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Objective: Hybrid of reversed image of positive endolymph signal and negative image of perilymph signal (HYDROPS) in delayed gadolinium‐enhanced magnetic resonance imaging (MRI) typically depicts normal inner ear as "white‐tone" and endolymphatic hydrops as "black‐transparent" appearances, whereas ears with auditory and vestibular disorders are occasionally depicted as "gray‐tone." This study aimed to investigate the pathological basis of sudden sensorineural hearing loss (SSNHL) patients with "gray‐tone" appearances on HYDROPS. Methods: Delayed gadolinium‐enhanced MRI examinations were conducted on 29 subjects with unilateral SSNHL. We mainly analyzed positive perilymph image (PPI) and positive endolymph image (PEI), which were components HYDROPS. Results: On PPI, signal intensity (SI) values extracted from the cochlear and vestibular region of interest (ROI) were higher in the SSNHL ears with dizziness/vertigo symptom at the first visit compared to the healthy ear. Additionally, the PPI/PEI enhancement pattern in the vestibule was associated with a high prevalence of hearing and vestibular deteriorations at the first visit and poor hearing improvement after treatment. Conclusion: Enhancement on PPI/PEI may result from leakage of gadolinium into the inner ear following breakdown of the blood‐labyrinth barrier, with high SI being correlated with the amount of leakage. Particularly, a significant leakage into the endolymphatic space, defined as PPI+/PEI+, indicates severe inner ear pathology. Ultimately, we emphasize that the "gray‐tone" appearance in the inner ear on HYDROPS comprises enhancements on both PPI and PEI and propose a new classification for evaluating SSNHL Peri‐ and Endolymphatic image Enhancement pattern in Delayed gadolinium‐enhanced MRI (SPEED). Level of Evidence: 4. [ABSTRACT FROM AUTHOR]

To elucidate the relationship between vertigo and EH volume after medical treatment, we investigated changes in endolymphatic hydrops (EH) volume using inner ear magnetic resonance imaging (ieMRI) in relation to clinical results for vertigo and hearing after administration of the anti-vertiginous medications betahistine, adenosine triphosphate (ATP), isosorbide (ISO), and saireito (SAI) for Meniere's disease (MD). We retrospectively enrolled 202 consecutive patients diagnosed with unilateral MD from 2015 to 2021 and assigned them to four groups: Group I (G-I), symptomatic oral medication with betahistine only (CONT); Group II (G-II), inner ear vasoactive oral medication (ATP); Group III (G-III), osmotic diuretic oral medication (ISO); and Group IV (G-IV), kampo oral medication (SAI). In total, 172 patients completed the planned one-year-follow-up, which included the assessment of vertigo frequency, hearing improvement, and changes in EH using ieMRI (G-I, n=40; G-II, n=42; G-III, n=44; G-IV, n=46). We constructed 3D MRI images semi-automatically and fused the 3D images of the total fluid space (TFS) of the inner ear and endolymphatic space (ELS). After fusing the images, we calculated the volume ratios of the TFS and ELS (ELS ratios). One year after treatment, vertigo was controlled with zero episodes per month in 57.5% (23/40) of patients in G-I, 78.6% (33/42) in G-II, 81.8% (36/44) in G-III, and 82.6% (38/46) in G-IV (statistical significance: G-I 10 dB in 5.0% (2/40) of patients in G-I, 16.7% (7/42) in G-II, 18.2% (8/44) in G-III, and 21.7% (10/46) in G-IV (statistical significance: G-I=G-II=G-III=G-IV). ELS ratios were significantly reduced after treatment only in the vestibule for G-II, G-III, and G-IV when compared with G-I. Especially among patients with complete control of vertigo after treatment, ELS ratios were significantly reduced after treatment in the vestibule and total inner ear for G-II; in the cochlea, vestibule, and total inner ear for G-III; and in the cochlea, vestibule, and total inner ear for G-IV compared with G-I. However, there were no significant findings in the relationship between hearing results and changes in ELS ratios. These results indicate that daily administration of anti-vertiginous medications including ATP, ISO, and SAI could be an effective treatment option for patients with MD at an early stage before it becomes intractable. Treatments to reduce EH might offer better control of vertigo rather than improve hearing. [ABSTRACT FROM AUTHOR]

