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PubMed1982

Scanning electron microscopy of the developing chick tegmentum vasculosum.

The developing tegmentum vasculosum in the chick cochlea was analyzed by means of scanning electron microscopy. Chick embryos representative of Hamilton and Hamburger stages 35, 37, 41 and 45 were examined in order to study the morphogenesis of the "lamellae" (Knowlton, 1967), or folds, of the tegmentum vasculosum and the differentiation of the light and dark cell luminal surfaces. At stage 35 low folds are distinguishable in the proximal segment of the cochlear duct only. In subsequent stages a complex series of lamellae develop throughout the entire tegmentum vasculosum in conjunction with a developing capillary network. Dark cell luminal surfaces are clearly distinguishable from the adjacent light cell surfaces by stage 37. Stages 41 and 45 show a progressive increase in dark cell surface area as well as a considerable increase in the number and size (height and diameter) of surface microvilli. The avian tegmentum vasculosum is thought to be the functional equivalent of the stria vascularis in mammals. Analysis of the morphogenesis of the tegmentum vasculosum is vital to a thorough understanding of its functional relationships with the maturing endolymphatic fluid ionic composition and endocochlear potential.

Animals↗
PubMed1996

Anatomical correlates of the passive properties underlying the developmental shift in the frequency map of the mammalian cochlea.

As the cochlea develops, the cells in the basal cochlea become sensitive to progressively higher frequencies. To identify features of cochlear morphology that may underlie the place code shift, measurements of infant and adult gerbil cochleas were made at both the light and electron microscopic levels. The measurements included areas of the cochlear duct, basilar membrane, and organ of Corti, height and width of the basilar membrane, thickness of the tympanic cover layer, thickness of the upper and lower basilar membrane fiber bands, and optical density of the basilar membrane. The results indicated that basilar membrane dimensions do not change as the place code shifts and that regions that code for the roughly the same frequency (e.g., approximately 11.2 kHz) at different ages can have basilar membranes of very different dimensions. In contrast, the size of the organ of Corti and the thickness of fiber bands inside the basilar membrane do change in ways consistent with the shift in the frequency map.

Acoustic Stimulation↗
PubMed1998

Dye-coupling of melanocytes with endothelial cells and pericytes in the cochlea of gerbils.

Intercellular connections via gap junctions in the stria vascularis, which constitutes the lateral wall of the cochlear duct, were investigated by the Lucifer yellow microinjection method with the aid of a confocal laser microscope. The dye injected into an intermediate cell (melanocyte) diffused into capillary endothelial cells and pericytes as well as other intermediate cells, basal cells, and fibrocytes in the spiral ligament; whereas the dye injected into a marginal cell (epithelial cell) was confined to the injected cell. The observation of dye-coupling between intermediate cells and endothelial cells and pericytes makes likely the possibility that these cells work together to play a role in the specific function of the stria vascularis (i.e., production of the positive endocochlear potential and the endolymph) and adds endothelial cells and pericytes to the current "two-cell model" of the stria vascularis.

Animals↗
PubMed1991

Positive and negative DC potential in the vestibular system of pigeons.

DC potential in the ampulla of pigeons was studied using a glass microelectrode. After the extirpation of the cochlear duct no change in the DC potential was found. A reduction of the negative DC potential due to anoxia (anoxia-sensitive negative potential, ASNP) was found in the ethacrynic acid (EA)-intoxicated ear, while this finding was minimal or absent in the ouabain-intoxicated ear. The perilymphatic perfusion with K(+)-substituted Ringer's solution resulted in a rapid reduction of the negativity due to EA or ouabain. These findings indicate that the positive DC potential in the ampulla seems to be produced by itself and K+ diffusion potential is the main source of negative DC potential. ASNP may be the unique potential in the EA-intoxicated ear in warm-blooded animals.

Animals↗
PubMed1996

Standard atlas of the gross anatomy of the developing inner ear of the chicken.

