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At least 469 records · Page 26Linked to original sources
PubMed1977

[A proposition for mutual genesis of hearing loss, recruitment and ear murmurs in the case of acute inner ear alterations (author's transl)].

Pathological changes on the stereocilia of cochlear hair cells observed by Bredberg et al. (1972) after noise exposure and in the early stages of antibiotic intoxication are suggested to cause a mechanical decoupling between the tectorial membrane and the hair cells. During acute episodes of endolymphatic hydrops a similar decoupling is suggested to occur, although for different reasons. Harris (1968) calculated the noise generated at the input to the hair cells on account of the Brownian motion of air particles in front of the tympanic membrane. For tight coupling, he obtained a level of (--)22 dB re auditory threshold. For loose coupling this noise was found to increase to +33 dB, i.e., for 55 dB. These two independent findings are used to account for the combination of hearing loss, recruitment, and tinnitus observed with the inner-ear pathologies mentioned. The proposed hypothesis is in good agreement with clinical observations.

Anti-Bacterial Agents↗
PubMed2002

The early kinetics of gentamicin uptake into the inner ear.

Transtympanic gentamicin administration has become a popular modality in the treatment of Ménière's disease. This modality and other inner-ear medical therapy are gaining increased clinical and scientific attention. We previously described the kinetics and effects of gentamicin uptake into the inner ear after delivery of the medicine into the middle ear using a variety of different techniques and sustained-release modalities [1]. In our previous work, we reported an early peak perilymph concentration and the presence of intracellular gentamicin at the 4-hour time point. We also demonstrated the activation of inner-ear damage pathways at this early time point. In this report, we examine the kinetics of gentamicin at very early time points, 1 and 2 hours after administration. Healthy adult chinchillas underwent implantation of middle-ear sustained-release devices (one to each ear) containing gentamicin. The animals then were maintained in a neutral position and underwent perilymph gentamicin sampling at the two predetermined time points. This technique allowed us to assess accurately very early time point inner-ear gentamicin kinetics and to compare the activity. The samples then were run for concentration using mass spectrometry. The information gained from this study may increase our scientific understanding about the effects of gentamicin on the inner ear and may allow clinicians to treat patients more effectively for inner-ear disorders.

Animals↗
PubMed1991

Sodium hyaluronate application to the open inner ear: an ultrastructural investigation.

The effect of 1 percent sodium hyaluronate on the open inner ear was tested in a series of guinea pigs. By removing the stapes footplate from its original position in the oval window, direct access to the vestibule from the inner ear was achieved. The oval window niche was filled with either 1 percent sodium hyaluronate or 0.9 percent NaCl. The animals were examined with regard to both the cochlear and the vestibular partitions of the inner ear. No marked differences could be seen between the test group and the controls. Thus the organ of Corti as well as the vestibular end organs presented with normal anatomy throughout. Neither did the behavior of the animals in any way indicate any signs of inner ear disturbance. It is concluded that 1 percent sodium hyaluronate does not seem to harm the inner ear sensory structures even in the case of direct access to the vestibule as can be foreseen if the compound is used during stapes surgery.

Animals↗
PubMed1992

Bovine temporal bones as a source of inner ear antigen.

Modern immunologic techniques of immunostaining, immunoblotting, and creation of monoclonal antibodies are gaining wide application in studies of development, function, and pathology of the ear. These techniques require a source of inner ear tissue for production of antigen extract. Human tissue is not readily available, and other mammalian species common in auditory research are small in size. Bovine temporal bones are readily available, and the membranous portions of the inner ear are abundant and easily accessible. Herein we report our technique for acquisition and dissection of bovine temporal bones and preparation and preservation of inner ear antigen.

Animals↗
PubMed1985

Structure and function of the adult inner ear in the mouse following prenatal irradiation.

