Publication date 06-04-2023
Meniere disease (MD) is a rare disorder of the inner ear defined by sensorineural hearing loss (SNHL) associated with episodes of vertigo and tinnitus. The phenotype is variable, and it may be associated with other comorbidities such as migraine, respiratory allergies, and several autoimmune disorders. The condition has a significant heritability according to epidemiological and familial segregation studies. Familial MD is found in 10% of cases, the most frequently found genes being OTOG, MYO7A, and TECTA, previously associated with autosomal dominant and recessive non-syndromic SNHL. These findings suggest a new hypothesis where proteins involved in the extracellular structures in the apical surface of sensory epithelia (otolithic and tectorial membranes) and proteins in the stereocilia links would be key elements in the pathophysiology of MD. The ionic homeostasis of the otolithic and tectorial membranes could be critical to suppress the innate motility of individual hair cell bundles. Initially, focal detachment of these extracellular membranes may cause random depolarization of hair cells and will explain changes in tinnitus loudness or trigger vertigo attacks in early stages of MD. With the progression of the disease, a larger detachment will lead to an otolithic membrane herniation into the horizontal semicircular canal with dissociation in caloric and head impulse responses. Familial MD shows different types of inheritance, including autosomal dominant and compound recessive patterns and implementation of genetic testing will improve our understanding of the genetic structure of MD.
Pubmed PDF WebMR Iyer,R Kalluri
Publication date 17-03-2023
Purpose Nuclear position is precisely orchestrated during cell division, migration, and maturation of cells and tissues. Here we report a previously unrecognized, programmed movement of the nucleus in rat and mouse cochlear inner hair cells (IHCs) coinciding with the functional maturation of inner hair cells around the onset of hearing. Methods We measured hair cell length and nuclear position from confocal scans of immunofluorescence-labeled hair cells from whole-mount cochlear preparations throughout post-natal development. Results In early post-natal days, the IHC experiences a period of sustained growth, during which the nucleus sits at the very basal pole of the cell, far from the apically located mechano-transducing stereocilia, but close to where synapses with primary afferent and efferent neurons are forming. After IHCs reach their final length, the nucleus moves to occupy a new position half-way along the length of the cell. Nuclear translocation begins in the middle turn, completes throughout the cochlea within 2–3 days, and coincides with the emergence of endolymphatic potential, the acquisition of big-conductance potassium channels (BK), and the onset of acoustic hearing. IHCs cultured in-vitro without endolymphatic potential (EP) do not grow, do not express BK, and do not experience nuclear movement. IHCs cultured in high K+ solutions (to simulate EP) grow but do not experience nuclear movement or acquire BK channels. Conclusion Nuclear migration at the onset of hearing is a key step in the morphological maturation of IHCs. Whether this plays a role in functional maturation remains to be explored.
Pubmed PDF WebY Tai,S Shahsavarani,RA Khan,SA Schmidt,FT Husain
Publication date 03-03-2023
Speech-in-noise (SiN) recognition difficulties are often reported in patients with tinnitus. Although brain structural changes such as reduced gray matter (GM) volume in auditory and cognitive processing regions have been reported in the tinnitus population, it remains unclear how such changes influence speech understanding, such as SiN performance. In this study, pure-tone audiometry and Quick Speech-in-Noise test were conducted on individuals with tinnitus and normal hearing and hearing-matched controls. T1-weighted structural MRI images were obtained from all participants. After preprocessing, GM volumes were compared between tinnitus and control groups using whole-brain and region-of-interest analyses. Further, regression analyses were performed to examine the correlation between regional GM volume and SiN scores in each group. The results showed decreased GM volume in the right inferior frontal gyrus in the tinnitus group relative to the control group. In the tinnitus group, SiN performance showed a negative correlation with GM volume in the left cerebellum (Crus I/II) and the left superior temporal gyrus; no significant correlation between SiN performance and regional GM volume was found in the control group. Even with clinically defined normal hearing and comparable SiN performance relative to controls, tinnitus appears to change the association between SiN recognition and regional GM volume. This change may reflect compensatory mechanisms utilized by individuals with tinnitus who maintain behavioral performance.
