Middle Turns Research Articles

Clinico-Radiological Manifestations of Cochlear Schwannomas.

Cochlear schwannomas, which are categorized into intracochlear and intravestibulocochlear schwannomas (ICs and IVCs, respectively) are rare and may cause hearing loss (HL). The affected region is invariably correlated with tumor location, which can be detected on magnetic resonance imaging (MRI). We describe the cochleovestibular manifestations of ICs and IVCs. The study included 31 patients with ICs or IVCs. Tumor extent and exact locations were delineated using MRI. Types of HL were subcategorized into the low-to-mid frequency (250 Hz to 1 kHz), mid-to-high frequency (>1 kHz), and all-frequency (universal) HL groups. The tumors involved the entire cochlear turn (two ICs) or extended beyond the cochleae (nine IVCs) in 11 patients, and 20 ICs were located in specific locations as follows: 14 in the basal, 3 in the middle, and 3 in the middle and apical turns. No patient showed tumor invasion of the internal auditory canal or middle ear. The pattern of HL usually reflects the location or extent of a tumor. We observed HL at all frequencies, at low-to-mid frequencies, and at mid-to-high frequencies in 13, 4, and 14 patients, respectively. Dizziness or tinnitus was observed in >50% of patients. Surgical tumor removal was performed in 10 patients, and the remaining patients are undergoing annual monitoring. Cochlear schwannomas may be associated with HL, which may worsen over time and reflect tumor location. Therefore, these lesions should be considered in the differential diagnosis in patients who present with idiopathic, fluctuating, progressive or sudden HL.

Microneedle-Mediated Delivery of siRNA via Liposomal-Based Transfection for Inner Ear Gene Therapy.

Microneedle-mediated intracochlear injection of siRNA-Lipofectamine through the round window membrane (RWM) can be used to transfect cells within the cochlea. Our laboratory has developed 100-μm diameter hollow microneedles for intracochlear injection through the guinea pig RWM. In this study, we test the feasibility of microneedle-mediated injection of siRNA and Lipofectamine, a commonly used reagent with known cellular toxicity, through the RWM for cochlear transfection. Fluorescently labeled scramble siRNA was diluted into Lipofectamine RNAiMax and OptiMEM. One microliter of 5 μM siRNA was injected through the RWM of Hartley guinea pigs at a rate of 1 μl/min (n = 22). In a control group, 1.0 μl of Lipofectamine, with no siRNA, was diluted into OptiMEM and injected in a similar fashion (n = 5). Hearing tests were performed before and either at 24 hours, 48 hours, or 5 days after injection. Afterward, animals were euthanized, and cochleae were harvested for imaging. Control cochleae were processed in parallel to untreated guinea pigs. Fluorescence, indicating successful transfection, was observed within the basal and middle turns of the cochlea with limited distribution in the apex at 24 and 48 hours. Signal was most intense in the organ of Corti, spiral ligament, and spiral ganglion. Little to no fluorescence was observed at 5 days post-injection. No significant changes in auditory brainstem response (ABR) were noted post-perforation at 5 days, suggesting that siRNA-Lipofectamine at low doses does not cause cochlear toxicity. Small volumes of siRNA and Lipofectamine can be effectively delivered to cochlear structures using microneedles, paving the way for atraumatic cochlear gene therapy.

Age-related alterations in efferent medial olivocochlear-outer hair cell and primary auditory ribbon synapses in CBA/J mice.

Hearing decline stands as the most prevalent single sensory deficit associated with the aging process. Giving compelling evidence suggesting a protective effect associated with the efferent auditory system, the goal of our study was to characterize the age-related changes in the number of efferent medial olivocochlear (MOC) synapses regulating outer hair cell (OHC) activity compared with the number of afferent inner hair cell ribbon synapses in CBA/J mice over their lifespan. Organs of Corti of 3-month-old CBA/J mice were compared with mice aged between 10 and 20 months, grouped at 2-month intervals. For each animal, one ear was used to characterize the synapses between the efferent MOC fibers and the outer hair cells (OHCs), while the contralateral ear was used to analyze the ribbon synapses between inner hair cells (IHCs) and type I afferent nerve fibers of spiral ganglion neurons (SGNs). Each cochlea was separated in apical, middle, and basal turns, respectively. The first significant age-related decline in afferent IHC-SGN ribbon synapses was observed in the basal cochlear turn at 14 months, the middle turn at 16 months, and the apical turn at 18 months of age. In contrast, efferent MOC-OHC synapses in CBA/J mice exhibited a less pronounced loss due to aging which only became significant in the basal and middle turns of the cochlea by 20 months of age. This study illustrates an age-related reduction on efferent MOC innervation of OHCs in CBA/J mice starting at 20 months of age. Our findings indicate that the morphological decline of efferent MOC-OHC synapses due to aging occurs notably later than the decline observed in afferent IHC-SGN ribbon synapses.