The function and morphology of the vestibular and cochlear parts of the inner ear have been examined after prenatal irradiation on the 12th, 13th and 16th gestational days in the CBA/CBA mouse. Irradiation was performed with a 0.5, 1 or 2 Gy single dose, whole body irradiation of the pregnant female. The irradiated fetuses were born after full term pregnancies and reached maturity (were 1--2 months old) before inner ears were analyzed with regard to vestibular tests, auditory thresholds and morphology. Morphology was studied by light microscopy (LM), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Auditory function was analyzed by frequency specific auditory brainstem response (ABR). Irradiation doses exceeding 2 Gy caused death to the pregnant female, abortion or malformed litters which were eaten by their mothers. Doses of 0.5, 1 and 2 Gy caused malformed cristae ampullares and maculae utriculi, in particular after exposure on the 12th or 13th gestational days. After those doses no abnormality of clinical behaviour of the animals was found. Ultrastructurally, type I hair cells (HC) of the vestibular part seemed more vulnerable to irradiation than the type II HC while the outer (OHC) and inner (IHC) hair cells appeared equally vulnerable. The ultrastructural changes of hair cells were predominantly localized to the hair cell surface showing a defect cuticle which was sometimes malformed and bulging. Sensory hair fusion occurred with a resulting poor maturation of sensory hair rootlets. The efferent nerve endings were estimated to be reduced in number but, if present, they had a normal ultrastructure. Otoconia showed severe morphological damage following irradiation particularly if exposed on the 16th gestational day. Malformed and fused otoconia were frequent having a disarrayed matrix. The irradiation induced morphological alterations in vivo could be reproduced in the in vitro systems. In addition, a retarded growth of the in vitro developing inner ear anlage was estimated to be the same for the vestibular and cochlear parts. The cochlear part of the inner ear showed a dose and age dependent hearing loss following irradiation. A shift of the ABR threshold was recorded in all exposed groups that were irradiated with 2 Gy. A correlation was found between the individual ABR-audiograms and the degree of morphological HC damage in the cochlea along the basilar membrane. The 12th gestational day inner ear anlage was most vulnerable to irradiation. The 13th gestational day inner ear was almost equally vulnerable and showed a dose-response relationship.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1981

Biochemical studies on the embryonic development of the mammalian inner ear in organ culture.

Adenylate cyclase activity and phospholipid labeling were compared during embryonic development of the mouse inner ear in vivo and in vitro. Inner ears were explanted on the 16th gestational day and cultured in vitro for 3-12 days. The gestation time in vivo is 21 days. During the 1st week in vitro there is very little growth of the inner ear with regard to total protein content. In contrast, the labyrinth increases its protein content threefold during the corresponding period of time in vivo. The activity of adenylate cyclase develops parallel in vivo and in vitro until the 19th gestational day whereafter the specific activity of the enzyme in vitro surpasses that of the enzyme in vivo three- to fivefold suggesting a lack of control mechanisms in organ culture. Phospholipids are labeled by 32P in an essentially similar quantitative relationship in vivo and vitro, while some quantitative differences exist. According to the present study the usefulness of the organ culture for the investigation of inner ear development appears limited to a culture period corresponding to an age prior to birth.

Adenylyl Cyclases↗
PubMed2005

Survival and neural differentiation of adult neural stem cells transplanted into the mature inner ear.

The cochlear sensory epithelium and spiral ganglion neurons (SGNs) in the adult mammalian inner ear do not regenerate following severe injury. To replace the degenerated SGNs, neural stem cell (NSC) is an attractive alternative for substitution cell therapy. In this study, adult mouse NSCs were transplanted into normal and deafened inner ears of guinea pigs. To more efficiently drive the implanted cells into a neuronal fate, NSCs were also transduced with neurogenin 2 (ngn2) before transplantation. In deafened inner ears and in animals transplanted with ngn2-transduced NSCs, surviving cells expressed the neuronal marker neural class III beta-tubulin. Transplanted cells were found close to the sensory epithelium and adjacent to the SGNs and their peripheral processes. The results illustrate that adult NSCs can survive and differentiate in the injured inner ear. It also demonstrates the feasibility of gene transfer to generate specific progeny for cell replacement therapy in the inner ear.

Animals↗
PubMed2005

Distinct roles for hindbrain and paraxial mesoderm in the induction and patterning of the inner ear revealed by a study of vitamin-A-deficient quail.

