Development Of Endolymphatic Hydrops Research Articles

Endolymphatic Hydrops on Magnetic Resonance Imaging May Be an Independent Finding on Aging in Neurotologic Patients.

To clarify whether age impacts the development of endolymphatic hydrops (ELH) in neurotologic patients. Documentation of ELH in living patients on magnetic resonance imaging (MRI) allows analysis of patient age and formation of ELH, which is impossible by means of postmortem temporal bone pathology. Retrospective case review. Tertiary referral center. Fifty patients (100 ears) with top 3 diagnoses of definite Menière's disease, delayed ELH, or probable Menière's disease. Endolymph MRI after intravenous gadolinium injection and pure-tone audiometry. Cochlear and vestibular ELH confirmed by MRI. The prevalences of ears showing both cochlear and vestibular ELH were similar among age groups <30 years (30%), 30-59 years (25.9%), and ≥60 years (34.4%; p > 0.05; χ2 test). Using logistic regression modeling, mean hearing level at the six frequencies was positively associated with a higher risk of cochlear ELH (odds ratio, 1.3; 95% confidence interval, 1.1-1.5 per 10-dB increment). In the same regression model, age did not impact the outcome of cochlear ELH (odds ratio, 1.0; 95%confidence interval, 0.7-1.4 per 10-year increment). Age did not differ among ears with no ELH (mean ± standard deviation age, 48.6 ± 14.4 yr), ears with only cochlear ELH (59.3 ± 10.7 yr), ears with only vestibular ELH (50.4 ± 16.9 yr), or ears with both cochlear and vestibular ELH (51.5 ± 18.4 yr; p > 0.05, analysis of variance). Chronological age was not associated with the formation of ELH. Aging per se may not be associated with the development of ELH in neurotologic patients.

The Concept of a Rupture Risk Envelope for the Cochleo-Saccular Membranes.

Introduction Alterations in endolymphatic pressure have long been suspected of being associated with the development of endolymphatic hydrops and rupture of the membranous labyrinth. More recently, there has been a focus on how membrane mechanics might contribute to membrane rupture. This is suspected to involve the viscoelastoplastic properties of these membranes. Objective To construct a rupture risk envelope for the cochleo-saccular membranes based on viscoelastoplasticity to provide insight into lesion behavior in Meniere disease. Methods Reported deformation data from a collagen model of the cochleo-saccular membranes was utilized. Yield stress was defined as 80% of ultimate failure stress. The yield points at various strain rates were used to construct a rupture risk envelope for the membranes. Results The rupture risk envelope was found to be downward sloping in configuration. At the highest strain rate of 385% per minute, the membrane yield was associated with greater stress (7.0 kPa) and lesser strain (30%); while at the lowest strain rate of 19.2% per minute, there was substantially less membrane yield stress (4.3 kPa) but it was associated with greater strain (44%). Conclusion The concept of a rupture risk envelope based on viscoelastoplasticity provides insight into hydropic lesion behavior in Meniere disease. This concept helps to explain how variations in membrane distensibility might occur as suspected in the double hit theory of lesion generation in Meniere disease. Slowly developing lesions would appear have a lower rupture risk while rapidly developing lesions would appear to have a greater risk of early membrane rupture.

Pathophysiologic Findings in the Human Endolymphatic Sac in Endolymphatic Hydrops: Functional and Molecular Evidence.

The endolymphatic sac (ES) is a cystic structure situated on the posterior fossa dura and is connected to the luminal space of the vestibular organ through the endolymphatic duct, which branches into the utricular and saccular ducts. Unlike the cochlea and vestibule, the ES does not contain sensory epithelium in its luminal space, and a single layer of epithelial cells line the luminal surface area. The ES in the inner ear is thought to play a role in the regulation of inner ear homeostasis, fluid volume, and immune reaction. If these functions of the ES are disrupted, dysfunction of the inner ear may develop. The most well-known pathology arising from dysfunction of the ES is endolymphatic hydrops, characterized by an enlarged endolymphatic space due to the accumulation of excessive endolymphatic fluid. Although, molecular identities and functional evidence for the roles were identified in animal studies, basic studies of the human ES are relatively uncommon compared with those using animal tissues, because of limited opportunity to harvest the human ES. In this study, molecular and functional evidence for the role of the human ES in the development of endolymphatic hydrops are reviewed. Although evidence is insufficient, studies using the human ES have mostly produced findings similar to those of animal studies. This review may provide a basis for planning further studies to investigate the pathophysiology of disorders with the finding of endolymphatic hydrops.

