Impact of endolymphatic hydrops on the function of the horizontal canal during caloric stimulation in Ménière's disease.

PURPOSE: When a dizzy patient with episodic vertigo has an abnormal caloric and a normal video head impulse test (vHIT), this caloric-vHIT dissociation provides vital information for a diagnosis of Ménière's disease (MD). Endolymphatic hydrops (EH), a histological marker of MD, is hypothesized to be involved in the caloric-vHIT dissociation in MD through hydropic duct distension of the horizontal semicircular canal (SC). This study was designed to determine the impact of EH on the function of horizontal SC during caloric stimulation. METHODS: Caloric test and vHIT were used to evaluate the function of horizontal SC every six months, annual magnetic resonance imaging (MRI) was used to evaluate the degree of EH size in the vestibule, and monthly vertigo and hearing evaluation was done for 12 months. EH shrinkage was defined as the size change of vestibular EH from significant to none. RESULTS: Among 133 MD patients evaluated for eligibility, 67 patients with caloric-vHIT dissociation entered the study. Fifteen participants had EH shrinkage (G-I), while 52 participants had no remarkable EH change (G-II). Average values (IQR) of the maximum slow phase velocity in G-I and G-II were 29.6 (13.0-34.0) and 25.9 (17.3-31.3), respectively, at baseline, 26.1 (9.0-38.0) and 23.6 (18.0-28.3) at 12 months. Two-factor repeated-measures ANOVA showed no significant differences between the groups (P = 0.486). The values of vestibulo-ocular reflex gain of the horizontal SC in G-I and G-II remained above 0.8 during the study period. CONCLUSIONS: EH detected by MRI shows limited correlation with caloric stimulation results.

Factors associated with spontaneous nystagmus changes in acute Ménière's disease.

BACKGROUND: Neuro-otological factors that influence changes in spontaneous nystagmus (SN) during vertigo attacks in Ménière's disease (MD) remain unclear. OBJECTIVE: To identify neuro-otological factors that might influence the initial direction of SN and the directional change of SN. METHODS: A prospective, observational study of 22 patients with definite MD to evaluate the initial direction and directional change of SN during vertigo attacks, endolymphatic hydrops (EH) volume, and the function of horizontal semicircular canal and hearing levels. RESULTS: SN consistently began as irritative in 17 of 22 cases, and 9 of 17 cases showed a definite change in direction after onset. SN consistently began as paralytic in 5 of 22 cases, and 3 of 5 cases showed a definite change in direction after onset. Subjects in the irritative initial SN group had less severe degrees of hearing loss, smaller cochlear and vestibular EH volume than the paralytic initial SN group (P = 0.017, < 0.001, and 0.009, respectively). Subjects in the SN direction change group had significantly smaller maximum slow phase velocity, percentage of caloric weakness and canal paresis than the no SN direction change group (P = 0.001, 0.006, and 0.001, respectively). Simple logistic regression analysis showed that smaller EH volume was significantly associated with initial irritative SN (OR = 0.867, 95% CI 0.762-0.988, P = 0.032) and that the degree of canal paresis was negatively associated with the presence of directional change of SN (OR = 0.022, 95% CI 0.002-0.289, P = 0.004). CONCLUSIONS: The morphology of EH and canal paresis may independently affect the characteristics of SN in patients with MD.

Assessment of inner ear morphology and function in response to local positive pressure for Ménière's disease: a nonrandomized controlled trial.

Ménière's disease (MD) is an inner ear disorder in which the main pathological feature is endolymphatic hydrops (EH). Positive pressure therapy (PPT) using a portable device is now a second-line therapy for intractable MD when initial medical treatment fails. However, it remains unknown whether PPT causes the morphological and functional changes of inner ear in patients with active MD in accordance with reduction of vertigo attacks. In this nonrandomized controlled trial of 52 patients with MD, the volume of EH significantly decreased with reduction of vertigo attacks during 8 months of PPT combined with medications while the volume of that significantly increased with medications alone. There was no difference between Control group (n = 26) and PPT group (n = 26) regarding the vertigo control, however, PPT group achieved a significant functional improvement of vertical semicircular canals. The effect of volume reduction by PPT has been firstly demonstrated and the functional changes of all semicircular canals during PPT have been firstly examined. Morphological and functional changes in the inner ear by administrating local positive pressure are quite different from those caused by medications alone.Clinical trial registration: UMIN-CTR UMIN000041164 (registered on July 20, 2020).

