Nanomechanical mapping reveals localized stiffening of the basilar membrane after cochlear implantation.

Cochlear implantation leads to many structural changes within the cochlea which can impair residual hearing. In patients with preserved low-frequency hearing, a delayed hearing loss can occur weeks-to-years post-implantation. We explore whether stiffening of the basilar membrane (BM) may be a contributory factor in an animal model. Our objective is to map changes in morphology and Young's modulus of basal and apical areas of the BM after cochlear implantation, using quantitative nanomechanical atomic force microscopy (QNM-AFM) after cochlear implant surgery. Cochlear implantation was undertaken in the guinea pig, and the BM was harvested at four time-points: 1 day, 14 days, 28 days and 84 days post-implantation for QNM-AFM analysis. Auditory brainstem response thresholds were determined prior to implantation and termination. BM tissue showed altered morphology and a progressive increase in Young's modulus, mainly in the apex, over time after implantation. BM tissue from the cochlear base demonstrated areas of extreme stiffness which are likely due to micro-calcification on the BM. In conclusion, stiffening of the BM after cochlear implantation occurs over time, even at sites far apical to a cochlear implant.

Influence of middle ear disorder in round-window stimulation using a finite element human ear model.

PURPOSE: The aim of this work was to study the effect of middle ear disorder on round window (RW) stimulation, so as to provide references for the optimal design of RW stimulation type middle ear implants (MEIs). METHODS: A human ear finite-element model was built by reverse engineering technique based on micro-computed tomography scanning images of human temporal bone, and was validated by three sets of comparisons with experimental data. Then, based on this model, typical disorders in otosclerosis and otitis media were simulated. Finally, their influences on the RW stimulation were analyzed by comparison of the displacements of the basilar membrane. RESULTS: For the otosclerosis, the stapedial abnormal bone growth severely deteriorated the equivalent sound pressure of the RW stimulation at higher frequencies, while the hardening of ligaments and tendons prominently decreased the RW stimulation at lower frequencies. Besides, among the hardening of the studied tissues, the influence of the stapedial annular ligament's hardening was much more significant. For the otitis media, the round window membrane (RWM)'s thickening mainly decreased the RW stimulation's performance at lower frequencies. When the elastic modulus' reduction of the RWM was considered at the same time especially for the acute otitis media, it would raise the lower-frequency performance of the RW stimulation. CONCLUSIONS: The influence of the middle ear disorder on the RW stimulation is considerable and variable, it should be considered during the design of the RW stimulation type MEIs.

Effects of Various Trajectories on Tissue Preservation in Cochlear Implant Surgery: A Micro-Computed Tomography and Synchrotron Radiation Phase-Contrast Imaging Study.

OBJECTIVES: The purpose of this study was to evaluate the three-dimensional (3D) anatomy and potential damage to the hook region of the human cochlea following various trajectories at cochlear implantation (CI). The goal was to determine which of the approaches can avoid lesions to the soft tissues, including the basilar membrane and its suspension to the lateral wall. Currently, there is increased emphasis on conservation of inner ear structures, even in nonhearing preservation CI surgery. DESIGN: Micro-computed tomography and various CI approaches were made in an archival collection of macerated and freshly fixed human temporal bones. Furthermore, synchrotron radiation phase-contrast imaging was used to reproduce the soft tissues. The 3D anatomy was investigated using bony and soft tissue algorithms, and influences on inner ear structures were examined. RESULTS: Micro-computed tomography with 3D rendering demonstrated the topography of the round window (RW) and osseous spiral laminae, while synchrotron imaging allowed reproduction of soft tissues such as the basilar membrane and its suspension around the RW membrane. Anterior cochleostomies and anteroinferior cochleostomies invariably damaged the intracochlear soft tissues while inferior cochleostomies sporadically left inner ear structures unaffected. CONCLUSIONS: Results suggest that cochleostomy approaches often traumatize the soft tissues at the hook region at CI surgery. For optimal structural preservation, the RW approach is, therefore, recommended.