Copyright of Acta Oto-Laryngologica is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Nowadays, the endolymphatic space size can be evaluated by 3D-analysis of 3 T-MRI after intravenous injection of gadolinium enhancement. In the present study, to elucidate the relationships between vertigo and endolymphatic hydrops (EH) volume after middle ear pressure therapy (MEPT), we investigated changes in EH volume after MEPT for intractable Meniere's disease (MD) by means of the inner ear MRI (ieMRI) in relation to clinical results. We enrolled 202 successive definite MD cases with intractable vertiginous symptoms from 2015 to 2020, assigning Group-I of MEPT, and Group-II of endolymphatic sac drainage (ELSD). Ninety patients completed the planned 2-year-follow-up, which included assessment of vertigo frequency and changes in EH volume using ieMRI (Group-I/MEPT: n = 40; Group-II/ELSD: n = 50). Two years after surgery, vertigo was completely controlled in 77.5% of patients in Group-I and 90.0% in Group-II. Hearing improved by >10 dB in 7.5% of patients in Group-I and 24.0% in Group-II. ELS ratios were significantly reduced after treatments of Group-I and Group-II only in the vestibule. The obtained results indicate that MEPT as well as ELSD could be a good treatment option for patients with intractable MD. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate the endolymphatic hydrops (EH)-positivity rates among patients with recurrent audiovestibular symptoms using intravenous injection of gadolinium-enhanced inner ear magnetic resonance imaging (ieMRI).Methods: We reviewed 710 successive patients with recurrent audiovestibular symptoms at the Vertigo/Dizziness Center of Nara Medical University and other related hospitals, between May 2014 and April 2020. We performed ieMRI on 153 patients with unilateral recurrent cochleovestibular symptoms (rCV), 51 with recurrent vertigo symptoms (rVO), and 84 with unilateral recurrent cochlear symptoms (rCO).Results: EH was observed in 69.4% of the participants: 81.7% in the rCV group, 19.6% in the rVO group, and 77.4% in the rCO group. The participants were divided into two groups according to the disease duration: short-duration and long-duration groups. In the short-duration group (less than 4 years), EH was observed in 82.3%, 42.9%, and 71.4% of the patients in rCV, rVO, and rCO groups, respectively; in the long-duration group (more than 5 years), EH was observed in 81.1%, 10.8%, and 81.6% of the patients in rCV, rVO, and rCO groups, respectively.Conclusions: The longer the duration of the disease, the larger the EH-positivity rates in patients with rCO, smaller in those with rVO, and unchanged in those with rCV. Although ieMRI could not detect EH with 100% accuracy in Ménière's disease, the present pathological statistics of patients with recurrent audiovestibular symptoms might be helpful in considering the pathology-based treatment strategy. [ABSTRACT FROM AUTHOR]