Intratympanic gadolinium magnetic resonance imaging supports the role of endolymphatic hydrops in the pathogenesis of immune-mediated inner-ear disease.

To evaluate the presence of endolymphatic hydrops in patients with immune-mediated inner-ear disease. The presence of endolymphatic hydrops was prospectively evaluated in 17 patients clinically diagnosed with secondary (n = 5) or primary (n = 12) immune-mediated inner-ear disease, who attended the ENT department of a tertiary care centre for evaluation or treatment over the previous year. All patients underwent magnetic resonance imaging of the temporal bone. Intratympanic gadolinium three-dimensional magnetic resonance imaging diagnosed hydrops in 11 of 12 patients with primary immune-mediated inner-ear disease (92 per cent). Of these, seven patients (64 per cent) presented only cochlear (n = 5) or predominantly cochlear (n = 2) hydrops. A positive magnetic resonance imaging result was observed in only one of five patients with secondary immune-mediated inner-ear disease (20 per cent). This study confirms the presence of endolymphatic hydrops in immune-mediated inner-ear disease patients. The virtual absence of hydrops in patients with secondary immune-mediated inner-ear disease is remarkable, although firm conclusions cannot be drawn; this should be explored in a multicentre study with a larger sample of patients. A different immune reaction without development of endolymphatic hydrops should not be ruled out in secondary immune-mediated inner-ear disease patients.

Inhibition of phosphodiesterase 3, 4, and 5 induces endolymphatic hydrops in mouse inner ear, as evaluated with repeated 9.4T MRI

Conclusion: The data indicate important roles for phosphodiesterase (PDE) 3, 4, 5, and related cAMP and cGMP pools in the regulation of inner ear fluid homeostasis. Thus, dysfunction of these enzymes might contribute to pathologies of the inner ear.Objective: The mechanisms underlying endolymphatic hydrops, a hallmark of inner ear dysfunction, are not known in detail; however, altered balance in cAMP and cGMP signaling systems appears to be involved. Key components of these systems are PDEs, enzymes that modulate the amplitude, duration, termination, and specificity of cAMP and cGMP signaling.Method: To evaluate the role of PDE3, 4, and 5 and associated cAMP and cGMP pools in inner ear function, the effect of cilostamide (PDE3 inhibitor), rolipram (PDE4 inhibitor), and sildenafil (PDE5 inhibitor), administrated via mini-osmotic pumps, on mouse inner ear fluid homeostasis was evaluated using 9.4T in vivo MRI in combination with intraperitoneally administered Gadolinium contrast. Also, using human saccule as a model, the expression of PDEs and related signaling molecules and targets was studied using immunohistochemistry.Results: PDE3, PDE4, as well as PDE5 inhibitors resulted in the development of endolymphatic hydrops. Furthermore, PDE3B, PDE4D, and some related signaling components were shown to be expressed in the human saccule.

Preceding profound deafness and co-factors promote development of endolymphatic hydrops in preliminary patients with delayed endolymphatic hydrops

Conclusion: Profound deafness (PD) is unlikely to be the only cause of endolymphatic hydrops (EH) in patients with delayed endolymphatic hydrops (DEH). Further studies in large patient cohorts are required to determine the etiologic co-factors involved in the development of EH in patients with PD and DEH.Objectives: DEH usually occurs in patients with sustained unilateral PD who then develop episodic vertigo or fluctuating hearing loss. The latency can vary markedly between PD and development of DEH, but the factors affecting inner ear homeostasis and causing EH during this latency period remain unclear. The study aimed to assess the differences in EH and functional status of the inner ear between patients with PD only and those with DEH.Method: Two PD and 10 DEH patients who had developed PD in early childhood were enrolled. Gadolinium-enhanced magnetic resonance imaging of the inner ear was performed in all patients to assess the degree of EH in the vestibule and cochlea.Results: There was no evidence of EH in the affected ears of patients with PD alone. DEH patients, however, showed significant EH in either the cochlea or vestibule, suggesting that EH development and DEH onset were strongly correlated.

