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Endolymphatic hydrops, increased endolymphatic fluid within the cochlea, is the key pathologic finding in patients with Meniere's disease, a disease of episodic vertigo, fluctuating hearing loss, tinnitus, and aural fullness. Endolymphatic hydrops also can occur after noise trauma and its presence correlates with cochlear synaptopathy, a form of hearing loss caused by reduced numbers of synapses between hair cells and auditory nerve fibers. Here we tested whether there is a mechanistic link between these two phenomena by using multimodal imaging techniques to analyze the cochleae of transgenic mice exposed to blast and osmotic challenge. In vivo cochlear imaging after blast exposure revealed dynamic increases in endolymph that involved hair cell mechanoelectrical transduction channel block but not the synaptic release of glutamate at the hair cell–auditory nerve synapse. In contrast, ex vivo and in vivo auditory nerve imaging revealed that synaptopathy requires glutamate release from hair cells but not endolymphatic hydrops. Thus, although endolymphatic hydrops and cochlear synaptopathy are both observed after noise exposure, one does not cause the other. They are simply co-existent sequelae that derive from the traumatic stimulation of hair cell stereociliary bundles. Importantly, these data argue that Meniere's disease derives from hair cell transduction channel blockade. [ABSTRACT FROM AUTHOR]

Type I spiral ganglion neurons are peripheral neurons essential for hearing perception. While they can be subdivided in mice based on characteristic gene expression patterns, detailed examinations of these subtypes in primates and humans are lacking. In this study, we investigated the developmental subtypes of spiral ganglion neurons in the common marmoset (Callithrix jacchus). We confirmed that Type I spiral ganglion can be divided based on the characteristic gene expression patterns of several marker genes. However, some combinations of these genes differ from those in rodents, suggesting common marmoset's suitability for advancing our understanding of human cochlear development. Additionally, identifying the essential time points for subtype specifications and subsequent maturation will aid in studying the primate-specific developmental biology of the inner ear. This could lead to new treatment strategies for hearing loss in humans and be valuable for studying age-related hearing loss, as well as designing regenerative therapies. [ABSTRACT FROM AUTHOR]

Noise-induced hidden hearing loss (HHL) is a newly uncovered form of hearing impairment that causes hidden damage to the cochlea. Patients with HHL do not have significant abnormalities in their hearing thresholds, but they experience impaired speech recognition in noisy environments. However, the mechanisms underlying HHL remain unclear. In this study, we developed single-cell transcriptome profiles of the cochlea of mice with HHL, detailing changes in individual cell types. Our study revealed a transient threshold shift, reduced auditory brainstem response wave I amplitude, and decreased number of ribbon synapses in HHL mice. Our findings suggest elevated oxidative stress and GDF15 expression in cochlear hair cells of HHL mice. Notably, the upregulation of GDF15 attenuated oxidative stress and auditory impairment in the cochlea of HHL mice. This suggests that a therapeutic strategy targeting GDF15 may be efficacious against HHL. HHL mice had a transient threshold shift, reduced ABR wave I amplitude, and decreased number of ribbon synapses. HHL mice's cochlear hair cells exhibited increased oxidative stress and elevated GDF15 expression. Upregulation of GDF15 attenuated oxidative stress and auditory damage in the cochlea of HHL mice, implying that GDF15-targeted treatment techniques may be useful for HHL. [ABSTRACT FROM AUTHOR]

The complex fluid–solid coupling movement of macro–micro structures and lymphatic fluid in the cochlea plays a crucial role in the mechanism of sound perception in the human ear. However, previous studies have primarily focused on the macrostructure and overlooked the microstructure of the Organ of Corti (OC). In reality, the microstructure of the OC can regulate the vibration of the basilar membrane, which is important for sound perception. To address this, a three-dimensional spiral passive cochlear model containing a complete OC that conforms to the real physiology of the human ear was developed, but the significant amplification of its motion by the action of outer hair cells (OHC) in the living cochlea was not considered. The fluid–solid coupling calculations were conducted on this model, specifically examining the mechanical response of the OC microstructure and the pressure changes in the lymphatic fluid. The results showed that the lower stiffness structure in the OC has a lower stress level, which contributes to the realization of sound perception. As the frequencies increases, the region of peak stress and displacement in the OHC moves from the apex to the base of the cochlea, reflecting frequency-selective characteristics. The tunnel of the OC amplifies pressure waves at specific locations, enabling more accurate frequency recognition. Furthermore, the presence of the OC not only causes significant radial differences in lymphatic fluid pressure in the scala vestibule, but also enhances internal cochlear vibration, playing an undeniable regulatory role in the sound perception.Kindly check and verify edit made in article title.We have checked and verified the editing in the article title. [ABSTRACT FROM AUTHOR]

Objectives: Objective measurements to predict the position of a cochlear electrode during cochlear implantation surgery may serve to improve the surgical technique and postoperative speech outcome. There is evidence that electrically evoked compound action potentials (ECAP) are a suitable approach to provide information about the site of stimulation. This study aims to contribute to the knowledge about the association between the intraoperative intracochlear ECAP characteristics and the site of stimulation. Methods: In a retrospective cohort study, patients undergoing cochlear implant surgery with flexible lateral wall electrode arrays (12 stimulating channels) between 2020 and 2022 were analyzed. The CDL was measured using a CT-based clinical planning software. ECAP were measured for all electrode contacts and associated to the CDL as well as to the site of stimulation in degree. Results: Significant differences among the amplitudes and slopes for the individual stimulated electrode contacts at the stimulation sites of 90°, 180°, 270°, 360°, 450° and 540° were found. The values showed a trend for linearity among the single electrodes. Conclusions: ECAP characteristics correlate with the electrode's position inside the cochlea. In the future, ECAP may be applied to assess the intracochlear position inside the cochlea and support anatomy-based fitting. [ABSTRACT FROM AUTHOR]

Objective: Blood-labyrinthine barrier leakage has been reported in sudden sensorineural hearing loss (SSNHL). We compared immediate post-contrast 3D heavily T2-weighted fluid-attenuated inversion recovery (FLAIR), T1 spin echo (SE), and 3D T1 gradient echo (GRE) sequences, and heavily T2-weighted FLAIR (hvT2F) with and without deep learning-based reconstruction (DLR) in detecting perilymphatic enhancement. Methods: Fifty-four patients with unilateral SSNHL who underwent ear MRI with three sequences were included. We compared asymmetry scores, confidence scores, and detection rates of perilymphatic enhancement among the three sequences and obtained 3D hvT2F with DLR from 35 patients. The above parameters and subjective image quality between 3D hvT2F with and without DLR were compared. Results: Asymmetry scores and detection rate of 3D hvT2F were significantly higher than 3D GRE T1 and SE T1 (respectively, 1.37, 0.11, 0.19; p < 0.001). Asymmetry scores significantly increased with DLR compared to 3D hvT2F for experienced and inexperienced readers (respectively, 1.77 vs. 1.40, p = 0.036; 1.49 vs. 1.03, p = 0.012). The detection rate significantly increased only for the latter (57.1% vs. 31.4%, p = 0.022). Patients with perilymphatic enhancement had significantly higher air conduction thresholds on initial (77.96 vs. 57.79, p = 0.002) and 5 days after presentation (63.38 vs. 41.85, p = 0.019). Conclusion: 3D hvT2F significantly increased the detectability of perilymphatic enhancement compared to 3D GRE T1 and SE T1. DLR further improved the conspicuity of perilymphatic enhancement in 3D hvT2F. 3D hvT2F and DLR are useful for evaluating blood-labyrinthine barrier leakage; furthermore, they might provide prognostic value in the early post-treatment period. Clinical relevance statement: Ten-minute post-contrast 3D heavily T2-weighed FLAIR imaging is a potentially efficacious sequence in demonstrating perilymphatic enhancement in patients with sudden sensorineural hearing loss and may be further improved by deep learning-based reconstruction. Key Points: • 3D heavily T2-weighted FLAIR (3D hvT2F) is a sequence sensitive in detecting low concentrations of contrast in the perilymphatic space. • 3D hvT2F sequences properly demonstrated perilymphatic enhancement in sudden sensorineural hearing loss compared to T1 sequences and were further improved by deep learning-based reconstruction (DLR). • 3D hvT2F and DLR are efficacious sequences in detecting blood-labyrinthine barrier leakage and with potential prognostic information. [ABSTRACT FROM AUTHOR]