Copyright of Acta Oto-Laryngologica is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Acta Oto-Laryngologica is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: Our aim was to elucidate relationships between results from the caloric test (c-test), video Head Impulse Test (vHIT) and inner ear gadolinium-enhanced MRI (ieMRI) in patients with endolymphatic hydrops (EH), especially patients with Ménière's disease (MD).Methods: We managed 1789 successive patients at the Vertigo/Dizziness Center in Nara Medical University from May 2014 to December 2018. After providing informed consent for vertigo/dizziness examinations, 281 patients were hospitalized to check their inner ear function for proper diagnosis and treatment. Then 76 participants underwent the c-test, vHIT and ieMRI. Among these 76 cases, 20 were diagnosed with MD (20/76; 26.3%) and 56 were non-MD (56/76; 73.7%) according to the 2015 diagnostic guideline of the International Classification of Vestibular Disorders. The MD group included 15 unilateral and 5 bilateral cases. The non-MD group included 22 benign paroxysmal positional vertigo, 10 vestibular neuritis, 8 sudden deafness with vertigo, 6 orthostatic dysregulation, 4 vestibular neuropathy and 6 others. Results in these examinations in the side of an active lesioned inner ear were representative in each peripheral case.Results: Twenty-nine of the 76 patients (38.1%) showed discrepant results between the c-test (outside of normal range) and vHIT (within normal range). Twenty-two of 76 patients (28.9%) had a positive EH sign on ieMRI. The c-test/vHIT discrepancy percentage in MD (14/20; 70.0%) was significantly higher than that in non-MD (15/56; 26.8%) (p=0.00179). The positive EH sign in ieMRI percentage in MD (15/20; 75.0%) was significantly higher than that in non-MD (7/56; 12.5%) (p=0.0015). There was a significant positive relationship between the c-test/vHIT discrepancy and the positive EH sign (p=0.00058) in all 76 cases combined. However, there was no significant relationship between c-test/vHIT discrepancy and positive EH sign (p=0.13) in the 20 MD cases. Considering the 15 unilateral and 5 bilateral MD cases, the c-test/vHIT discrepancy was observed in 14 of the 25 affected ears. Positive signs of vestibular EH herniation into the cupula in the lateral semicircular canal was seen in 14 of the 25 MD ears. There was significant relationship between the c-test/vHIT discrepancy and EH herniation (p=0.0012) in MD ears.Conclusion: The present results suggest that patients with MD could have inner ear EH significantly more often than those with non-MD. In cases with MD, a positive EH sign on ieMRI did not always indicate a c-test/vHIT discrepancy; both findings may occur due to herniation of vestibular EH adjacent to the lateral semicircular canal. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to evaluate the association of neuro-otological examination, blood tests, and scoring questionnaire data with treatment-resistant intractability of persistent dizziness in Ménière's disease.Methods: We managed 1520 successive vertigo/dizziness patients at the Vertigo/Dizziness Center in Nara Medical University from May 2014 to April 2018. Five hundred and twenty-two patients were diagnosed with Ménière's disease (522/1520; 34.3%) according to the 2015 diagnostic guideline of the International Classification of Vestibular Disorders. Among the patients with Ménière's disease there were 102 with intractable rotatory vertigo attacks for more than 3-6 months (102/522; 19.5%), including 20 bilateral cases (20/102; 19.6%), and 88 with intractable unremitting floating sensation rather than rotatory vertigo attacks for more than 3-6 months (88/522; 16.9%), including 28 bilateral cases (28/88; 31.8%). Sixty out of 88 cases with intractable unremitting floating sensation were unilateral and were enrolled for hospitalization to undergo neuro-otological examinations including pure-tone audiometry (PTA), the caloric test (C-test), vestibular evoked cervical myogenic potentials (cVEMP), subjective visual vertical (SVV) test, glycerol test (G-test), electrocochleogram (ECoG), inner ear magnetic resonance imaging (ieMRI), blood tests including anti-diuretic hormone (ADH) and bone alkaline phosphatase (BAP), and self-rating questionnaires of depression score (SDS). Data are presented as positive (+) ratios of the number of patients with examination and questionnaire data outside of the normal range.Results: The ratios (+) were as follows: C-test=33.3% (20/60), cVEMP=25.0% (15/60), SVV=50.0% (30/60), G-test=55.0% (33/60), ECoG=63.3% (38/60), ieMRI=86.7% (52/60), ADH=35.0% (21/60), BAP=11.7% (7/60), and SDS=40.0% (24/60). Multivariate regression analysis revealed that the periods of persistent dizziness were significantly longer in unilateral Ménière's patients with C-test(+), SVV(+), and SDS(+) compared with those with negative findings. Additionally, the periods in bilateral cases were significantly longer than those in unilateral ones.Conclusions: Although approximately 70% of patients with Ménière's disease are usually treatable through the appropriate conservative medical therapy, the presence of canal paresis, gravity-sensitive dysfunction, neurosis/depression, and bilaterality may make the persistent dizziness intractable and may thus require additional treatments. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We sought to establish a more efficient technique for induction of inner ear hair cell-like cells (HC-like cells) from embryonic stem cells (ES cells) by using a combination of two previously reported methods; ST2 stromal cell-conditioned medium, known to be favorable for HC-like cell induction (HIST2 method), and ES cells with transfer of the Math1 gene (Math1-ES cells). Math1-ES cells carrying Tet-inducible Math1 were cultured for 14 days with doxycycline in conditioned medium from cultures of ST2 stromal cells following formation of 4-day embryoid bodies (EBs). Although each of the previously introduced methods have been reported to induce approximately 20% HC-like cells and 10% HC-like cells in their respective populations in EB outgrowths at the end of the culture periods, the present combined method was able to generate approximately 30% HC-like cells expressing HC-related markers ( myosin6 , myosin7a , calretinin , α 9AchR , Brn3c ), which showed remarkable formation of stereocilia-like structures. Analysis of expressions of marker genes specific for cochlear ( Lmod3 , Emcn ) and vestibular ( Dnah5 , Ptgds ) cells indicated that our HIST2 method may lead to induction of cochlear- and vestibular-type cells. In addition, continuous Math1 induction by doxycycline without use of the HIST2 method preferentially induced cochlear markers with negligible effects on vestibular marker induction. [ABSTRACT FROM AUTHOR]