Vasopressin induces endolymphatic hydrops in mouse inner ear, as evaluated with repeated 9.4 T MRI

From histopathological specimens, endolymphatic hydrops has been demonstrated in association with inner ear disorders. Recent studies have observed findings suggestive of hydrops using MRI in humans. Previous studies suggest that vasopressin may play a critical role in endolymph homeostasis and may be involved in the development of Ménière's disease. In this study we evaluate the effect of vasopressin administration in vivo in longitudinal studies using two mouse strains. High resolution MRI at 9.4 T in combination with intraperitoneally delivered Gadolinium contrast, was performed before and after chronic subcutaneous administration of vasopressin via mini-osmotic pumps in the same mouse. A development of endolymphatic hydrops over time could be demonstrated in C57BL6 mice (5 mice, 2 and 4 weeks of administration) as well as in CBA/J mice (4 mice, 2 weeks of administration; 6 mice, 3 and 4 weeks of administration). In most C57BL6 mice hydrops developed first after more than 2 weeks while CBA/J mice had an earlier response. These results may suggest an in vivo model for studying endolymphatic hydrops and corroborates the future use of MRI as a tool in the diagnosis and treatment of inner ear diseases, such as Ménière's disease. MRI may also be developed as a critical tool in evaluating inner ear homeostasis in genetically modified mice, to augment the understanding of human disease.This article is part of a Special Issue entitled <IEB Kyoto>.

Developmental changes of ENaC expression and function in the inner ear of pendrin knock-out mice as a perspective on the development of endolymphatic hydrops.

Pendrin mutations cause enlarged vestibular aqueducts and various degrees of sensorineural hearing loss. The selective abolition of pendrin causes dilation of the membranous labyrinth known as endolymphatic hydrops, loss of the endocochlear potential, and consequently loss of hearing function. Because Na+ transport is one of the most important driving forces for fluid transport, the epithelial Na+ channel (ENaC) is believed to play an important role in fluid volume regulation in the inner ear. Therefore, the dysfunction of Na+ transport through ENaC by the acidification of endolymph in Pendred syndrome is one of the potential causes of endolymphatic hydrops. We investigated the changes of ENaC expression and function during the development of the pendrin knock-out mouse. In the cochlea, the expression of β and γENaC was significantly increased at P56 in Pds−/− mice compared with Pds+/+ mice. In the vestibule, the expression of βENaC was significantly increased at P56, and γENaC expression significantly increased from P6 to P56 in Pds−/− mice. The ENaC-dependent trans-epithelial current was not significantly different between Pds+/+ and Pds−/− mice in Reissner’s membrane or the saccular extramacular roof epithelium at P0, but the current was significantly increased in Pds−/− mice at P56 compared with Pds+/+ mice. These findings indicate that the expression and function of ENaC were enhanced in Pds−/− mice after the development of endolymphatic hydrops as a compensatory mechanism. This result provides insight into the role of Na+ transport in the development and regulation of endolymphatic hydrops due to pendrin mutations.