Purpose: Tone-pip-evoked otoacoustic emissions (PEOAEs) are transient-evoked otoacoustic emissions (OAEs) that are hypothesized to originate from reflection of energy near the best-frequency (BF) cochlear place of the stimulus frequency. However, individual PEOAEs have energy with a wide range of delays. We sought to determine whether some PEOAE energy is consistent with having been generated far from BF. Methods: PEOAEs from 35 and 47 dB SPL tone pips were obtained by removing pip-stimulus energy by subtracting the ear-canal sound pressure from scaled-down 59 dB SPL tone pips (which evoke relatively small OAEs). PEOAE delays were measured at each peak in the PEOAE absolute-value waveforms. While measuring PEOAEs and auditory-nerve compound action potentials (CAPs), amplification was blocked sequentially from apex to base by cochlear salicylate perfusion. The perfusion time when a CAP was reduced identified when the perfusion reached the tone-pip BF place. The perfusion times when each PEOAE peak was reduced identified where along the cochlea it received cochlear amplification. PEOAEs and CAPs were measured simultaneously using one pip frequency in each ear (1.4 to 4 kHz across 16 ears). Results: Most PEOAE peaks received amplification primarily between the BF place and 1–2 octaves basal of the BF place. PEOAE peaks with short delays received amplification basal of BF place. PEOAE peaks with longer delays sometimes received amplification apical of BF place, consistent with previous stimulus-frequency-OAE results. Conclusion: PEOAEs provide information about cochlear amplification primarily within ~ 1.5 octave of the tone-pip BF place, not about regions > 3 octaves basal of BF. [ABSTRACT FROM AUTHOR]

Background: Ménière's disease is a chronic condition of the inner ear that causes vertigo, tinnitus and hearing loss. Its diagnosis relies on clinical criteria that are subjective and pure-tone audiometry results that are not specific. Its pathological substrate is endolymphatic hydrops. Its imaging was recently made possible by the late-enhanced 3D FLAIR sequence. This technique was primarily tested on 3 T. Our objective was to prove its feasibility using a 1.5 T magnet. Methods: We conducted a prospective study including 30 patients who fulfilled the Bárány society criteria for Ménière's disease. We performed the late-enhanced 3D FLAIR sequence on all patients. We used it to look for and grade endolymphatic hydrops in the utricle, the saccule and the cochlear canal using the Kahn method. Results: We found endolymphatic hydrops in all of the 30 patients who fulfilled the diagnostic criteria for Ménière's disease. We had no false positives and only one false negative with a patient presenting with bilateral disease clinically but having endolymphatic hydrops only on one side. Thus, our correspondence rate between clinical and imaging findings was 97%. Conclusions: It is possible to diagnose endolymphatic hydrops with the late-enhanced 3D FLAIR sequence using a 1.5 T MRI machine. Since Ménière's disease diagnosis is sometimes tricky, imaging endolymphatic hydrops can aid in the diagnosis when the clinical picture is incomplete. It also helps guide invasive treatment plans. Feasibility at 1.5 T ensures broader access to the late-enhanced 3D FLAIR sequence. Beyond the scope of Ménière's disease, this sequence offers the possibility to better understand pressure-related inner ear diseases. [ABSTRACT FROM AUTHOR]

Purpose: While cochlea is adult size at birth, etiologies and bone density may differ between children and adults. Differences in neural response thresholds (tNRT) and the spread of excitation (SOE) width may impact the use of artificial intelligence algorithms in speech processor fitting. Aim: To identify whether neural response telemetry threshold and spread of excitation width are similar in adults and children. Methods: Retrospective cross-sectional study approved by the Ethical Board. Intraoperative tNRT and SOE recordings of consecutive cochlear implant surgeries in adults and children implanted with Cochlear devices (Cochlear™, Australia) were selected. SOE was recorded on electrode 11 (or adjacent, corresponding to the medial region of the cochlea) through the standard forward-masking technique in Custom Sound EP software, which provides SOE width in millimeters. Statistical comparison between adults and children was performed using the Mann–Whitney test (p ≤ 0.05). Results: Of 1282 recordings of intraoperative evaluations, 414 measurements were selected from children and adults. Despite the tNRT being similar between adults and children, SOE width was significantly different, with lower values in children with perimodiolar arrays. Besides, it was observed that there is a difference in the electrode where the SOE function peak occurred, more frequently shifted to electrode 12 in adults implanted. In straight arrays, there was no difference in any of the parameters analyzed on electrode 11. Conclusion: Although eCAP thresholds are similar, SOE measurements differ between adults and children in perimodiolar electrodes. [ABSTRACT FROM AUTHOR]

This study describes the clinical profile, operative findings, surgical technique, type of implant and complications encountered in implantation of abnormal cochlea by the transcanal (veria) technique in a tertiary care centre. This is a retrospective study done amongst 337 patients who underwent cochlear implantation by veria technique between January 2013 to August 2023. Based on pre-operative imaging with high-resolution computed tomography and magnetic resonance imaging the cochleovestibular malformations in this study were classified according to Sennaroglu classification and the cochlear ossification was graded from I to IV. Amongst the 337 patients who underwent cochlear implantation during the study period there were 79 cases (23.4%) with abnormalities of cochlea. This included 45 patients (13.4%) with congenital malformations, 20 patients (5.9%) with cochlear fibrosis and 14 patients (4.2%) with cochlear ossification. The commonest cochlear malformation was Incomplete Partition 2 which was present in 21 patients (46.7%). The other common malformations were cochlear hypoplasia (31.1%), Incomplete Partition 1(13.3%) and common cavity (8.9%). Out of the 20 patients with cochlear fibrosis, 17 patients had fibrosis only in the basal turn. Out of the 14 patients with cochlear ossification 8 patients (57.1%) had a grade 1 ossification, 2 patients (14.3%) had a grade 2 ossification and 4 patients (28.6%) had a grade 3 ossification. One of the patients required re-exploration for correcting the placement of electrode. The type of implant were chosen depending on individual malformation or length of ossification and fibrosis. In the past, inner ear anomalies were considered as a contraindication for cochlear implantation however it is now possible to implant most of these abnormal cochlea by careful planning, a modification of the surgical technique and the type of electrode used. [ABSTRACT FROM AUTHOR]

Background: Subtotal petrosectomy (STP) has attracted massive interest over last two decades. The aim is to present our experience of this uncommon surgery. The indications, outcomes, and our variation in surgical technique would be presented and literature reviewed. Methods: A retrospective observational study of all patients who underwent STP at a tertiary care center in India was analyzed. Results: A total of 9 ears (in 8 patients) underwent STP over last 5 years at our center. The pathological conditions for which STP was done included chronic otitis media squamous (four ears), middle ear tumors (three ears), petrous apicitis (one ear), and traumatic cerebrospinal fluid (CSF) otorhinorrhea (one ear). The indication of STP included disease clearance (eight ears), unserviceable hearing (seven ears), hearing rehabilitation with otological implants (six ears), and intraoperative CSF gusher (one ear). Intraoperative indications included CSF gusher, large tegmen defect with erosion of apical turn of cochlea, and erosion of anterior bony wall of external auditory canal. The mean follow-up period was 36 months (range of 6 months to 60 months). None of the patients had any dehiscence of blind sac closure or secondary acquired cholesteatoma on imaging. Conclusions: STP facilitates disease clearance by providing unmatchable exposure in difficult otological scenarios and additionally isolates middle ear cleft from external environment, thereby eliminating problems of mastoid cavity. Furthermore, it also prepares ear for second stage otological implants. It is a safe surgery with minimal complications. [ABSTRACT FROM AUTHOR]

