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PubMed1986

Long-term intracochlear implantation in man.

Whether long-term intracochlear implantation and direct electrical stimulation of the acoustic nerve will induce intracochlear bone growth or cause further degeneration of a severely compromised auditory system is an important clinical consideration. Thin-section CT evaluations of the cochleas of six subjects who have used their cochlear implant devices on a daily basis for 3 or more years demonstrated no evidence of osteoneogenesis of the cochlea in the vicinity of the active electrode. No corrosion of the electrode or insulation material was noted on electron microscopy of an explanted electrode system. Electrical threshold and dynamic range measurements have remained stable or even improved during the period of observation. Performance measures using a variety of audiologic tests and speech-tracking scores have demonstrated stability of performance.

Adult↗
PubMed1991

Labyrinthitis ossificans: histopathologic consideration for cochlear implantation.

Labyrinthitis ossificans may be a hindrance to cochlear implantation by making electrode insertion difficult. We performed a histopathologic study of 24 temporal bones with labyrinthitis ossificans from multiple causes. The organ of Corti was graphically reconstructed and the degree of obstruction was estimated for each millimeter of the cochlea. Correlations were calculated between the degree of new bone formation and the cause, patient's age and sex, and time from the original temporal bone insult. Our results demonstrate that complete cochlear ossification is rare. The scala tympani in the basal turn of the cochlea is the most frequent area of ossification, regardless of the cause of the labyrinthitis ossificans. Meningogenic labyrinthitis, usually a childhood disease, was associated with the greatest amount of ossification. When ossification resulted from tympanogenic labyrinthitis, the scala tympani was completely ossified near the round window niche in all temporal bones. Neo-ossification of the basal turn associated with otosclerosis was limited to the proximal 6 mm of the scala tympani in all cases. Three temporal bones had a patent round window niche and basal turn, but significant apical and middle-turn ossification. Peripheral sensorineural elements were severely degenerated in the region of the ossification in all specimens, and spiral ganglion cell counts were decreased.

Adolescent↗
PubMed1995

The prolactin receptor in the fetal rat: cellular localization of messenger ribonucleic acid, immunoreactive protein, and ligand-binding activity and induction of expression in late gestation.

The cellular distribution and developmental expression of the PRL receptor (PRLR) in the late gestational fetal rat were examined by in situ hybridization, immunohistochemistry, and radioligand binding. Antisense and sense strand RNA probes encoding the long and short isoforms of the rat PRLR were hybridized to tissue sections under stringent conditions. Messenger RNA (mRNA) encoding the two isoforms of the receptor was expressed widely in tissues derived from all three germ layers; these included various tissues not known previously to contain lactogenic receptors, such as the olfactory neuronal epithelium and olfactory bulb, trigeminal and dorsal root ganglia, cochlear duct, brown adipose tissue, submandibular glands, whisker follicles, tooth primordia, and proliferative and maturing chondrocytes of developing bones. Prominent expression of PRLR mRNA was also detected in the fetal adrenal cortex, gastrointestinal and bronchial mucosae, renal tubular epithelia, choroid plexus, thymus, liver, pancreas, and epidermis. Immunohistochemical studies using monoclonal anti-PRLR antibodies demonstrated that the distribution of PRLR immunoreactivity was similar to that of PRLR mRNA, suggesting that the PRLR mRNA is translated to receptor protein in the fetus in vivo. The encoding of functional PRL receptor proteins by fetal PRLR mRNA was revealed by the presence of specific rat placental lactogen II-binding sites in fetal adrenal cortex, renal tubules, small intestinal villi, pancreatic ductules and islets, hepatic parenchymal cells, choroid plexus ependymal cells, and microsomal fractions of fetal lung and thymus. Levels of expression of PRLR mRNA and protein increased between days 17.5 and 20.5 of gestation in a number of fetal tissues, including the adrenal, pancreas, small intestine, pituitary, thymus, liver, and submandibular gland. The widespread expression of the PRLR in the fetal rat and the induction of receptor expression in late gestation suggest novel roles for the lactogenic hormones in fetal and neonatal development.

