Apical Turn Research Articles

Amplification mode differs along the length of the mouse cochlea as revealed by connexin 26 deletion from specific gap junctions

The sharp frequency tuning and exquisite sensitivity of the mammalian cochlea is due to active forces delivered by outer hair cells (OHCs) to the cochlear partition. Force transmission is mediated and modulated by specialized cells, including Deiters’ cells (DCs) and pillar cells (PCs), coupled by gap-junctions composed of connexin 26 (Cx26) and Cx30. We created a mouse with conditional Cx26 knock-out (Cx26 cKO) in DCs and PCs that did not influence sensory transduction, receptor-current-driving-voltage, low-mid-frequency distortion-product-otoacoustic-emissions (DPOAEs), and passive basilar membrane (BM) responses. However, the Cx26 cKO desensitizes mid-high-frequency DPOAEs and active BM responses and sensitizes low-mid-frequency neural excitation. This functional segregation may indicate that the flexible, apical turn cochlear partition facilitates transfer of OHC displacements (isotonic forces) for cochlear amplification and neural excitation. DC and PC Cx26 expression is essential for cochlear amplification in the stiff basal turn, possibly through maintaining cochlear partition mechanical impedance, thereby ensuring effective transfer of OHC isometric forces.

Streptococcus pneumoniae-induced ototoxicity in organ of Corti explant cultures

Hearing loss remains the most common long-term complication of pneumococcal meningitis (PM) reported in up to 30% of survivors. Streptococcus pneumoniae have been shown to possess different ototoxic properties. Here we present a novel ex vivo experimental setup to examine in detail the pattern of hair cell loss upon exposure to different S. pneumoniae strains, therefore recapitulating pathogen derived aspects of PM-induced hearing loss. Our results show a higher susceptibility towards S. pneumoniae-induced cochlear damage for outer hair cells (OHC) compared to inner hair cells (IHC), which is consistent with in vivo data. S. pneumoniae-induced hair cell loss was both time and dose-dependent. Moreover, we have found significant differences in the level of cell damage between tissue from the basal and the apical turns. This shows that the higher vulnerability of hair cells located at high frequency regions observed in vivo cannot be explained solely by the spatial organisation and bacterial infiltration from the basal portion of the cochlea. Using a wild type D39 strain and a mutant defective for the pneumolysin (PLY) gene, we also have shown that the toxin PLY is an important factor involved in ototoxic damages. The obtained results indicate that PLY can cause both IHC and OHC loss. Finally, we are reporting here for the first time a higher vulnerability of HC located at the basal and middle cochlear region to pneumolysin-induced damage. The detailed description of the susceptibility of hair cells to Streptococcus pneumoniae provided in this report can in the future determine the choice and the development of novel otoprotective therapies during pneumococcal meningitis.

Assessment of Cochlea Endolymphatic Hydrops Using 3-D FLAIR and 3-D Real IR Sequence in Guinea Pigs via 3T MRI After Intratympanic Gadolinium: A Histopathological Comparison.