Pending questions regarding cochlear amplification and tuning are hinged upon the organ of Corti (OoC) active mechanics: how outer hair cells modulate OoC vibrations. Our knowledge regarding OoC mechanics has advanced over the past decade thanks to the application of tomographic vibrometry. However, recent data from live cochlea experiments often led to diverging interpretations due to complicated interaction between passive and active responses, lack of image resolution in vibrometry, and ambiguous measurement angles. We present motion measurements and analyses of the OoC sub-components at the close-to-true cross-section, measured from acutely excised gerbil cochleae. Specifically, we focused on the vibrating patterns of the reticular lamina, the outer pillar cell, and the basilar membrane because they form a structural frame encasing active outer hair cells. For passive transmission, the OoC frame serves as a rigid truss. In contrast, motile outer hair cells exploit their frame structures to deflect the upper compartment of the OoC while minimally disturbing its bottom side (basilar membrane). Such asymmetric OoC vibrations due to outer hair cell motility explain how recent observations deviate from the classical cochlear amplification theory. We analyzed the organ of Corti motions, component by component. Outer hair cells exploit their supporting cells to boost vibrations of the upper part of the organ of Corti while minimally disturbing the basilar membrane. [ABSTRACT FROM AUTHOR]

Objective: We compared the signal intensity ratio (SIR) of the cochlear basal turn between Meniere's disease and healthy controls to investigate potential damage of the blood–labyrinth barrier in Meniere's disease. Methods: Thirty patients diagnosed with unilateral definite Meniere's disease and 24 healthy controls were enrolled. 3D-FLAIR scan was conducted to assess the grades of endolymphatic hydrops in Meniere's patients while measuring the SIR of cochlear basal turns in both groups. The differences of bilateral SIR between Meniere's disease and healthy control were compared, and the correlation between the SIR on affected ear in Meniere's disease and the grades of cochlear and vestibular hydrops were analyzed. Results: SIR of affected ear in Meniere's disease exhibited significant increase compared to that of unaffected ear. No significant difference was observed in SIR between the two ears in the healthy control. Furthermore, the SIR of unaffected side in Meniere's disease was higher than that of both ears in healthy controls. The SIR in affected ear of Meniere's disease exhibited positive correlation with hydrops in both cochlea and vestibula. Conclusion: The permeability of blood–labyrinth barrier is increased in Meniere's disease, in combination with the typical criteria of Meniere's disease it may be a good biological marker. Destruction of blood–labyrinth barrier may be one of the causes of endolymphatic hydrops in Meniere's disease. [ABSTRACT FROM AUTHOR]

Purpose: The small size of the cochlea, and its location deeply embedded in thick temporal bone, poses a challenge for intra-cochlear guidance and diagnostics. Current radiological imaging techniques are not able to visualize the cochlear microstructures in detail. Rotational optical coherence tomography (OCT) fibers show great potential for intra-cochlear guidance. The generated images could be used to map, and study, the tiny cochlear microstructures relevant for hearing. Methods: This work describes the design of a rotational OCT probe with an outer diameter of 0.9 mm. It further discusses a robotic system, which features a remote center of motion mechanism, dedicated to the probe's positioning, fine manipulation and stable insertion into the cochlear micro-spaces. Furthermore, the necessary calibration steps for 3D reconstruction are described, followed by a detailed quantitative analysis, comparing the 3D reconstructions using a synthetic, 2:1 scaled scala tympani model with a reconstruction from micro-CT, serving as the ground truth. Finally, the potential of the system is demonstrated by scanning a single ex vivo cadaveric human cochlea. Results: The study investigates five insertions in the same 2:1 scaled tympani model, along with their corresponding 3D reconstruction. The comparison with micro-CT results in an average root-mean-square error of 74.2 µm, a signed distance error of 38.1 µm and a standard deviation of 63.6 µm. The average F-score of the reconstructions, using a distance threshold of 100 and 74.2 µm, resulted in 83.0% and 71.8%, respectively. Insertion in the cadaveric human cochlea showed the challenges for straight insertion, i.e., navigating the hook region. Conclusion: Overall, the system shows great potential for intra-cochlear guidance and diagnostics, due to the system's capability for precise and stable insertion into the basal turn in the scala tympani. The system, combined with the calibration procedure, results in detailed and precise 3D reconstructions. [ABSTRACT FROM AUTHOR]

Moderate noise exposure induces cochlear synaptopathy, the loss of afferent ribbon synapses between cochlear hair cells and spiral ganglion neurons, which is associated with functional hearing decline. Prior studies have demonstrated noise-induced changes in the distribution and number of synaptic components, but the dynamic changes that occur after noise exposure have not been directly visualized. Here, we describe a live imaging model using RIBEYE-tagRFP to enable direct observation of pre-synaptic ribbons in mature hearing mouse cochleae after synaptopathic noise exposure. Ribbon number does not change, but noise induces an increase in ribbon volume as well as movement suggesting unanchoring from synaptic tethers. A subgroup of basal ribbons displays concerted motion towards the cochlear nucleus with subsequent migration back to the cell membrane after noise cessation. Understanding the immediate dynamics of synaptic damage after noise exposure may facilitate identification of specific target pathways to treat cochlear synaptopathy. Direct visualization of synaptic ribbons in neonatal and juvenile mouse cochlea demonstrates that excitotoxic stimulus or noise exposure induces increases in ribbon volume and movement. [ABSTRACT FROM AUTHOR]

Purpose: Pneumococcal meningitis is a major cause of hearing loss and permanent neurological impairment despite widely available antimicrobial therapies to control infection. Methods to improve hearing outcomes for those who survive bacterial meningitis remains elusive. We used a mouse model of pneumococcal meningitis to evaluate the impact of mononuclear phagocytes on hearing outcomes and cochlear ossification by altering the expression of CX3CR1 and CCR2 in these infected mice. Methods: We induced pneumococcal meningitis in approximately 500 C57Bl6 adult mice using live Streptococcus pneumoniae (serotype 3, 1 × 105 colony forming units (cfu) in 10 µl) injected directly into the cisterna magna of anesthetized mice and treated these mice with ceftriaxone daily until recovered. We evaluated hearing thresholds over time, characterized the cochlear inflammatory response, and quantified the amount of new bone formation during meningitis recovery. We used microcomputed tomography (microCT) scans to quantify cochlear volume loss caused by neo-ossification. We also performed perilymph sampling in live mice to assess the integrity of the blood-perilymph barrier during various time intervals after meningitis. We then evaluated the effect of CX3CR1 or CCR2 deletion in meningitis symptoms, hearing loss, macrophage/monocyte recruitment, neo-ossification, and blood labyrinth barrier function. Results: Sixty percent of mice with pneumococcal meningitis developed hearing loss. Cochlear fibrosis could be detected within 4 days of infection, and neo-ossification by 14 days. Loss of spiral ganglion neurons was common, and inner ear anatomy was distorted by scarring caused by new soft tissue and bone deposited within the scalae. The blood-perilymph barrier was disrupted at 3 days post infection (DPI) and was restored by seven DPI. Both CCR2 and CX3CR1 monocytes and macrophages were present in the cochlea in large numbers after infection. Neither chemokine receptor was necessary for the induction of hearing loss, cochlear fibrosis, ossification, or disruption of the blood-perilymph barrier. CCR2 knockout (KO) mice suffered the most severe hearing loss. CX3CR1 KO mice demonstrated an intermediate phenotype with greater susceptibility to hearing loss compared to control mice. Elimination of CX3CR1 mononuclear phagocytes during the first 2 weeks after meningitis in CX3CR1-DTR transgenic mice did not protect mice from any of the systemic or hearing sequelae of pneumococcal meningitis. Conclusions: Pneumococcal meningitis can have devastating effects on cochlear structure and function, although not all mice experienced hearing loss or cochlear damage. Meningitis can result in rapid progression of hearing loss with fibrosis starting at four DPI and ossification within 2 weeks of infection detectable by light microscopy. The inflammatory response to bacterial meningitis is robust and can affect all three scalae. Our results suggest that CCR2 may assist in controlling infection and maintaining cochlear patency, as CCR2 knockout mice experienced more severe disease, more rapid hearing loss, and more advanced cochlear ossification after pneumococcal meningitis. CX3CR1 also may play an important role in the maintenance of cochlear patency. [ABSTRACT FROM AUTHOR]

