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At least 109 records · Page 6Linked to original sources
PubMed2006

Differential expression of LIM domain-only (LMO) genes in the developing mouse inner ear.

The vertebrate inner ear, a complex sensory organ with vestibular and auditory functions, is derived from a single ectoderm structure called the otic placode. Currently, the molecular mechanisms governing the differentiation and specification of the otic epithelium are poorly understood. We present here a detailed expression study of LMO1-4 in the developing mouse inner ear using a combination of in situ hybridization and immunohistochemistry. LMO1 is specifically expressed in the vestibular and cochlear hair cells as well as the vestibular ganglia of the developing inner ear. LMO2 expression is detected in the periotic mesenchyme of the developing mouse cochlea from E12.5 to E14.5. The expression of LMO3 expression is first observed in the cochlea at E13.5 and becomes confined to the lesser epithelial ridge (LER) from E14.5 to E17.5. LMO3 is also expressed in some of the vestibular ganglion cells. LMO4 is initially expressed in the dorsolateral portion of the otic vesicle and its expression persists in the semicircular canals, macula, crista, and the spiral ganglia throughout embryogenesis. Thus, the regionalized expression patterns of LMO1-4 are closely associated with the morphogenesis of the inner ear.

Adaptor Proteins, Signal Transducing↗
PubMedDate not supplied

On the influence of altered gravity on the growth of fish inner ear otoliths.

Inner ear stones (otoliths) of developing cichlid fish (Oreochromis mossambicus) were marked with the calcium tracer alizarin-complexone (AC) at 1g-earth gravity before and after a longterm (20 days) stay of the animals at moderate hypergravity conditions (3g; centrifuge). AC deposition at the otoliths resulted in two fluorescence bands, which enclosed the area grown during exposure to altered gravity. This area was measured with regard to size and asymmetry (size difference between the left and the right stones). Both utricular and saccular otoliths (lapilli and sagittae, respectively) were significantly smaller after hyper-g exposure as compared to parallely raised 1 g-control specimens. The asymmetry concerning the lapilli was pronouncedly decreased in comparison to the 1g-controls. These findings suggest, that the growth and the development of bilateral asymmetry of otoliths is guided by the environmental gravity vector. Some of the hyper-g animals revealed a kinetotic behaviour at the transfer from hyper-g to normal 1g-earth gravity conditions, which was qualitatively similar to the behaviour observed in previous experiments at the transfer from 1 g to microgravity in the course of parabolic aircraft flights. The lapillar asymmetry of kinetotic samples was found to be significantly higher than that of normally behaving experimental specimens. This result supports an earlier theoretical concept, according to which human static space sickness might be based on asymmetric utricular otoliths

Animals↗
PubMed1989

Antigen-specific immune response in the inner ear.

The specificity of inner ear immune responses was investigated by challenging each inner ear of presensitized animals with different antigens. Animals presensitized systemically with keyhole limpet hemocyanin (KLH) and bovine serum albumin (BSA) were challenged with KLH in the right and BSA in the left inner ears. Two weeks later perilymph anti-KLH levels were increased significantly in the right inner ears compared to the levels in the left inner ears. In contrast, perilymph anti-BSA levels were increased significantly in the left inner ears compared to the levels in the right inner ears. These results suggested that the rise in perilymph antibody following inner ear antigen challenge was predominantly the result of an antigen-specific immune response in the inner ear and not simply the result of an increase in vascular permeability of serum contamination from the experimental procedure itself.

Animals↗
PubMed2004

Application of cell therapy to inner ear diseases.

Most inner ear disorders involve irreversible loss of hair cells and their associated neurons. Recent advances in genetics and cell biology have raised hopes for the regeneration or protection of these cells. Cell therapy is a rapidly growing research area, and is potentially applicable to the treatment of inner ear disorders. Recent studies on cell transplantation into the inner ear have suggested that such cell therapy may be progressing towards the clinical application. This review highlights recent advances in cell transplantation studies focusing on the inner ear.

Animals↗
PubMed1980

Embryogenesis of the inner ear. IV. Post-natal maturation of the secretory epithelia of the inner ear in correlation with the elemental composition in the endolymphatic space.

The rise of the potassium concentration in the endolymphatic space occurred between the 4th and 8th day after birth (DAB). During this time morphological maturation of the stria vascularis was ended. The increasing concentration of potassium in the developing endolymph parallelled in the vestibular and cochlear parts of the labyrinth. The dark cell epithelium surrounding vestibular organs was, however, ultrastructurally mature at birth except for an increase of the number of intercellular digitations toward the basal membrane maturing during the first days postpartum. The maturation of endolymph thus took place prior to the development of the endocochlear potential.