Dependability of Electrode to Modiolus Distance in Patients Specific Electrode Selection: A Cadaveric Model Study.

This study aims to discern the disparities in the electrode-to-modiolus distance (EMD) between cochleostomy and round window approaches when performed sequentially in the same temporal bone. Additionally, the study seeks to identify the cochlear metrics that contribute to these differences. A cross-sectional study was conducted, involving the sequential insertion of a 12-electrode array through both round window and cochleostomy approaches in cadaveric temporal bones. Postimplantation high-resolution CT scans were employed to calculate various parameters. A total of 12 temporal bones were included in the imaging analysis, revealing a mean cochlear duct length of 32.892 mm. The EMD demonstrated a gradual increase from electrode 1 (C1) in the apex (1.9 ± 0.07 mm; n = 24) to electrode 12 (C12) in the basal turn (4.6 ± 0.24 mm; n = 12; p < 0.01). Significantly higher EMD values were observed in the cochleostomy group. Correlation analysis indicated a strong positive correlation between EMD and cochlear perimeter (CP) (rs = 0.64; n = 12; p = 0.03) and a strong negative correlation with the depth of insertion (DOI) in both the middle and basal turns (rs = - 0.78; n = 20; p < 0.01). Additionally, EMD showed a strong negative correlation with the DOI-CP ratio (rs = -0.81; n = 12; p < 0.01). The cochleostomy group exhibited a significantly higher EMD compared with the round window group. The strong negative correlation between EMD and DOI-CP ratio suggests that in larger cochleae with shallower insertions, EMD is greater than in smaller cochleae with deeper insertions. NA Laryngoscope, 134:4736-4744, 2024.

The endoscopic transcanal approach to the internal auditory canal: an anatomic study.

The internal auditory canal (IAC) plays a key role in lateral skull base surgery. Although several approaches to the IAC have been proposed, endoscope-assisted transcanal corridors to the IAC have rarely been studied. We sought to provide a step-by-step description of the transcanal transpromontorial approach to the IAC and analyze anatomic relationships that might enhance predictability and safety of this approach. Ten cadaveric specimens were dissected and the extended transcanal transpromontorial approach to the IAC was established. Various morphometric measurements and anatomic landmarks were reviewed and analyzed. The proposed technique proved feasible and safe in all specimens. There was no inadvertent injury to the jugular bulb or internal carotid artery. The chorda tympani, a key landmark for the mastoid segment of the facial nerve, was identified in all dissections. The spherical recess of the vestibule and middle turn of cochlea are important landmarks for identification of the labyrinthine segment of the facial nerve. Identification of all boundaries of the working area is also essential for safe access. Among various morphometric measurements, the modiolus-IAC angle (≈150°) proved particularly consistent; given its ease of use and low variability, we believe it could serve as a landmark for identification and subsequent dissection of the IAC. The extended transcanal transpromontorial approach to the IAC is feasible and safe. Relying on anatomic landmarks to ensure preservation of the involved neurovascular structures is essential for a successful approach. The modiolus-IAC angle is a consistent, reproducible landmark for IAC identification and dissection.

Cochlear implant electrode design for safe and effective treatment.