Close-distance coal seams (CDCS) are widely distributed, and the layout of the upper and lower panels can be divided into "=" type and "+" type. The "+" superposition of upper and lower coal pillars in CDCS caused strong mine pressure, but there are few studies on the panel crossing residual coal pillars (RCP) when the upper and lower coal seams are "+" type layout. In view of the special spatial position ("+" type layout), this paper takes the typical panel 4-301 of a particular mine as the project indagation background and studies mining and crossing the overlying coal pillars by dint of field measurement, numerical simulation, indoor test, and engineering application. Compared with vertical stress or horizontal stress alone, the indexes of deviatoric stress and plastic zone can reflect the failure evolution of surrounding rock more comprehensively. Hence, this paper analyzes the expansion form of the plastic zone and the variation law of deviatoric stress before and after mining influence in the underlying mining roadway. The research results show that: (1) There is a sub-peak zone of deviatoric stress under the RCP. The deviatoric stress is bimodal in the range of 9 m below. After the peak value decays to 7.4 MPa, it changes to a single peak located in the area directly below the middle of the RCP. (2) The maximum plastic zones of the roof and two ribs of the roadway below the RCP are 3.4 m and 5 m, respectively. The crest value of deviatoric stress reaches 10 MPa. As the distance between the panel and the RCP decreases, the shape of the high deviatoric stress area presents the evolution law from the "ellipse" of the roof → the "crescent" of two ribs → the "cochlea" of the tips of the ribs. (3) When the mining of the underlying panel is 10 m, 0 m, or − 10 m away from the RCP (without passing through the RCP). The crest value of deviatoric stress within 5–10 m in advance of the roadway increases in turn. However, the peak value is significantly reduced when it is − 20 m away from the RCP (through the RCP). The crest value of deviatoric stress of two ribs decreases in turn along the panel rib → section coal pillar rib → solid coal rib. Based on this, the underlying 45 m of the RCP is divided into area I (10 m), area II (overlapping area 20 m), and area III (15 m) based on the degree of disturbance. And propose the technical scheme of asymmetric combined control in different zones by using asymmetric channel steel truss anchor cable for the top-ribs of areas I and III, and top-ribs asymmetric channel steel truss anchor cable + door-type support in area II. On-site project practice shows that the partitioned control technology successfully resisted the roadway instability and failure caused by the dynamic-static superimposed stress disturbance under the RCP and realized the primary support of the sectional coal roadway. The conclusion provides technical support and scheme design for the partitioning support of roadways under similar "+" type cross‐panels. [ABSTRACT FROM AUTHOR]

Purpose: The focus on treating patients with Menière's Disease (MD) lies on the reduction of vertigo attacks and the preservation of sensory function. Endolympathic hydrops is considered as an epiphenomenon in MD, which can potentially be altered by endolymphatic sac surgery (ESS). Purpose of the study was to investigate the influences on vertigo control through manipulation of the perilymphatic system with or without ESS. Methods: Retrospective data analysis of 86 consecutive patients with MD according to current diagnostic criteria after endolymphatic sac surgery alone (ESSalone; n = 45), cochlear implantation (CI) alone (CIalone; n = 12), and ESS with CI (ESS + CI; n = 29), treated at a tertiary referral center. Main Outcome Measures: vertigo control, speech perception pre- and postoperatively. Results: Gender, side, and preoperative treatment were similar in all groups. Age was younger in the ESSalone-group with 56.2 ± 13.0 years (CIalone = 64.2 ± 11.4 years; ESS + CI = 63.1 ± 9.7 years). Definitive MD was present in all the CIalone, in 79.3% of the ESS + CI and in 59.6% of the ESSalone-patients. Likewise, vertigo control rate was 100% in the CIalone, 89.7% in the ESS + CI and 66.0% in the ESSalone-group. Conclusions: Vertigo control was improved in all three groups, however, superior in groups treated with CI, potentially contributed by the manipulation of both the endo- and perilymphatic systems. A more systematic characterization of the patients with larger case numbers and documentation of follow up data would be needed to evaluate a clinical effect more properly. [ABSTRACT FROM AUTHOR]

Due to ethical issues and the very fine and complex structure of the cochlea, it is difficult to directly perform experimental measurement on the human cochlea. Therefore, the finite element method has become an effective and replaceable new research means. Accurate numerical analysis on human ear using finite element method can provide better understanding of sound transmission and can be used to assess the influence of diseases on hearing and to treat hearing loss. In this research, a three-dimensional (3D) finite element model (FEM) of the human ear of cochlea was presented to investigate the destruction of basilar membrane (BM), round window (RW) sclerosis and perilymph fistula, the key structures of the cochlea, and analyze the effects of these abnormal pathological states in the cochlea on cochlear hearing, resulting in the changes in cochlear sense structure biomechanical behavior and quantitative prediction of the degree and harm of the disorder to the decline of human hearing. Therefore, this paper can deepen reader's understanding of the cochlear biomechanical mechanism and provide a theoretical foundation for clinical otology. [ABSTRACT FROM AUTHOR]

Macrophages are essential components of the innate immune system and constitute a non-specific first line of host defense against pathogens and inflammation. Mitochondria regulate macrophage activation and innate immune responses in various inflammatory diseases, including cochlear inflammation. The distribution, number, and morphological characteristics of cochlear macrophages change significantly across different inner ear regions under various pathological conditions, including noise exposure, ototoxicity, and age-related degeneration. However, the exact mechanism underlying the role of mitochondria in macrophages in auditory function remains unclear. Here, we summarize the major factors and mitochondrial signaling pathways (e.g., metabolism, mitochondrial reactive oxygen species, mitochondrial DNA, and the inflammasome) that influence macrophage activation in the innate immune response. In particular, we focus on the properties of cochlear macrophages, activated signaling pathways, and the secretion of inflammatory cytokines after acoustic injury. We hope this review will provide new perspectives and a basis for future research on cochlear inflammation. [ABSTRACT FROM AUTHOR]