Conclusion:This study described the lateralities of axial length of inner ear (ALIE), of the volume of inner ear (VIE) and age-related differences of the volume of inner ear components in patients with chronic rhinosinusitis (CRS). Age-related differences were found in ALIE and the positive correlation in ALIE and the volume of the cochlea (VC) of the affected ear in patients with Meniere’s disease (MD).Objective:To identify side or sex-related differences in the ALIE, the length of the spiral canal of cochlea (LSCC), and the volume of components of the inner ear in MD and CRS. Methods:Thirty-two with unilateral MD and 14 with CRS were included. Images were acquired with a 3.0-tesla unit using SPACE sequences. The ALIE was measured and the VIE, VC, the volume of the vestibule (VV), and of the semi-circular canals (VSC) were also measured. Results:In CRS, ALIE of the right ear in males was significantly longer than in females. Patients younger than 60 years old with CRS had a significantly larger VIE, VC, and VSC than older than 60. In MD, the ALIE in older than 60 was longer than below 60. [ABSTRACT FROM PUBLISHER]

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 [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The aim of the present study was to elucidate the time course and frequency patterns of transient low-tone air-bone gaps (ABGs) after canal plugging for intractable BPPV. Methods: We investigated eight patients with intractable BPPV who underwent canal plugging. Four were cases with posterior type (pBPPV) and the other four were those with horizontal type (hBPPV). Pure-tone audiometries (PTAs) were performed before and 7 days, 1 month and 6 months after surgery. ABGs (+) were defined as the three-tone-average ≥20dB formulated by (a + b + c)/3, where a, b, and c are ABGs at 0.25, 0.5, and 1kHz, respectively. Results: The ratio of the number of patients with ABGs (+) at the post-operative 7th day and 1st month was 100.0% (8/8). The ratio at the post-operative 6th month was 0.0% (0/8). There were no significant differences in the time course or frequency patterns of the ABGs between pBPPV and hBPPV. Conclusions: We clearly demonstrated eight cases with intractable BPPV showing transient low-tone ABGs during convalescence immediately after canal plugging. During that period, patients also complained of motion-evoked dizziness. All these findings suggest that, during such a convalescence period, the plugged area might not be fixed yet and could still induce the dizziness and low-tone ABGs, as enlarged vestibular aqueduct syndrome and superior semicircular canal deficiency syndrome exhibit low-tone ABGs due to the third mobile inner ear window. More than one month after surgery, both the ABGs and dizziness could disappear according to fixation of the plugged area. [Copyright &y& Elsevier]