Systematic review: Radiological and histological evidence of cochlear implant insertion trauma in adult patients.

INTRODUCTION: Cochlear implantation (CI) has developed from its origins in the 1980s. Initially, CI was for profound bilateral hearing impairment. However, candidacy for CI have become more widespread in recent years with unilateral implantation and an emphasis on hearing preservation. Evidence supports full electrode insertion in an atraumatic fashion into the scala tympani (ST) provides optimal hearing outcomes. The main aim of this systematic review was to elucidate the degree of trauma associated with CI insertion. METHODS: A systematic literature search was undertaken using PubMed Medline. A grading system described by Eshraghi was used to classify cochlear trauma. Both radiological and histological studies were included. RESULTS: Twenty one papers were identified which were relevant to our search. In total, 653 implants were inserted and 115 (17.6%) showed evidence of trauma. The cochleas with trauma had basilar membrane elevation in 5.2%, ruptured in 5.2%, the electrode passed from the ST to the SV in 84.4% and there was grade 4 trauma in 5.2%. The studies used a variety of histological and radiological methods to assess for evidence of trauma in both cadaveric temporal bones and live recipients. CONCLUSIONS: Minimizing cochlear trauma during implant insertion is important to preserve residual hearing and optimize audiological performance. An overall 17.6% trauma rate suggests that CI insertion could be improved with more accurate and consistent electrode insertion such as in the form of robotic guidance. The correlation of cochlea trauma with post-operative hearing has yet to be determined.

Insertion forces and intracochlear trauma in temporal bone specimens implanted with a straight atraumatic electrode array.

The aim of the study was to evaluate insertion forces during manual insertion of a straight atraumatic electrode in human temporal bones, and post-implantation histologic evaluation of the samples to determine whether violation of intracochlear structures is related to insertion forces. In order to minimize intracochlear trauma and preserve residual hearing during cochlear implantation, knowledge of the insertion forces is necessary. Ten fresh frozen human temporal bones were prepared with canal wall down mastoidectomy. All samples were mounted on a one-axis force sensor. Insertion of a 16-mm straight atraumatic electrode was performed from different angles to induce "traumatic" insertion. Histologic evaluation was performed in order to evaluate intracochlear trauma. In 4 of 10 samples, dislocation of the electrode into scala vestibuli was observed. The mean insertion force for all 10 procedures was 0.003 ± 0.005 N. Insertion forces measured around the site of dislocation to scala vestibuli in 3 of 4 samples were significantly higher than insertion forces at the same location of the cochleae measured in samples without trauma (p < 0.04). Mean force during the whole insertion process of the straight atraumatic electrode is lower than reported by other studies using longer electrodes. Based on our study, insertion forces leading to basilar membrane trauma may be lower than the previously reported direct rupture forces.

Dynamic activation of basilar membrane macrophages in response to chronic sensory cell degeneration in aging mouse cochleae.

In the sensory epithelium, macrophages have been identified on the scala tympani side of the basilar membrane. These basilar membrane macrophages are the spatially closest immune cells to sensory cells and are able to directly respond to and influence sensory cell pathogenesis. While basilar membrane macrophages have been studied in acute cochlear stresses, their behavior in response to chronic sensory cell degeneration is largely unknown. Here we report a systematic observation of the variance in phenotypes, the changes in morphology and distribution of basilar membrane tissue macrophages in different age groups of C57BL/6J mice, a mouse model of age-related sensory cell degeneration. This study reveals that mature, fully differentiated tissue macrophages, not recently infiltrated monocytes, are the major macrophage population for immune responses to chronic sensory cell death. These macrophages display dynamic changes in their numbers and morphologies as age increases, and the changes are related to the phases of sensory cell degeneration. Notably, macrophage activation precedes sensory cell pathogenesis, and strong macrophage activity is maintained until sensory cell degradation is complete. Collectively, these findings suggest that mature tissue macrophages on the basilar membrane are a dynamic group of cells that are capable of vigorous adaptation to changes in the local sensory epithelium environment influenced by sensory cell status.