Cochlear melanocytes are intermediate cells in the stria vascularis that generate endocochlear potentials required for auditory function. Human PAX3 mutations cause Waardenburg syndrome and abnormalities of skin and retinal melanocytes, manifested as congenital hearing loss (~ 70%) and hypopigmentation of skin, hair and eyes. However, the underlying mechanism of hearing loss remains unclear. Cochlear melanocytes in the stria vascularis originated from Pax3-traced melanoblasts and Plp1-traced Schwann cell precursors, both of which derive from neural crest cells. Here, using a Pax3-Cre knock-in mouse that allows lineage tracing of Pax3-expressing cells and disruption of Pax3, we found that Pax3 deficiency causes foreshortened cochlea, malformed vestibular apparatus, and neural tube defects. Lineage tracing and in situ hybridization show that Pax3+ derivatives contribute to S100+, Kir4.1+ and Dct+ melanocytes (intermediate cells) in the developing stria vascularis, all of which are significantly diminished in Pax3 mutant animals. Taken together, these results suggest that Pax3 is required for the development of neural crest cell-derived cochlear melanocytes, whose absence may contribute to congenital hearing loss of Waardenburg syndrome in humans. [ABSTRACT FROM AUTHOR]

Hearing loss has become increasingly prevalent and causes considerable disability, thus gravely burdening the global economy. Irreversible loss of hair cells is a main cause of sensorineural hearing loss, and currently, the only relatively effective clinical treatments are limited to digital hearing equipment like cochlear implants and hearing aids, but these are of limited benefit in patients. It is therefore urgent to understand the mechanisms of damage repair in order to develop new neuroprotective strategies. At present, how to promote the regeneration of functional hair cells is a key scientific question in the field of hearing research. Multiple signaling pathways and transcriptional factors trigger the activation of hair cell progenitors and ensure the maturation of newborn hair cells, and in this article, we first review the principal mechanisms underlying hair cell reproduction. We then further discuss therapeutic strategies involving the co-regulation of multiple signaling pathways in order to induce effective functional hair cell regeneration after degeneration, and we summarize current achievements in hair cell regeneration. Lastly, we discuss potential future approaches, such as small molecule drugs and gene therapy, which might be applied for regenerating functional hair cells in the clinic. [ABSTRACT FROM AUTHOR]

Although several well-preserved crania are known for the Mesozoic Eutriconodonta, three-dimensional reconstructions of the character-rich inner ear and basicranial region based on high-resolution computed tomography scans have previously only been published for the Late Jurassic Priacodon. Here we present a description of the petrosal and inner ear morphology of a triconodontid eutriconodontan from the Lower Cretaceous Cloverly Formation, which we provisionally assign to Astroconodon. The bony labyrinth of Astroconodon is plesiomorphic for mammaliaforms in lacking a primary osseous lamina, cribriform plate, and osseous cochlear ganglion canal. However, as in Priacodon and the zhangheotheriid Origolestes, Astroconodon has a secondary osseous lamina base that extends nearly the complete length of the cochlear canal. The cochlear canal is straighter in Astroconodon and other eutriconodontans compared to several basal mammaliaform clades (e.g., morganucodontans, docodontans), that exhibit varying degrees of cochlear canal curvature. The pars cochlearis of the petrosal was well vascularized in Astroconodon, exhibiting a network of venous canals that crossed the cochlea transversely on its ventral and dorsal aspects. Of particular note are several canals that passed along the base of the secondary osseous lamina. As in Priacodon and Origolestes, those canals do not show the extensive connections to the cochlear labyrinth as seen in the basal mammaliaforms Morganucodon and Borealestes. The inner ear of Astroconodon thus highlights the complex history of the mammaliaform cochlear canal, in which different clades appear to follow independent evolutionary trajectories and various key morphological features (e.g., cochlear canal length, curvature, vascularization and osseous supports for the basilar membrane) exhibit considerable homoplasy. [ABSTRACT FROM AUTHOR]

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The cochlear auditory epithelium contains two types of sound receptors, inner hair cells (IHCs) and outer hair cells (OHCs). Mouse models for labelling juvenile and adult IHCs or OHCs exist; however, labelling for embryonic and perinatal IHCs or OHCs are lacking. Here, we generated a new knock-in Fgf8P2A-3×GFP/+ (Fgf8GFP/+) strain, in which the expression of a series of three GFP fragments is controlled by endogenous Fgf8 cis-regulatory elements. After confirming that GFP expression accurately reflects the expression of Fgf8, we successfully obtained both embryonic and neonatal IHCs with high purity, highlighting the power of Fgf8GFP/+. Furthermore, our fate-mapping analysis revealed, unexpectedly, that IHCs are also derived from inner ear progenitors expressing Insm1, which is currently regarded as an OHC marker. Thus, besides serving as a highly favorable tool for sorting early IHCs, Fgf8GFP/+ will facilitate the isolation of pure early OHCs by excluding IHCs from the entire hair cell pool. [ABSTRACT FROM AUTHOR]

Background: Otosclerosis is one of the most common causes of hearing loss in adults with clinical onset between 20 and 40 years of age. Vestibular symptoms may be the most agonizing and primary symptom in cases with otosclerosis, so the assessment of patients is important. The vestibular-evoked myogenic potentials test (VEMP) is used to assess the saccular and the utricular functions using cervical and ocular vestibular-evoked myogenic potentials (cVEMP and oVEMP), respectively. The video head impulse test (vHIT) which measure vestibulo-ocular reflex (VOR) to rapid impulsive head acceleration in the plane of each semicircular canal (SCC) has allowed quantitative monitoring of each canal function. Methods: Twenty subjects with bilateral otosclerosis were studied, ranging in age from 30 to 55 years, divided into two groups. One group consisted of 10 adult patients with bilateral conductive otosclerosis. The second group consisted of 10 adult patients with bilateral mixed otosclerosis. All the patients underwent cVEMP and oVEMP, using a BC 500Hz tone burst stimulus and vHIT in three planes, left anterior right posterior (LARP), right anterior left posterior (RALP), and lateral SCCs. Results: The findings indicate statistically significant differences in the peak-to-peak amplitudes of cVEMP and oVEMP in the two studied groups, and the mixed cases had lower amplitudes than conductive cases and a significant increase in p13 latencies. Also, there is a statistically significant difference in the lateral SCC gain between the two groups, as mixed cases had lower gain than conductive cases, but not for anterior or posterior SCCs, with no gain less than 0.8 in all three canals. Conclusion: The findings suggested that the saccule is more liable to be affected by cochlear otosclerosis followed by the utricle. The three SCCs are mostly spared. [ABSTRACT FROM AUTHOR]

Feedback networks in the brain regulate downstream auditory function as peripheral as the cochlea. However, the upstream neural consequences of this peripheral regulation are less understood. For instance, the medial olivocochlear reflex (MOCR) in the brainstem causes putative attenuation of responses generated in the cochlea and cortex, but those generated in the brainstem are perplexingly unaffected. Based on known neural circuitry, we hypothesized that the inhibition of peripheral input is compensated for by positive feedback in the brainstem over time. We predicted that the inhibition could be captured at the brainstem with shorter (1.5 s) than previously employed long duration (240 s) stimuli where this inhibition is likely compensated for. Results from 16 normal-hearing human listeners support our hypothesis in that when the MOCR is activated, there is a robust reduction of responses generated at the periphery, brainstem, and cortex for short-duration stimuli. Such inhibition at the brainstem, however, diminishes for long-duration stimuli suggesting some compensatory mechanisms at play. Our findings provide a novel non-invasive window into potential gain compensation mechanisms in the brainstem that may have implications for auditory disorders such as tinnitus. Our methodology will be useful in the evaluation of efferent function in individuals with hearing loss. [ABSTRACT FROM AUTHOR]