The optimal placement of a cochlear implant (CI) electrode inside the scala tympani compartment to create an effective electrode-neural interface is the base for a successful CI treatment. The characteristics of an effective electrode design include (a) electrode matching every possible variation in the inner ear size, shape, and anatomy, (b) electrically covering most of the neuronal elements, and (c) preserving intra-cochlear structures, even in non-hearing preservation surgeries. Flexible electrode arrays of various lengths are required to reach an angular insertion depth of 680° to which neuronal cell bodies are angularly distributed and to minimize the rate of electrode scalar deviation. At the time of writing this article, the current scientific evidence indicates that straight lateral wall electrode outperforms perimodiolar electrode by preventing electrode tip fold-over and scalar deviation. Most of the available literature on electrode insertion depth and hearing outcomes supports the practice of physically placing an electrode to cover both the basal and middle turns of the cochlea. This is only achievable with longer straight lateral wall electrodes as single-sized and pre-shaped perimodiolar electrodes have limitations in reaching beyond the basal turn of the cochlea and in offering consistent modiolar hugging placement in every cochlea. For malformed inner ear anatomies that lack a central modiolar trunk, the perimodiolar electrode is not an effective electrode choice. Most of the literature has failed to demonstrate superiority in hearing outcomes when comparing perimodiolar electrodes with straight lateral wall electrodes from single CI manufacturers. In summary, flexible and straight lateral wall electrode type is reported to be gentle to intra-cochlear structures and has the potential to electrically stimulate most of the neuronal elements, which are necessary in bringing full benefit of the CI device to recipients.

Gene expression analysis of oxidative stress-related genes in the apical, middle, and basal turns of the cochlea

It can be observed from aminoglycoside-induced hair cell damage that the cochlea basal turn is more susceptible to trauma than the apex. Drug-induced hearing loss is closely related to oxidative damage. The basilar membrane directly exposed to these ototoxic drugs exhibits differences in damage, indicating that there is an inherent difference in the sensitivity to oxidative damage from the apex to the base of the cochlea. It has been reported that the morphology and characteristics of the cochlea vary from the apex to the base. Therefore, we investigated oxidative stress-related gene expression profiles in the apical, middle, and basal turns of the cochlea. The Oxidative Stress RT2 Profiler™ PCR Array revealed that three of the 84 genes (Mb, Mpo, and Ncf1) were upregulated in the middle turn compared to their level in the apical turn. Moreover, eight genes (Mb, Duox1, Ncf1, Ngb, Fmo2, Gpx3, Mpo, and Gstk1) were upregulated in the basal turn compared to their level in the apical turn. The qPCR verification data were similar to that of the PCR Array. We found that MPO was expressed in the rat cochlea and protected against gentamicin-induced hair cell death. This study summarized the data for the gradient of expression of oxidative stress-related genes in the cochlea and found potential candidate targets for prevention of ototoxic deafness, which may provide new insights for cochlear pathology.

Intralabyrinthine schwannoma: Surgical management and cochlear lumen preservation

The present video reports the surgical removal of an intralabyrinthine schwannoma. The video contains patient's medical history, preoperative radiological evaluations and detailed description of surgical steps of the procedure, consisting in labyrinthectomy, cochleostomy and insertion of a dummy electrode in the preserved cochlear lumen within the context of a subtotal petrosectomy.

The efficacy of a TrkB monoclonal antibody agonist in preserving the auditory nerve in deafened guinea pigs

The auditory nerve typically degenerates following loss of cochlear hair cells or synapses. In the case of hair cell loss neural degeneration hinders restoration of hearing through a cochlear implant, and in the case of synaptopathy suprathreshold hearing is affected, potentially degrading speech perception in noise. It has been established that neurotrophins such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) can mitigate auditory nerve degeneration. Several potential BDNF mimetics have also been investigated for neurotrophic effects in the cochlea. A recent in vitro study showed favorable effects of M3, a TrkB monoclonal antibody agonist, when compared with BDNF. In the present study we set out to examine the effect of M3 on auditory nerve preservation in vivo. Thirty-one guinea pigs were bilaterally deafened, and unilaterally treated with a single 3-µl dose of 7 mg/ml, 0.7 mg/ml M3 or vehicle-only by means of a small gelatin sponge two weeks later. During the experiment and analyses the experimenters were blinded to the three treatment groups. Four weeks after treatment, we assessed the treatment effect (1) histologically, by quantifying survival of SGCs and their peripheral processes (PPs); and (2) electrophysiologically, with two different paradigms of electrically evoked compound action potential (eCAP) recordings shown to be indicative of neural health: single-pulse stimulation with varying inter-phase gap (IPG), and pulse-train stimulation with varying inter-pulse interval. We observed a consistent and significant preservative effect of M3 on SGC survival in the lower basal turn (approximately 40% more survival than in the untreated contralateral cochlea), but also in the upper middle and lower apical turn of the cochlea. This effect was similar for the two treatment groups. Survival of PPs showed a trend similar to that of the SGCs, but was only significantly higher for the highest dose of M3. The protective effect of M3 on SGCs was not reflected in any of the eCAP measures: no statistically significant differences were observed between groups in IPG effect nor between the M3 treatment groups and the control group using the pulse-train stimulation paradigm. In short, while a clear effect of M3 was observed on SGC survival, this was not clearly translated into functional preservation.