Adipose Tissue↗
PubMed2004

Suppression of neural fate and control of inner ear morphogenesis by Tbx1.

Inner ear sensory organs and VIIIth cranial ganglion neurons of the auditory/vestibular pathway derive from an ectodermal placode that invaginates to form an otocyst. We show that in the mouse otocyst epithelium, Tbx1 suppresses neurogenin 1-mediated neural fate determination and is required for induction or proper patterning of gene expression related to sensory organ morphogenesis (Otx1 and Bmp4, respectively). Tbx1 loss-of-function causes dysregulation of neural competence in otocyst regions linked to the formation of either mechanosensory or structural sensory organ epithelia. Subsequently, VIIIth ganglion rudiment form is duplicated posteriorly, while the inner ear is hypoplastic and shows neither a vestibular apparatus nor a coiled cochlear duct. We propose that Tbx1 acts in the manner of a selector gene to control neural and sensory organ fate specification in the otocyst.

Animals↗
PubMed1998

Inner ear and maternal reproductive defects in mice lacking the Hmx3 homeobox gene.

The Hmx homeobox gene family is of ancient origin, being present in species as diverse as Drosophila, sea urchin and mammals. The three members of the murine Hmx family, designated Hmx1, Hmx2 and Hmx3, are expressed in tissues that suggest a common functional role in sensory organ development and pregnancy. Hmx3 is one of the earliest markers for vestibular inner ear development during embryogenesis, and is also upregulated in the myometrium of the uterus during pregnancy. Targeted disruption of the Hmx3 gene results in mice with abnormal circling behavior and severe vestibular defects owing to a depletion of sensory cells in the saccule and utricle, and a complete loss of the horizontal semicircular canal crista, as well as a fusion of the utricle and saccule endolymphatic spaces into a common utriculosaccular cavity. Both the sensory and secretory epithelium of the cochlear duct appear normal in the Hmx3 null animals. The majority of Hmx3 null females have a reproductive defect. Hmx3 null females can be fertilized and their embryos undergo normal preimplantation development, but the embryos fail to implant successfully in the Hmx3 null uterus and subsequently die. Transfer of preimplantation embryos from mutant Hmx3 uterine horns to wild-type pseudopregnant females results in successful pregnancy, indicating a failure of the Hmx3 null uterus to support normal post-implantation pregnancy. Molecular analysis revealed the perturbation of Hmx, Wnt and LIF gene expression in the Hmx3 null uterus. Interestingly, expression of both Hmx1 and Hmx2 is downregulated in the Hmx3 null uterus, suggesting a hierarchical relationship among the three Hmx genes during pregnancy.

Alleles↗
PubMed2005

Tympanal travelling waves in migratory locusts.

Hearing animals, including many vertebrates and insects, have the capacity to analyse the frequency composition of sound. In mammals, frequency analysis relies on the mechanical response of the basilar membrane in the cochlear duct. These vibrations take the form of a slow vibrational wave propagating along the basilar membrane from base to apex. Known as von Békésy's travelling wave, this wave displays amplitude maxima at frequency-specific locations along the basilar membrane, providing a spatial map of the frequency of sound--a tonotopy. In their structure, insect auditory systems may not be as sophisticated at those of mammals, yet some are known to perform sound frequency analysis. In the desert locust, this analysis arises from the mechanical properties of the tympanal membrane. In effect, the spatial decomposition of incident sound into discrete frequency components involves a tympanal travelling wave that funnels mechanical energy to specific tympanal locations, where distinct groups of mechanoreceptor neurones project. Notably, observed tympanal deflections differ from those predicted by drum theory. Although phenomenologically equivalent, von Békésy's and the locust's waves differ in their physical implementation. von Békésy's wave is born from interactions between the anisotropic basilar membrane and the surrounding incompressible fluids, whereas the locust's wave rides on an anisotropic membrane suspended in air. The locust's ear thus combines in one structure the functions of sound reception and frequency decomposition.