Purpose: Due to the specificity of cochlear implantation (CI) programming parameters and outcomes in cochlear nerve deficiency (CND) patients, this study aimed to investigate the correlation between programming parameters and outcomes and further compare the difference between normal and CND groups. Methods: Ninety (95 ears) CND patients (normal cochlea, 39; malformed cochlea, 56) and seventy-nine (81 ears) normal cochlea patients who underwent CI surgery with either Med-El or Cochlear devices were included. The programming parameters and outcomes evaluated by the questionnaires were collected and compared among the normal CND, malformed CND, and normal groups in the two device groups, and their correlation was analyzed. Results: In the CND group, a reduced stimulation rate, higher pulse width, and triphasic pulse were needed in some cases. The stimulus levels of the CND group were significantly higher than that of the normal group (p < 0.05), but the outcomes of the CND group were significantly worse than that of the normal group (p < 0.05), and the stimulus level was significantly correlated with the outcomes (p < 0.05). However, there was no difference between normal and malformed CND groups. The non-auditory response was observed in the CND group, especially the ones with malformations. Conclusion: The CI programming parameters of some CND patients need to be adjusted, and a slower stimulation rate and higher pulse width are required sometimes. CND patients need a higher stimulus level than normal patients but their outcomes are poorer. Non-auditory response should be noticed in CND patients during programming. [ABSTRACT FROM AUTHOR]

Quantifying the survival patterns of spiral ganglion cells (SGCs), the cell bodies of auditory-nerve fibers, is critical to studies of sensorineural hearing loss, especially in human temporal bones. The classic method of manual counting is tedious, and, although stereology approaches can be faster, they can only be used to estimate total cell numbers per cochlea. Here, a machine-learning algorithm that automatically identifies, counts, and maps the SGCs in digitized images of semi-serial human temporal-bone sections not only speeds the analysis, with no loss of accuracy, but also allows 3D visualization of the SGCs and fine-grained mapping to cochlear frequency. Applying the algorithm to 62 normal-aging human ears shows significantly faster degeneration of SGCs in the basal than the apical half of the cochlea. Comparison to fiber counts in the same ears shows that the fraction of surviving SGCs lacking a peripheral axon steadily increases with age, reaching more than 50% in the apical cochlea and almost 66% in basal regions. [ABSTRACT FROM AUTHOR]

Purpose: To study effects of chemoradiation therapy on hearing in patients with malignancy of head and neck. Methods and materials: Patients receiving drugs other than cisplatin as well as those with any otology-related pathology or abnormalities were excluded from the study. Patients with primary biopsy-proven malignancy of the Nasopharynx, Oropharynx, Paranasal Sinuses, Oral Cavity, and Parotid with chemoradiation by cisplatin and different radiation modalities were all eligible. Areas of interest and OARs are indicated on CT images. All patients' hearing was assessed using pure tone audiometry at the beginning of treatment, at its conclusion, and six months later. Variations in pure tone thresholds from baseline and CTCAE - Common Terminology Criteria for Adverse Events grading are related to cochlear dose. Results: The study involves 75 patients. At cochlear dosage levels of more than 40 Gy, significant SNHL (>10 dB loss) is seen. Absolute PTA threshold values do not statistically differ from baseline to completion at any frequency. For 4000 and 8000 Hz, the absolute PTA threshold values differed from baseline to follow-up, but only for 8000 Hz was the difference statistically significant after six months of follow-up. Following treatment, 64% of patients had grade I CTCAE scoring and 16% and 12%, respectively, had otitis media with effusion and Eustachian tube dysfunction. Conclusion: The inner ear may be harmed in patients receiving radiation to the head and neck. Radiation-induced SNHL typically goes unreported in routine clinical practise because of its long-term nature. In the group of head and neck tumours with high-risk locations, nearly 90% of patients with SNHL were affected. Therefore, it's critical to reduce cochlear dosage in these patient populations. More investigation is needed to distinguish between cochlear and retro-cochlear types of sensorineural hearing loss. [ABSTRACT FROM AUTHOR]

This article, published in the journal Pediatric Radiology, discusses a case study of a 3-year-old boy with bilateral sensorineural hearing loss. The boy underwent CT and MRI scans, which revealed abnormalities in the cochlea, internal auditory canal, and modiolus. The patient was found to have a pathogenic variant in the POU3F4 gene, which is associated with X-linked stapes gusher syndrome. This syndrome is characterized by progressive hearing loss and can also affect hypothalamic development, potentially leading to hypothalamic hamartoma. The article provides important insights into the genetic and anatomical factors contributing to hearing loss in children. [Extracted from the article]

Abstract Deafness affects 5% of the world's population, yet there is a lack of treatments to prevent hearing loss due to genetic causes. Norrie disease is a recessive X‐linked disorder, caused by NDP gene mutation. It manifests as blindness at birth and progressive sensorineural hearing loss, leading to debilitating dual sensory deprivation. To develop a gene therapy, we used a Norrie disease mouse model (Ndptm1Wbrg), which recapitulates abnormal retinal vascularisation and progressive hearing loss. We delivered human NDP cDNA by intravenous injection of adeno‐associated viral vector (AAV)9 at neonatal, juvenile and young adult pathological stages and investigated its therapeutic effects on the retina and cochlea. Neonatal treatment prevented the death of the sensory cochlear hair cells and rescued cochlear disease biomarkers as demonstrated by RNAseq and physiological measurements of auditory function. Retinal vascularisation and electroretinograms were restored to normal by neonatal treatment. Delivery of NDP gene therapy after the onset of the degenerative inner ear disease also ameliorated the cochlear pathology, supporting the feasibility of a clinical treatment for progressive hearing loss in people with Norrie disease.

Hearing loss induced by noise and combinations of factors is a common occupational disease among workers. This study aimed to investigate the impact of acute exposure to white noise and Al2O3 NPs, alone and in combination, on changes in the hearing and structural functions of the cochlea in rats. Thirty-six rats were randomly assigned to one of six groups: Control, acute exposure to white noise, exposure to γ-Al2O3 NPs, exposure to noise plus γ-Al2O3 NPs, exposure to α-Al2O3 NPs, and exposure to the combination of noise plus α-Al2O3 NPs. TTS and PTS were examined using DPOAE, while oxidative index (MDA, GSH-Px), gene expression (NOX3, TGF-ß, CYP1A1), protein expression (ß-Tubulin, Myosin VII), and histopathological changes were examined in the cochlea. The morphology of Al2O3 NPs was examined by TEM. The results of the DPOAE test showed a significant increase in TTS in all groups and an increase in PTS in the groups exposed to noise, γ-Al2O3 NPs, and a combination of noise plus Al2O3 NPs (P < 0.05). In the group exposed to white noise plus Al2O3 NPs, the MDA levels increased, the level of GSH-Px decreased, and the expression percentage of ß-Tubulin and Myosin VII decreased, while the expression of NOX3, TGF-ß, and CYP1A1 (except for the α-Al2O3 NPs group) significantly increased (P < 0.05). Histopathological changes of the cochlea indicated damage to hair and ganglion cells, which was more severe in the combined exposure group. The combined and independent exposure to white noise and Al2O3 NPs damaged hair and ganglion cells for high-frequency perception, affecting the function and structure of the cochlea and leading to TTS and PTS. [ABSTRACT FROM AUTHOR]

The current review gives a comprehensive overview of the recent development in Chinese medicine (CM) for treating several kinds of acquired nerve deafness and tinnitus, as well as links the traditional principle to well-established pharmacological mechanisms for future research. To date, about 24 herbal species and 40 related ingredients used in CM to treat hearing loss and tinnitus are reported for the treatment of endocochlear potential, endolymph growth, lowering toxic and provocative substance aggregation, inhibiting sensory cell death, and retaining sensory transfer. However, there are a few herbal species that can be used for medicinal purposes. Nevertheless, clinical studies have been hampered by a limited population sample, a deficiency of a suitable control research group, or contradictory results. Enhanced cochlear blood flow, antiinflammatory antioxidant, neuroprotective effects, and anti-apoptotic, as well as multi-target approach on different auditory sections of the inner ear, are all possible benefits of CM medications. There are numerous unknown natural products for aural ailment and tinnitus identified in CM that are expected to be examined in the future utilizing various aural ailment models and processes. [ABSTRACT FROM AUTHOR]