Antivertiginous Effect of Caloric Stimulation for Acute Peripheral Vertigo.

OBJECTIVE: To clarify therapeutic effect of caloric stimulation for acute peripheral vertigo. PATIENTS: Two patients with acute peripheral vertigo accompanied by spontaneous nystagmus. INTERVENTIONS: Therapeutic. MAIN OUTCOMES AND MEASURES: Changes in the maximum slow phase velocity of spontaneous nystagmus and subjective vertigo. RESULTS: Reduction in the maximum slow phase velocity of spontaneous nystagmus and mitigation of subjective vertigo was observed in both patients. CONCLUSION: Caloric stimulation could be one potential option as a suppressant for acute peripheral vertigo.

Case Report: Positive Pressure Therapy Combined With Endolymphatic sac Surgery in a Patient With Ménière's Disease.

Positive pressure therapy (PPT) is applied for medically-intractable vertigo in Ménière's disease (MD); however, it remains unknown whether PPT affects in vivo endolymphatic hydrops (EH). In this case report, we describe a 5-year course of MD in a patient in which EH was repeatedly observed. As the patient experienced recurrent vertigo attacks after endolymphatic sac surgery, he began to use the PPT device additionally and vertiginous episodes decreased in accordance with a decrease in the EH volume. The mechanism of PPT is suggested that the pressure increase in the middle ear inhibits EH development. PPT, if added after surgery, might be more effective to reduce EH volume compared with surgery alone. A larger study group size is required to test these preliminary data concerning EH changes.

Rupture-Like Shrinkage and Regrowth of Endolymphatic Hydrops in Ménière's Disease During Remission.

OBJECTIVE: To clarify pathophysiological characteristics of Ménière's disease during the remission phase. PATIENTS: Two Ménière's disease patients with different disease durations, whose endolymphatic hydrops was longitudinally observed using 3-T magnetic resonance imaging. INTERVENTIONS: Diagnostic. MAIN OUTCOMES AND MEASURES: Morphological changes of endolymphatic hydrops visualized using 3-T magnetic resonance imaging. RESULTS: Rupture-like shrinkage and regrowth of endolymphatic hydrops during the remission phase was observed in both patients. CONCLUSION: The remission phase with hearing improvement could be as important as vertigo attacks in Ménière's disease.

Assessment of the Progression of Vertical Semicircular Canal Dysfunction and Increased Vestibular Endolymphatic Hydrops in Patients With Early-Stage Ménière Disease.