Conclusion: We reported previously that hyperactivation of vasopressin type-2 receptor (V2R)-mediated signaling in the endolymphatic sac could affect endolymphatic fluid metabolism, resulting in the pathogenesis of endolymphatic hydrops. Taken together with the present endolymphatic sac tumor (ELST) study, it is suggested that disorder of V2R signaling in the endolymphatic sac for any reason could be involved in the pathogenesis of endolymphatic hydrops. Although it is due to tumor genesis in ELST, it is idiopathic in nature in Meniere's disease. Objective: We encountered two cases of ELST showing Meniere's disease-like symptoms. Both cases were suspected of having endolymphatic hydrops using neuro-otological examinations. To clarify the histopathological diagnosis of ELST and the molecular pathogenesis of endolymphatic hydrops, we performed histopathological and molecular biological examinations of the endolymphatic sac. Methods: ELSTs in two rare cases were removed completely through the transmastoidal approach. V2R mRNA expression was examined using real-time PCR. Results: The first case was diagnosed as inflammatory granulation adjacent to the endolymphatic sac, i.e. pseudo-ELST, and the second case was diagnosed as papillary adenoma of ELST. V2R mRNA expression was up-regulated in the endolymphatic sac of both cases as seen in Meniere's disease compared with controls. [ABSTRACT FROM AUTHOR]

Conclusion: The detection rate of endolymphatic hydrops was significantly higher in patients with Meniere's disease compared with those with sudden deafness, indicating that 3 T magnetic resonance imaging (MRI) with intratympanic gadolinium injection was effective in diagnosing endolymphatic hydrops. Objectives: To compare the detection rate of endolymphatic hydrops between patients with Meniere's disease and sudden deafness as controls by 3 T MRI after intratympanic gadolinium injection with conventional pulse sequence such as two-dimensional fluid-attenuated inversion recovery. Methods: Ten patients with unilateral Meniere's disease and eight with sudden deafness underwent inner ear MRI 24 h after intratympanic gadolinium injection. Results: The endolymphatic space was detected as a low signal intensity area, while the perilymphatic space showed high intensity by gadolinium enhancement. Due to faint enhancement, images could not be evaluated in 1 of 10 patients with Meniere's disease. However, the other nine patients together with two of the eight with sudden deafness were diagnosed as having hydrops. The difference in detection rates between the two diseases was statistically significant. Two hydrops-positive cases with sudden deafness were considered to be of the secondary type of hydrops, because images were taken after partial recovery from hearing loss several months after the onset of the disease. [ABSTRACT FROM AUTHOR]

Abstract: The transient receptor potential cation channel subfamily V (TRPV) is a non-specific cation ion channel receptor family that is gated by heat, protons, low extracellular osmolarity and arachidonic acid derivatives. Since some of these endogenous agonists of TRPV receptors are reactive oxygen intermediates produced by lipoxygenases, it has been hypothesized that some members of the TRPV family may respond to challenges by reactive oxygen species. This study used real-time PCR to quantitatively track changes in TRPV1-4 mRNA expression in the spiral, vestibular, and trigeminal ganglia and the kidney from kanamycin (KM)-treated mice. TRPV1, TRPV2, TRPV3 and TRPV4 mRNAs were expressed in spiral and vestibular ganglia, and TRPV2 and TRPV1 mRNAs were most predominant in control mice. After KM (700 mg/kg s.c. b.i.d., 14 days), TRPV1 mRNA and protein expression were significantly up-regulated both in the spiral and vestibular ganglia, but expression was unaffected in the trigeminal ganglion and kidney. Real-time PCR also demonstrated a significant down-regulation in TRPV4 mRNA expression in the inner ear ganglia and kidney after KM treatment. All these mRNA and protein expression changes were eliminated by simultaneous administration of dihydroxybenzoate (300 mg/kg s.c. b.i.d., 14 days), an anti-oxidant that blocks KM ototoxicity. It is proposed that up-regulated TRPV1 expression during KM exposure may promote ganglion cell survival by contributing to neuronal depolarization, with KM-induced tinnitus and dizziness as consequences. [Copyright &y& Elsevier]