During development, the chicken inner ear undergoes a series of morphological changes which give rise to the various structures found in the adult, including the mature semicircular canals, utricle, saccule, cochlear duct, endolymphatic duct and sac, and neurons of the eighth cranial nerve ganglion. Beginning as a hollow epithelial sphere, the inner ear is sculpted into this complex labyrinth of fluid-filled ducts punctuated by their associated sensory end organs. In this report, the three-dimensional complexity of the developing inner ear of the chicken embryo is documented in the form of a standard atlas. The protocol involved fixation, dehydration, and clearing of embryonic heads harvested at daily intervals, followed by injection of an opaque dye (enamel paint suspension) into the fluid ducts of the inner ear. The position of the ear is shown relative to surface landmarks at seven different stages of development, ranging from embryonic day 5 (E5) to E18. Also shown are higher-power photomicrographs of the inner ear in isolation taken at daily intervals at E3-E17 and viewed from two orthogonal positions. Three orthogonal views are shown at 6-hour intervals during the critical stages of semicircular canal formation (E6-E7). Quantitative measurements of the linear dimensions of the inner ear (dorsoventral, anteroposterior, and mediolateral axes) as a function of time indicate a linear increase in the growth of the ear from E3 through E18. This atlas should prove valuable for evaluating mutant phenotypes in inner ear morphogenesis following gene perturbation experiments in the chicken.

Anatomy, Artistic↗
PubMed2005

Functional consequences of polyamine synthesis inhibition by L-alpha-difluoromethylornithine (DFMO): cellular mechanisms for DFMO-mediated ototoxicity.

L-Alpha-difluoromethylornithine (DFMO) is a chemopreventive agent for colon cancer in clinical trials. Yet, the drug produces an across-frequency elevation of the hearing threshold, suggesting that DFMO may affect a common trait along the cochlear spiral. The mechanism for the ototoxic effects of DFMO remains uncertain. The cochlear duct is exclusively endowed with endocochlear potential (EP). EP is a requisite for normal sound transduction, as it provides the electromotive force that determines the magnitude of the receptor potential of hair cells. EP is generated by the high throughput of K(+) across cells of the stria vascularis, conferred partly by the activity of Kir4.1 channels. Here, we show that the ototoxicity of DFMO may be mediated by alteration of the inward rectification of Kir4.1 channels, resulting in a marked reduction in EP. These findings are surprising given that the present model for EP generation asserts that Kir4.1 confers the outflow of K(+) in the stria vascularis. We have proposed an alternative model. These findings should also enable the rational design of new pharmaceuticals devoid of the untoward effect of DFMO.

Amino Acid Sequence↗
PubMed1993

Effect of lymph composition on an in vitro preparation of the alligator lizard cochlea.

The effects of different artificial lymphs on the cochlear duct of the alligator lizard were studied in an in vitro preparation. The duct was dissected and cemented to the glass floor of a chamber that had been filled with an artificial lymph. The vestibular membrane was removed and latex beads (1-5 microns in diameter) were allowed to settle on the endolymphatic surface of the duct. During perfusion with an artificial lymph solution, the positions of beads were measured and video images of the duct were obtained. Artificial lymphs were isosmotic and included artificial endolymph (AE), artificial perilymph (AP), Leibovitz's L-15 culture medium, an AE solution whose calcium concentration was the same as that of AP, and AE and AP solutions in which gluconate was substituted for chloride ions. Results obtained in AE were consistently different from those in other lymphs. The displacements of beads, the projected area of the papilla, the occurrence of blebs, and direct observation of cells in the duct all indicated that the tissue swelled in AE (with or without 2 mmol/l Ca) but showed no consistent shrinking or swelling in any of the other artificial lymphs. Thus for the solutions we used, the presence of both potassium and chloride was required to elicit the swelling response to isosmotic artificial lymphs. There were some regional differences in the swelling response: the swelling of the endolymphatic surface of the tissue in a direction orthogonal to the basilar membrane surface was smaller on the free-standing region of the basilar papilla than either on the tectorial membrane or on the hyaline epithelial cells. The preparation was osmotically stable in AP and in both AE and AP solutions in which gluconate was substituted for chloride ions. After exposure to these solutions for as much as 300 min, the preparation showed no gross signs of deterioration visible with the light microscope, and continued to exhibit a highly specific osmotic response to the composition of the bathing medium.