The hindbrain and cranial paraxial mesoderm have been implicated in the induction and patterning of the inner ear, but the precise role of the two tissues in these processes is still not clear. We have addressed these questions using the vitamin-A-deficient (VAD) quail model, in which VAD embryos lack the posterior half of the hindbrain that normally lies next to the inner ear. Using a battery of molecular markers, we show that the anlagen of the inner ear, the otic placode, is induced in VAD embryos in the absence of the posterior hindbrain. By performing grafting and ablation experiments in chick embryos, we also show that cranial paraxial mesoderm which normally lies beneath the presumptive otic placode is necessary for otic placode induction and that paraxial mesoderm from other locations cannot induce the otic placode. Two members of the fibroblast growth factor family, FGF3 and FGF19, continue to be expressed in this mesodermal population in VAD embryos, and these may be responsible for otic placode induction in the absence of the posterior hindbrain. Although the posterior hindbrain is not required for otic placode induction in VAD embryos, the subsequent patterning of the inner ear is severely disrupted. Several regional markers of the inner ear, such as Pax2, EphA4, SOHo1 and Wnt3a, are incorrectly expressed in VAD otocysts, and the sensory patches and vestibulo-acoustic ganglia are either greatly reduced or absent. Exogenous application of retinoic acid prior to 30 h of development is able rescue the VAD phenotype. By performing such rescue experiments before and after 30 h of development, we show that the inner ear defects of VAD embryos correlate with the absence of the posterior hindbrain. These results show that induction and patterning of the inner ear are governed by separate developmental processes that can be experimentally uncoupled from each other.

Animals↗
PubMedDate not supplied

Antibody activity in perilymph from rats with type II collagen-induced autoimmune inner ear disease.

Rats were immunized with native type II bovine collagen to induce autoimmune inner ear disease, and the antibody activity in the inner ear fluid was measured. Antibody activity against type II collagen was detected in the perilymph at about 10% to 20% of serum level. Thus, the presence of antibody against type II collagen in inner ear fluid may imply an immune injury mechanism in inner ear diseases.

Animals↗
PubMed1997

Otogelin: a glycoprotein specific to the acellular membranes of the inner ear.

Efforts to identify the specific components of the mammalian inner ear have been hampered by the small number of neuroepithelial cells and the variety of supporting cells. To circumvent these difficulties, we used a PCR-based subtractive method on cDNA from 2-day-old mouse cochlea. A cDNA encoding a predicted 2910-amino acid protein related to mucin has been isolated. Several lines of evidence indicate, however, that this protein does not undergo the O-glycosylation characteristic to mucins. As confirmed by immunocytochemistry and biochemical experiments, this protein is specific to the inner ear. Immunohistofluorescence labeling showed that this protein is a component of all the acellular membranes of the inner ear: i.e., the tectorial membrane of the cochlea, the otoconial and accessory membranes of the utricule and saccule, the cupula of the semicircular canals, and a previously undescribed acellular material covering the otoconia of the saccule. The protein has been named otogelin with reference to its localization. A variety of nonsensory cells located underneath these membranes could be identified as synthesizing otogelin. Finally, this study revealed a maturation process of the tectorial membrane, as evidenced by the progressive organization of otogelin labeling into thick and spaced radial fiber-like structures.

Amino Acid Sequence↗
PubMed2006

Alternatives to systemic steroid therapy for refractory immune-mediated inner ear disease: A physiopathologic approach.

Immune-mediated inner ear disease (IMIED) is one of the few forms of reversible sensorineural hearing loss. Corticosteroids-responsive patients are usually associated with hearing improvement. Due to the long clinical course of IMIED that frequently present recurrences (hearing loss and vertigo), alternatives to corticosteroids such as methotrexate and recently TNF-alpha blockers have been proposed. Likewise new procedures for delivering corticosteroids to the inner ear have been developed. The aim of this article is to assess the efficacy of methotrexate and transtympanic 6-methylprednisolone in refractory IMIED. From a database of 200 patients affected by IMIED, 16 selected patients with refractory disease were included in the present study. Five patients were treated with methotrexate and 11 by means of transtympanic injection of 6-methylprednisolone. All patients treated with methotrexate had an improvement in their vestibular symptoms. However, hearing loss did not improve. Most patients treated with local 6-methylprednisolone (68.75%) showed an improvement in hearing loss and vestibular symptoms. Methotrexate has been shown to be ineffective in maintaining long-term remissions of hearing relapses although patients presented an improvement in vestibular symptoms. However, transtympanic 6-methylprednisolone has been shown to be a safe, easy and useful therapy in refractory IMIED and it may actually become the first-line treatment for these patients based on the existence of glucocorticoid receptors and the possible targets of immune-mediated damage within the inner ear.

