Mechanism Of Hearing Loss Research Articles

Connexin 43 and hearing: Possible implications for retrocochlear auditory processing

To examine the relationship between hearing and connexin 43, a dominant gap junctional protein in the central nervous system. Original research. Connexin 43 heterozygous mice are used to assess its mutational effect on hearing. Results are compared to controls consisting of connexin 43, wild type and CBA/J mice. Hearing is assessed using auditory brainstem response and distortion product otoacoustic emissions tests. Distribution of connexin 43 in the organ of Corti and the retrocochlear auditory centers (eight nerve, cochlear nucleus, olivary complex, lateral lemniscus, inferior colliculus, respectively) is examined. Fluorescent markers are used to elucidate cell types. Mean click auditory brainstem response threshold for the young connexin 43 heterozygous mice (3-4 months) was 36.7 ± 12.6 dB compared to 25 ± 0 dB for control mice (P < 0.05). Mean threshold difference became more pronounced (68 ± 7.5 dB vs. 31 ± 2.2 dB) at 10 months (P < 0.05). Tonal auditory brainstem response testing showed elevated thresholds (>60 dB) at all frequencies (4-32 kHz) compared to the controls. Distortion product otoacoustic emissions (DPOAE) were present in all the mice, although the older connexin 43 heterozygous mice responded at higher thresholds. The pattern of connexin 43 immunoreactivity was distinctive from connexin 26 and 30, showing minimal presence in the organ of Corti but robustly present in the retrocochlear centers. Connexin 43 heterozygous mice demonstrated greater degree of hearing loss compared to age-matched controls. It is abundantly found in the retrocochlear auditory centers. The mechanism of hearing loss in these mice does not appear to be related to hair cell loss.

Loss of osteoprotegerin expression in the inner ear causes degeneration of the cochlear nerve and sensorineural hearing loss

Osteoprotegerin (OPG) is a key regulator of bone remodeling. Mutations and variations in the OPG gene cause many human diseases that are characterized by not only skeletal abnormalities but also poorly understood hearing loss: Paget's disease, osteoporosis, and celiac disease. To gain insight into the mechanisms of hearing loss in OPG deficiency, we studied OPG knockout (Opg−/−) mice. We show that they develop sensorineural hearing loss, in addition to conductive hearing loss due to abnormal middle-ear bones. OPG deficiency caused demyelination and degeneration of the cochlear nerve in vivo. It also activated ERK, sensitized spiral ganglion cells (SGC) to apoptosis, and inhibited proliferation and survival of cochlear stem cells in vitro, which could be rescued by treatment with exogenous OPG, an ERK inhibitor, or bisphosphonate. Our results demonstrate a novel role for OPG in the regulation of SGC survival, and suggest a mechanism for sensorineural hearing loss in OPG deficiency.

The study of auditory effects after concomitant radiotherapy and chemotherapy in patients with head and neck cancer

Aims and Objectives: The objective of this study was to assess the prevalence and patterns of hearing loss after concomitant radiochemotherapy in patients enrolled in a larynx preservation protocol. Materials and Methods: The study comprised of audiological evaluation of 30 patients prior to and at 1, 3, and 6 months after treatment using pure tone audiometry and impedance audiometry. Results: At the end of 6 months, 43.33% suffered sensorineural hearing loss (SNHL), 8.33% conductive hearing loss, 16.67% mixed hearing loss, and 6.67% showed improvement in hearing. Discussion: The possible mechanism for hearing loss are discussed and compared with the result of such studies in literature. Conclusion: There exist a small but definite potential risk of hearing loss after concomitant radiotherapy and chemotherapy in patients with head and neck cancer.