Animals↗
PubMed1987

Ultrastructural and electrophysiological maturation of the chick tegmentum vasculosum.

We have examined the ultrastructural and electrophysiological events associated with the embryonic development of the tegmentum vasculosum, the ion-transporting epithelium in the chick cochlear duct. The cytodifferentiation of the light and dark cells in the epithelium from embryonic day 6 through post-hatching day 7 was studied with transmission electron microscopy. The predominant ultrastructural change in the developing tegmentum vasculosum was the elaboration of the complex basolateral infoldings on the dark cells from embryonic day 11 through post-hatching day 7. The relationship between the development of the endocochlear transepithelial electrical potential difference (PD) and the cytodifferentiation of the tegmentum vasculosum was examined with in vitro studies. Microelectrode impalements of the scala media showed that the positive endocochlear PD was first detectable on embryonic day 20 but did not reach a mature value of +16 mV until post-hatching day 7. Maturation of the endocochlear PD paralleled the time during which the dark cells in the tegmentum vasculosum displayed the most extensive increase in basolateral infoldings. This correlation suggests that the development of the endocochlear PD may result from an increase in the number of Na+-K+ pump sites located on the basolateral infoldings of the dark cells.

Animals↗
PubMed1999

K+ and Na+ absorption by outer sulcus epithelial cells.

Transduction of sound into nerve impulses by hair cells depends on modulation of a current carried primarily by K+ into the cell across apical transduction channels that are permeable to cations. The cochlear function thus depends on active secretion of K+ accompanied by absorption of Na+ by epithelial cells enclosing the cochlear duct. The para-sensory cells which participate in the absorption of Na+ (down to the uniquely low level of 1 mM) were previously unidentified and the existence of a para-sensory pathway which actively absorbs K+ was previously unknown. A relative short circuit current (Isc,probe, measured as the extracellular current density with a vibrating electrode) was directed into the apical side of the outer sulcus epithelium, decreased by ouabain (1 mM), an inhibitor of Na+, K(+)-ATPase, and found to depend on bath Na+ and K+ but on neither Ca2+ nor Cl-. Isc,probe was shown to be an active current by its sensitivity to ouabain. On-cell patch clamp recordings of the apical membrane of outer sulcus cells displayed a channel activity, which carried inward currents under conditions identical to those used to measure Isc,probe. Both Isc,probe and non-selective cation channels (27.4+/-0.6 ps, n = 22) in excised outside-out patches from the apical membrane were inhibited by Gd3+ (1 mM). Ics,prob was also inhibited by 5 mM lidocaine, 1 mM quinine and 500 microM amiloride but not by 10 microM amiloride. These results demonstrate that outer sulcus epithelial cells contribute to the homeostasis of endolymph by actively absorbing Na+ and K+. An entry pathway in the apical membrane was shown to be through non-selective cation channels that were sensitive to Gd3+.

Absorption↗
PubMedDate not supplied

Sudden deafness: histopathologic correlation in temporal bone.