Pubmed PDF WebT Chen,G Li,W Liu,Z Fan,L Li
Publication date 23-02-2023
Otitis media with effusion (OME), also known as secretory otitis media, is a common condition in otorhinolaryngology. The main manifestations include middle ear effusion and conductive hearing loss. Recently, increasing attention has been paid to the etiology of OME, wherein immune dysfunction is one important pathogenic mechanism. However, it is unknown whether changes in surfactant protein A (SPA) secretion affect the phagocytic activity of macrophages in the Eustachian tube, thereby altering pathogen clearance, during the pathogenesis of OME. In our study, an OME animal model was established and evaluated. Differences in SPA levels in Eustachian tube lavage fluid between the experimental and control groups were analyzed. Cell-based experiments revealed that SPA decreased the expression of CD64 and SYK and inhibited phagocytosis by RAW264.7 cells. By using flow cytometry and immunofluorescence, we confirmed that macrophage phagocytosis decreased with increasing SPA levels. Finally, we concluded that SPA affects macrophage function and plays a role in the occurrence and development of OME.
Pubmed PDF WebM Makuszewska,M Cieślińska,MM Winnicka,B Skotnicka,K Niemczyk,T Bonda
Publication date 21-02-2023
The significance of plasminogen activation during the tympanic membrane (TM) healing is known mainly from studies performed on knock-out mice. In the previous study, we reported activation of genes coding proteins of plasminogen activation and inhibition system in rat’s TM perforation healing. The aim of the present study was the evaluation of protein products expressed by these genes and their tissue distribution using Western blotting and immunofluorescent method, respectively, during 10-day observation period after injury. Otomicroscopical and histological evaluation were employed to assess the healing process. The expression of urokinase plasminogen activator (uPA) and its receptor (uPAR) were significantly upregulated in the proliferation phase, with subsequent gradual attenuation during remodeling phase of healing process, when keratinocyte migration was weakening. The expression of plasminogen activator inhibitor type 1 (PAI-1) also showed the highest levels during the proliferation phase. The increase of tissue plasminogen activator (tPA) expression was observed during the whole observation period, with the highest activity during the remodeling phase. Immunofluorescence of these proteins was present mainly in migrating epithelium. Our study found that plasminogen activation (uPA, uPAR, tPA) and inhibitory (PAI-1) molecules form a well-structured regulatory system of the epithelial migration that is critical to the healing of TM after its perforation.
Pubmed PDF WebSS Goodman,JT Lichtenhan,SG Jennings
Publication date 16-02-2023
Physiology of the cochlea and auditory nerve can be assessed with electrocochleography (ECochG), a technique that involves measuring auditory evoked potentials from an electrode placed near or within the cochlea. Research, clinical, and operating room applications of ECochG have in part centered on measuring the auditory nerve compound action potential (AP) amplitude, the summating potential (SP) amplitude, and the ratio of the two (SP/AP). Despite the common use of ECochG, the variability of repeated amplitude measurements for individuals and groups is not well understood. We analyzed ECochG measurements made with a tympanic membrane electrode in a group of younger normal-hearing participants to characterize the within-participant and group-level variability for the AP amplitude, SP amplitude, and SP/AP amplitude ratio. Results show that the measurements have substantial variability and that, especially with smaller sample sizes, significant reduction in variability can be obtained by averaging measurements across repeated electrode placements within subjects. Using a Bayesian-based model of the data, we generated simulated data to predict minimum detectable differences in AP and SP amplitudes for experiments with a given number of participants and repeated measurements. Our findings provide evidence-based recommendations for the design and sample size determination of future experiments using ECochG amplitude measurements, and the evaluation of previous publications in terms of sensitivity to detecting experimental effects on ECochG amplitude measurements. Accounting for the variability of ECochG measurements should result in more consistent results in the clinical and basic assessments of hearing and hearing loss, either hidden or overt.