Importance: Vertical semicircular canals and endolymphatic hydrops play important roles in the pathophysiological mechanisms of Ménière disease. However, their characteristics and associations with disease progression during medical treatment have not been determined. Objective: To examine the function of both the horizontal and vertical semicircular canals in patients with Ménière disease and to evaluate the change in endolymphatic hydrops volume during medical treatment, including treatment with diuretic therapy, over a 2-year period. Design, Setting, and Participants: This prospective longitudinal observational cohort study included 55 patients with definite unilateral Ménière disease and was performed in a tertiary care hospital in Japan. Participants were enrolled between April 1, 2017, and January 31, 2018, and those with vestibular migraine were excluded. All participants received education regarding diet and lifestyle modifications and treatment with betahistine mesylate (36 mg daily) and/or an osmotic diuretic (42-63 mg daily). Patients were followed up for vertigo and hearing evaluations at least once per month for more than 12 months and were instructed to record episodes of vertigo in a self-check diary. Audiometry was performed monthly, video head impulse testing and caloric testing were performed every 4 months, and magnetic resonance imaging was conducted annually. Data were analyzed from May 15, 2017, to January 31, 2020. Main Outcomes and Measures: Neurootological testing to evaluate vestibuloocular reflex gain over time, magnetic resonance imaging to evaluate the change in endolymphatic hydrops volume over time, and monthly vertigo and hearing evaluations for more than 12 months. Results: Among 55 participants with definite Ménière disease, 32 patients (58.2%) were female, and the mean (SD) age was 59.0 (15.1) years. The median disease duration was 2 years (interquartile range, 0-4 years), with 43 patients (78.2%) having an early stage (ie, disease duration ≤4 years) of Ménière disease. Over the 2-year study period, the vestibuloocular reflex gain decreased from 0.76 to 0.56 in the superior semicircular canals, for a difference of 0.20 (95% CI, 0.14-0.26) and from 0.68 to 0.50 in the posterior semicircular canals, for a difference of 0.18 (95% CI, 0.14-0.22). The maximum slow-phase velocity and vestibuloocular reflex gain in the horizontal semicircular canals were maintained. The volume ratio of vestibular endolymphatic hydrops increased from 19.7% to 23.3%, for a difference of 3.6% (95% CI, 1.4%-5.8%). The frequency of vertiginous episodes decreased, and the hearing level over the study period worsened from 40.9 dB to 44.5 dB, for a difference of 3.5 dB (95% CI, 0.7-6.4 dB). Conclusions and Relevance: In this study, during a 2-year period of medical treatment among patients with Ménière disease, vestibuloocular reflex gain decreased in the vertical semicircular canals but was maintained in the horizontal semicircular canals; the endolymphatic hydrops volume ratio increased, and the frequency of vertiginous episodes decreased. These findings describe the pathological progression of chronic Ménière disease and expand the understanding of its pathophysiological characteristics during the early stage of disease.

Vertical head impulse and caloric are complementary but react opposite to Meniere's disease hydrops.

OBJECTIVES/HYPOTHESIS: Meniere's disease (MD) patients can show normal head impulses despite poor caloric test results. This study aimed to investigate the discrepancy in the vestibulo-ocular reflex (VOR) in MD patients and whether endolymphatic hydrops (EH) influence the VOR. STUDY DESIGN: Prospective, cross-sectional observational study. METHODS: Ninety MD patients were enrolled. Neuro-otological testing, including a video head impulse test (vHIT) of all semicircular canals (SCs), and gadolinium-enhanced inner ear magnetic resonance imaging were performed. The vestibular EH volume was quantitatively evaluated by processing magnetic resonance images. RESULTS: Abnormal vHIT results in MD patients were found most frequently in the posterior (44.4%) SCs, followed by the horizontal (13.3%) and anterior (10%) SCs. Canal paresis (CP) was assessed using the vHIT and the caloric test, and results were not significant when vHIT responses were assessed as CP only using the horizontal SC. The difference in the vestibular EH between the presence and absence of CP was not significant if assessed using the vHIT (P = .5591), but it was statistically different if assessed using the caloric test (P = .0467). CONCLUSIONS: The contradictory reaction of VOR in MD patients may result from the high specificity but low sensitivity of CP in the horizontal vHIT. EH volume in the vestibule affects the caloric response but does not affect the vHIT response. LEVEL OF EVIDENCE: 2b Laryngoscope, 129:1660-1666, 2019.

A new immunohistochemical method to evaluate the development of vestibular compensation after unilateral labyrinthectomy in rats.

BACKGROUND: Unilateral labyrinthectomy (UL) causes the disappearance of ipsilateral medial vestibular nuclear (ipsi-MVe) activity and induces spontaneous nystagmus (SN), which disappears during the initial process of vestibular compensation (VC). Ipsi-MVe-activity restores in the late process of VC. OBJECTIVE: We evaluated the late process of VC after UL in rats and examined the effects of thioperamide (H3 antagonist) on VC. MATERIALS AND METHODS: MK801 (NMDA antagonist)-induced Fos-like immunoreactive (-LIR) neurons in contra-MVe, which had been suppressed by NMDA-mediated cerebellar inhibition in UL rats was used as an index. RESULTS: The number of MK801-induced Fos-LIR neurons in contra-MVe gradually decreased to the same level as that of sham-operated rats 14 days after UL. Thioperamide moved the disappearance of the MK801-induced Fos-LIR neurons 2 days earlier. The number of MK801-induced Fos-LIR neurons in thioperamide-treated rats was significantly decreased, compared with that of vehicle rats on days 7 and 12 after UL. But, thioperamide did not influence the decline of SN frequency in UL rats. CONCLUSION: These findings suggested that the number of MK801-induced Fos-LIR neurons in contra-MVe was decreased in concordance with the restoration of ipsi-MVe-activity during the late process of VC after UL and that thioperamide accelerated the late, but not the initial process of VC.