The three-dimensional stria vascularis (SV) and cochlear blood vessel structure is essential for inner ear function. Here, modified Sca/eS, a sorbitol-based optical-clearing method, was reported to visualize SV and vascular structure in the intact mouse cochlea. Cochlear macrophages as well as perivascular-resident macrophage-like melanocytes were detected as GFP-positive cells of the CX3CR1+/GFP mice. This study's method was effective in elucidating inner ear function under both physiological and pathological conditions. [ABSTRACT FROM AUTHOR]

Purpose: Analysis of cochlear structures and postoperative temporal bone (TB) imaging are gaining importance in the evaluation of cochlear implantation (CI°). Our aims were to explore the microarchitecture of human cochlea using micro-computed tomography (μCT), analyze electrode's placement inside cochlea after CI°, and compare pre-/post-implantation μCT scans with cone-beam CT (CBCT) scans of same TBs. Methods: Cadaveric TBs were scanned using μCT and CBCT then underwent CI° using straight electrodes. Thereafter, they underwent again μCT and CBCT-imaging. Results: Ten TBs were studied. μCT allowed visualization of scala tympani, scala vestibuli, basilar membrane, osseous spiral lamina, crista fenestrae, and spiral ligament. CBCT showed same structures except spiral ligament and crista fenestrae. After CI°, μCT and CBCT displayed the scalar location and course of electrode array within the cochlea. There were 7 cases of atraumatic electrode insertion and 3 cases of insertion trauma: basilar membrane elevation, electrode foldover with limited migration into scala vestibuli, and electrode kinking with limited migration into scala vestibuli. Insertion trauma was not correlated with cochlea's size or crista's maximal height but with round window membrane diameter. Resolution of μCT was higher than CBCT but electrode artifacts were similar. Conclusions: μCT was accurate in visualizing cochlear structures, and course and scalar position of electrode array inside cochlea with any possible trauma to cochlea or array. CBCT offers a good alternative to μCT in clinical practice for cochlear imaging and evaluation of CI°, with lower radiation and higher resolution than multi-slice CT. Difficulties related to non-traumatic CI° are multifactorial. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The frequency selectivity of the mammalian auditory system is critical for discriminating complex sounds like speech. This selectivity derives from the sharp tuning of the cochlea's mechanical response to sound, which is largely attributed to the amplification of cochlear vibrations by outer hair cells (OHCs). Due to its nonlinearity, the amplification process also leads to the generation of distortion products (DPs), some of which propagate out to the ear canal as DP otoacoustic emissions (DPOAEs). However, the insight that these signals provide about the tuned micro- and macro-mechanics underlying their generation remains unclear. Using optical coherence tomography to measure cochlear vibrations in mice, we show that the cochlea's frequency tuning is reflected in the bandpass shape that is observed in DPOAE amplitudes when the ratio of the two evoking stimulus frequencies is varied (here termed DPOAE "ratio functions"). The tuning sharpness of DPOAE ratio functions and cochlear vibrations co-varied with stimulus level, with a similar quantitative agreement in tuning sharpness observed for both apical and mid-cochlear locations. Measurement of intracochlear DPs revealed that the tuning of the DPOAE ratio functions was not caused by mechanisms that shape DPs locally near where they are generated. Instead, simple model simulations indicate that the bandpass shape is due to a more global wave interference phenomenon. It appears that the filtering of DPOAEs by wave interactions over an extended spatial region allows them to provide a window onto the frequency tuning of single cochlear locations. [ABSTRACT FROM AUTHOR]

Isoforms of a gene may contribute to diverse biological functions. In the cochlea, the repertoire of alternative isoforms remains unexplored. We integrated single-cell short-read and long-read RNA sequencing techniques and identified 236,012 transcripts, 126,612 of which were unannotated in the GENCODE database. Then we analyzed and verified the unannotated transcripts using RNA-seq, RT-PCR, Sanger sequencing, and MS-based proteomics approaches. To illustrate the importance of identifying spliced isoforms, we investigated otoferlin, a key protein involved in synaptic transmission in inner hair cells (IHCs). Upon deletion of the canonical otoferlin isoform, the identified short isoform is able to support normal hearing thresholds but with reduced sustained exocytosis of IHCs, and further revealed otoferlin functions in endocytic membrane retrieval that was not well-addressed previously. Furthermore, we found that otoferlin isoforms are associated with IHC functions and auditory phenotypes. This work expands our mechanistic understanding of auditory functions at the level of isoform resolution. The repertoire of mRNA isoforms in the cochlea remains unknown. Here, authors generated a full-length transcriptome atlas by ScISOr-seq, identified and studied Otof short isoform, extended our understanding of auditory function in isoform resolution. [ABSTRACT FROM AUTHOR]

Explaining the mechanism of the cochlear active phonosensitive amplification has been a major problem in medicine. The basilar membrane (BM) is the key infrastructure. In 1960, Nobel Laureate von Békésy first discovered BM's traveling wave motion. Since that time, BM's models only have considered the traveling wave but not the biological activity. Therefore, a new model considering changes of BM's stiffness in space and time is established based on the immersed boundary method to describe its biological activity. It not only reproduces the results of traveling wave motion but also explains the mechanization on the generation of traveling wave. An important discovery is that changes of BM's stiffness in space and time will cause the unstable global resonance, which will induce amplification of sounds in cochlea. An important inference is that biological activity shall be included in the application of mechanical principles to the analysis of life, which is the essential difference between biomechanics and general mechanics. [ABSTRACT FROM AUTHOR]

Blast-induced auditory trauma is a common injury in military service members and veterans that leads to hearing loss. While the inner ear response to blast exposure is difficult to characterize experimentally, computational models have advanced to predict blast wave transmission from the ear canal to the cochlea; however, published models have either straight or spiral cochlea with fluid-filled two chambers. In this paper, we report the recently developed 3D finite element (FE) model of the human ear mimicking the anatomical structure of the 3-chambered cochlea. The model consists of the ear canal, middle ear, and two and a half turns of the cochlea with three chambers separated by the Reissner's membrane (RM) and the basilar membrane (BM). The blast overpressure measured from human temporal bone experiments was applied at the ear canal entrance and the Fluent/Mechanical coupled fluid–structure interaction analysis was conducted in ANSYS software. The FE model-derived results include the pressure in the canal near the tympanic membrane (TM) and the intracochlear pressure at scala vestibuli, the TM displacement, and the stapes footplate (SFP) displacement, which were compared with experimentally measured data in human temporal bones. The validated model was used to predict the biomechanical response of the ear to blast overpressure: distributions of the maximum strain and stress within the TM, the BM displacement variation from the base to apex, and the energy flux or total energy entering the cochlea. The comparison of intracochlear pressure and BM displacement with those from the FE model of 2-chambered cochlea indicated that the 3-chamber cochlea model with the RM and scala media chamber improved our understanding of cochlea mechanics. This most comprehensive FE model of the human ear has shown its capability to predict the middle ear and cochlea responses to blast overpressure which will advance our understanding of auditory blast injury. [ABSTRACT FROM AUTHOR]