Evaluation of the relationship between endolymphatic hydrops and hearing loss in Meniere’s disease based on three-dimensional real inversion recovery sequence

ObjectivesThe degree of endolymphatic hydrops in Meniere's disease may be related to hearing loss. However, the results of prior studies have been inconsistent. We aimed to investigate the relationship between endolymphatic hydrops and hearing loss characteristics in Meniere’s disease. MethodsThis study included 54 patients (62 ears) with Meniere’s disease. Patients underwent three-dimensional real inversion recovery sequences for magnetic resonance imaging and pure-tone audiometry. Endolymphatic hydrops were assessed according to Gurkov’s criteria (2011). Correlations between different degrees of endolymphatic hydrops and pure-tone audiometry, as well as staging, were analysed. ResultsPure tone audiometry and staging were higher for vestibular endolymphatic hydrops complicated by cochlear ones than isolated cochlear or vestibular hydrops (both p < 0.05). There was no significant correlation between vestibular endolymphatic hydrops and pure-tonal audiometry or staging (all p > 0.05). The degree of hydrops in the middle turn was correlated with the mid-frequency hearing threshold (p < 0.05). The degree of cochlear hydrops was correlated with the audiometry, low-frequency hearing thresholds, mid-frequency hearing thresholds and staging (p < 0.01). ConclusionThe types and sites of endolymphatic hydrops based on a 3D-real inversion recovery sequence can be used to indicate the degree of hearing loss in patients with Meniere’s disease. Level of evidenceLevel III.

Eddy Current and Loss of Graded-Resistance No-Insulation Coils in HTS Synchronous Machines of Electrical Aircraft

The No-insulation (NI) high temperature superconductor (HTS) machine is a promising propulsion technique for future large-scale electrical aircraft because of its high power density and enhanced thermal stability. However, in the machine environment, the ripple magnetic fields can induce significant eddy currents and losses on the NI coil. A grading turn-to-turn resistivity technique has been proposed to solve this problem, in which higher turn-to-turn resistivity is applied on the outermost turns of the NI coil, and lower turn-to-turn resistivity is kept on middle turns. The purpose of this research is to study the effects of grading turn-to-turn resistivity technique on the eddy current and loss of both single and multiple NI HTS coils exposed to ripple fields. To investigate the electromagnetic behavior and loss mechanism of NI HTS coils, a simulation model is proposed that couples the equivalent circuit model and finite element model. Results show that the grading turn-to-turn resistivity can effectively reduce the induced eddy current and lead to a uniform distribution of eddy current among turns of both single and multiple windings. It reduces magnetization loss in superconducting layers but increases the turn-to-turn loss on the radial contacts. These results are useful for the development of NI HTS machines with high thermal stability.

Quantitative Evaluation of the 3D Anatomy of the Human Osseous Spiral Lamina Using MicroCT

PurposeThe osseous spiral lamina (OSL) is an inner cochlear bony structure that projects from the modiolus from base to apex, separating the cochlear canal into the scala vestibuli and scala tympani. The porosity of the OSL has recently attracted the attention of scientists due to its potential impact on the overall sound transduction. The bony pillars between the vestibular and tympanic plates of the OSL are not always visible in conventional histopathological studies, so imaging of such structures is usually lacking or incomplete. With this pilot study, we aimed, for the first time, to anatomically demonstrate the OSL in great detail and in 3D.MethodsWe measured width, thickness, and porosity of the human OSL by microCT using increasing nominal resolutions up to 2.5-µm voxel size. Additionally, 3D models of the individual plates at the basal and middle turns and the apex were created from the CT datasets.ResultsWe found a constant presence of porosity in both tympanic plate and vestibular plate from basal turn to the apex. The tympanic plate appears to be more porous than vestibular plate in the basal and middle turns, while it is less porous in the apex. Furthermore, the 3D reconstruction allowed the bony pillars that lie between the OSL plates to be observed in great detail.ConclusionBy enhancing our comprehension of the OSL, we can advance our comprehension of hearing mechanisms and enhance the accuracy and effectiveness of cochlear models.