Animals↗
PubMed1980

The prognostic value of the glycerol test: a review of 60 ears with unidirectional inner ear valve implants.

The following are our conclusions in regard to glycerol test interpretation based on 60 valve implants: Negative Tests 1. A negative glycerol test result and no audiometric evidence of significant hearing fluctuations indicate that a patient is unlikely to have postoperative hearing that is better than his best preoperative hearing. 2. The patient with a negative test can still have an excellent chance (greater than 80 per cent) to be relieved of vertigo. 3. A negative test and no audiometric evidence of significant hearing fluctuations in a patient with cochlear Meniere's disease would contraindicate valve surgery. Positive Tests 1. A positive glycerol test, done under appropriate conditions with adequate audiometric controls, clinically confirms the histopathologic diagnosis of endolymphatic hydrops. 2. The patient will have a 30 to 40 per cent chance of having better postoperative hearing than his best preoperative hearing. 3. The patient will have an 80 to 90 per cent chance to be free of vertigo. 3. The patient will have an 80 to 90 per cent chance to be free of vertigo. 4. A positive glycerol test would be a contraindication for labyrinthectomy, since the patient has the potential for some hearing improvement as well as absence of vertigo.

Ear, Inner↗
PubMed1977

[Chronic mucous effusions of the middle ear and the influence on inner ear function (author's transl)].

Audiometric recordings of children suffering from chronic mucous effusion of the middle ear have revealed a statistically significant and permanent sensorineural hearing loss of high frequences. Attemps for mechanical or physical factors as explanation are not convincing. We believe that inner ear disturbances in chronic mucous effusion rise by direct intoxication of the basal turns of the cochlea caused by pathologic alterations of mucous membrane tissue. Certain substances like lysozymes or histamine are supposed to diffuse via round window membrane to the inner ear. On the other hand mucous effusion which fills the middle cavity prevents oxygen to diffuse from the middle ear to the inner ear. Maass et al. (1976) and Morgenstern (1977) clearly have shown that under physiological conditions oxygen tension in the perilymph of the basal cochlear turn partly depends on diffusion from the middle ear. The results of our clinical observations indicate that early diagnosis and prompt treatment is necessary to prevent permanent sensorineural hearing loss of high frequencies, especially in infants and children.

Audiometry↗
PubMed2005

Cell therapy for inner ear diseases.

Degeneration of inner ear cells, especially sensory hair cells and associated neurons, results in hearing impairment and balance disorders. These disabilities are incurable because loss of hair cells and associated neurons is currently irreversible. Protection or regeneration of hair cells and associated neurons is an important area of research for developing an effective treatment for inner ear diseases. Cell therapy is a rapidly growing area of research and has potential applications in the treatment of inner ear disorders. The first attempts to examine the feasibility of cell therapy in the treatment of inner ear disorders have been performed using neural stem cells (NSCs). Grafted NSCs can survive in the inner ear and differentiate into neural, glial and/or hair cell-phenotypes, making NSC transplantation for the restoration of inner ear cells a potentially viable treatment. Further studies have suggested embryonic stem cells (ESCs), dorsal ganglion cells and cell lines derived from fetal inner ear cells could be used to restore damaged inner ear cells. Cell transplantation has also been suggested as a strategy for drug delivery into the inner ear, and the ability of NSC-derived cells to produce neurotrophins in the inner ear has been demonstrated. Results from studies using autologous bone marrow stromal cells (MSCs) indicate a high survival and migration potential suggesting that MSCs can be used as a drug delivery vehicle to the inner ear. These cell transplantation findings provide a sound foundation for the development of therapies to treat inner ear disorders.

Animals↗
PubMed2007

Comparative analysis of Gata3 and Gata2 expression during chicken inner ear development.

The inner ear is a complex sensory organ with hearing and balance functions. Gata3 and Gata2 are expressed in the inner ear, and to gain more insight into their roles in otic development, we made a detailed expression analysis in chicken embryos. At early stages, their expression was highly overlapping. At later stages, Gata2 expression became prominent in vestibular and cochlear nonsensory epithelia. In contrast to Gata2, Gata3 was mainly expressed in the developing sensory epithelia, reflecting the importance of this factor in the sensory-neural development of the inner ear. While the later expression patterns of both Gata3 and Gata2 were highly conserved between chicken and mouse, important differences were observed especially with Gata3 during early otic development, providing indications of divergent molecular control during placode invagination in mice and chickens. We also found indications that the regulatory hierarchy observed in mouse, where Gata3 is upstream of Gata2 and Fgf10, could be conserved in chicken.