Mechanisms of Hearing Loss in Neurofibromatosis Type 2

IntroductionPatients with neurofibromatosis type 2 (NF2) develop bilateral cochleovestibular schwannomas (CVSs) that cause binaural deafness in most individuals. Hearing loss occurs in an unpredictable manner and the underlying mechanisms are not known. To gain insight into the pathophysiologic basis for hearing loss in NF2, we performed a prospective cross-sectional study of untreated ears in NF2 patients.MethodsOne hundred consecutive NF2 patients in a prospective natural history study were included. Clinical and audiometric data were analyzed for treatment naïve ears. In addition to standard MR-imaging sequences, alterations in intralabyrinthine protein content were determined utilizing high resolution FLAIR, the presence of cochlear aperture obstruction was determined by examining 3D T2 sequences, and endolymphatic hydrops was identified on delayed post-contrast FLAIR sequences.ResultsEighty-nine ears harboring 84 untreated CVSs in 56 consecutive NF2 patients (age 30±16 years) were analyzed. Thirty-four (38%) ears had varying degrees of hearing loss. Elevated intralabyrinthine protein was identified in 70 (75%) ears by FLAIR MR-imaging and was strongly associated with the presence of hearing loss (32/34 hearing loss ears; 94%)(Fisher's exact test; P = .005). Elevated intralabyrinthine protein was associated with the presence of CVS-associated cochlear aperture obstruction (64 of 67 ears with elevated protein; 96%)(Fisher's exact test; P<0.0001) in both normal and hearing loss ears. Elevated intralabyrinthine protein was not identified in ears without CVS (5 ears). While larger tumor size was associated with hearing loss (P = 0.006), 16 hearing loss ears (47%) harbored CVSs less than 0.5 cm3, including 14 ears (88%) with block of the cochlear aperture and elevated protein.DiscussionThese findings are consistent with a model in which hearing loss develops as a result of cochlear aperture obstruction and accumulation of intralabyrinthine protein. MRI based identification of elevated intralabyrinthine protein may help identify the ear at-risk for developing hearing loss.

Electrophysiological Insertion Properties in the Gerbil Using a Flexible Array

Aims: To evaluate our animal model of hearing preservation cochlear implantation and our ability to detect intracochlear trauma using a flexible electrode carrier in the gerbil. Background: Hearing preservation during cochlear implantation has become progressively more important. Specifically, non-traumatic electrode insertions might help to facilitate preservation and subsequent electric acoustic stimulation (EAS or Hybrid stimulation). However, the mechanisms of hearing loss during cochlear implantation remain unknown. In an effort to improve our understanding and the outcomes of hearing preservation during cochlear implantation, we have developed an animal model. This model allows us to record early auditory parameters during electrode insertions and thus correlate electrophysiological and mechanical findings. Previously, we demonstrated our ability to detect cochlear trauma using a rigid electrode. However, human surgery features flexible electrodes and in an effort to simulate this, we have developed a flexible array suitable for implantation in the gerbil.

Tissue‐specific calibration of extracellular matrix material properties by transforming growth factor‐β and Runx2 in bone is required for hearing

Physical cues, such as extracellular matrix stiffness, direct cell differentiation and support tissue-specific function. Perturbation of these cues underlies diverse pathologies, including osteoarthritis, cardiovascular disease and cancer. However, the molecular mechanisms that establish tissue-specific material properties and link them to healthy tissue function are unknown. We show that Runx2, a key lineage-specific transcription factor, regulates the material properties of bone matrix through the same transforming growth factor-β (TGFβ)-responsive pathway that controls osteoblast differentiation. Deregulated TGFβ or Runx2 function compromises the distinctly hard cochlear bone matrix and causes hearing loss, as seen in human cleidocranial dysplasia. In Runx2+/⁻ mice, inhibition of TGFβ signalling rescues both the material properties of the defective matrix, and hearing. This study elucidates the unknown cause of hearing loss in cleidocranial dysplasia, and demonstrates that a molecular pathway controlling cell differentiation also defines material properties of extracellular matrix. Furthermore, our results suggest that the careful regulation of these properties is essential for healthy tissue function.

Intratumoral hemorrhage and fibrosis in vestibular schwannoma: a possible mechanism for hearing loss

Vestibular schwannomas (VSs) are benign lesions with an unpredictable natural history. Perhaps the greatest barrier to predicting which patients need treatment is our poor understanding of how these tumors cause hearing loss in the first place. In this case-control study, the authors investigated the relationship between preoperative hearing loss and histological changes such as intratumoral microhemorrhage and extensive fibrosis. From a prospectively collected database, the authors selected all patients with VS who had undergone microsurgical resection as their initial treatment for histopathologically confirmed VS. Histological specimens obtained in 274 of these patients were systematically reviewed by a blinded neuropathologist who graded the extent of microhemorrhage and fibrosis in these tumors. The effect of these variables on preoperative hearing loss was studied using binary logistic regression. On univariate analysis, patients with extensive intratumoral microhemorrhage or fibrosis (p < 0.0001), patients with larger tumors (p < 0.05), and patients 65 years of age or older (p < 0.05) were significantly more likely to have unserviceable hearing at the time of surgery. On multivariate analysis, only patients with extensive intratumoral microhemorrhage or fibrosis had an increased risk of having unserviceable hearing at the time of surgery (OR 3.72, 95% CI 1.3-10; p = 0.01). Older age and tumor size greater than 3 cm were not statistically significant risk factors for hearing loss, controlling for the effect of microhemorrhage and fibrosis. In this study, the authors have demonstrated a correlation between the extent of nonneoplastic histological changes, such as microhemorrhage and fibrosis, and hearing loss. This alternate hypothesis has the potential to explain many of the exceptions to previously described mechanisms of hearing loss in patients with VS. The advent of high-resolution MR imaging technology to identify microhemorrhages may provide a method to screen for patients with VS at risk for hearing loss.