Contralateral type of delayed endolymphatic hydrops may consist of two phenotypes based on a magnetic resonance imaging preliminary study.

OBJECTIVE: This study was performed to determine the volume distribution of EH in contralateral DEH. PATIENTS AND METHODS: Five contralateral DEH patients (age range = 21-77 years) and one ipsilateral DEH patient. Visualization of in vivo EH using 3T magnetic resonance (MR) imaging was performed by intravenous administration of gadolinium. The EH volume was determined quantitatively by adding the area of EH in consecutive MR images. RESULTS: The total EH volume of the patients with contralateral DEH varied from 24.2 to 56.6 µL in the first ear and 20.2 to 35.7 µL in the contralateral ear. EH was dominantly developed in the first ear for Patient no. 3 and 4, and not dominantly developed in the first ear for Patient no. 1, 2, and 5. CONCLUSIONS: The volume distribution of endolymphatic hydrops (EH) in contralateral delayed endolymphatic hydrops (DEH) was classified into two phenotypes. This suggests that contralateral DEH may consist of two etiologies.

Longitudinal up-regulation of endolymphatic hydrops in patients with Meniere's disease during medical treatment.

Objective/Hypothesis: Meniere's disease (MD) is a common inner ear disease characterized by repeated episodic vertigo, fluctuating sensorineural hearing loss, and tinnitus. Its pathology is defined as endolymphatic hydrops (EH) in the inner ear and EH has been hypothesized to correlate with the clinical symptoms of MD. We presented the dynamics of in vivo EH in MD patients during medical treatments. Study Design: Prospective, single-arm repeated measures. Methods: Eleven MD patients were enrolled. All subjects prospectively underwent gadolinium-enhanced inner ear magnetic resonance (MR) imaging and neuro-otological testing before and after medical treatment. The volume of EH was quantitatively evaluated by processing MR images. All MD patients were administered continuous medication and followed up for more than 12 months. Results: The frequency of vertigo episodes decreased in all patients and vestibular function decreased to 13-91% of the pre-treatment level. The volume ratio of post-treatment EH-to-pre-treatment EH ranged from 1.01-3.22. The total volume of pre-treatment EH was significantly correlated with cochlear symptom disease duration and the affected ear's hearing level. Conclusion: EH in MD patients developed longitudinally with deterioration of inner ear function during medical treatment. The natural course of MD may progress with development of EH at least for a certain period. Level of Evidence: 2b.

Factors relating to the vertigo control and hearing changes following intratympanic gentamicin for intractable Ménière's disease.

OBJECTIVE: To look for factors relating to the vertigo control and hearing changes after intratympanic injections of gentamicin (GM). STUDY DESIGN: Prospective. SETTING: Tertiary referral medical center. PATIENTS: Twenty-eight patients with intractable Ménière's disease. INTERVENTIONS: Three intratympanic injections of GM (once per day for three consecutive days). MAIN OUTCOME MEASURES: Although five patients needed further GM injections or vestibular neurectomy because of poor control (Group I), 23 patients had their vertigo controlled for more than two years without further treatment (Group II). The number of vertigo spells per month, pure-tone audiometry, electrocochleography, caloric response, post-head shake nystagmus, and plasma vasopressin as a stress marker were examined. RESULTS: Before GM injections, there was no difference in the number of vertigo spells per month between Groups I and II. However, the hearing thresholds were higher in Group I. Hearing improvement, increase in percentage of canal paresis and induction of post-head shake nystagmus were observed after GM injections only in Group II. Even in the 11 patients who showed an improvement in hearing of more than 10 dB (hearing improvement group), percentage of canal paresis was increased after GM. More, premedication plasma vasopressin levels were lower in the hearing improvement group as compared with the hearing loss/no changes group. Four of eight patients became negative for dominant negative summating potential in electrocochleography after GM injections in the hearing improvement group. CONCLUSION: Our data indicate that the frequency of vertigo is not a key factor in the vertigo control after GM injections, that induction of vestibular damage in the injected ear is essential for the control of vertigo and this effect is mostly pronounced in patients with milder hearing loss, and that hearing improvement is not only a consequence of good vertigo control but also affected by the stress level before treatment.

