of interdigitation amongst the cells of the stria was observed. These ultrastructural anomalies were associated with strial dysfunction. In the normal adult mammal, the stria produces an endocochlear potential (EP), a resting dc potential in the endolymph in the cochlear duct, which in mice is normally about +100 mV. In our control mice, EP rose to adult levels between 6 and 16 days after birth. In most of the mutants we studied, EP was close to zero at all ages from 6 to 20 days. Melanocyte-like cells appear to be vital for normal stria vascularis development and function. They may be necessary to facilitate the normal process of interdigitation between marginal and basal cell processes at a particular stage during development, and the lack of adequate interdigitation in the mutants may be the cause of their strial dysfunction. Alternatively, melanocytes may have some direct, essential role in the production of an EP by the stria. Melanocytes may be important both for normal strial development and for the production of the EP. We believe this is the clearest demonstration yet of a role for migratory melanocytes other than their role in pigmentation.

Animals↗
PubMed1980

CM tuning can be compatible with sharply tuned receptor potentials.

There is convincing evidence that cochlear microphonics (CM) arise primarily from outer hair cells and have a frequency distribution that is much broader than that measured in inner hair cells by Russel and Sellick [6,7]. The broad tuning results from the fact that CM generated at each location decays exponentially along the cochlear duct. This implies that the sources of CM (the outer hair cells) must be more sharply tuned than the CM itself. We modeled approximately the tuning of outer hairs on the assumption that it is proportional to the shear motion between the tectorial membrane and the reticular lamina. At each frequency the spatial distribution of CM is computed by convolving the shear distribution with an exponential decay function. The frequency dependence of CM at a given location can then be found by making a cut through a family of such frequency curves. The resulting CM tuning is much flatter than that of the modeled outer hair-cell receptor potentials and roughly parallels basilar-membrane tuning below the best frequency. Above the best frequency, the theoretical curves show a frequency-dependent plateau similar to that found in physiological CM measurements.

Basilar Membrane↗
PubMed2000

Essential role of BETA2/NeuroD1 in development of the vestibular and auditory systems.

BETA2/NeuroD1 is a bHLH transcription factor that is expressed during development in the mammalian pancreas and in many locations in the central and peripheral nervous systems. During inner ear ontogenesis, it is present in both sensory ganglion neurons and sensory epithelia. Although studies have shown that BETA2/NeuroD1 is important in the development of the hippocampal dentate gyrus and the cerebellum, its functions in the peripheral nervous system and in particular in the inner ear are unclear. Mice carrying a BETA2/NeuroD1 null mutation exhibit behavioral abnormalities suggestive of an inner ear defect, including lack of responsiveness to sound, hyperactivity, head tilting, and circling. Here we show that these defects can be explained by a severe reduction of sensory neurons in the cochlear-vestibular ganglion (CVG). A developmental study of CVG formation in the null demonstrates that BETA2/NeuroD1 does not play a primary role in the proliferation of neuroblast precursors or in their decision to become neuroblasts. Instead, the reduction in CVG neuron number is caused by a combination both of delayed or defective delamination of CVG neuroblast precursors from the otic vesicle epithelium and of enhanced apoptosis both in the otic epithelium and among those neurons that do delaminate to form the CVG. There are also defects in differentiation and patterning of the cochlear duct and sensory epithelium and loss of the dorsal cochlear nucleus. BETA2/NeuroD1 is, thus, the first gene to be shown to regulate neuronal and sensory cell development in both the cochlear and vestibular systems.

Acoustic Stimulation↗
PubMed2003

Preoperative high resolution CT and MR imaging in cochlear implantation.

INTRODUCTION: Accurate preoperative imaging of the temporal bone in patients receiving cochlear implants is important. High resolution computed tomography (HRCT) and magnetic resonance (MR) imaging are the 2 preoperative imaging modalities that provide critical information on abnormalities of the otic capsule, pneumatisation of the mastoid, middle ear abnormalities, cochlear ducts patency and presence of cochlear nerve. MATERIALS AND METHODS: The HRCT and MR imaging in 46 cochlear implant patients in our department were reviewed. RESULTS: Majority of our patients [34 patients (73.9%)] showed normal HRCT of the temporal bone; 5 (10.9%) patients had labyrinthitis ossificans, 2 (4.3%) had Mondini's abnormality and 2 (4.3%) had middle ear effusion. One patient each had high jugular bulb, hypoplasia of the internal auditory canal and single cochlear cavity, respectively. CONCLUSION: The above findings contribute significantly to our surgical decisions regarding candidacy for surgery, side selection and surgical technique in cochlear implantation.

Cochlear Diseases↗
PubMed1994

[Observation of cochlear microcirculation in experimental endolymphatic hydrops].

30 guinea pigs were made as a model of endolymphatic hydrops by obliteration of endolymphatic sac and duct. Cochlear microcirculation of the lateral wall in the third turn was observed and recorded. The diameters and velocities of the vessels were analysed in IBAS image system. The stria vascular vessels and spiral ligament vessels were analysed respectively. The data showed: 1. 1, 2 and 3 months after operation, the diameter of SLV averaely decreased 0.80 microns, 0.87 microns, 1.21 microns (P < 0.05) respectively and velocity decreased 100.8 microns/s, 141.0 microns/s, 136.0 microns/s (P < 0.05) respectively. 2. The diameter of SVV dilated 3 months after operation. With the elapse of time, SVV had a dilation tendency. These indicated that hydrops effect different changes in SLV and SVV. The overpressure of endolymphatic fluid may be the possible cause of changes in SVV and SLV.

Animals↗
PubMed1975

[Studies on the patency of the reuniting duct (author's transl)].