Pubmed PDF WebJC Middlebrooks,LK Javier-Tolentino,A Arneja,ML Richardson
Publication date 16-02-2023
Most accounts of single- and multi-unit responses in auditory cortex under anesthetized conditions have emphasized V-shaped frequency tuning curves and low-pass sensitivity to rates of repeated sounds. In contrast, single-unit recordings in awake marmosets also show I-shaped and O-shaped response areas having restricted tuning to frequency and (for O units) sound level. That preparation also demonstrates synchrony to moderate click rates and representation of higher click rates by spike rates of non-synchronized tonic responses, neither of which are commonly seen in anesthetized conditions. The spectral and temporal representation observed in the marmoset might reflect special adaptations of that species, might be due to single- rather than multi-unit recording, or might indicate characteristics of awake-versus-anesthetized recording conditions. We studied spectral and temporal representation in the primary auditory cortex of alert cats. We observed V-, I-, and O-shaped response areas like those demonstrated in awake marmosets. Neurons could synchronize to click trains at rates about an octave higher than is usually seen with anesthesia. Representations of click rates by rates of non-synchronized tonic responses exhibited dynamic ranges that covered the entire range of tested click rates. The observation of these spectral and temporal representations in cats demonstrates that they are not unique to primates and, indeed, might be widespread among mammalian species. Moreover, we observed no significant difference in stimulus representation between single- and multi-unit recordings. It appears that the principal factor that has hindered observations of high spectral and temporal acuity in the auditory cortex has been the use of general anesthesia.
Pubmed PDF WebF Guérit,JM Deeks,D Arzounian,R Gransier,J Wouters,RP Carlyon
Publication date 08-02-2023
Two EEG experiments measured the sustained neural response to amplitude-modulated (AM) high-rate pulse trains presented to a single cochlear-implant (CI) electrode. Stimuli consisted of two interleaved pulse trains with AM rates F1 and F2 close to 80 and 120 Hz respectively, and where F2 = 1.5F1. Following Carlyon et al. (J Assoc Res Otolaryngol, 2021), we assume that such stimuli can produce a neural distortion response (NDR) at F0 = F2-F1 Hz if temporal dependencies (“smoothing”) in the auditory system are followed by one or more neural nonlinearities. In experiment 1, the rate of each pulse train was 480 pps and the gap between pulses in the F1 and F2 pulse trains ranged from 0 to 984 µs. The NDR had a roughly constant amplitude for gaps between 0 and about 200–400 µs, and decreased for longer gaps. We argue that this result is consistent with a temporal dependency, such as facilitation, operating at the level of the auditory nerve and/or with co-incidence detection by cochlear-nucleus neurons. Experiment 2 first measured the NDR for stimuli at each listener’s most comfortable level (“MCL”) and for F0 = 37, 40, and 43 Hz. This revealed a group delay of about 42 ms, consistent with a thalamic/cortical source. We then showed that the NDR grew steeply with stimulus amplitude and, for most listeners, decreased by more than 12 dB between MCL and 75% of the listener’s dynamic range. We argue that the NDR is a potentially useful objective estimate of MCL.
Pubmed PDF WebGR Popelka,AN Popper
Publication date 01-02-2023
We review the history of the creation of the Journal of the Association for Research in Otolaryngology (JARO). We begin with the pre-history events that cover the initial concept, committee work and discussions that led the ARO to decide to publish its own journal. Finally, we provide a brief look at the initial stages of forming JARO.