Building the mammalian cochlea — an overview

The mammalian cochlea is a highly intricate organ responsible for hearing. Numerous specialized cell types residing in the cochlear participate in processing and relaying sound information to the brain. In general, cells in the cochlea are divided into three major types: sensory, neural, and non-sensory. Sensory cells are a group of cells in the organ of Corti consisting of hair cells and supporting cells. Sensory hair cells play a primary role in detecting and processing sound in the form of vibrations. Neural cells are the neurons and glia in the spiral (cochlear) ganglion that relay the processed sound signals in the form of a neurotransmitter to the brain. Other non-sensory cells include all other cell types providing architectural and functional support. Building a functional cochlea requires tightly orchestrated, spatial and temporal regulation of gene expressions. Disruption of the normal gene expression patterns can cause developmental failure of the organ, which can lead to permanent hearing loss. Thus, comprehensive understanding of genes contributing to cochlear development is crucial for elucidating the pathological mechanisms of hearing loss. This article is intended to provide an overview of mammalian cochlear development, focusing on genes involved in its early patterning.

Role of oxidative stress in hearing impairment in patients with type two diabetes mellitus

Although many clinical investigations have found a relationship between hearing loss and diabetes mellitus, the pathophysiology of this effect remains controversial. To date, the mechanisms of hearing loss in diabetic patients have been explained in terms of microangiopathy, neuropathy and encephalopathy. However, many reports indicate that some diabetic complications are associated with oxidative stress related to the diabetes itself. In the present study, we hypothesised that oxidative stress may be a cause of hearing loss in diabetic patients. The study group comprised non-insulin dependent diabetic patients with no signs of microangiopathy or peripheral neuropathy. The control group comprised sex-, age- and body weight matched, non-diabetic subjects. Auditory function was evaluated using pure tone audiometry and tympanometry. Subjects with normal hearing and sensorineural hearing loss were included in the study, whereas subjects with conductive hearing loss were excluded. Both the study group (n = 63) and the control group (n = 37) were divided into subgroups based on the presence and absence of hearing loss. Oxidative stress was evaluated by measuring serum indicators of protein oxidation and lipid peroxidation, serum levels of nitric oxide and various non-enzymatic antioxidants, and the activity of various enzymatic antioxidants. The non-insulin dependent diabetic patients had significantly higher serum levels of protein oxidation products, nitric oxide, enzymatic antioxidant activity (i.e. glutathione peroxidase and superoxide dismutase), compared with the control group (p < 0.05). When we compared the groups in relation to the presence of hearing loss, the nitric oxide level was significantly increased in the diabetic group with good hearing, compared with diabetic patients with hearing loss (p = 0.014). In the diabetic group, a clear, negative correlation was observed between serum levels of nitric oxide and vitamins C and E, and hearing impairment (r = -0.395, r = -0.318, r = -0.500, respectively). There was also a positive correlation between serum vitamin C concentrations and hearing levels in the control group (r = 0.417). These results suggest that oxidative stress may play an important role in hearing impairment in diabetic patients. In this process, increased protein oxidation appears to be more important than lipid peroxidation. Nitric oxide may have a protective effect on hearing, as may some nonenzymatic antioxidants such as vitamin C and E.

Mechanisms of hearing loss from trauma and inflammation: otoprotective therapies from the laboratory to the clinic

This article reviews a series of in vitro and in vivo studies that examined the otoprotective efficacy of locally delivered dexamethasone and explored the mechanisms by which dexamethasone protects auditory hair cells. These studies used auditory threshold testing in response to pure tone stimuli, organ of Corti explant cultures, FITC-phalloidin-stained explants, and surface preparations to determine hair cell density, osmotic pump delivery of dexamethasone into the scala tympani, an animal model of electrode insertion trauma (EIT)-induced hearing loss, and real-time RT-PCR studies of gene expression levels. Local delivery of two different formulations of dexamethasone conserved hearing and protected hair cells in an animal model of cochlear implantation. Dexamethasone treatment protected hair cells in organ of Corti explants exposed to an ototoxic level of an inflammatory cytokine, and gene expression studies showed that this protection was accomplished by increased expression levels of anti-apoptosis genes (e.g. Bcl-2) and decreased levels of pro-apoptosis genes (e.g. Bax). We conclude that dexamethasone is an effective otoprotective drug for both the conservation of hearing and preservation of hair cells against trauma-induced losses. Locally delivered dexamethasone is a promising therapeutic approach for the conservation of hearing during the process of cochlear implantation.