Uncoupling proteins (UCPs) are a proton transporter family located in the mitochondrial inner membrane. The molecular expression and activity of UCPs in brown adipose tissue and skeletal muscle are regulated by factors as diverse as chronic overeating and cold exposure, suggesting roles in energy expenditure and heat production. Although UCP2, UCP4 and brain mitochondrial carrier protein-1 (BMCP-1, i.e. UCP5) mRNAs are expressed in the central nervous system, their central function is unknown. This study presents the first evidence on localization and quantitative expression of UCPs in the rat inner ear by real-time PCR and immunohistochemistry. Real-time PCR studies revealed that UCP2 mRNA was expressed in the vestibular and spiral ganglia more abundantly than any other UCP. Neocortex, by contrast, contained UCP2 and UCP4 equally. Notably, UCP3 and UCP4 mRNAs were expressed in inner ear ganglia, but brain UCP3 mRNA expression level was undetectable by simple PCR. Immunohistochemical studies confirmed that both UCP2- and UCP3-like immunoreactivities were detected in vestibular and spiral ganglion cells and co-localized with a mitochondrial marker, MitoFluorGreen. According to previous reports, UCP2 and UCP3 are thermogenic in yeast and brain UCP2 has been suggested to modulate pre- and post-synaptic events by axonal thermogenesis. It has also been reported recently that UCP2 and UCP3 responses to superoxide application may be an antioxidant protective mechanism. Therefore, it is suggested that mitochondrial UCPs (UCP2, UCP3, UCP4) may play both a protective role against oxidative damage and a thermal signaling role in the eighth nerve. [Copyright &y& Elsevier]

In order to elucidate the role of the vestibulocerebellar neural circuits during two-stage bilateral labyrinthectomy (BL) we examined Fos-like immunoreactive (-LIR) neurons as a marker of neural activation in the rat brainstem after BL and the projections of these neurons into the vestibulocerebellum using retrograde tracing and immunohistochemical techniques. Simultaneous BL did not show any Fos expression in the medial vestibular nucleus (MVe). However, with an interval of >6 h between the two stages of BL, Fos-LIR neurons were induced in the ipsilateral (ipsi-) MVe of the side operated on second, partially projecting into the ipsi-vestibulocerebellum. A previous study demonstrated that some of the unilateral labyrinthectomy-induced Fos-LIR neurons in the ipsi-MVe projected into the ipsi-vestibulocerebellum and inhibited the contra-MVe neurons, resulting in the restoration of the right-left balance. Taken together with our present data, it is suggested that some of the labyrinthectomy-induced Fos expression in the ipsi-MVe is representative of a switch-on signal for the vestibulo-cerebello-vestibular inhibitory neural circuits, which remain turned off after symmetrical lesions such as simultaneous BL but are turned on after severe asymmetrical lesions in order to restore the balance. [ABSTRACT FROM AUTHOR]