Gadolinium-enhanced inner ear magnetic resonance imaging for evaluation of delayed endolymphatic hydrops, including a bilateral case.

CONCLUSION: The data suggests that gadolinium-enhanced inner ear MR imaging is useful for diagnosis of delayed endolymphatic hydrops (DEH) because it is independent of inner ear function, and the size of the affected endolymphatic space is clearly enlarged. OBJECTIVE: This study was performed to semi-quantitatively evaluate the endolymphatic space in patients with all types of DEH using gadolinium-enhanced inner ear magnetic resonance (MR) imaging. PATIENTS AND METHODS: Seven patients (age range = 21-77 years; five female, two male) with ipsilateral DEH (n = 5), contralateral DEH (n = 1), and bilateral DEH (n = 1). All patients underwent 3T MR imaging 4 h after intravenous injection of gadolinium. Software was used to determine the size of the endolymphatic space. Pure tone audiometry and caloric testing using an electronystagmogram were carried out. RESULTS: One side of the endolymphatic space was dominantly extended in patients with ipsilateral DEH, and both sides of the space were extended in patients with contralateral and bilateral DEH. In patients with ipsilateral DEH, the volume ratio of endolymph to vestibule was 2.5-4.3-times that in the unaffected ear. The volume ratio of endolymph to vestibule was nearly equal in patients with contralateral and bilateral DEH.

A Two-Year Randomized Trial of Interventions to Decrease Stress Hormone Vasopressin Production in Patients with Meniere's Disease-A Pilot Study.

UNLABELLED: Meniere's disease, a common inner ear condition, has an incidence of 15-50 per 100,000. Because mental/physical stress and subsequent increase in the stress hormone vasopressin supposedly trigger Meniere's disease, we set a pilot study to seek new therapeutic interventions, namely management of vasopressin secretion, to treat this disease. We enrolled 297 definite Meniere's patients from 2010 to 2012 in a randomized-controlled and open-label trial, assigning Group-I (control) traditional oral medication, Group-II abundant water intake, Group-III tympanic ventilation tubes and Group-IV sleeping in darkness. Two hundred sixty-three patients completed the planned 2-year-follow-up, which included assessment of vertigo, hearing, plasma vasopressin concentrations and changes in stress/psychological factors. At 2 years, vertigo was completely controlled in 54.3% of patients in Group-I, 81.4% in Group-II, 84.1% in Group-III, and 80.0% in Group-IV (statistically I < II = III = IV). Hearing was improved in 7.1% of patients in Group-I, 35.7% in Group-II, 34.9% in Group-III, and 31.7% in Group-IV (statistically I < II = III = IV). Plasma vasopressin concentrations decreased more in Groups-II, -III, and -IV than in Groups-I (statistically I < II = III = IV), although patients' stress/psychological factors had not changed. Physicians have focused on stress management for Meniere's disease. However, avoidance of stress is unrealistic for patients who live in demanding social environments. Our findings in this pilot study suggest that interventions to decrease vasopressin secretion by abundant water intake, tympanic ventilation tubes and sleeping in darkness is feasible in treating Meniere's disease, even though these therapies did not alter reported mental/physical stress levels. TRIAL REGISTRATION: ClinicalTrials.gov NCT01099046.

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.

Neuro-rehabilitation Approach for Sudden Sensorineural Hearing Loss.