Mechanosensitive hair cells (HCs) in the cochlear sensory epithelium are critical for sound detection and transduction. Mammalian HCs in the cochlea undergo cytogenesis during embryonic development, and irreversible damage to hair cells postnatally is a major cause of deafness. During the development of the organ of Corti, HCs and supporting cells (SCs) originate from the same precursors. In the neonatal cochlea, damage to HCs activates adjacent SCs to act as HC precursors and to differentiate into new HCs. However, the plasticity of SCs to produce new HCs is gradually lost with cochlear development. Here, we delineate an essential role for the guanine nucleotide exchange factor Net1 in SC trans-differentiation into HCs. Net1 overexpression mediated by AAV-ie in SCs promoted cochlear organoid formation and HC differentiation under two and three-dimensional culture conditions. Also, AAV-Net1 enhanced SC proliferation in Lgr5-EGFPCreERT2 mice and HC generation as indicated by lineage tracing of HCs in the cochleae of Lgr5-EGFPCreERT2/Rosa26-tdTomatoloxp/loxp mice. We further found that the up-regulation of Wnt/β-catenin and Notch signaling in AAV-Net1-transduced cochleae might be responsible for the SC proliferation and HC differentiation. Also, Net1 overexpression in SCs enhanced SC proliferation and HC regeneration and survival after HC damage by neomycin. Taken together, our study suggests that Net1 might serve as a potential target for HC regeneration and that AAV-mediated gene regulation may be a promising approach in stem cell-based therapy in hearing restoration. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnoea syndrome (OSAS) is a condition that is characterised by frequent apnoea and hypopnoea attacks occurring during sleep. The blood supply to cochlea and acoustic nerves is from terminal arteries, thereby making them susceptible to hypoxia. To compare the audiological profiles in patients with OSAS according to Apnoea Hypopnoea index (AHI) score. Descriptive study was conducted in 32 patients diagnosed to have OSAS in a tertiary referral centre over two year period. The study group was divided into mild, moderate, severe OSAS based on AHI score. The hearing evaluation was done using pure tone audiogram (PTA) and distortion product otoacoustic emission test (DPOAE). Moderate and severe OSAS participants had elevated thresholds at higher frequencies in PTA (4 kHz, 8 kHz), although this was not statistically significant. We also noticed, absent DPOAE responses at higher frequencies (4 k, 6 k, 8 k), with increase in the severity of OSAS at higher frequency, which was statistically significant (p value < 0.05). This study revealed elevated hearing thresholds at higher frequencies (4 kHz, 8 kHz) in PTA and DPOEA with an increase in the severity of OSAS. All OSAS patients, especially with AHI > 30 should be regularly screened for hearing loss. [ABSTRACT FROM AUTHOR]

Meningitis is a known complication in patients with inner ear malformations. Here we present a case of recurrent meningitis following cochlear implantation, in a patient with cochleovestibular anomaly. Good knowledge in radiology to identify the inner ear malformations, presence of cochlea and cochlear nerve is essential before planning cochlear implantation and meningitis can occur several decades after cochlear implantation. [ABSTRACT FROM AUTHOR]

Purpose: We reviewed the genotypes and the imaging appearances of cochleae in CHARGE patients from two large tertiary centres and analysed the observed cochlear anomalies, providing detailed anatomical description and a grading system. The goal was to gain insight into the spectrum of cochlear anomalies in CHARGE syndrome, and thus, in the role of the CHD7 gene in otic vesicle development. Methods: We retrospectively reviewed CT and/or MR imaging of CHARGE patients referred to our institutions between 2005 and 2022. Cochlear morphology was analysed and, when abnormal, divided into 3 groups in order of progressive severity. Other radiological findings in the temporal bone were also recorded. Comparison with the existing classification system of cochlear malformation was also attempted. Results: Cochlear morphology in our CHARGE cohort ranged from normal to extreme hypoplasia. The most common phenotype was cochlear hypoplasia in which the basal turn was relatively preserved, and the upper turns were underdeveloped. All patients in the cohort had absent or markedly hypoplastic semicircular canals and small, misshapen vestibules. Aside from a stenotic cochlear aperture (fossette) being associated with a hypoplastic or absent cochlear nerve, there was no consistent relationship between cochlear nerve status (normal, hypoplasia, or aplasia) and cochlear morphology. Conclusion: Cochlear morphology in CHARGE syndrome is variable. Whenever the cochlea was abnormal, it was almost invariably hypoplastic. This may shed light on the role of CHD7 in cochlear development. Accurate morphological description of the cochlea contributes to proper clinical diagnosis and is important for planning surgical treatment options. [ABSTRACT FROM AUTHOR]

The short spined crown-of-thorns starfish Acanthaster brevispinus inhabits deeper water soft bottom habitats, in contrast to the more infamous Indo-Pacific Acanthaster species complex of which population outbreaks have been responsible for widespread coral mortality throughout the Indo-West Pacific region. Acanthaster brevispinus has not previously been regarded as a threat to corals or coral reefs. Here, we report A. brevispinus occurring on mesophotic off-reef or inter-reef habitats in 20–70-m depths dominated by solitary corals off both the western and eastern coasts of Australia. On Ningaloo Reef, A. brevispinus were found on mushroom coral (Cycloseris distorta) beds using an underwater towed camera and further exploration using a remotely operated vehicle (ROV) confirmed predation by A. brevispinus on C. distorta. On the southern Great Barrier Reef, A. brevispinus in large numbers were found in habitat dominated by the dendrophylliid Heteropsammia cf. cochlea. Predation on H. cf. cochlea was also directly observed. This is the first confirmed report of predation on hard corals by A. brevispinus, and while there are yet to be any records of population outbreaks of this species, such outbreaks could have a significant effect on mesophotic solitary coral assemblages. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The presence of a coiled cochlea is a unique feature of the therian inner ear. While some aspects of the cochlea are already known to affect hearing capacities, the full extent of the relationships between the morphology and function of this organ are not yet understood—especially when the effect of body size differences between species is minimized. Here, focusing on Euarchontoglires, we explore cochlear morphology of 33 species of therian mammals with a restricted body size range. Using μCT scans, 3D models and 3D geometric morphometrics, we obtained shape information of the cochlea and used it to build phylogenetically corrected least square models with 12 hearing variables obtained from the literature. Our results reveal that different taxonomic groups differ significantly in cochlea shape. We further show that these shape differences are related to differences in hearing capacities between these groups, despite of similar cochlear lengths. Most strikingly, rodents with good low-frequency hearing display "tower-shaped" cochleae, achieved by increasing the degree of coiling of their cochlea. In contrast, primates present relatively wider cochleae and relative better high frequency hearing. These results suggest that primates and rodents increased their cochlea lengths through different morpho-evolutionary trajectories. [ABSTRACT FROM AUTHOR]

Cochlear implant restores hearing loss through electrical stimulation of the hearing nerve from within the cochlea. Unfortunately, surgical implantation of this neuroprosthesis often traumatizes delicate intracochlear structures, resulting in loss of residual hearing and compromising hearing in noisy environments and appreciation of music. To avoid cochlear trauma, insertion techniques and devices have to be adjusted to the cochlear microanatomy. However, existing techniques were unable to achieve a representative visualization of the human cochlea: classical histology damages the tissues and lacks 3D perspective; standard microCT fails to resolve the cochlear soft tissues; and previously used X-ray contrast-enhancing staining agents are destructive. In this study, we overcame these limitations by performing contrast-enhanced microCT imaging (CECT) with a novel polyoxometalate staining agent Hf-WD POM. With Hf-WD POM-based CECT, we achieved nondestructive, high-resolution, simultaneous, 3D visualization of the mineralized and soft microstructures in fresh-frozen human cochleae. This enabled quantitative analysis of the true intracochlear dimensions and led to anatomical discoveries, concerning surgically-relevant microstructures: the round window membrane, the Rosenthal's canal and the secondary spiral lamina. Furthermore, we demonstrated that Hf-WD POM-based CECT enables quantitative assessment of these structures as well as their trauma. [ABSTRACT FROM AUTHOR]