Correlation between word recognition score and intracochlear new bone and fibrous tissue after cochlear implantation in the human.

Cochlear implantation is an effective, established procedure for patients with profound deafness. Although implant electrodes have been considered as biocompatible prostheses, surgical insertion of the electrode induces various changes within the cochlea. Immediate changes include insertional trauma to the cochlea. Delayed changes include a tissue response consisting of inflammation, fibrosis and neo-osteogenesis induced by trauma and an immunologic reaction to a foreign body. The goal of this study was to evaluate the effect of these delayed changes on the word recognition scores achieved post-operatively. Seventeen temporal bones from patients who in life had undergone cochlear implantation were prepared for light microscopy. We digitally calculated the volume of fibrous tissue and new bone within the cochlea using Amira(®) three-dimensional reconstruction software and assessed the correlations of various clinical and histologic factors. The postoperative CNC word score was positively correlated with total spiral ganglion cell count. Fibrous tissue and new bone were found within the cochlea of all seventeen specimens. The postoperative CNC word score was negatively correlated with the % volume of new bone within the scala tympani, scala media/vestibuli and the cochlea, but not with the % volume of fibrous tissue. The % volume of new bone in the scala media/vestibuli was positively correlated with the degree of intracochlear insertional trauma, especially trauma to the basilar membrane. Our results revealed that the % volume of new bone as well as residual total spiral ganglion cell count are important factors influencing post-implant hearing performance. New bone formation may be reduced by limiting insertional trauma and increasing the biocompatibility of the electrodes.

SMAD4 Defect Causes Auditory Neuropathy Via Specialized Disruption of Cochlear Ribbon Synapses in Mice.

More than 100 genes have been associated with deafness. However, SMAD4 is rarely considered a contributor to deafness in humans, except for its well-defined role in cell differentiation and regeneration. Here, we report that a SMAD4 defect in mice can cause auditory neuropathy, which was defined as a mysterious hearing and speech perception disorder in human for which the genetic background remains unclear. Our study showed that a SMAD4 defect induces failed formation of cochlear ribbon synapse during the earlier stage of auditory development in mice. Further investigation found that there are nearly normal morphology of outer hair cells (OHCs) and post-synapse spiral ganglion nerves (SGNs) in SMAD4 conditional knockout mice (cKO); however, a preserved distortion product of otoacoustic emission (DPOAE) and cochlear microphonic (CM) still can be evoked in cKO mice. Moreover, a partial restoration of hearing detected by electric auditory brainstem response (eABR) has been obtained in the cKO mice using electrode stimuli toward auditory nerves. Additionally, the ribbon synapses in retina are not affected by this SMAD4 defect. Thus, our findings suggest that this SMAD4 defect causes auditory neuropathy via specialized disruption of cochlear ribbon synapses.

Evaluation of Intracochlear Trauma Caused by Insertion of Cochlear Implant Electrode Arrays through Different Quadrants of the Round Window.

HYPOTHESIS: This study aimed to evaluate whether there is a difference in the degree of intracochlear trauma when the cochlear implant electrode arrays is inserted through different quadrants of the round window membrane. BACKGROUND: The benefits of residual hearing preservation in cochlear implant recipients have promoted the development of atraumatic surgeries. Minimal trauma during electrode insertion is crucial for residual hearing preservation. METHODS: In total, 25 fresh human temporal bones were subjected to mastoidectomy and posterior tympanotomy. The cochlear implant electrode array was inserted through the anterosuperior quadrant of the round window membrane in 50% of the bones and through the anteroinferior quadrant in the remaining 50%. The temporal bones were dehydrated, embedded in epoxy, serially polished, stained, viewed through a stereomicroscope, and photographed with the electrode arrays in situ. The resulting images were analyzed for signs of intracochlear trauma. RESULTS: Histological examinations revealed varying degrees of damage to the intracochlear structures, although the incidence and severity of intracochlear trauma were not influenced by the quadrant of insertion. CONCLUSIONS: The incidence and severity of intracochlear trauma were similar in all samples, irrespective of electrode array insertion through the anterosuperior or anteroinferior quadrant of the round window membrane.