Sudden sensorineural hearing loss (SSHL) is characterized by acute, idiopathic hearing loss. The estimated incidence rate is 5-30 cases per 100,000 people per year. The causes of SSHL and the mechanisms underlying SSHL currently remain unknown. Based on several hypotheses such as a circulatory disturbance to the cochlea, viral infection, and autoimmune disease, pharmaco-therapeutic approaches have been applied to treat SSHL patients; however, the efficacy of the standard treatment, corticosteroid therapy, is still under debate. Exposure to intense sounds has been shown to cause permanent damage to the auditory system; however, exposure to a moderate level enriched acoustic environment after noise trauma may reduce hearing impairments. Several neuroimaging studies recently suggested that the onset of SSHL induced maladaptive cortical reorganization in the human auditory cortex, and that the degree of cortical reorganization in the acute SSHL phase negatively correlated with the recovery rate from hearing loss. This article reports the development of a novel neuro-rehabilitation approach for SSHL, "constraint-induced sound therapy (CIST)". The aim of the CIST protocol is to prevent or reduce maladaptive cortical reorganization by using an enriched acoustic environment. The canal of the intact ear of SSHL patients is plugged in order to motivate them to actively use the affected ear and thereby prevent progress of maladaptive cortical reorganization. The affected ear is also exposed to music via a headphone for 6 hr per day during hospitalization. The CIST protocol appears to be a safe, easy, inexpensive, and effective treatment for SSHL.

Fos induction in the amygdala by vestibular information during hypergravity stimulation.

Altered gravity environments including both hypo- and hypergravity can elicit motion sickness. Vestibular information is known to be essential for motion sickness, but its other neural substrates are poorly understood. We previously showed that bilateral lesions of the amygdala suppressed hypergravity-induced motion sickness in rats, using pica behavior as an emetic index. We show in the present study that during hypergravity stimulation, vestibular information activated the central nucleus of the amygdala (CeA), as determined by the induction of Fos expression, in comparison between normal and bilaterally labyrinthectomized rats. The finding that Fos expression was confined to the CeA and almost completely absent in other subnuclei of the amygdala contrasted with many previous studies that used other stressful stimuli such as foot shock, restraint and forced swimming, suggesting a specific vestibular effects on the amygdala. Prolongation of hypergravity resulted in reduction of Fos expression in the CeA, suggesting a process of habituation. Such decreases appeared earlier than in the vestibular nucleus, suggesting that adaptive changes in the CeA to hypergravity were independent of changes in the vestibular input. Our results suggest the amygdala is a neural substrate involved in the development of and habituation to motion sickness.

Up-regulation of cochlear aquaporin-3 mRNA expression after intra-endolymphatic sac application of dexamethasone.

The final aim of the present study is to see if the endolymphatic sac is really available as a drug delivery system to have effect on the inner ear organs. In the present study, we examined effects of a single insertion of dexamethasone into the rat unilateral endolymphatic sac on mRNA expression of the inner ear aquaporin (AQP) family, transmembrane water transporters and putative endolymphatic fluid modulators, by means of real-time quantitative PCR. Only AQP-3 mRNA expression in the ipsilateral cochlea was significantly up-regulated in comparison with controls and the up-regulation was demonstrated both in dose-dependent and time-dependent manners. These findings suggest that the intra-endolymphatic sac steroids could make regulatory effects on the inner ear AQP-3 expression via vestibular aqueduct and modulate the homeostasis of endolymphatic fluids, encouraging the possibility that the endolymphatic sac could be a therapeutic window for the inner ear disease.

Effects of intratympanic injection of steroids on changes in rat inner ear aquaporin expression.

Although steroid treatment is generally administered for patients with inner ear disorders, including Meniere's disease, the mechanism via which steroids exert their effects remains to be clarified. The aquaporins (AQPs) are a family of small transmembrane water transporters, and it has recently been revealed that they play a role in regulating homeostasis in the inner ear fluids. In order to elucidate the action points of steroids in the inner ear, we firstly identified AQPI, 2, 3, 4, 5 and 6 mRNAs in the rat cochlea and AQP1, 3, 4, 5 and 6 in the rat endolymphatic sac by means of reverse transcription-polymerase chain reaction. Subsequently, we found that intratympanic injections of steroids upregulated AQPI mRNA of the rat cochlea in a dose-dependent manner. These results suggest that steroids may affect water homeostasis in the rat inner ear mainly via AQP1.