Administration, Oral↗
PubMed1981

The effect of noise on deoxyglucose uptake into inner ear tissues of the mouse.

The uptake of deoxyglucose into inner ear tissues was studied in the mouse. Sixty minutes after a single i.v. injection of 5 mCi 2-deoxy-D-[3H]glucose/kg body weight, stria vascularis/spiral ligament and organ of Corti as well as other body tissues were dissected and analyzed for radioactivity. Uptake into inner ear tissues was three to five times lower than into brain or heart. The ratio of deoxyglucose-6-phosphate to deoxyglucose was 60:40 and the compounds were eliminated from the inner ear with a half life of approximately 60 min. Exposure to 100 dB of white noise during the radioactive pulse decreased uptake of deoxyglucose into both stria vascularis/spiral ligament and organ of Corti by 50%.

Animals↗
PubMed1995

[Western blot analysis of serum autoantibodies against inner ear antigens in patients with systemic lupus erythematosus].

The purpose of this study was to identify the cross-reacting autoantibodies against inner ear antigens in patients with systemic lupus erythematosus (SLE). Inner ear antigens of guinea pigs were prepared. The sera from 18 patients with SLE without hearing loss and 11 normal subjects were analysed by immunoblotting assay. The results showed that 16 patients with SLE had cross-reacting autoantibodies, while 11 normal objects were all negative (P < 0.01), these suggested that the inner ear may be one of the targets involved by SLE. To further investigate the correlation between hearing status of SLE and autoantibodies against inner ear antigens will be of great value to explore the pathogenesis of inner ear insults resulted from certain systemic autoimmune diseases.

Adolescent↗
PubMed2002

Transgene expression in neonatal mouse inner ear explants mediated by first and advanced generation adenovirus vectors.

The mouse serves as a valuable model for treatment leading to the prevention and therapy of inner ear disease. Transgenic correction of genetic inner ear disease in mice may help develop treatment for human genetic inner ear disease. In mutations involving hair cells (HCs) or supporting cells (SCs), it is necessary to insert the wild-type transgenes directly into these cells. We used inner ear explants to characterize the transgenic expression using adenovirus-mediated reporter genes (bacterial lacZ). The variable parameters were the age of the explants (P1-P5), the type of vector (first and advanced generation adenovirus) and the genotype of the mouse (wild-type versus shaker-2 mutant). Transduction of cochlear HCs was detected at P1 and in some of the P3 cochleae. Low efficiency transduction of SCs was observed in P1 explants, but the efficiency increased with age and reached high levels at P5. The pattern of transduction was similar regardless of the genotype and the type of vector used. The data demonstrate that differentiating HCs and SCs in mouse explants can be transduced by adenovirus vectors, suggesting that cultures of mouse ears are a valuable model for developing inner ear gene therapy protocols.

Adenoviruses, Human↗
PubMed1998

Molecular markers for cell types of the inner ear and candidate genes for hearing disorders.

To identify genes expressed in the vertebrate inner ear, we have established an assay that allows rapid analysis of the differential expression pattern of mRNAs derived from an auditory epithelium-specific cDNA library. We performed subtractive hybridization to create an enriched probe, which then was used to screen the cDNA library. After digoxigenin-labeled antisense cRNAs had been transcribed from hybridization-positive clones, we conducted in situ hybridization on slides bearing cryosections of late embryonic chicken heads, bodies, and cochleae. One hundred and twenty of the 196 clones analyzed encode 12 proteins whose mRNAs are specifically or highly expressed in the chicken's inner ear; the remainder encode proteins that occur more widely. We identified proteins that have been described previously as expressed in the inner ear, such as beta-tectorin, calbindin, and type II collagen. A second group of proteins abundant in the inner ear includes five additional types of collagens. A third group, including Coch-5B2 and an ear-specific connexin, comprises proteins whose human equivalents are candidates to account for hearing disorders. This group also includes proteins expressed in two unique cell types of the inner ear, homogene cells and cells of the tegmentum vasculosum.