HiFocus Helix™ electrode insertion: surgical approach.

BACKGROUND: Cochlear implants have been used for almost 30 years as a device for the rehabilitation of individuals with severe-to-profound hearing loss. One of the important aspects of cochlear implantation is the type of electrode selected and proper insertion of the electrode array in scala tympani to minimize cochlear damage. The HiFocus Helix™ electrode is a precurved design aimed at placing the electrode contacts close to the spiral ganglion cells in the modiolus. The prescribed insertion techniques are intended to minimize the likelihood of damage to the basilar membrane or lateral wall of the cochlea. CASE PRESENTATION: To describe the first insertion of a HiFocus Helix™ electrode in Brazil exposing surgical particularities and device details in a patient with profound hearing loss, due to Mondini's dysplasia. CONCLUSION: No problems were encountered during the surgical procedure. The patient experienced improvement in hearing thresholds and speech perception. The HiFocus Helix™ electrode proved easy to insert and provided expected hearing benefits for the patient. This manuscript indicates that the HiResolution™ Bionic Ear System with HiFocus Helix™ electrode comprise a cochlear implant system that is practical and beneficial for the treatment of severe-to-profound hearing loss.

Air, bone and soft tissue excitation of the cochlea in the presence of severe impediments to ossicle and window mobility.

Clinical conditions have been described in which one of the two cochlear windows is immobile (otosclerosis) or absent (round window atresia), but nevertheless bone conduction (BC) thresholds are relatively unaffected. To clarify this apparent paradox, experimental manipulations which would severely impede several of the classical osseous mechanisms of BC were induced in fat sand rats, including discontinuity or immobilization of the ossicular chain, coupled with window fixation. Effects of these manipulations were assessed by recording auditory nerve brainstem evoked response (ABR) thresholds to stimulation by air conduction (AC), by osseous BC and by non-osseous BC (also called soft tissue conduction-STC) in which the BC bone vibrator is applied to skin sites. Following the immobilization, discontinuity and window fixation, auditory stimulation was also delivered to cerebro-spinal fluid (CSF) and to saline applied to the middle ear cavity. While the manipulations (immobilization, discontinuity, window fixation) led to an elevation of AC thresholds, nevertheless, there was no change in osseous and non-osseous BC thresholds. On the other hand, ABR could be elicited in response to fluid pressure stimulation to CSF and middle ear saline, even in the presence of the severe restriction of ossicular chain and window mobility. The results of these experiments in which osseous and non-osseous BC thresholds remained unchanged in the presence of severe restriction of the classical middle ear mechanisms and in the absence of an efficient release window, while ABR could be recorded in response to fluid pressure auditory stimulation to fluid sites, indicate that it is possible that the inner ear may be activated at low sound intensities by fast fluid pressure stimulation. At higher sound intensities, a slower passive basilar membrane traveling wave may serve to excite the inner ear.

Role of p19ink4d in the pathogenesis of hearing loss.

This study aimed to investigate the p19 expression in cisplatin-treated rats and the role of p19 in the degeneration of inner ear cells. It also searched for p19 gene alterations in patients with profound sensorineural deafness. P19ink4d is essential for the postmitotic maintenance of hair cells. It is presumed that a mutation in the functional homolog of p19 or a disturbance in its regulated expression can be the underlying cause of hearing loss. Experiments were conducted on male and female Sprague-Dawley rats (aged 6-7 weeks, 280-320 g) with thresholds of auditory brainstem responses <30 dB in the sound pressure level, and signs of middle ear infection were used for the experiment. For clinical evaluation, 400 children (age less than 13 years) from unrelated families with severe or profound sensorineural hearing loss (SNHL) were recruited at the second Xiangya Hospital of Central South University between 2005 and 2013, and genomic DNA for deafness gene analysis was obtained from peripheral blood samples of the patients and their lineal relatives. It was found that the p19 expression increased over time in the inner ear cells after cisplatin administration, but the p19 mRNA and protein levels significantly decreased in rats with manifested hearing loss induced by cisplatin. However, no mutation existed within the coding exons of p19 in the patients with profound sensorineural deafness. To conclude, the results support the concept that p19 may play an important role in the ototoxic effects of cisplatin and is probably involved in the pathogenesis of hearing loss.