Ca2+ Dynamics of Gap Junction Coupled and Uncoupled Deiters' Cells in the Organ of Corti in Hearing BALB/c Mice.

ATP, as a paracrine signalling molecule, induces intracellular Ca2+ elevation via the activation of purinergic receptors on the surface of glia-like cochlear supporting cells. These cells, including the Deiters' cells (DCs), are also coupled by gap junctions that allow the propagation of intercellular Ca2+ waves via diffusion of Ca2+ mobilising second messenger IP3 between neighbouring cells. We have compared the ATP-evoked Ca2+ transients and the effect of two different gap junction (GJ) blockers (octanol and carbenoxolone, CBX) on the Ca2+ transients in DCs located in the apical and middle turns of the hemicochlea preparation of BALB/c mice (P14-19). Octanol had no effect on Ca2+ signalling, while CBX inhibited the ATP response, more prominently in the middle turn. Based on astrocyte models and using our experimental results, we successfully simulated the Ca2+ dynamics in DCs in different cochlear regions. The mathematical model reliably described the Ca2+ transients in the DCs and suggested that the tonotopical differences could originate from differences in purinoceptor and Ca2+ pump expressions and in IP3-Ca2+ release mechanisms. The cochlear turn-dependent effect of CBX might be the result of the differing connexin isoform composition of GJs along the tonotopic axis. The contribution of IP3-mediated Ca2+ signalling inhibition by CBX cannot be excluded.

Influence of CX3CR1 Deletion on Cochlear Hair Cell Survival and Macrophage Expression in Chronic Suppurative Otitis Media.

Our objective was to determine whether the receptor CX3CR1 is necessary for the recruitment of macrophages to the cochlea in chronic suppurative otitis media (CSOM) and if its deletion can prevent hair cell loss in CSOM. CSOM is a neglected disease that afflicts 330 million people worldwide and is the most common cause of permanent hearing loss among children in the developing world. It is characterized by a chronically discharging infected middle ear. We have previously demonstrated that CSOM causes macrophage associated sensory hearing loss. The receptor CX3CR1 is expressed on macrophages, which have been shown to be increased at the time point of outer hair cell (OHC) loss in CSOM. In this report, we examine the influence of CX3CR1 deletion (CX3CR1-/-) in a validated model of Pseudomonas aeruginosa (PA) CSOM. The data show no difference in OHC loss between the CX3CR1-/- CSOM group and CX3CR1+/+ CSOM group (p = 0.28). We observed partial OHC loss in the cochlear basal turn, no OHC loss in the middle and apical turns in both CX3CR1-/- and CX3CR1+/+ CSOM mice at 14 days after bacterial inoculation. No inner hair cell (IHC) loss was found in all cochlear turns in all groups. We also counted F4/80 labeled macrophages in the spiral ganglion, spiral ligament, stria vascularis and spiral limbus of the basal, middle, and apical turn in cryosections. We did not find a significant difference in the total number of cochlear macrophages between CX3CR1-/- mice and CX3CR1+/+ mice (p = 0.97). The data did not support a role for CX3CR1 macrophage associated HC loss in CSOM.

A prestin-targeting peptide-guided drug delivery system rearranging concentration gradient in the inner ear: An improved strategy against hearing loss