Animals↗
PubMed2003

Expression of mouse fibroblast growth factor and fibroblast growth factor receptor genes during early inner ear development.

The inner ear, which mediates hearing and equilibrium, develops from an ectodermal placode located adjacent to the developing hindbrain. Induction of the placode and its subsequent morphogenesis and differentiation into the inner ear epithelium and its sensory neurons, involves signalling interactions within and between otic and non-otic tissues. Several members of the fibroblast growth factor (FGF) family play important roles at various stages of otic development; however, there are additional family members that have not been evaluated. In this study, we surveyed the expression patterns of 18 mouse Fgf and 3 Fgf receptor (Fgfr) genes during early otic development. Two members of the Fgf family, Fgf4 and Fgf16, and all three tested members of the Fgfr family, Fgfr2c, Fgfr3c, and Fgfr4, were expressed in tissues relevant to inner ear development. Fgf4 transcripts were expressed in the preplacodal and placodal ectoderm, suggesting potential roles in placode induction and/or maintenance. Fgf16 was expressed in the posterior otic cup and vesicle, suggesting roles in otic cell fate decisions and/or axis formation.

Animals↗
PubMed1993

Tissue specific levels of glucocorticoid receptor within the rat inner ear.

Individual, rat inner ear tissues were isolated and processed for determination of levels of glucocorticoid (GR) receptor by an Enzyme Linked Immuno-Sorbant Assay (ELISA). Differing levels of GR receptor between seven sampled inner ear regions were measured. Levels of GR receptors in the spiral ligament tissues were found to be significantly higher compared to all other tissue samples. GR levels in the tissues of stria vascularis and organ of Corti were different from one another but both were statistically higher than those detected in the vestibular tissue samples (dark cell regions, cristae ampullares and maculae utriculi), which had the lowest GR receptor levels measured. Intermediate levels of GR receptor were found in the endolymphatic sac region. It is suggested that the varying levels of inner ear GR receptors may be indicative of differing biological responses among the given tissues, as well as differences in the magnitudes of such responses to circulating glucocorticoids.

Analysis of Variance↗
PubMed1997

Dissecting the frog inner ear with Gaussian noise. II. Temperature dependence of inner ear function.

The temperature dependence of the response of single primary auditory nerve fibers (n = 31) was investigated in the European edible frog, Rana esculenta (seven ears). Nerve fiber responses were analyzed with Wiener kernel analysis and polynomial correlation. The responses were described with a cascade model, consisting of a linear bandpass filter, a static nonlinearity, and a linear lowpass filter. From the computed Wiener kernels and the polynomial correlation functions, the characteristics of the three model components were obtained. With increasing temperature (1) tuning of the first filter increased in the majority (n = 16) of amphibian papilla fibers (best excitatory frequency, BEF < 1 kHz, n = 21) but remained unchanged in the majority (n = 10) of basilar papilla fibers (BEF > 1 kHz, n = 11), (2) the gain of the first filter remained unchanged, (3) the shape of nonlinear IO function remained unchanged, (4) the combined gain of the static nonlinearity and the second filter usually increased, but displayed considerable scatter across fibers (from -0.7 dB/degrees C to 3 dB/degrees C), and (5) the cutoff frequency of the second lowpass filter increases, with average 0.13 oct/degrees C. The immunity of the shape of the nonlinearity is considered evidence of a temperature independent gating mechanism in the transduction channels. The temperature dependence of the second filter may have resulted from a decrease of the hair cell membrane resistance, but may also reflect changes in subsequent staging of nerve fiber excitation.

Acoustic Stimulation↗
PubMed1988

Heterodyne interferometer for submicroscopic vibration measurements in the inner ear.

Conditions in the inner ear for interferometric measurements are quite different from those encountered in other mechanical systems: (i) The inner ear is not mechanically stable, due to blood pulsations and breathing artifacts; (ii) access to the inner ear is limited by anatomical constraints that make it difficult to visualize the structures of interest; (iii) vibration amplitudes to be measured in the inner ear are very low; (iv) the structures in the inner ear are nearly transparent; therefore, the reflectivity is low and attempts to change this reflectivity artificially usually alter the response characteristics; (v) cells are subject to light damage if the incident light intensity is too high, which limits the laser power that can be utilized in the interferometer. A heterodyne interferometer specially designed to measure vibrations in the living inner ear is described. Theoretical and experimental characteristics of this instrument are discussed in detail. In contrast to the homodyne system, the measurement accuracy of this interferometer is not affected by the low-frequency animal movements. This system does not require attachment of a reference mirror to the animal, thereby providing an unobstructed view of the structure to be measured. It has a high linearity and dynamic range. Its vibration sensitivity is high (2.8 X 10(-13) m for 1-Hz bandwidth) even under the condition of low light reflectivity (0.02%), with 0.5-mW incident laser power.