Objective Measurement of the Human Endolymphatic Sac Dimensions in Ménière's Disease

To identify structural differences between the endolymphatic sac of temporal bones with and without Ménière's disease by applying design-based stereology. The dimension of the human endolymphatic sac has previously been studied by extrapolating 2-dimensional irregularities on the sectional level into 3-dimensional quantities via unfolding algorithms. These computer renderings require certain geometrical assumptions of the object studied. The term design-based used in the present study signifies that the methods and sampling schemes are defined a priori, in such a manner that consideration of the size, shape, spatial orientation, and distribution of the investigated structures are eliminated. Archival materials of 15 human temporal bones with Ménière's disease and 15 control specimens were investigated by design-based stereology. The total surface area of the endolymphatic sac was significantly lower in the Ménière's disease group (24.8 mm) compared with the control group (47.0 mm), p = 0.006. The volume fraction of the homogenous substance was significantly higher in the Ménière's disease group (17.5%) compared with the control group (5.7%), p = 0.031. No significant differences were found between the volumes of the homogenous substance, the volumes of the endolymphatic sac, and the surface-to-volume ratio in the 2 groups. The study revealed a large biological variation. Design-based stereology is a robust, unbiased and efficient tool to quantify 3-dimensional structures derived from 2-dimensional histologic sections. A 2-fold reduction in the surface area of the endolymphatic sac and a 3-fold increase in the volume fraction of homogenous substance in temporal bones with Ménière's disease may, at least in part, be involved in the dysfunction of endolymph fluid homeostasis and the development of endolymphatic hydrops.

Oxidative Stress, Redox Homeostasis and Cellular Stress Response in Ménière’s Disease: Role of Vitagenes

Ménière's disease (MD) is characterized by the triad of fluctuating hearing loss, episodic vertigo and tinnitus, and by endolymphatic hydrops found on post-mortem examination. Increasing evidence suggests that oxidative stress is involved in the development of endolymphatic hydrops and that cellular damage and apoptotic cell death might contribute to the sensorineural hearing loss found in later stages of MD. While excess reactive oxygen species (ROS) are toxic, regulated ROS, however, play an important role in cellular signaling. The ability of a cell to counteract stressful conditions, known as cellular stress response, requires the activation of pro-survival pathways and the production of molecules with anti-oxidant, anti-apoptotic or pro-apoptotic activities. Among the cellular pathways conferring protection against oxidative stress, a key role is played by vitagenes, which include heat shock proteins (Hsps) as well as the thioredoxin/thioredoxin reductase system. In this study we tested the hypothesis that in MD patients measurable increases in markers of cellular stress response and oxidative stress in peripheral blood are present. This study also explores the hypothesis that changes in the redox status of glutathione, the major endogenous antioxidant, associated with abnormal expression and activity of carbonic anhydrase can contribute to increase oxidative stress and to disruption of systemic redox homeostasis which can be associated to possible alterations on vulnerable neurons such as spiral ganglion neurons and consequent cellular degeneration. We therefore evaluated systemic oxidative stress and cellular stress response in patients suffering from Meniere's disease (MD) and in age-matched healthy subjects. Systemic oxidative stress was estimated by measuring protein oxidation, such as protein carbonyls (PC) and 4-hydroxynonenal (HNE) in lymphocytes of MD patients, as well as ultraweak luminescence (UCL) as end-stable products of lipid oxidation in MD plasma and lymphocytes, as compared to age-matched controls, whereas heat shock proteins Hsp70 and thioredoxin (Trx) expression were measured in lymphocytes to evaluate the systemic cellular stress response. Increased levels of PC (P < 0.01) and HNE (P < 0.05) have been found in lymphocytes from MD patients with respect to control group. This was paralleled by a significant induction of Hsp70, and a decreased expression of Trx (P < 0.01), whereas a significant decrease in both plasma and lymphocyte ratio reduced glutathione GSH) vs. oxidized glutathione (GSSG) (P < 0.05) were also observed. In conclusion, patients affected by MD are under condition of systemic oxidative stress and the induction of vitagenes Hsp70 is a maintained response in counteracting the intracellular pro-oxidant status generated by decreased content of GSH as well as expression of Trx. The search for novel and more potent inducers of vitagenes will facilitate the development of pharmacological strategies to increase the intrinsic capacity of vulnerable ganglion cells to maximize antidegenerative mechanisms, such as stress response and thus cytoprotection.

Non-specific immunological determinations in Meniere’s disease: any role in clinical practice?