Amino Acid Sequence↗
PubMed1992

Influence of middle ear immune response on the immunological state and function of the inner ear.

According to clinical experience, a causative correlation between otitis media and sensorineural hearing loss is likely. During an otitis media, inflammatory mediators should be released and diffuse through the round window membrane to cause an immune response of the inner ear. Using 20 guinea pigs, an immunologically caused otitis media was induced. Auditory evoked potentials were registered by means of electrocochleography and electric response audiometry from day 0 to day 7. Each time, before and after starting the immune response serum, middle ear effusion and perilymph were sampled and the concentration of interleukin-2 (IL-2) analyzed. Decalcified temporal bones were examined immunohistochemically. In this study, IL-2 was found in the middle ear effusion and perilymph, and there was evidence of an immune response of the inner ear during an otitis media. Histological results were in close correlation with this event. Electrophysiological data showed conduction deafness and signs of sensorineural hearing loss with a maximum at day 3.

Animals↗
PubMed1988

Optimizing immunofluorescence for the testing of autoantibodies in inner ear disorders.

A method is described for the immunofluorescent testing of autoantibodies in the sera of patients with vestibulo-cochlear disorders, using fixed decalcified inner ear tissue preparations from guinea pigs. Fixation in cold ethanol and decalcification in EDTa at 4 degrees C preserved the immunological reactivity of the inner ear tissue in use and allowed excellent delineation of its structural details. Counterstaining of the sections with Evans-blue dye aided in a better identification of the inner ear anatomical structures and in a more precise location of the antibodies present. By mounting the sections in p-phenylenediamine-PBS-glycerin solution, the rapid extinction of the fluorescence seen during photomicroscopy was retarded and the intensity of the immunofluorescence was enhanced. Preservation of the slides for documentation was improved by fixing the intermediate layer of the antigen and the labeled antibody in cold ethanol. The inner ear tissue preparations retained their fluorescent staining up to 6 months. Our method is convenient for screening patients with inner ear disorders for autoantibodies against the different cellular elements and for testing the possible presence of antibodies against the inner ear tissue. So far, we believe that the antibodies detected are not tissue (inner ear) specific.

Animals↗
PubMed2003

Expression of aquaporin 1 and 5 in the developing mouse inner ear and audiovestibular assessment of an Aqp5 null mutant.

To examine the potential roles of aquaporins 1 and 5 (AQP1 and AQP5, respectively) in inner ear development and function, we defined their spatial and temporal expression patterns in the developing mouse inner ear and examined the morphologic and physiologic effects of loss of Aqp5 function. Standard in situ hybridization (ISH) and immunohistochemical (IHC) assays were used for expression studies with routine morphologic, behavioral, and physiologic assessments of hearing and balance in Aqp5 null mutant mice. AQP1 was first detected at embryonic day 10.5 (E10.5) in the otocyst but eventually localized to specific nonsensory portions of the inner ear and connective tissue cells surrounding the membranous labyrinth. AQP5 displayed specific cochlear expression, first detectable at E15.5 in the nonsensory epithelium and later restricted to the lateral wall of the cochlear duct near the spiral prominence. AQP5 expression continued through postnatal periods with a change of expression domain to the stria vascularis between postnatal day 7 (P7) and P14. By in situ hybridization and immunohistochemical techniques, subtle differences between transcript and protein expression patterns were noted for both AQP1 and 5. Although AQP5 is dynamically expressed in the developing mouse inner ear, adult Aqp5 knockout mice show normal hearing when tested and normal inner ear structural development. These results suggest redundant or alternative mechanisms that likely regulate water homeostasis in the developing and mature inner ear.

Aging↗