The histopathological study of two cases of sudden deafness is presented. The temporal bones showed cochleosaccular abnormality. The most striking pathological changes were collapse of the organ of Corti, atrophy of the tectorial membrane, atrophy of the stria vascularis, decrease in the number of the cochlear nerves, collapse of the saccular membrane and partial absence of the sensory epithelial layer in the saccular macula. These changes are quite similar in type to those occurring in labyrinthitis of known viral etiology and to those in previously reported cases of sudden deafness which were assumed to be of viral origin. This evidence suggests that a viral infection was the most probable etiology of sudden deafness in these ears. In addition, unusual findings of endolymphatic hydrops limited to the extreme basal end of the cochlear duct were found in Case 1. A patent cochlear aqueduct and circumscribed perilymphatic labyrinthine ossification in the superior seimicircular canal were also observed. With these histopathological findings, the possibility of viral infection via the meninges as well as via the hematogenous route into the inner ear is proposed.

Cochlea↗
PubMedDate not supplied

Carcinomatous encephalomyelitis with auditory and vestibular manifestations.

A clinical and pathological study of carcinomatous encephalomyelitis is presented. Attention is drawn to the various types of nonmetastatic paraneoplastic syndromes and their particular association with oat cell carcinoma of the lung. The feature of special interest in this study is the onset with otologic symptoms, sudden deafness in the left ear and vertigo, at a time when the neoplastic basis for the disease was not clinically evident. The most striking change in the left temporal bone is the almost total loss of cochlear neurons in Rosenthal's canal and degeneration of both divisions of the vestibular nerve. The organ of Corti and stria vascularis are normal throughout the cochlear duct. The vestibular sense organs are normal. The left cochlear nucleus is devoid of neurons, this neuronal loss is accompanied by a well developed astrocytic and microglial response similar to that in the medulla and spinal cord. This represents a carcinomatous sensory neuropathy involving the left VIII nerve with simultaneous involvement of the left cochlear nucleus. The pathogenesis of this condition still defies explanation, but there are some insights in the autoimmune sector.

Carcinoma, Small Cell↗
PubMed1999

The cochlear ganglion in human embryos of developmental stages 18 and 19.

The cochlear ganglion was investigated in serially sectioned human embryos at developmental stages 18 and 19 (44-46 postovulatory days). During this period the cochlear ganglion is separated from the vestibular ganglion, and it is adjacent to the cochlear duct. In embryos of investigated stages fibers of the cochlear ganglion enter the nuclei in the brain.

Embryonic and Fetal Development↗
PubMed1991

High-resolution magnetic resonance imaging of the human temporal bone.

A magnetic resonance imaging (MRI) system (Hitachi, Naka, Japan) with a superconductive magnet running at 2.11 T was used to obtain 2-mm-thick slices of fixed, decalcified and celloidin-embedded human temporal bone. The temporal bone was then sectioned and stained for routine histological evaluation. Both the MR images and the histological sections were in the mid-modiolar slice plane, and comparable images and sections were analyzed to confirm the identity of the inner-ear structures visualized on the MR images. The cochlear duct, scala tympani, scala vestibuli and basement membrane of all three cochlear turns were clearly imaged on MRI. In addition, the vestibule and three semicircular ducts were also clearly seen. This study raises the possibility of some day using MRI for the diagnosis of inner-ear diseases.

Basement Membrane↗
PubMed1992

Inner ear malformations induced by isotretinoin in hamster fetuses.

Inner ear malformations induced in anotic hamster fetuses following maternal treatment with 50 mg/kg isotretinoin (13-cis-retinoic acid) on gestational day 8 are described. Computer-assisted three dimensional reconstruction was used. Two general types of defective vestibulocochlear development were seen. Defects were bilateral and correlated with extent of middle ear deficiency and severity of mandibular defects. In the more severely affected fetuses the inner ear was limited to an epithelial sac with occasional small projections, no apparent innervation and a correspondingly reduced otic capsule. In most of the fetuses examined the inner ear was less severely affected and was characterized by a reduction in the number of semicircular ducts and alterations in the size and shape of the cochlear duct. These defects are similar to those seen in a child with the isotretinoin embryopathy. Pathogenesis may result from a direct effect on otic epithelium or from faulty inductive interactions with the rhombencephalon or with periotic neural crest cells.