Several studies supported the hypothesis that an autoimmune response may be a pathogenetic factor in Meniere's disease occurrence. It has been demonstrated that the endo-lymphatic sac has an important role in the immuno-mediated reaction and it has also become evident that an immunological mechanism may be involved in the development of endo-lymphatic hydrops. The present study was carried out in order to analyse the validity of serological non-specific immune tests in determining the possible role of immune pathology in 200 Meniere's suffering patients. The immune activity was investigated determining the erythrocyte sedimentation rate (ESR), the C-reactive protein levels, the rheumatoid factor, the serum immunoglobulin levels by group, the complement levels, the lymphocyte sub-populations, the cryoglobulines, the circulating immune complexes (CIC), organ and non-organ auto-antibodies. Levels of Ig, ESR, C-reactive protein, rheumatoid factor, complement fractions and cryoglobulines were either negative or non-significant in the considered cohort of Meniere's disease suffering patients. On the other hand, in more than half of the sample group high values of CIC were found. Data concerning T-lymphocyte sub-population indicates a clear increase in T-helper compared to T-cytotoxic cells, with an increase in the CD4/CD8 ratio. The datum of particular interest concerns analysis of T-cells activation complexes. Our present findings show that early activated T-lymphocytes change and in particular changes occur in the expression of the interleukin-2 receptor. Moreover, it seems to be possible to correlate the alteration of the immunological tests and the phase of the disease. Present data showed that the immunological factor should be considered a relevant element in most of the cases of Menière's disease.

Activation of caspase-3 is associated with oxidative stress in the hydropic guinea pig cochlea

The aim of this study was to investigate the involvement of oxidative stress and apoptosis in an animal model of Menière’s disease. Endolymphatic hydrops (ELH) is generally accepted as the decisive histological characteristic of Menière’s disease.Closure of the endolymphatic duct (Kimura’s method) was used to induce endolymphatic hydrops in guinea pigs. Sham-operated animals served as controls. After 4 weeks the animals operated showed a significant elevation of the hearing thresholds as measured by audiometric brainstem responses (ABR) pre- and postoperatively. Immediately after the second ABR measurement, the animals were sacrificed for further immunohistological examinations of the inner ear with specific antibodies to active caspase-3 (cas-3) as a marker for apoptosis and antibodies to 8-isoprostane (8-iso) and nitrotyrosine (NT) as indicators of oxidative stress.Compared with the sham-operated controls, hydropic cochleae showed strong immunostaining for both oxidative stress markers in spiral ganglion cells, in the blood-vessels and fibrocytes of the lateral wall, as well as in supporting cells of the organ of Corti. Activation of cas-3 in spiral ganglion cells and the lateral wall was found exclusively in hydropic cochleae.Our findings suggest that oxidative stress is involved in the development of endolymphatic hydrops and may lead to cellular damage which induces apoptosis by activation of cas-3. Apoptotic cell death might contribute to the sensorineural hearing loss found in later stages of Menière’s disease.

Cochlear Function in Ears with Immunomediated Inner Ear Disorder

The aim of the present study was to evaluate the performance of ears with inner ear disorder, responsive to immunosuppressive drugs, in advanced tests designed to assess primary cochlear functions (temporal integration, frequency selectivity, cochlear mechanics). The results of this study suggest that immunomediated inner ear disease results, in the acute clinical stage, in the development of endolymphatic hydrops, which increases the stiffness of the vibrating structures within the inner ear and causes dysfunctions of the outer hair cells. Our patients presented with upsloping or flat sensorineural hearing loss, absence of evoked otoacoustic emissions and distortion-product otoacoustic evoked emissions and abnormal temporal integration, frequency selectivity and cochlear mechanics. Following immunosuppressive treatment, hydrops recovered, hearing subsequently returned to normal, the audiometric curve became flat at low-to-middle frequencies and primary cochlear function tended to normalize. This study seems to support the usefulness of testing primary cochlear functions in order to monitor the clinical course of immunomediated inner ear disorders.