Ear, Inner↗
PubMed1989

Middle ear ototoxic treatment for inner ear disease.

Twenty-nine patients seriously disabled by Ménière's disease due to frequent attacks were treated with Gentamicin administered in the middle ear once daily until first sign of an inner ear disturbance, usually a spontaneous nystagmus and a sensation of unsteadiness. All patients except one were relieved from their vertiginous attacks and returned to normal activities. Tinnitus was usually diminished or absent, as was the feeling of pressure in the ear. The hearing was slightly improved in 5 patients, worse in 9 patients and two treated ears became deaf. The indication for an intratympanal treatment with Gentamicin should be a disabling form of Ménière's disease not responding to medical treatment. The risk for the cochlea increases after 6 days of treatment. The advantage versus intracranial surgery is the absence of the surgical risks for complications. The mode of action exerted by the ototoxic drug is a destruction of the vestibular sensory epithelium and the endolymph producing cells.

Adult↗
PubMed1997

Pathophysiological mechanisms in immune inner ear disease.

Immune inner ear disease is a somewhat controversial entity which describes cochleovestibular dysfunction that is related to immune-mediated mechanisms. The diagnosis of this disease is based on clinical presentation and response to various treatment protocols. Unfortunately, the presentation is variable and the treatment empirical, and this has caused much confusion in the diagnosis and management of the condition. To elucidate the variable nature of the disease, it is important to understand that more than one mechanism of immune injury may be involved. This paper attempts to classify clinical and experimental cases of immune inner ear disease with regard to the Gell and Coombs classification scheme of immune-mediated injury. By understanding the different pathophysiological mechanisms involved, the clinician should be better able to diagnose and manage this difficult problem in a directed fashion. The ramifications of the proposed classification system on the diagnosis, treatment and future research of immune inner ear disease are discussed.

Autoimmune Diseases↗
PubMedDate not supplied

Role of lymphokines in the immune response of the inner ear.

In secondary inner ear responses against keyhole limpet hemocyanin (KLH), the characterization of interleukin-2 levels in perilymph and serum developing over 5 days in Hartley guinea pigs was investigated using an immunoassay. No interleukin-2 levels were detectable at Day 0 in serum and perilymph. The earliest perilymph IL-2 levels were observed after 6 h, peaking at 18 h and decreasing to zero by Day 5. In contrast, during this observation period, no IL-2 was detectable in serum or perilymph from control ears. Since previous work has identified T-helper cells in the endolymphatic sac, this site appears to be the probable source of interleukins. This study provides further support for the existence of an inner ear immune response which is regulated by lymphokines. Furthermore, interleukins may be a chemoattractant for cells entering the cochlea during the immune response.

Animals↗
PubMed2001

Hes1 and Hes5 activities are required for the normal development of the hair cells in the mammalian inner ear.

The mammalian inner ear contains two sensory organs, the cochlea and vestibule. Their sensory neuroepithelia are characterized by a mosaic of hair cells and supporting cells. Cochlear hair cells differentiate in four rows: a single row of inner hair cells (IHCs) and three rows of outer hair cells (OHCs). Recent studies have shown that Math1, a mammalian homolog of Drosophila atonal is a positive regulator of hair cell differentiation. The basic helix-loop-helix (bHLH) genes Hes1 and Hes5 (mammalian hairy and Enhancer-of-split homologs) can influence cell fate determination by acting as negative regulators to inhibit the action of bHLH-positive regulators. We show by using reverse transcription-PCR analysis that Hes1, Hes5, and Math1 are expressed in the developing mouse cochleae. In situ hybridization revealed a widespread expression of Hes1 in the greater epithelial ridge (GER) and in lesser epithelial ridge (LER) regions. Hes5 is predominantly expressed in the LER, in supporting cells, and in a narrow band of cells within the GER. Examination of cochleae from Hes1(-/-) mice showed a significant increase in the number of IHCs, whereas cochleae from Hes5(-/-) mice showed a significant increase in the number of OHCs. In the vestibular system, targeted deletion of Hes1 and to a lesser extent Hes5 lead to formation of supernumerary hair cells in the saccule and utricle. The supernumerary hair cells in the mutant mice showed an upregulation of Math1. These data indicate that Hes1 and Hes5 participate together for the control of inner ear hair cell production, likely through the negative regulation of Math1.

Animals↗