Hearing loss is mainly due to outer hair cell (OHC) damage in three cochlear turns. Local administration via the round window membrane (RWM) has considerable otological clinical potential in bypassing the blood–labyrinth barrier. However, insufficient drug distribution in the apical and middle cochlear turns results in unsatisfactory efficacy. We functionalized poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) with targeting peptide A665, which specifically bound to prestin, a protein uniquely expressed in OHCs. The modification facilitated the cellular uptake and RWM permeability of NPs. Notably, the guide of A665 towards OHCs enabled more NPs perfusion in the apical and middle cochlear turns without decreasing accumulation in the basal cochlear turn. Subsequently, curcumin (CUR), an appealing anti-ototoxic drug, was encapsulated in NPs. In aminoglycoside-treated guinea pigs with the worst hearing level, CUR/A665-PLGA NPs, with superior performance to CUR/PLGA NPs, almost completely preserved the OHCs in three cochlear turns. The lack of increased low-frequencies hearing thresholds further confirmed that the delivery system with prestin affinity mediated cochlear distribution rearrangement. Good inner ear biocompatibility and little or no embryonic zebrafish toxicity were observed throughout the treatment. Overall, A665-PLGA NPs act as desirable tools with sufficient inner ear delivery for improved efficacy against severe hearing loss.

First report of Alternaria alternata causing leaf yellow spot on Ginger (Zingiber officinale Roscoe) in Laifeng, China.

Ginger (Zingiber officinale Roscoe) is a highly important commercial crop in China, which is widely cultivated for its medicinal and nutritional qualities. Fengtou ginger is a variety mainly grown in Central China. From June to September of 2021, leaf yellow spot symptoms were observed on ginger plants var. Fengtou in commercial fields, localized in Laifeng county (29.37゜N, 109.31゜E), Hubei Province, China. Early symptoms were small yellow spots (approximately 0.2 cm) on leaves, but these spots gradually expanded, and the middle turn brown. The incidence of yellow spot on plants was 15% to 35%. To identify the causal agent of the disease, 15 symptomatic leaves were collected on from plants in the field. From each ginger leaf, small fragments (2 to 4 mm) were cut from the margin of the lesions and surface disinfected with 75% ethanol and 2% sodium hypochlorite for 30 s and 60 s, respectively, and rinsed three times with sterile water (Zhong et al. 2022). The disinfected small fragments were placed on Rose Bengal Agar medium at 25 ℃. After 3 to 5 days of incubation, a total of 11 isolates from leaf samples were obtained, of which 8 showed a radial mycelial growth that was grayish and then darkened. Conidiophores were brown and branched. Conidia were multicellular, obclavate to obpyriform within 9.1-22.6 µm (average 14.3 µm) in length and 6.0-13.5 µm (average 7.9 µm) in width (n=30). The isolates were identified as Alternaria sp. according to their morphological characteristics (Simmons 2007). For further molecular identification, genomic DNAs of two representative isolates (isolate 1 and isolate 4) were extracted and amplificated using a set of primers ITS1/ITS4 (White et al. 1990), RPB2-5F/RPB2-7R (Liu et al. 1999) and gpd1/gpd2 (Berbee et al. 1999), for the internal transcribed spacer (ITS)-rDNA region, partial RNA polymerase II largest subunit (RPB2), and Glyceraldehyde 3-phosphate (GADPH), respectively. The sequences were submitted to GenBank with submission Nos. OM701795 and OM701794 for ITS-rDNA; OM864662 and OM864663 for RPB2; OM864664 and OM864665 for the GADPH gene. A BLAST analysis in GenBank showed 100% identity with A. alternata for ITS (GenBank No. MN907440), RPB2 (GenBank No. KP057228) and GADPH (GenBank No. MK637444), respectively. A pathogenicity test was performed on potted healthy plants of ginger var. Fengtou of 2.5-month-old in a greenhouse. A total of five plants were sprayed with a conidial suspension (105 spores/mL) of each isolate on leaves until runoff (3 to 5 ml per plant) occurred. Five plants were sprayed with sterile water. The plants were grown in a greenhouse at 25 ℃. Eight days after inoculation, the symptoms similar to diseased leaves in the field appeared on the inoculated leaves, while the controls remained healthy. The fugus re-isolated from infected tissues was morphologically and molecularly identical to the original isolates of A. alternata, which fulfill the Koch's postulates. To our knowledge, this is the first report of A. alternata causing yellow spot on ginger in China. The work will be beneficial to develop effective management methods for preventing and treating this disease and avoid yield and economic loss of ginger in China.

Cochlear Implant in cochlear Hypoplasia type 4 with Chiari Malformation- Case Report.