Using human temporal bone specimens the patency of the reuniting duct was studied. The endolymph was marked by various dyes and fluorescent substance, during the application the cochlea remained closed. It is shown that the substances in the endolymph flow from the first turn of the cochlear duct via the reuniting duct into the saccule. The patency of the reuniting duct is confirmed by histological serial sections, and the clinical significance of these findings is discussed.

Adult↗
PubMed2007

Dan is required for normal morphogenesis and patterning in the developing chick inner ear.

During vertebrate inner ear development, compartmentalization of the auditory and vestibular apparatuses along two axes depends on the patterning of transcription factors expressed in a region-specific manner. Although most of the patterning is regulated by extrinsic signals, it is not known how Nkx5.1 and Msx1 are patterned. We focus on Dan, the founding member of the Cerberus/Dan gene family that encodes BMP antagonists, and describe its function in morphogenesis and patterning. First, we confirmed that Dan is expressed in the dorso-medial region of the otic vesicle that corresponds to the presumptive endolymphatic duct and sac (ed/es). Second, we used siRNA knockdown to demonstrate that depletion of Dan induced both a severe reduction in the size of the ed/es and moderate deformities of the semicircular canals and cochlear duct. Depletion of Dan also caused suppression of Nkx5.1 in the dorso-lateral region, suppression of Msx1 in the dorso-medial region, and ectopic induction of Nkx5.1 and Msx1 in the ventro-medial region. Most of these phenotypes also appeared following misexpression of the constitutively active form of BMP receptor type Ib. Thus, Dan is required for the normal morphogenesis of the inner ear and, by inhibiting BMP signaling, for the patterning of the transcription factors Nkx5.1 and Msx1.

Animals↗
PubMed1978

Endolymphatic leakage in case of acute loss of cochlear microphonics.

Rapid loss of cochlear microphonics in guinea-pigs previously exposed to high-energy impulse noise was shown to be related to the breakdown of the endolymphatic boundary. The cochlear duct was rendered leaky by deterioration of the reticular membrane, and damage of sensory and supporting cells.

Animals↗
PubMed1987

Longitudinal flow of endolymph measured by distribution of tetraethylammonium and choline in scala media.

Longitudinal endolymph flow rate in the guinea pig cochlea was measured by determining the rate of migration of extrinsic ions, tetraethylammonium chloride (TEA) or choline, with a potassium sensitive ion-selective microelectrode (ISM). Low concentrations of iontophoretically injected TEA were detected with the ISM at various distances from the injection electrode. The results were variable when the ISM was used to record spread of TEA from turn II to turn I and vice versa. However, consistent data were obtained when the TEA spread was measured at different electrode separations (0.2, 0.5, 0.7 mm) within turn II. Electrode locations were systematically exchanged without changing their distance, i.e. the ISM electrode was placed basally or apically with respect to the TEA electrode. Comparison of data with a model, which combines the bulk diffusion of TEA and the flow of endolymph, is consistent with a rate of endolymph flow in turn II of about 0.2 mm/min, apex to base. A similar value was also obtained with the iontophoretic injection of choline. The endolymph flow rate may be different in turn I as indicated by measurements of compound action potential (CAP) changes. However, the results of experiments when TEA spread is measured at large distances must be interpreted cautiously because TEA may enter cellular walls of the cochlear duct and alternative routes of transport may be involved.

Action Potentials↗
PubMed1991

The use of intraoperative electrocochleography in Meniére's surgery.

Intra-operative electrocochleography was undertaken during surgery for Meniére's disease. It was found that the electrocochleogram (ECoG) provided a stable measure which accurately reflected changes within the inner ear during surgery. During salt osmosis of the round window, a rapid change in the summating potential versus action potential ratio (SP/AP) occurred which showed when the endolymphatic hydrops (ELH) had been altered. During a modified cochleostomy procedure, the ECoG showed when the cochlear duct had been ruptured. Forty ears were monitored during endolymphatic sac surgery. Twenty-five of these ears showed stable ECochG which did not alter at any time during the procedure; however, 8 of these ears showed normal SP/AP ratios during the surgery despite having been abnormal in the week prior to surgery. The SP/AP ratio was reduced in 8 ears, increased in 3 ears and showed other changes which were probably due to unstable electrode positioning in 4 ears. It was concluded that endolymphatic sac or duct surgery altered the inner ear physiology in a significant number of ears affected by endolymphatic hydrops.

Acoustic Stimulation↗
PubMed2001

Spiral ligament pathology: a major aspect of age-related cochlear degeneration in C57BL/6 mice.

Data from systematic, light microscopic examination of cochlear histopathology in an age-graded series of C57BL/6 mice (1.5-15 months) were compared with threshold elevations (measured by auditory brain stem response) to elucidate the functionally important structural changes underlying age-related hearing loss in this inbred strain. In addition to quantifying the degree and extent of hair cell and neuronal loss, all structures of the cochlear duct were qualitatively evaluated and any degenerative changes were quantified. Hair cell and neuronal loss patterns suggested two degenerative processes. In the basal half of the cochlea, inner and outer hair cell loss proceeded from base to apex with increasing age, and loss of cochlear neurons was consistent with degeneration occurring secondary to inner hair cell loss. In the apical half of the cochlea with advancing age, there was selective loss of outer hair cells which increased from the middle to the extreme apex. A similar gradient of ganglion cell loss was noted, characterized by widespread somatic aggregation and demyelination. In addition to these changes in hair cells and their innervation, there was widespread degeneration of fibrocytes in the spiral ligament, especially among the type IV cell class. The cell loss in the ligament preceded the loss of hair cells and/or neurons in both space and time suggesting that fibrocyte pathology may be a primary cause of the hearing loss and ultimate sensory cell degeneration in this mouse strain.

Aging↗