Objective: The caloric test (C-test) and video head impulse test (vHIT) are known to occasionally show contradictory results in patients with Meniere's disease (MD). The reasons underlying this discrepancy between the two tests are currently unclear. We aimed to reveal the mechanisms responsible for this discrepancy by performing volumetric evaluation of the endolymphatic space (ELS) by using endoluminal contrast-enhanced inner ear MRI (ieMRI).Methods: We enrolled 136 patients (174 ears) who visited the vertigo/dizziness center of our university and underwent the C-test and vHIT between February 2018 and February 2020. Inner ear MRI was also performed to determine the presence of endolymphatic hydrops (EH). The percentage of patients diagnosed with each vestibular disease was as follows: MD, 23.0%; benign paroxysmal positional vertigo (BPPV), 17.8%; bilateral vestibular disorder (BVD), 9.2%; sudden deafness with vertigo (SD), 8.0%; peripheral dizziness (PD), 7.5%; unilateral vestibular disorder (UVD), 6.9%; vestibular neuritis (VN), 6.3%; delayed endolymphatic hydrops (DEH), 3.4%; central dizziness (CD), 2.9%; Hunt syndrome (Hunt), 1.2%; and other disorders (OD), 13.8%.Results: Among the ears in the present study, 46.0% (80/174) showed a discrepancy in the results of the C-test and vHIT, and the disease-related distribution of patients showing this discrepancy was as follows; MD, 38.8% (27/80; p = 0.0019); BVD, 13.8% (11/80); UVD, 12.5% (10/80); SD, 7.5% (6/80); BPPV, 6.3% (5/80); PD, 6.3% (5/80); VN, 3.8% (3/80); DEH, 3.8% (3/80); CD, 2.5% (2/80); Hunt, 0.0% (0/80); and OD, 10.0% (8/80). In all cases, the discrepancy presented as a positive C-test result and negative vHIT result. The ELS ratio was measured for the whole inner ear, cochlea, vestibule, and semicircular canal, and the relationships between the rates and the presence of discrepancy was examined. Inner ear ELS ratio was 17.9% ± 10.8% in patients with the discrepancy and 15.2% ± 8.8% in those without the discrepancy (p = 0.036). Cochlear ELS ratio was 14.9% ± 11.3% in patients with the discrepancy and 11.9% ± 10.3% in those without the discrepancy (p = 0.0012). Vestibular ELS ratio was 22.3% ± 16.2% in patients with the discrepancy and 17.2% ± 12.7% in those without the discrepancy (p = 0.032). Semicircular canal ELS ratio was 18.0% ± 11.0% in patients with the discrepancy and 16.5% ± 9.6% in those without the discrepancy (p = 0.442).Conclusion: The volume of the ELS may affect the discrepancy of results between the C-test and vHIT. [ABSTRACT FROM AUTHOR]

Vestibular hair cells (V-HCs) residing in the inner ear have important roles related to balance. Although differentiation of pluripotent stem cells into HCs has been shown, an effective method has yet to be established. We previously reported that use of vestibular cell-derived conditioned medium (V-CM) was helpful to induce embryonic stem (ES) cells to differentiate into V-HC-like cells in two-dimensional (2D) cultures of ES-derived embryoid bodies (EBs). In the present report, V-CM was used with three-dimensional (3D) cultures of EBs, which resulted in augmented expression of V-HC-related markers (Math1, Myosin6, Brn3c, Dnah5), but not of the cochlear HC-related marker Lmod3. Gene expression analyses of both 2D and 3D EBs cultured for two weeks revealed a greater level of augmented induction of HC-related markers in the 3D-cultured EBs. These results indicate that a 3D culture in combination with use of V-CM is an effective method for producing V-HCs. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to measure the volume of the endolymphatic space (ELS) and to investigate prognosis in patients with acute low-tone sensorineural hearing loss (ALHL).Methods: A total of 61 ALHL patients participated; 47 were definite while 14 were probable ALHL cases. The definite ALHL patients were classified into three groups: A, "Cure"; B, "No cure"; and C, "Recurrence." Also, nine patients for whom diagnosis changed from ALHL to cochlear Meniere's disease (cMD) without vertigo (ALHL-cMD group). Images of the inner ear fluid space, positive perilymph, and positive endolymph were acquired using a 3T magnetic resonance scanner. Three-dimensional (3D) images were semi-automatically reconstructed using anatomical and tissue information to fuse the 3D images of the inner ear fluid space with the 3D ELS images.Results: Patients in the no cure group showed a significantly higher ELS/total fluid space (TFS) volume ratio in the affected cochlear region than the patients of the other groups. Additionally, the affected vestibular ELS/TFS volume ratio in the cure group was significantly lower than that in the recurrence group. There were significantly higher cochlear and vestibular ELS/TFS ratios in ALHL-cMD patients than in control subjects.Conclusions: These results indicate that the cochlear ELS/TFS volume ratio should be considered when investigating the extent of recovery, while the extended ELS in the vestibule should be considered when investigating cases of recurrence. Thus, our study suggests that the severe extended ELS appeared likely to change to cMD and that the prognostic determination of ALHL is possible. [ABSTRACT FROM AUTHOR]