Pubmed PDF WebLL Shen,NS Andresen,DA Chari,JM Pogson,AM Lauer,RD Rabbitt,JP Carey,F Santos,BK Ward
Publication date 01-02-2023
Ménière’s disease (MD) is a debilitating disorder with unclear pathophysiology whose diagnosis often relies on clinical judgment rather than objective testing. To complicate matters further, a dissociation has emerged between two vestibular function tests commonly used in patients with MD to examine the same end-organ (the semicircular canals): the caloric test and video head impulse testing (vHIT). Caloric responses are often abnormal, while vHIT results remain normal. Explaining this dissociation could reveal novel insights into MD pathophysiology. Here, we conduct a histopathological study using temporal bone specimens (N = 58, 21 MD-affected ears and 37 age-matched controls) and their clinical testing data to examine current hypotheses aimed at this dissociation. We find otolith membrane herniation into the horizontal semicircular canal in 69% of MD ears, with 90% of these ears demonstrating a diminished caloric response. No ears with a normal response had this herniation. Moreover, we evaluated the semicircular canals for endolymphatic hydrops, which had been hypothesized to contribute to the dissociation, and found no evidence of duct dilation/hydrops. We did, however, note a potentially novel morphologic finding—smaller bony labyrinth cross-sectional diameters/areas in some MD ear canals compared to controls, suggesting relative size of the membranous duct to the bony canal rather than absolute size may be of importance. Taken together, this study refines hypotheses on the vestibular test dissociation in MD, holding diagnostic implications and expanding our understanding of the mechanisms underlying this enigmatic disease.
Pubmed PDF WebR Biswas,E Genitsaridi,N Trpchevska,A Lugo,W Schlee,CR Cederroth,S Gallus,DA Hall
Publication date 01-02-2023
Aims/Hypothesis Identifying risk factors for tinnitus could facilitate not only the recommendations for prevention measures, but also identifying potential pathways for new interventions. This study reports the first comprehensive systematic review of analytical observational studies able to provide information about causality (i.e., case–control and cohort designs). Methods A literature search of four electronic databases identified epidemiological studies published on tinnitus and different exposures. Independent raters screened all studies, extracted data, and evaluated study quality using the Newcastle–Ottawa Scale. Reported relative risks (RR), hazard ratios (HR), odds ratios (OR), and prevalence ratios (PR) with 95% confidence intervals (CI) were used to compute crude estimates of RR for tinnitus risk factors. Results From 2389 records identified, a total of 374 articles were read as full text (24 reviews, 301 cross-sectional studies, 42 cohort studies, and 7 case–control studies). However, from 49 case–control and cohort studies, only 25 adequately reported risk ratios. Using the findings from these studies, positive causal associations were found for various hearing-related factors (i.e., unspecified hearing loss, sensorineural hearing loss, occupational noise exposure, ototoxic platinum therapy, and otitis media). Evidence was also found for a number of non-otological risk factors including temporo-mandibular joint disorder, depression, chronic obstructive pulmonary disease, and hyperlipidemia. Negative associations indicating preventative effects were found for diabetes and high alcohol consumption. No associations were found for low alcohol consumption, body mass index, head injury, heart failure, hypertension, leisure noise exposure, migraine, rheumatoid arthritis, sex, smoking, stroke, and whiplash. However, with the exception of unspecified hearing loss, these findings resulted from pooling no more than 4 studies, illustrating that the vast majority of the associations still remain inconclusive. Conclusions These systematic review and meta-analysis confirm a number of otological and non-otological risk factors for tinnitus. By highlighting major gaps in knowledge, our synthesis can help provide direction for future research that will shed light on the pathophysiology, improve management strategies, and inform more effective preventions.