Semiautomatic cochleostomy target and insertion trajectory planning for minimally invasive cochlear implantation.

A major component of minimally invasive cochlear implantation is atraumatic scala tympani (ST) placement of the electrode array. This work reports on a semiautomatic planning paradigm that uses anatomical landmarks and cochlear surface models for cochleostomy target and insertion trajectory computation. The method was validated in a human whole head cadaver model (n = 10 ears). Cochleostomy targets were generated from an automated script and used for consecutive planning of a direct cochlear access (DCA) drill trajectory from the mastoid surface to the inner ear. An image-guided robotic system was used to perform both, DCA and cochleostomy drilling. Nine of 10 implanted specimens showed complete ST placement. One case of scala vestibuli insertion occurred due to a registration/drilling error of 0.79 mm. The presented approach indicates that a safe cochleostomy target and insertion trajectory can be planned using conventional clinical imaging modalities, which lack sufficient resolution to identify the basilar membrane.

A novel perfusion-based method for cochlear implant electrode insertion.

A cochlear implant (CI) restores partial hearing to profoundly deaf individuals. CI electrodes are inserted manually in the cochlea and surgeons rely on tactile feedback from the implant to determine when to stop the insertion. This manual insertion method results in a large degree of variability in surgical outcomes and intra-cochlear trauma. Additionally, implants often span only the basal turn. In the present study we report on the development of a new method to assist CI electrode insertion. The design objectives are (1) an automated and standardized insertion technique across patients with (2) more apical insertion than is possible by the contemporary methods, while (3) minimizing insertion trauma. The method relies on a viscous fluid flow through the cochlea to carry the electrode array with it. A small cochleostomy (∼100-150 um in diameter) is made in scala vestibuli (SV) and the round window (RW) membrane is opened. A flow of diluted Sodium Hyaluronate (also known as Hyaluronic Acid, (HA)) is set up from the RW to the SV opening using a perfusion pump that sets up a unidirectional flow. Once the flow is established an implant is dropped into the ongoing flow. Here we present a proof-of-concept study where we used this technique to insert silicone implants all the way to the cochlear apex in rats and gerbils. In light-microscopic histology, the implantation occurred without cochlear trauma. To further assess the ototoxicity of the HA perfusion, we measured compound action potential (CAP) thresholds following the perfusion of HA, and found that the CAP thresholds were substantially elevated. Thus, at this point the method is promising, and requires further development to become clinically viable.

Reliability of cone beam computed tomography in scalar localization of the electrode array: a radio histological study.

Postoperative imaging plays a growing role in clinical studies concerning prognostic factors in cochlear implantation. Indeed, intracochlear position of the cochlear implant has recently been identified as a contributor in functional outcomes and radiological tools must be accurate enough to determine the final placement of the electrode array. The aim of our study was to validate cone beam computed tomography as a reliable technique for scalar localization of the electrode array. We performed therefore a temporal bone study on ten specimens that were implanted with a perimodiolar implant prototype. Cone beam reconstructions were performed and images were analyzed by two physicians both experienced in cochlear implant imaging, who determined the scalar localization of the implant. Temporal bones then underwent histological control to document this scalar localization and hypothetical intracochlear lesions. In four cases, a dislocation from scala tympani to scala vestibuli was suspected on cone beam reconstructions of the ascending part of the basal turn. In three of these four specimens, dislocation in pars ascendens was confirmed histologically. In the remaining temporal bone, histological analysis revealed an elevation with rupture of the basilar membrane. Histological assessment revealed spiral ligament tearing in another bone. We conclude that cone beam is a reliable tool to assess scalar localization of the selectrode array and may be used in future clinical studies.

Trichostatin A protects against cisplatin-induced ototoxicity by regulating expression of genes related to apoptosis and synaptic function.