UNDERWATER EARS AND THE PHYSIOLOGY OF IMPACTS: COMPARATIVE LIABILITY FOR HEARING LOSS IN SEA TURTLES, BIRDS, AND MAMMALS

From human and laboratory animal studies, we have extensive knowledge about mechanisms of hearing loss from noise as well as aging, trauma, genetic conditions, and disease. By contrast, little is known about causes of hearing loss in wild species. Although there is great concern for anthropogenic acoustic impacts in marine species, especially for marine mammals, we are far from a clear understanding of the potential scope of impacts on the thousands of marine species. We have acquired significant data on hearing in pinnipeds, cetaceans, and fish, but far less is known about hearing and possible impacts in turtles and seabirds and how or if they suffer irreparable hearing loss. This talk will review what is known about hearing loss mechanisms from human and animal studies and based on the comparisons for land and marine ears, how the combined data can aid us to understand how hearing may be impaired in marine animals. It will also examine the current evidence for natural loss processes (presbycusis, diseas...

Styrene Induced Alterations in Biomarkers of Exposure and Effects in the Cochlea: Mechanisms of Hearing Loss

It is known that styrene is ototoxic and causes cochlear damage starting from the middle turn. However, the cellular mechanism underlying styrene ototoxicity is still unclear. In this study, rats were exposed to styrene by gavage at different doses once a day for varying periods. Styrene levels in the cochlear tissues, styrene-induced permanent hearing loss, cochlear disruptions, and cell death pathways were determined. Styrene concentration in the cochlea varied along with the basilar membrane with the lowest level in the basal turn being consistent with the lowest styrene-induced threshold shift and hair cell loss in this region. After 3 weeks of exposure (5 days per week), a dose-dependent permanent hearing loss and a hair cell loss, especially in the midfrequency region, were observed. The styrene exposure at a dose of 200 mg/kg, which induced a blood level of 6.0 +/- 1.0 microg/g, caused an average of 4.4 +/- 0.5% OHC (outer hair cell) loss and 2-5 dB threshold shift in the cochlear region of 20-70% from the apex. A significant OHC loss was not observed until 7 days of exposure at a dose of 800 mg/kg. Deiters cells appeared to be the most vulnerable target of styrene. When condensed nuclei were observed in Deiters cells after a few days of styrene exposure (800 mg/kg), other cells were still intact. Apoptotic cell death appeared to be the main cell death pathway in the cochlea after styrene exposure. In the styrene-induced apoptotic OHCs, histochemical staining detected activated caspases-9 and 8, indicating that both mitochondrial-dependent pathway and death receptor-dependent pathway were involved in the styrene-induced cell death.

Audiological Features and Mitochondrial DNA Sequence in a Large Family Carrying Mitochondrial A1555G Mutation without Use of Aminoglycoside

To elucidate the pathophysiological and genetic mechanisms of hearing loss associated with the homoplasmic mitochondrial A1555G mutation in the absence of aminoglycoside exposure, we conducted audiological and genetic analyses on 67 maternally related members of a large Japanese family carrying this mutation. A consistent pattern was evident in the audiograms, with features of sensory presbycusis, cochlear origin at all levels of hearing loss, and a high degree of vulnerability of outer hair cells. That the degree of hearing loss was similar in affected subjects within the same sibling group but differed between sibling groups suggests the involvement of nuclear modifier genes. Total mitochondrial DNA sequences were completely identical among subjects with various levels of hearing loss, and lacked additional pathogenic mutations. For the diagnosis of sensorineural hearing loss, the mitochondrial A1555G mutation should be considered when these features are present even in the absence of aminoglycoside exposure.

The mechanism of hearing loss in Paget's disease of bone.