Acoustic Stimulation↗
PubMed1976

Human cochlear changes in noise induced hearing loss.

The temporal bone histopathological findings in 14 ears with noise induced hearing loss are presented. The morphological changes consist mainly of hair cell loss, which is more severe in the 9 mm to 13 mm region of the cochlear duct. Within the area of maximum hair cell loss, there is a greater loss of outer hair cells than of inner hair cells. There is a good correlation between the permanent auditory threshold shifts and the spatial location of the sensory lesion according to the anatomical frequency scale.

Auditory Threshold↗
PubMed1979

New patterns in genetic and congenital otonephropathies.

In a series of chronic renal and congenitally deaf patients 24 were identified as having inborn renal and otologic disease. Sixteen patients, representing 14 families, had genetic disorders. Only two had the features of Alport's syndrome. The patients were classified as follows: 1) Probable Alport's--2 patients (1 family); 2) Atypical hereditary nephritis and sensorineural hearing loss--7 patients; 3) Renal and inner ear anomalies--1 patient; 4) Renal, inner ear and multiple anomalies--4 patients. The temporal bone pathology in one case showed primary neural atrophy and a mild Mondini malformation. In another a Scheibe defect and unusual calcific structures were found in the cochlear duct. 5) Renal, external or middle ear and multiple anomalies--6 patients (5 families); 6 Renal, middle and inner ear anomalies and multiple anomalies--2 patients. A temporal bone obtained from one case showed combined middle and inner ear defects. In the other, who had a chromosome defect, predominantly middle ear anomalies were found. 7) Nephrotic syndrome and congenital hearing loss--1 patient; 8) Unclassified--1 patient. Some cases represent entities apparently not previously described. Probably most interesting is the delineation of hereditary nephritis and deafness distinct from Alport's disease.

Abnormalities, Multiple↗
PubMed1985

Furosemide ototoxicity: clinical and experimental aspects.

Furosemide is an ototoxic diuretic. Furosemide injection is followed by a rapid, but reversible decrease of the endocochlear potential and eighth nerve action potential with a more gradual decrease of the endolymph potassium concentration. In contrast to the reversible effects of furosemide alone on the cochlea, the combination of kanamycin with furosemide resulted in irreversible changes in cochlear function which were associated with elevated levels of kanamycin in the blood and perilymph of the experimental animals. There was a striking similarity between the blood level measured by high pressure liquid chromatography at the time of recovery of auditory function in experimental animals and the ototoxic blood levels proposed by others in clinical literature. These findings help to provide a pharmacologic basis for the clinical observation of furosemide-induced hearing loss.

Animals↗
PubMed1992

Three-dimensional surgical anatomy for stapes surgery computer-aided reconstruction and measurement.

To define anatomical relationships relevant to stapes surgery, computer-aided three-dimensional reconstruction and measurement were performed on nine normal temporal bones. The mean distance from the inferior portion of the long process of the incus to the center of the oval window was 3.80 mm. The shortest distance from the center of the oval window to the utricular macula, saccular membrane, and macula averaged 1.37, 1.60, and 2.13 mm. Surgery directed posteromedial-superior from the oval window was found to be most dangerous because it would come so close to the utricular macula; a posteromedial-inferior approach was found to be safest. The distance from the inferior margin of the oval window inferiorly to the cochlear duct in the hook portion ranged between 0.58 and 1.29 mm, suggesting that when a drill hole is made on the inferior margin of the oval window to lift up a depressed stapes footplate, the hole should not be greater than 0.5 mm in diameter.

Adolescent↗
PubMed1993

Insertional trauma of multichannel cochlear implants.