Intercellular Adhesion Molecule-1 Expression in the Inner Ear of Rats following Secondary Immune Reaction in the Endolymphatic Sac

An immunological aetiology for inner ear diseases has long been proposed. The endolymphatic sac (ES) is the only immunoprivileged site in the inner ear with a resident population of immunocompetent cells. By keyhole limpet hemocyanin (KLH) challenge into the ES of systemically pre-immunized guinea pigs, we previously demonstrated an infiltration of inflammatory cells into the perilymphatic space of the cochlea. In order to understand the mechanisms involved in the recruitment of immunocompetent cells into the inner ear, and their relation to the development of endolymphatic hydrops (EH), we investigated the expression and time-kinetics of intercellular adhesion molecule 1 (ICAM-1) in the inner ear of systemically pre-immunized rats after antigen (KLH) challenge into the ES, its relation to cell infiltration in the cochlea and subsequent development of EH. By immunohistochemistry, strong ICAM-1 expression was detected in the spiral ligament, suprastrial region, spiral prominence, spiral modiolar veins, spiral collecting venules, surface membrane of the perilymphatic compartment, perilymphatic space and ES of immunized rats, but not of control rats. ICAM-1 expression was detected at 5-6 h, peaked at 10-15 h, and gradually reduced by 2 weeks. Cell infiltration into the cochlea started at 6-12 h and peaked at day one. By 6 h, 50% of challenged rats developed EH. This figure rose to 70% at 12 h, and then gradually reduced. However, immunoreactivity for KLH (antigen) was only detected in the ES. These results emphasize that the sac is the central immunological organ of the inner ear, and suggest that ICAM-1 may play a pivotal role in the aetiology of immune-mediated inner ear diseases through the recruitment of immunocompetent cells into the inner ear and subsequent development of EH.

Submillimeter magnetic resonance imaging of the temporal bone in Meniere's disease.

The pathoetiology of Meniere's disease remains elusive. Histopathologic and imaging studies have implicated congenital or developmental abnormality of the endolymphatic duct as a likely predisposing factor to the development of endolymphatic hydrops and clinical Meniere's disease. Recently, improved high-resolution magnetic resonance imaging (MRI) protocols have allowed better demonstration of the soft tissues of the endolymphatic duct and sac. This study is a prospective evaluation of the ability of submillimeter MRI to detect the endolymphatic duct in Meniere's disease patients and control subjects. In addition, the development of the temporal bone in the region of the endolymphatic sac and duct is evaluated by measurements of the distance from the posterior semicircular canal to the subarachnoid space and the distance from the vestibule to the subarachnoid space. Visualization of the endolymphatic duct was found to be significantly less frequent in the Meniere's disease patients (29%) than in the control subjects (91%). Temporal bone measurements in the region of the endolymphatic duct showed patients with Meniere's disease to have smaller dimensions than control subjects.

Acoustic trauma and development of endolymphatic hydrops among the personnel in the self defense forces

An investigation was carried out among the military personnel in the Self Defense Forces to assess acoustic trauma in association with the onset of endolymphatic hydrops (ELH). Four hundred seventy servicemen were offered general physical examinations in an inpatient setting prior to their discharge from the SDF for mandatory age retirement. A questionnaire on the history of intense acoustic exposure and of dizzy spells was given to the same individuals. A routine ENT examination and audiography were performed for each of them. The following results were noteworthy: five men had a history of Ménière's disease, and 32.5 percent of those questioned had experienced dizzy spells. Hearing thresholds in those who reported that they had had dizzy spells were considerably higher than those who had not had such spells. Although a quantitative analysis as well as a well-established control study seems necessary to implicate acoustic trauma as one of the etiological factors of ELH, this study strongly suggests a relationship between acoustic trauma and development of ELH among the SDF personnel examined.