OBJECTIVE: Although inhibition of histone deacetylases (HDACs) has been shown to protect against cisplatin-induced hearing loss, the underlying mechanism is still poorly understood. In the present study, we aim to investigate the protective effect of trichostatin A (TSA), a specific inhibitor of HDACs, on cisplatin-induced ototoxicity and to determine the differentially expressed genes involved in this process. METHODS: The basilar membrane of the cochlea was isolated from 3-day newborn Wistar rats. Organotypic cultures were treated with 150 µM cisplatin or 200 nM TSA. For combination treatment, cells were pre-incubated with TSA for 1h, followed by TSA plus cisplatin treatment. Rhodamine-phalloidin staining was used to label hair cells, and immunocytochemistry with an anti-neurofilament-200 antibody was applied to label spiral ganglion neurons (SGNs). Global expression profile microarray analysis was used to identify differentially expressed genes. Molecular function and signal pathway analysis were performed using a protein analysis through evolutionary relationships (PANTHER) classification system. Real-time quantitative PCR (qPCR) was carried out for data validation. RESULTS: Severe loss of hair cells and SGNs occurred after 48 h of cisplatin incubation, while TSA significantly increased the number of hair cells and SGNs in the combination treatment group (P<0.05). Compared with control, expression of 71 genes were up-regulated and 383 genes were down-regulated upon cisplatin treatment. Addition of TSA induced the up-regulation of 1387 genes and down-regulation of 1226 genes as compared with cisplatin administration alone. After cisplatin treatment, we observed significant down-regulation of mRNA for several genes related to synaptic function genes, including Camk2a, Camk2b, Vglut1, Snap25 and Rab3b, whereas pretreatment with TSA elevated mRNA levels of these genes. TSA greatly decreased expression of genes related to the calcium signaling pathway (Capn1 and Capn2) and apoptosis signaling pathway (Tnfrsf1a and Tp53), while addition of TSA significantly reduced levels of Tnfrsf1a and Tp53 compared with cisplatin alone (P<0.01). CONCLUSIONS: Our results suggested that TSA might protect against cisplatin-induced ototoxicity via mediating expression of genes responsible for regulating apoptosis, intracellular calcium homeostasis, neurotransmitter synthesis and release, and synaptic plasticity.

A mouse model for human deafness DFNB22 reveals that hearing impairment is due to a loss of inner hair cell stimulation.

The gene causative for the human nonsyndromic recessive form of deafness DFNB22 encodes otoancorin, a 120-kDa inner ear-specific protein that is expressed on the surface of the spiral limbus in the cochlea. Gene targeting in ES cells was used to create an EGFP knock-in, otoancorin KO (Otoa(EGFP/EGFP)) mouse. In the Otoa(EGFP/EGFP) mouse, the tectorial membrane (TM), a ribbon-like strip of ECM that is normally anchored by one edge to the spiral limbus and lies over the organ of Corti, retains its general form, and remains in close proximity to the organ of Corti, but is detached from the limbal surface. Measurements of cochlear microphonic potentials, distortion product otoacoustic emissions, and basilar membrane motion indicate that the TM remains functionally attached to the electromotile, sensorimotor outer hair cells of the organ of Corti, and that the amplification and frequency tuning of the basilar membrane responses to sounds are almost normal. The compound action potential masker tuning curves, a measure of the tuning of the sensory inner hair cells, are also sharply tuned, but the thresholds of the compound action potentials, a measure of inner hair cell sensitivity, are significantly elevated. These results indicate that the hearing loss in patients with Otoa mutations is caused by a defect in inner hair cell stimulation, and reveal the limbal attachment of the TM plays a critical role in this process.

Surgical planning and evaluation of implanting a penetrating cochlear nerve implant in human temporal bones using microcomputed tomography.