Cochlear hypoplasia type IV is a rare cochlear malformation with hypoplastic middle and apical turns while basal turn develops normally, it often coexist with other genetic mutations. We present a case of 4 year old with chiari malformation type 1 along with bilateral Cochlear hypoplasia type IV who underwent cochlear implantation.

Microneedles Facilitate Small-Volume Intracochlear Delivery Without Physiologic Injury in Guinea Pigs.

Microneedle-mediated intracochlear injection through the round window membrane (RWM) will facilitate intracochlear delivery, not affect hearing, and allow for full reconstitution of the RWM within 48 hours. We have developed polymeric microneedles that allow for in vivo perforation of the guinea pig RWM and aspiration of perilymph for diagnostic analysis, with full reconstitution of the RWM within 48 to 72 hours. In this study, we investigate the ability of microneedles to deliver precise volumes of therapeutics into the cochlea and assess the subsequent consequences on hearing. Volumes of 1.0, 2.5, or 5.0 μL of artificial perilymph were injected into the cochlea at a rate of 1 μL/min. Compound action potential (CAP) and distortion product otoacoustic emission were performed to assess for hearing loss (HL), and confocal microscopy was used to evaluate the RWM for residual scarring or inflammation. To evaluate the distribution of agents within the cochlea after microneedle-mediated injection, 1.0 μL of FM 1-43 FX was injected into the cochlea, followed by whole mount cochlear dissection and confocal microscopy. Direct intracochlear injection of 1.0 μL of artificial perilymph in vivo , corresponding to about 20% of the scala tympani volume, was safe and did not result in HL. However, injection of 2.5 or 5.0 μL of artificial perilymph into the cochlea produced statistically significant high-frequency HL persisting 48 hours postperforation. Assessment of RWMs 48 hours after perforation revealed no inflammatory changes or residual scarring. FM 1-43 FX injection resulted in distribution of the agent predominantly in the basal and middle turns. Microneedle-mediated intracochlear delivery of small volumes relative to the volume of the scala tympani is feasible, safe, and does not cause HL in guinea pigs; however, injection of large volumes induces high-frequency HL. Injection of small volumes of a fluorescent agent across the RWM resulted in significant distribution within the basal turn, less distribution in the middle turn, and almost none in the apical turn. Microneedle-mediated intracochlear injection, along with our previously developed intracochlear aspiration, opens the pathway for precision inner ear medicine.

Nuclear Translocation Triggered at the Onset of Hearing in Cochlear Inner Hair Cells of Rats and Mice

PurposeNuclear 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.MethodsWe measured hair cell length and nuclear position from confocal scans of immunofluorescence-labeled hair cells from whole-mount cochlear preparations throughout post-natal development.ResultsIn 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.ConclusionNuclear 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.

Cochlear Ossification After Vestibular Schwannoma Surgery: A Temporal Bone Study.

This study aims to investigate patterns of cochlear ossification (CO) in cadaveric temporal bones of patients who underwent vestibular schwannoma(VS) surgery via the translabyrinthine (TL), middle cranial fossa (MF), or retrosigmoid (RS) approaches. Histopathologic analysis of cadaveric temporal bones. Multi-institutional national temporal bone repository. The National Institute of Deafness and Communication Disorders and House Temporal Bone Laboratory at the University of California, Los Angeles and the Massachusetts Eye and Ear Otopathology Laboratory were searched for cadaveric temporal bones with a history of VS for which microsurgery was performed. Exclusion criteria included non-VS and perioperative death within 30 days of surgery. Temporal bones were analyzed histologically for CO of the basal, middle, and apical turns. Of 92 temporal bones with a history of schwannoma from both databases, 12 of these cases met the inclusion criteria. The approaches for tumor excision included 2 MF, 4 RS, and 6 TL approaches. CO was observed in all temporal bones that had undergone TL surgery. Among temporal bones that had undergone MF or RS surgeries, 5/6 had no CO, and 1/6 had partial ossification. This single case was noted to have intraoperative vestibular violation after RS surgery upon histopathologic and chart review. In this temporal bone series, all temporal bones that had undergone TL demonstrated varying degrees of CO on histological analysis. MF and RS cases did not exhibit CO except in the case of vestibular violation. When cochlear implantation is planned or possible after VS surgery, surgeons may consider using a surgical approach that does not violate the labyrinth.