The Relationship between Vasopressin and Endolymphatic Hydrops in the Guinea Pig

Clinical studies have shown that plasma vasopressin level is significantly elevated in patients with Meniere's disease. Other reports indicated that histamine induced a very quick and high elevation of vasopressin level and caused nystagmus in experimentally produced endolymphatic hydrops. We became interested in further investigating the details of this relationship by studying the effect of experimental endolymphatic hydrops and histamine upon plasma vasopressin level in the guinea pig. The results are as follows: 1) Histamine increased the plasma vasopressin level in normal guinea pigs. 2) There was no statistically significant difference in the plasma vasopressin level between the hydrops model and normal guinea pigs. 3) Histamine increased the plasma vasopressin level more in the hydrops model group than in normals. 4) Plasma vasopressin level was elevated in the vertiginous model caused by inner ear anesthesia. Our results support those of clinical investigators who reported that the plasma vasopressin level was elevated more in the Meniere's disease group than any other equilibrium disorder group. It is possible that vasopressin is in someway involved in the development of endolymphatic hydrops.

Endolymphatic hydrops induced by immune response of the endolymphatic sac: relation to perilymph antibody levels.

This study investigated the effect of a secondary immune response in the endolymphatic sac on the development of endolymphatic hydrops in guinea pigs. Following secondary keyhole limpet hemocyanin (KLH) challenge directly to the sac in systemically presensitized animals, hydrops rapidly developed within 1 week, then gradually reduced by 4 weeks. After 5 weeks, hydrops gradually recurred and developed again. Mean perilymph anti-KLH antibody levels rose from day 1 to 4 weeks and then decreased. The elevation of perilymph anti-KLH antibody levels on day 2 was due to an increased vascular permeability and there was a local regeneration by the challenge of the sac after day 7. The development of hydrops correlated well with mean perilymph anti-KLH antibody levels in the period from day 1 to day 7. After 2 weeks, there was no correlation between them. These results suggest that an immune response of the sac may induce an excess secretion of endolymph in the initial stage and may further lead to irreversible dysfunction of the sac at a later stage.

Time-related alteration of endolymph composition in an experimental model of endolymphatic hydrops.

The electrochemical changes of the inner ear fluids were studied in the guinea pig during the development of endolymphatic hydrops in an experimental model of Meniere's disease obtained by the blockage of the vestibular aqueduct. The endocochlear potential (first and third turns) was recorded, and the sodium, potassium, and chloride concentrations, and osmolality of the endolymph (first and third turns) and perilymph were determined at different intervals from 2 to 24 weeks after the induction of the hydrops. The development of hydrops was monitored by the compound action potential once a week during the observation period. In normal, nonoperated guinea pigs, longitudinal endolymphatic gradients of endocochlear potential, potassium and chloride concentrations, and osmolality, increasing from the apex to the base of the cochlea, were observed. After 2 weeks of hydrops, no alteration of this pattern was detected. After 6 and 9 weeks of hydrops, a progressive decrease of endocochlear potential, potassium and chloride concentrations, and osmolality was noticed at the first turn (6 and 9 weeks) and then at the third turn (9 weeks) which resulted in the disappearance of longitudinal gradients. At 24 weeks, the endocochlear potential was still diminished by 60%, whereas potassium and chloride concentrations and osmolality increased as compared to 9-week values but remained lower than in controls. The changes in composition of endolymph induced by the development of the hydrops could be related to the progressive alteration of the ionic permeability of the cochlear epithelium, which should be localized at the distended Reissner's membrane.

Development of endolymphatic hydrops following immune response in the endolymphatic sac of the guinea pig.

The present study investigated immune injury associated with endolymphatic hydrops (e.hydrops) following locally mounted immune reaction in the endolymphatic sac (e.sac) of guinea pigs. E.hydrops occurred, progressing rapidly within the first week post secondary Keyhole limpet hemocyanin (KLH) challenge in the e.sac and developed into two phases, acute and chronic. On the other hand, primary KLH challenge of the e.sac, PBS inoculation into the e.sac or intradural secondary KLH challenge were incapable of inducing e.hydrops. These results indicate that reversible and irreversible e.hydrops are induced by the immune response of the e.sac, suggesting that local immunological events of the e.sac may provide an animal model of Meniere's disease.