Pubmed PDF WebR de Sousa Lobo Ferreira Querido,X Ji,R Lakha,RJ Goodyear,GP Richardson,CL Vizcarra,ES Olson
Publication date 01-02-2023
Purpose A probe that binds to unfixed collagen fibrils was used to image the shapes and fibrous properties of the TM and BM. The probe (CNA35) is derived from the bacterial adhesion protein CNA. We present confocal images of hydrated gerbil TM, BM, and other cochlear structures stained with fluorescently labeled CNA35. A primary purpose of this article is to describe the use of the CNA35 collagen probe in the cochlea. Methods Recombinant poly-histidine-tagged CNA35 was expressed in Escherichia coli, purified by cobalt-affinity chromatography, fluorescence labeled, and further purified by gel filtration chromatography. Cochleae from freshly harvested gerbil bullae were irrigated with and then incubated in CNA35 for periods ranging from 2 h — overnight. The cochleae were fixed, decalcified, and dissected. Isolated cochlear turns were imaged by confocal microscopy. Results The CNA35 probe stained the BM and TM, and volumetric imaging revealed the shape of these structures and the collagen fibrils within them. The limbal zone of the TM stained intensely. In samples from the cochlear base, intense staining was detected on the side of the TM that faces hair cells. In the BM pectinate zone, staining was intense at the upper and lower boundaries. The BM arcuate zone was characterized by a prominent longitudinal collagenous structure. The spiral ligament, limbus and lamina stained for collagen, and within the spiral limbus the habenula perforata were outlined with intense staining. Conclusion The CNA35 probe provides a unique and useful view of collagenous structures in the cochlea.
Pubmed PDF WebF Guérit,AJ Harland,ML Richardson,R Gransier,JC Middlebrooks,J Wouters,RP Carlyon
Publication date 01-02-2023
To obtain combined behavioural and electrophysiological measures of pitch perception, we presented harmonic complexes, bandpass filtered to contain only high-numbered harmonics, to normal-hearing listeners. These stimuli resemble bandlimited pulse trains and convey pitch using a purely temporal code. A core set of conditions consisted of six stimuli with baseline pulse rates of 94, 188 and 280 pps, filtered into a HIGH (3365–4755 Hz) or VHIGH (7800–10,800 Hz) region, alternating with a 36% higher pulse rate. Brainstem and cortical processing were measured using the frequency following response (FFR) and auditory change complex (ACC), respectively. Behavioural rate change difference limens (DLs) were measured by requiring participants to discriminate between a stimulus that changed rate twice (up-down or down-up) during its 750-ms presentation from a constant-rate pulse train. FFRs revealed robust brainstem phase locking whose amplitude decreased with increasing rate. Moderate-sized but reliable ACCs were obtained in response to changes in purely temporal pitch and, like the psychophysical DLs, did not depend consistently on the direction of rate change or on the pulse rate for baseline rates between 94 and 280 pps. ACCs were larger and DLs lower for stimuli in the HIGH than in the VHGH region. We argue that the ACC may be a useful surrogate for behavioural measures of rate discrimination, both for normal-hearing listeners and for cochlear-implant users. We also showed that rate DLs increased markedly when the baseline rate was reduced to 48 pps, and compared the behavioural and electrophysiological findings to recent cat data obtained with similar stimuli and methods.
Pubmed PDF WebA Altoè,CA Shera
Publication date 01-02-2023
The cochlea of the mammalian inner ear includes an active, hydromechanical amplifier thought to arise via the piezoelectric action of the outer hair cells (OHCs). A classic problem of cochlear biophysics is that the RC (resistance-capacitance) time constant of the hair-cell membrane appears inconveniently long, producing an effective cut-off frequency much lower than that of most audible sounds. The long RC time constant implies that the OHC receptor potential—and hence its electromotile response—decreases by roughly two orders of magnitude over the frequency range of mammalian hearing, casting doubt on the hypothesized role of cycle-by-cycle OHC-based amplification in mammalian hearing. Here, we review published data and basic physics to show that the “RC problem” has been magnified by viewing it through the wrong lens. Our analysis finds no appreciable mismatch between the expected magnitude of high-frequency electromotility and the sound-evoked displacements of the organ of Corti. Rather than precluding significant OHC-based boosts to auditory sensitivity, the long RC time constant appears beneficial for hearing, reducing the effects of internal noise and distortion while increasing the fidelity of cochlear amplification.