OBJECTIVE: To develop a transmastoid-posterior tympanotomy approach for the implantation of a penetrating auditory prosthesis in the most distal portion of the cochlear nerve. BACKGROUND: Animal studies suggest that penetrating cochlear nerve implants may overcome limitations of current cochlear implant systems. One step toward human implantation is the development of a suitable surgical approach. METHODS: In computer-rendered 3-dimensional (3-D) models (based on micro-CT scans of 10 human temporal bones), we simulated trajectories through the most basal part of the cochlea that gave access to the most distal portion of the cochlear nerve with minimal damage to intracochlear structures. We determined their vectors with respect to the mid-modiolar axis and posterior round window edge and assessed if they intersected the chorda tympani nerve. RESULTS: The typical vector obtained with these 3-D models ran in an anterosuperior direction, through the inferior part of the facial recess and anterior round window edge. In 7 of 10 temporal bones, this trajectory intersected the chorda tympani nerve. Based on the vectors, dummy probes were implanted in 3 of 10 temporal bones, and the need for chorda tympani removal was confirmed in accordance with the 3-D models. Postoperative micro-CT scans revealed that all probes were successfully implanted in the cochlear nerve, whereas the osseous spiral lamina and basilar membrane were preserved. CONCLUSION: The vector for drilling and implantation found in this study can be used as a guideline for real-life surgery and, therefore, is another step toward the clinical implementation of cochlear nerve implants.

Cell-cell junctions: a target of acoustic overstimulation in the sensory epithelium of the cochlea.

BACKGROUND: Exposure to intense noise causes the excessive movement of the organ of Corti, stretching the organ and compromising sensory cell functions. We recently revealed changes in the transcriptional expression of multiple adhesion-related genes during the acute phases of cochlear damage, suggesting that the disruption of cell-cell junctions is an early event in the process of cochlear pathogenesis. However, the functional state of cell junctions in the sensory epithelium is not clear. Here, we employed graded dextran-FITC, a macromolecule tracer that is impermeable to the organ of Corti under physiological conditions, to evaluate the barrier function of cell junctions in normal and noise-traumatized cochlear sensory epithelia. RESULTS: Exposure to an impulse noise of 155 dB (peak sound pressure level) caused a site-specific disruption in the intercellular junctions within the sensory epithelium of the chinchilla cochlea. The most vulnerable sites were the junctions among the Hensen cells and between the Hensen and Deiters cells within the outer zone of the sensory epithelium. The junction clefts that formed in the reticular lamina were permeable to 40 and 500 but not 2,000 kDa dextran-FITC macromolecules. Moreover, this study showed that the interruption of junction integrity occurred in the reticular lamina and also in the basilar membrane, a site that had been considered to be resistant to acoustic injury. Finally, our study revealed a general spatial correlation between the site of sensory cell damage and the site of junction disruption. However, the two events lacked a strict one-to-one correlation, suggesting that the disruption of cell-cell junctions is a contributing, but not the sole, factor for initiating acute sensory cell death. CONCLUSIONS: Impulse noise causes the functional disruption of intercellular junctions in the sensory epithelium of the chinchilla cochlea. This disruption occurs at an early phase of cochlear damage. Understanding the role of this disruption in cochlear pathogenesis will require future study.

Effects of a perilymphatic fistula on the passive vibration response of the basilar membrane.

In this study, a three-dimensional finite-element model of the passive human cochlea was created. Dynamic behavior of the basilar membrane caused by the vibration of the stapes footplate was analyzed considering a fluid-structure interaction with the cochlear fluid. Next, the effects of a perilymphatic fistula (PLF) on the vibration of the cochlea were examined by making a small hole on the wall of the cochlea model. Even if a PLF existed in the scala vestibuli, a traveling wave was generated on the basilar membrane. When a PLF existed at the basal end of the cochlea, the shape of the traveling wave envelope showed no remarkable change, but the maximum amplitude became smaller at the entire frequency range from 0.5 to 5kHz and decreased with decreasing frequency. In contrast, when a PLF existed at the second turn of the cochlea, the traveling wave envelope showed a notch at the position of the PLF and the maximum amplitude also became smaller. This model assists in elucidating the mechanisms of hearing loss due to a PLF from the view of dynamics.