Abnormalities, Drug-Induced↗
PubMed1999

Notch signalling pathway mediates hair cell development in mammalian cochlea.

The mammalian cochlea contains an invariant mosaic of sensory hair cells and non-sensory supporting cells reminiscent of invertebrate structures such as the compound eye in Drosophila melanogaster. The sensory epithelium in the mammalian cochlea (the organ of Corti) contains four rows of mechanosensory hair cells: a single row of inner hair cells and three rows of outer hair cells. Each hair cell is separated from the next by an interceding supporting cell, forming an invariant and alternating mosaic that extends the length of the cochlear duct. Previous results suggest that determination of cell fates in the cochlear mosaic occurs via inhibitory interactions between adjacent progenitor cells (lateral inhibition). Cells populating the cochlear epithelium appear to constitute a developmental equivalence group in which developing hair cells suppress differentiation in their immediate neighbours through lateral inhibition. These interactions may be mediated through the Notch signalling pathway, a molecular mechanism that is involved in the determination of a variety of cell fates. Here we show that genes encoding the receptor protein Notch1 and its ligand, Jagged 2, are expressed in alternating cell types in the developing sensory epithelium. In addition, genetic deletion of Jag2 results in a significant increase in sensory hair cells, presumably as a result of a decrease in Notch activation. These results provide direct evidence for Notch-mediated lateral inhibition in a mammalian system and support a role for Notch in the development of the cochlear mosaic.

Animals↗
PubMed1989

Tolerance of membranous inner ear structures to pressure.

Pressure tolerance of round and oval labyrinthine windows and a cochlear segment represented by a part of the cochlear duct were investigated in experiments on cadaveric human temporal bones. The cochlear segment is less resistant than both the windows. Inner ear spaces are protected from pressure changes in the surroundings of the temporal bone by a system of narrow and comparatively long connections and some of them include also other structures strengthening the protective function (the valve described near the place where the cochlear aqueduct leads to scala tympani). Experiments with guinea pigs showed significance of inner ear integrity in protection from pressure changes. Tolerance of both windows was significantly higher in live animals than in cadaveric guinea pig bullae. Pressure tolerance of the windows was in turn higher in bullae than in isolated inner ear labyrinth. Conclusions were arrived at on the basis of the above facts that the inner ear is considerably resistant to pressure changes around it under normal circumstances. Ruptures in its parts appear only under special conditions and a number of factors participate in them. Window ruptures accompany most frequently injuries in other inner ear structures to which different degrees of hearing loss correspond. An isolated injury of windows is, from this viewpoint, rare even though it can be found and treated surgically best.

Animals↗
PubMed1987

Immunoreactivity to calcitonin gene-related peptide in the superior olivary complex and cochlea of cat and rat.

In both cat and rat, the cells of origin, axons, and terminals of the lateral olivocochlear system exhibit immunoreactivity to antisera to calcitonin gene-related peptide (CGRP). In the cat, immunoreactive neurons in the brainstem are located in the hilus of the lateral superior olivary nucleus and around its margins. In the rat, immunoreactive neurons are located within the lateral superior olivary nucleus proper. In both species, immunoreactivity in the cochlear duct is limited to the region beneath the inner hair cells. Immunoreactive axons in the cochlear nucleus could not be traced to their source but may arise as collaterals of the lateral olivocochlear system. No other components of the brainstem auditory system react to any extent with the antisera.

Animals↗
PubMed1999

Expression of mouse semaphorin H mRNA in the inner ear of mouse fetuses.

Semaphorins constitute a large family of secreted and cell-surfaced proteins that appear to function as chemorepellents to guide axons. We examined the expression pattern of M-semaH mRNA in the inner ear of mouse fetuses by in situ hybridization histochemistry. M-semaH mRNA expression was high in the endolymphatic sac involved in endolymph homeostasis. It was also high in the semicircular ducts except for the crista ampullaris, whereas no expression was detected in the epithelium of cochlear ducts.

Animals↗