Objectives/HypothesisThe mechanism of hearing loss (HL) in Paget's disease of bone was investigated. The present study was a systematic, prospective, controlled set of clinical investigations to test the hypothesis that there is a general underlying mechanism of HL in Paget's disease of bone and to gain additional insights into the auditory and otologic dynamics of this disease. Specific questions were 1) whether the mechanism is cochlear or retrocochlear and 2) whether the bone mineral density of the cochlear capsule is related to hearing levels.Study DesignSeveral double-blinded, cross-sectional, prospective, correlational studies were conducted in a population of elderly human subjects with skull involvement with Paget's disease versus a control population of elderly subjects free of Paget's disease. Demographic and clinical data were recorded. Longitudinal observations were made in subjects under treatment.MethodsSubjects were recruited from a Paget's disease clinic. Pure-tone auditory thresholds, word recognition, and auditory brainstem responses (ABRs) were recorded. The dimensions of the internal auditory canals were measured using computed tomographic (CT) images and digital image analysis. The precision, accuracy, and temporal stability of methods to measure the bone mineral density of the cochlear capsule and an adjacent area of nonotic capsule bone were validated and applied. Correlations were sought between hearing levels and cochlear capsule bone mineral density.ResultsABRs were recorded in 64 ears with radiographically confirmed Paget's disease involving the skull. Responses were absent in eight ears, all of which had elevated high pure-tone thresholds. ABRs were interpreted as normal in 56 ears; none were abnormal. The mid-length diameter and minimum diameter of the internal auditory canal of 68 temporal bones from subjects with Paget's disease were found to have no statistically significant relationship to hearing thresholds. The Pearson product-moment correlation coefficients (age- and sex-adjusted) in the group with Paget's disease involving the temporal bone were −0.63 for left ears and −0.73 for right ears for high-frequency air conduction pure-tone thresholds (mean of 1, 2, and 4 kHz) versus cochlear capsule density. Correlation coefficients (age- and sex-adjusted) between cochlear capsule density and air-bone gap (mean at 0.5 and 1 kHz) for the affected group were −0.67 for left ears and −0.63 for right ears. All correlations between hearing thresholds and cochlear capsule density in pagetic subjects were significant at P < .001. The regressions were consistent throughout the ranges of hearing level. There were no significant correlations between cochlear capsule mean density and hearing level in the volunteer subjects.ConclusionsThe evidence supports the existence of a general, underlying, cochlear mechanism of pagetic HL that is closely related to loss of bone mineral density in the cochlear capsule. This mechanism accounts well for both the high-frequency sensorineural HL and the air-bone gap. Early identification, radiographic diagnosis of temporal bone involvement, and vigorous treatment with third-generation bisphosponates are important to limit the development and progression of pagetic HL.

C101 耳管開放症による伝音難聴と自声強聴発生機序の解明

C101 耳管開放症による伝音難聴と自声強聴発生機序の解明

Auditory dysfunction in Stickler syndrome.

To characterize the natural history and possible mechanisms of hearing loss in Stickler syndrome (OMIM 108300; or hereditary progressive arthro-ophthalmopathy) and to determine if the auditory phenotype is a useful discriminating feature for the differential diagnosis of this group of disorders. Multifamily study. Outpatient audiology and otolaryngology clinics at the Warren Grant Magnuson Clinical Center of the National Institutes of Health, Rockville, Md. Forty-six affected individuals from 29 different families segregating Stickler syndrome. Clinical audiologic and otolaryngological examinations were performed on all individuals, including pure-tone audiometry, speech audiometry, and middle ear immittance testing. Otoacoustic emissions, auditory brainstem response, infrared video electronystagmography, and temporal bone computed tomography were performed on a subset of participants. The hearing loss was most often sensorineural in adults, and approximately 28 (60%) of the 46 adult patients had 2 or more thresholds greater than the corresponding 95th percentile values for an age-matched, otologically normal population. The hearing loss most often affected high frequencies (4000-8000 Hz) and was generally no more progressive than that due to age-related hearing loss. Type A(D) tympanograms (classification using the Jerger model), indicating hypermobile middle ear systems, were observed in 21 (46%) of the 46 affected individuals. Computed tomography of the temporal bones revealed no inner ear malformations in 19 affected individuals. The hypermobile middle ear systems observed in ears with normal-appearing tympanic membranes represent a novel finding for Stickler syndrome and are likely to be a useful diagnostic feature for this disorder. The overall sensorineural hearing loss in type I Stickler syndrome is typically mild and not significantly progressive. It is less severe than that reported for types II and III Stickler syndrome linked to COL11A2 (OMIM 120290) and COL11A1 (OMIM 120280) mutations, respectively, or the closely related Marshall syndrome. This difference will be a useful discriminatory feature in the differential diagnosis of this group of disorders.