Pubmed PDF WebH Farahbod,C Rogalsky,LM Keator,J Cai,SB Pillay,K Turner,A LaCroix,J Fridriksson,JR Binder,JC Middlebrooks,G Hickok,K Saberi
Publication date 01-02-2023
Auditory stream segregation and informational masking were investigated in brain-lesioned individuals, age-matched controls with no neurological disease, and young college-age students. A psychophysical paradigm known as rhythmic masking release (RMR) was used to examine the ability of participants to identify a change in the rhythmic sequence of 20-ms Gaussian noise bursts presented through headphones and filtered through generalized head-related transfer functions to produce the percept of an externalized auditory image (i.e., a 3D virtual reality sound). The target rhythm was temporally interleaved with a masker sequence comprising similar noise bursts in a manner that resulted in a uniform sequence with no information remaining about the target rhythm when the target and masker were presented from the same location (an impossible task). Spatially separating the target and masker sequences allowed participants to determine if there was a change in the target rhythm midway during its presentation. RMR thresholds were defined as the minimum spatial separation between target and masker sequences that resulted in 70.7% correct-performance level in a single-interval 2-alternative forced-choice adaptive tracking procedure. The main findings were (1) significantly higher RMR thresholds for individuals with brain lesions (especially those with damage to parietal areas) and (2) a left–right spatial asymmetry in performance for lesion (but not control) participants. These findings contribute to a better understanding of spatiotemporal relations in informational masking and the neural bases of auditory scene analysis.
Pubmed PDF WebKC Schvartz-Leyzac,DJ Colesa,DL Swiderski,Y Raphael,BE Pfingst
Publication date 01-02-2023
The cochlear implant (CI) is widely considered to be one of the most innovative and successful neuroprosthetic treatments developed to date. Although outcomes vary, CIs are able to effectively improve hearing in nearly all recipients and can substantially improve speech understanding and quality of life for patients with significant hearing loss. A wealth of research has focused on underlying factors that contribute to success with a CI, and recent evidence suggests that the overall health of the cochlea could potentially play a larger role than previously recognized. This article defines and reviews attributes of cochlear health and describes procedures to evaluate cochlear health in humans and animal models in order to examine the effects of cochlear health on performance with a CI. Lastly, we describe how future biologic approaches can be used to preserve and/or enhance cochlear health in order to maximize performance for individual CI recipients.
Pubmed PDF WebN Senofsky,J Faber,D Bozovic
Publication date 01-02-2023
Meniere’s disease (MD) is a condition of the inner ear with symptoms affecting both vestibular and hearing functions. Some patients with MD experience vestibular drop attacks (VDAs), which are violent falls caused by spurious vestibular signals from the utricle and/or saccule. Recent surgical work has shown that patients who experience VDAs also show disrupted utricular otolithic membranes. The objective of this study is to determine if otolithic membrane damage alone is sufficient to induce spurious vestibular signals, thus potentially eliciting VDAs and the vestibular dysfunction seen in patients with MD. We use a previously developed numerical model to describe the nonlinear dynamics of an array of active, elastically coupled hair cells. We then reduce the coupling strength of a selected region of the membrane to model the effects of tissue damage. As we reduce the coupling strength, we observe large and abrupt spikes in hair bundle position. As bundle displacements from the equilibrium position have been shown to lead to depolarization of the hair-cell soma and hence trigger neural activity, this spontaneous activity could elicit false detection of a vestibular signal. The results of this numerical model suggest that otolithic membrane damage alone may be sufficient to induce VDAs and the vestibular dysfunction seen in patients with MD. Future experimental work is needed to confirm these results in vitro.