Objective: To employ magnetic resonance imaging (MRI) to measure the volume of the inner ear endolymphatic space (ELS) in patients with acute low-tone sensorineural hearing loss (ALHL), sudden deafness (SD), cochlear Meniere's disease (cMD), and unilateral MD (uMD) compared with control subjects (CS) with chronic rhinosinusitis.Methods: Forty-one patients with ALHL, 82 with SD, 48 with cMD, 72 with uMD, and 47 CS participated in the study. With the exception of all uMD patients, none of the subjects had vertigo. Images of the inner ear fluid space, positive perilymph signal, and positive endolymph signal were acquired using a 3-T MRI scanner. Three-dimensional images were reconstructed semi-automatically by using anatomical and tissue information to fuse the inner ear fluid space images and the ELS images.Results: The cochlear ELS/total fluid space (TFS) volume ratio was 10.2±6.7% (mean±standard deviation) in the CS group, 12.1±5.7% in ALHL patients, 15.2±8.7% in SD patients, 18.1±8.2% in cMD patients, and 21.9±16.4% in uMD patients. The vestibular ELS/TFS volume ratio was 17.7±10.2% in the CS group, 18.9±8.3% in ALHL patients, 19.9±11.3% in SD patients, 22.5±13.7% in cMD patients, and 35.7±24.1% in uMD patients. The cochlear ELS/TFS volume ratio in patients with uMD was similar to that in the cMD group and significantly higher than that in the CS, ALHL, and SD groups (CS=ALHLConclusion: The cochlear ELS volume of patients with MD and other endolymphatic hydrops-related diseases differed from that of CS. Our results suggest that ALHL may not be caused by endolymphatic hydrops. We confirmed the presence of extended ELS in patients with SD. [ABSTRACT FROM AUTHOR]

Abstract It has been long considered that air and bone are the two major mediators that conduct sounds to the inner ear. In 2004, Hosoi found that vibration of aural cartilage, generated by placing gently a transducer on it, could create audible sound with the same level of clarity as air- and bone-conduction sound. He thus proposed the term "cartilage conduction" for this concept. This research identified a third mediator for sound conduction to the inner ear. Hosoi also proposed the development of novel communication devices, such as hearing aids, telephones, etc. using his findings. For cartilage conduction, three sound pathways can be assumed. The transducer vibration may cause airborne sound which passes into the external auditory canal through the canal entrance (direct air pathway). Alternatively, the vibration at the cartilage may generate audible sound in the external auditory canal (cartilage-air pathway), or propagate directly to the inner ear through the skull bone (cartilage-bone pathway). A series of studies has illustrated that the cartilage-air pathway is dominant for hearing sensations in listeners with normal ears. The cartilage-bone pathway works for patients with bony aural atresia. A fourth pathway, the fibrotic-tissue pathway, is considered to act in the case of fibrotic aural atresia. In this review, we summarize this series of studies and discuss the nature of cartilage conduction. [ABSTRACT FROM AUTHOR]

Abstract: The 5-hydroxytryptamine type 3 (5-HT3) receptor is a ligand-gated ion channel and a member of the Cys-loop family of receptors. Previous studies have shown 5-HT3 receptor expression in various neural cells of the central and peripheral nervous systems. Although the function and distribution of the 5-HT3 receptor has been well established, its role in the inner ear is still poorly understood. Moreover, no study has yet determined its localization and function in the peripheral vestibular nervous system. In the present study, we reveal mRNA expression of both 5-HT3A and 5-HT3B receptor subunits in the mouse vestibular ganglion (VG) by RT-PCR and in situ hybridization (ISH). We also show by ISH that 5-HT3 receptor mRNA is only expressed in the VG (superior and inferior division) in the peripheral vestibular nervous system. Moreover, we performed Ca2+ imaging to determine whether functional 5-HT3 receptors are present in the mouse VG, using a selective 5-HT3 receptor agonist, SR57227A. In wild mice, 32% of VG neurons responded to the agonist, whereas there was no response in 5-HT3A receptor knockout mice. These results indicate that VG cells express functional 5-HT3 receptor channels and might play a modulatory role in the peripheral vestibular nervous system. [Copyright &y& Elsevier]