Hearing loss as a complication of Paget's disease of bone.

Hearing loss has long been known to be a complication of Paget's disease of bone. Older ideas about the mechanisms of hearing loss are being replaced by a new view based on experimental evidence from patients. Studies reviewed show no evidence of auditory nerve dysfunction and confirm a cochlear site of lesion. A loss of bone mineral density in the cochlear capsule is associated with both a high-tone hearing loss and a low-tone air-bone gap.

Efferent suppression of oto-acoustic emissions in acoustic neuroma

In a previous study1[1 PRasher D.K. & LUxon L.M. (1995). ] we postulated that one possible mechanism of hearing loss in patients with acoustic neuroma may be loss of efferent control of active mechanical tuning leading to loss of selectivity in the early stages and then loss of sensitivity. As the vestibular nerve is the carrier of the efferent bundle and acoustic neuromas arise from the Schwann cells of the vestibular nerve, disruption of the efferent fibres may affect the control of cochlear mechanics. This study explored this hypothesis further by examining the contralateral sound activated efferent suppression ofoto-acoustic emissions in 13 patients with an acoustic neuromawith hearing better than 30 dB. In all patients the suppression was significantly reduced on the side of the tumour and in nine of the 13 patients the suppression was also reduced on the unaffected side. In all cases, the transient evoked oto-acoustic emissions were within the normal range of amplitudes. Loss of efferent suppression in these patients with lesions in the cerebello-pontine angle indicates the involvement of theefferent auditory system and further implies that in those patients with bilateral loss of suppression, that not only is the vestibular nerve efferent bundle affected but also the superior olivary complex on the tumour side which controls the contralateral cochlear mechanics.

Hearing in the MRL/lpr mouse as a possible model of immune-mediated sensorineural hearing loss.

In order to clarify the possible mechanism of hearing loss in immune-mediated sensorineural hearing loss, basic research needed includes animal model studies. In the present investigation, we examined hearing thresholds and cochlear histologies of the MRL/lpr mouse which is now well-known as a model for pathology consistent with systemic lupus erythematosis (SLE). Present findings demonstrated that there were no statistically significant differences in auditory brainstem response (ABR) thresholds between 4- to 6-week-old "young" and 20- to 25-week-old "old" MRL mice. These differences were not sex-dependent. Under light microscopy, there were no abnormal morphological findings in the cochleas of either young or old MRL mice. With immunohistochemistry, mouse IgG was detected around the capillary walls in the stria vascularis in both young and old MRL mice. Serum IgG level of the MRL mice significantly decreased after predonisolone (PSL) administration. However, expression of mouse IgG in the stria vascularis was not observed in the MRL mice after PSL administration. From these results, we speculate that the hearing of the MRL mouse does not always deteriorate, and the deposition of mouse IgG on the capillary wall in the stria vascularis is not a sufficient factor to induce hearing loss. At this point, we conclude that the MRL mouse should not be considered a useful model for immune-mediated sensorineural hearing loss.

Effect of artificial endolymph injection into the cochlear duct on the endocochlear potential

We investigated the effect of acute endolymphatic hydrops on the positive endocochlear potential (+EP) and negative endocochlear potential (−EP). The +EP was measured in guinea pigs during injection (without outlet) and perfusion (with outlet) of artificial endolymph into the cochlear duct. The −EP was measured during anoxia after the injection or the perfusion had finished. Injection of artificial endolymph produced a slight transient increase in the +EP, and a significant decrease in the magnitude of the −EP. Chronic endolymphatic hydrops produces both +EP and −EP decrease. The +EP decrease in chronic endolymphatic hydrops may cause the chronic change of the inner ear. The +EP increase in acute endolymphatic hydrops may be caused by a shift of the basilar membrane. However, the mechanism of the `transient' +EP increase is not clear. The −EP decrease was not observed in animals whose cochlear duct was perfused with artificial endolymph. Therefore, the artificial endolymph itself did not cause the decrease in magnitude of the −EP. Dysfunction of the hair cells is a possible explanation for the −EP decrease but the mechanism of such a decrease is not clear in the present study. However, the results of this study support the notion that small increases in endolymphatic pressure below the resolution of recent measurements ( DeMott and Salt, 1997) can lead directly to a reduction of the −EP during hydrops. The animal model described here can eliminate the chronic effect of hydrops, therefore, this model is useful for investigations into the effect of hydrops itself on the inner ear and the mechanism of hearing loss in Ménière's disease.