Pubmed PDF WebWS Konerding,P Baumhoff,A Kral
Publication date 01-02-2023
One severe side effect of the use of cochlear implants (CI) is coincidental facial nerve stimulation (FNS). Clinical methods to alleviate FNS range from the reprogramming of processor settings to revision surgery. We systematically assessed different changes in CI stimulation modes that have been discussed in the literature as “rescue factors” from FNS: electrode configuration (broad to focused), pulse shape (symmetric biphasic to pseudo-monophasic), and pulse polarity (cathodic to anodic). An FNS was assessed, based on electrophysiological thresholds, in 204 electrically evoked compound action potential (eCAP) input/output functions recorded from 33 ears of 26 guinea pigs. The stimulation level difference between auditory nerve eCAP threshold and FNS threshold was expressed as the eCAP-to-FNS offset. Coincidental FNS occurred in all animals and in 45% of all recordings. A change from monopolar to focused (bipolar, tripolar) configurations minimized FNS. The Euclidean distance between the CI contacts and the facial nerve explained no more than 33% of the variance in FNS thresholds. For both the FNS threshold and the eCAP-to-FNS offset, the change from cathodic to anodic pulse polarity significantly reduced FNS and permitted a gain of 14–71% of the dynamic range of the eCAP response. This “anodic rescue effect” was stronger for pseudo-monophasic pulses as compared to the symmetric biphasic pulse shape. These results provide possible mechanisms underlying recent clinical interventions to alleviate FNS. The “anodic-rescue effect” may offer a non-invasive therapeutic option for FNS in human CI users that should be tested clinically, preferably in combination with current-focusing methods.
Pubmed PDF WebL Huang,Q Wang,C Huang,Z Zhou,A Peng,Z Zhang
Publication date 30-01-2023
Dysfunction of the endolymphatic sac (ES) is one of the etiologies of Meniere’s disease (MD), the mechanism of which remains unclear. The aim of the present study was to explore the molecular pathological characteristics of ES during the development of MD. Metabolomic profiling of ES luminal fluid from patients with MD and patients with acoustic neuroma (AN) was performed. Diluted ES luminal fluid (ELF) samples were obtained from 10 patients who underwent endolymphatic duct blockage for the treatment of intractable MD and from 6 patients who underwent translabyrinthine surgery for AN. ELF analysis was performed using liquid chromatography-mass spectrometry before the raw data were normalized and subjected to subsequent statistical analysis by Metabo Analyst. Using thresholds of P ≤ 0.05 and variable important in projection > 1, a total of 111 differential metabolites were screened in the ELF, including 52 metabolites in negative mode and 59 in positive mode. Furthermore, 15 differentially altered metabolites corresponding to 15 compound names were identified using a Student’s t-test, including 7 significant increased metabolites and 8 significant decreased metabolites. Moreover, two differentially altered metabolites, hyaluronic acid (HA) and 4-hydroxynonenal (4-HNE), were validated to be upregulated in the epithelial lining of the ES, as well as in the subepithelial connective-tissue in patients with MD comparing with that in patients with AN. Among these differentially altered metabolites, an upregulated expression of HA detected in the ES lumen of the patients with MD was supposed to be associated with the increased endolymph in ES, while an increased level of 4-HNE found in the ELF of the patients with MD provided direct evidence to support that oxidative damage and inflammatory lesions underlie the mechanism of MD. Furthermore, citrate and ethylenediaminetetraacetic acid were detected to be decreased substantially in the ELF of the patients with MD, suggesting the elevated endolymphatic Ca2+ in the ears with chronic endolymphatic hydrops is likely to be associated with the reduction of these two chelators of Ca2+ in ES. The results in the present study indicate metabolomic analysis in the ELF of the patients with MD can potentially improve our understanding on the molecular pathophysiological mechanism in the ES during the development of MD.
Pubmed PDF WebJF Ashmore,JS Oghalai,JB Dewey,ES Olson,CE Strimbu,Y Wang,CA Shera,A Altoè,C Abdala,AB Elgoyhen,RA Eatock,RM Raphael
Publication date 17-01-2023
In 1985, Bill Brownell and colleagues published the remarkable observation that cochlear outer hair cells (OHCs) express voltage-driven mechanical motion: electromotility. They proposed OHC electromotility as the mechanism for the elusive “cochlear amplifier” required to explain the sensitivity of mammalian hearing. The finding and hypothesis stimulated an explosion of experiments that have transformed our understanding of cochlear mechanics and physiology, the evolution of hair cell structure and function, and audiology. Here, we bring together examples of current research that illustrate the continuing impact of the discovery of OHC electromotility.
Pubmed PDF Web