Insertional trauma to the cochlea from three different multichannel cochlear implant electrodes was evaluated in a single-blind controlled study in fresh human temporal bones. Sixteen fresh human temporal bones were implanted with one of three types of multichannel electrodes (Symbion/InnerAid, Cochlear/Nucleus, or Storz/UCSF). Seven temporal bones were used as controls where a cochleostomy only was created. The temporal bones were evaluated histologically and cochlear histograms of the trauma were created. Although the three electrode designs caused damage which was unlikely to hinder implant performance, a distinct pattern of trauma was seen with each of the three electrode types. The least traumatic of the three electrode designs in this study was the Nucleus type. The degree of insertional trauma may be relevant to changing indications for insertion of cochlear implants as well as for patients with device failure who require reimplantation.

Basilar Membrane↗
PubMed1994

Cochlear polyamines: markers of otitis media-induced cochlear damage.

High-performance liquid chromatography (HPLC) set to the femtomole [corrected] sensitivity level was used to identify and quantify the polyamines spermidine and spermine as well as the diamine putrescine in the different tissues of the inner ears of guinea pigs with experimentally induced otitis media. The tissues examined were the lateral wall (stria vascularis and the spiral ligament), the organ of Corti, and the cochlear nerve. The difference in polyamine profile in the different tissues of the control noninfected guinea pigs suggests a relation to the particular function of each of these tissues [see erratum notice re: preceding sentence]. The difference in polyamine profile in infected different inner ear tissues compared to controls encourages the assumption that the polyamines may be involved in a repair process of the inner ear after injury and that they may be considered as biochemical markers for inner ear damage secondary to acute otitis media.

Animals↗
PubMed1997

Frequency selectivity on aspirin-induced hearing loss in rats with auditory stimulus-induced conditioned suppression.

The conditioned suppression technique was employed to examine the acute effects of aspirin on auditory function in rats. Lever pressing behavior for water reinforcement was suppressed in the presence of an auditory stimulus that had been previously paired with electric shocks. A single intravenous injection of aspirin at a dose of 225 mg/kg caused an erroneous lever pressing response in the broad sound intensities of 2 kHz tone stimulus during the conditioned stimulus period. A statistically significant increase in the threshold for 2 kHz was found 1 to 72 hr after dosing but not for 4, 8 and 10 kHz. These results suggest that the hearing for low sound frequency in rats is vulnerable to the effects of aspirin. This paradigm in rats may be useful to further assess the different outer hair cells along the cochlear duct and provide an additional evidence for the aspirin ototoxicity research.

Acoustic Stimulation↗
PubMed1997

A characteristic of aspirin-induced hearing loss in auditory brainstem response of conscious rats.

The acute effects of aspirin on auditory functions were examined electrophysiologically in conscious rats with chronically implanted electrodes for auditory brainstem response (ABR) recording. A single intravenous injection of aspirin at a dose of 225 mg/kg caused a reduction in the amplitude of the ABR P1 wave evoked by a 2 kHz tone pip 1 and 24 hr after dosing at almost all sound intensity levels, while the P1 amplitude at 4 kHz was reduced mainly 1 hr after dosing, and the P1 amplitude at 8 kHz was not significantly affected at middle and high intensities even 1 hr after dosing. The audiogram obtained from the P1 amplitude showed a significant increase in the sound threshold 1 and 24 hr after dosing at 2 kHz, and 1 hr after dosing at 4 kHz, but not at 8 kHz. The peak latency of the P1 wave was also prolonged. Furthermore, reduction of the P2 and P4 wave amplitude and prolongation of the P1-P2 and P2-P4 interpeak latency were also observed at 2 kHz but not a 4 or 8 kHz. These results suggest that the rat auditory function for low frequency is vulnerable to the effects of aspirin. This paradigm, i.e., frequency selectivity, n rats may be useful to further assess the different outer hair cells along the cochlear duct and provide additional evidence for the mechanism(s) or site underlying aspirin ototoxicity.

Acoustic Stimulation↗
PubMed2006

Molecular and functional characterization of gap junctions in the avian inner ear.

To analyze the fundamental role of gap junctions in the vertebrate inner ear, we examined molecular and functional characteristics of gap junctional communication (GJC) in the auditory and vestibular system of the chicken. By screening inner ear tissues for connexin isoforms using degenerate reverse transcription-PCR, we identified, in addition to chicken Cx43 (cCx43) and the inner-ear-specific cCx30, an as yet uncharacterized connexin predicted to be the ortholog of the mammalian Cx26. In situ hybridization indicated that cCx30 and cCx26 transcripts were both widely expressed in the cochlear duct and utricle in an overlapping pattern, suggesting coexpression of these isoforms similar to that in the mammalian inner ear. Immunohistochemistry demonstrated that cCx43 was present in gap junctions connecting supporting cells of the basilar papilla, in which its immunofluorescence colocalized with that of cCx30. However, cCx43 was absent from supporting cell gap junctions of the utricular macula. This variation in the molecular composition of gap junction plaques coincided with differences in the functional properties of GJC between the auditory and vestibular sensory epithelia. Fluorescence recovery after photobleaching, adapted to examine the diffusion of calcein in inner ear explants, revealed asymmetric communication pathways among supporting cells in the basilar papilla but not in the utricular macula. This study supports the hypothesis that the coexpression of Cx26/Cx30 is unique to gap junctions in the vertebrate inner ear. Furthermore, it demonstrates asymmetric GJC within the supporting cell population of the auditory sensory epithelium, which might mediate potassium cycling and/or intercellular signaling.

Animals↗
PubMed2005

Expression and functional phenotype of mouse ERG K+ channels in the inner ear: potential role in K+ regulation in the inner ear.

An outcome of the intricate K+ regulation in the cochlear duct is the endocochlear potential (EP), approximately 80 mV, the "battery" that runs hair-cell transduction; however, the detailed molecular mechanisms for the generation of the EP remain unclear. We provide strong evidence indicating that the intermediate cells (ICs) of the stria vascularis (StV) express outward K+ current that rectifies inwardly at positive potentials. The channel belongs to the ether-a-go-go-related gene (erg) family of K+ channels. We cloned an ERG1a channel in the mouse inner ear (MERG1a). The cellular distribution of MERG1a in the cochlea displayed the highest levels of immunoreactivity in the ICs and modest reactivity in the marginal cells as well as in several extrastrial cells (e.g., hair cells). Functional expression of the StV-specific MERG1a channel reveals a current that activates at relatively negative potentials (approximately-50 mV) and shows rapid inactivation reflected as inward rectification at depolarized potentials. The current was sensitive to the methanesulfonanilide drug E-4031 (IC50, approximately 165 nM) and the recombinant peptide rBeKm-1 (IC50, approximately 16 nM), and the single-channel conductance in symmetrical K+ was approximately 14 pS. The site of expression of MERG1a and its functional phenotype (e.g., modulation of the current by external K+ make it one of the most likely candidates for establishing the high throughput of K+ ions across ICs to generate EP. In addition, the property of the channel that produces marked K+ extrusion in increased external K+ may be important in shaping the dynamics of K+ cycling in the inner ear.

Amino Acid Sequence↗
PubMed1989

Microanatomy of the mouse osseous cochlea: a scanning electron microscopic study.

This is the first scanning electron microscopic demonstration of the three-dimensional architecture and detailed surface structures of the entire osseous labyrinth of the cochlea. Mouse cochleae were observed after dissolving the soft tissues with KOH and NaOCl solutions. The precise shapes, surface structures, and orientations of the primary osseous spiral lamina and secondary osseous spiral lamina in the cochlea were observed along their entire course from the hook at the base to the helicotrema at the apex. The primary osseous spiral lamina showed three half turns after the hook; the lengths of the hook and each half turn and the slope angle of the spiral were obtained. The widths of the primary and secondary spiral laminae and the spiral fissure for the basilar membrane between the free edges of the two spiral laminae were measured along the course of the cochlear duct. The surface of the lateral wall under the stria vascularis was also viewed. Scanning electron microscopy can provide more precise microanatomical data than has been previously available for the osseous cochlea, giving a better understanding of hearing mechanisms with regard to the width, support, and movement of the basilar membrane and the functions of various components of the cochlea.

Animals↗