We assessed whether the three-dimensional fluid-attenuated inversion-recovery (3-D FLAIR) and three-dimensional inversion-recovery with real reconstruction (3-D real IR) sequences can be used to detect cochlea endolymphatic hydrops (EHs) in guinea pigs using 3 Tesla magnetic resonance imaging (3T MRI). The results of 3-D real IR imaging were compared with histopathological outcomes. Fourteen healthy men and women albino guinea pigs were used in this study. Their right ears received procedures that promoted EHs, and their left ears were used as untreated controls. High-resolution 3T MRI, combined with the intratympanic injection of gadolinium (Gd) in both ears, was performed 8 to 12 weeks after surgery. Both sides of the cochlea midmodiolar sections were observed under a light microscope and saved as the histopathological images. The signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) between the T2-weighted 3-D FLAIR and T2-weighted 3-D real IR sequences were compared. The appearance of EHs in the basal, second, third, and apical turns of the cochlea was further evaluated using 3-D FLAIR, 3-D real IR, and the histopathological images. Moreover, the maximum scala media area ratios (SMRs) on the histopathological sections were compared with the grading of the EHs on the 3-D real IR sequence with regard to each turn of the cochlea. Significant differences were found between the 3-D FLAIR and 3-D-real IR sequences with regard to the SNRs and CNRs (p < 0.05): the 3-D FLAIR sequence exhibited higher SNRs (SNRROI: 347.95 ± 105.01; SNRB: 103.28 ± 17.61) compared with the 3-D real IR sequence (SNRROI: 86.71 ± 30.11; SNRB: 11.11 ± 3.45), whereas the 3-D real IR sequence showed higher CNRs (2.78 ± 0.58) compared with the 3-D FLAIR sequence (2.18 ± 0.55). Various degrees of EHs were observed in each turn of the cochlea in the experimental ears on the basis of the histopathological images. Thirteen, 10, 4, and 0 EHs were observed in the basal, second, third, and apical turns of the cochlear using 3-D FLAIR images, respectively, whereas 14, 14, 14, and 13 EHs were found using 3-D real IR images, respectively. Significant differences were found between the two sequences when evaluating the second, third, and apical turns of the cochlear but not with regard to the basal turn (p < 0.05). The SMRs were proportional to the extent of the EHs on 3-D real IR imaging in each turn of the cochlea. 3-D real IR images are clearer than 3-D FLAIR images, and they can display cochlea EHs more precisely using 3T MRI in guinea pigs. The extent of the EHs on 3-D real IR imaging was more consistent with the histopathological observations in each turn of the cochlea.

Acoustic schwannoma with intracochlear extension and primary intracochlear schwannoma: removal through translabyrinthine approach with facial bridge cochleostomy and transcanal approach.

Intracochlear schwannomas can occur either as an extension of a larger tumor from the internal auditory canal, or as a solitary labyrinthine tumor. They are currently removed via a translabyrinthine approach extended to the basal turn, adding a transotic approach for tumors lying beyond the basal turn. Facial bridge cochleostomy may be associated with the translabyrinthine approach to enable the whole cochlea to be approached without sacrificing the external auditory canal and tympanum. We describe seven cases, five of which underwent cochlear schwannoma resection with facial bridge cochleostomy, one case with the same procedure for a suspect tumor and one, previously subjected to radical tympanomastoidectomy, who underwent schwannoma resection via a transotic approach. Facial bridge cochleostomy involved removing the bone between the labyrinthine and tympanic portions of the fallopian canal, and exposing the cochlea from the basal to the apical turn. Patients' recovery was uneventful, and long-term magnetic resonance imaging showed no residual tumor. Facial bridge cochleostomy can be a flexible extension of the translabyrinthine approach for tumors extending from the internal auditory canal to the cochlea. The transcanal approach is suitable for the primary exclusive intralabyrinthine tumor. The indications for the different approaches are discussed.

Dose-dependent cochlear and vestibular toxicity of trans-tympanic cisplatin in the rat

In vivo studies are needed to study cisplatin ototoxicity and to evaluate candidate protective treatments. Rats and mice are the preferred species for toxicological and pharmacological pre-clinical research, but systemic administration of cisplatin causes high morbidity in these species. We hypothesized that trans-tympanic administration of cisplatin would provide a good model for studying its auditory and vestibular toxicity in the rat. Cisplatin was administered by the trans-tympanic route in one ear (50μl, 0.5–2mg/ml) of rats of both sexes and two different strains. Cochlear toxicity was corroborated by histological means. Vestibular toxicity was demonstrated by behavioral and histological analysis. Cisplatin concentrations were assessed in inner ear after trans-tympanic and i.v. administration. In all experiments, no lethality and only scant body weight loss were recorded. Cisplatin caused dose-dependent cochlear toxicity, as demonstrated by hair cell counts in the apical and middle turns of the cochlea, and vestibular toxicity, as demonstrated by behavioral analysis and hair cell counts in utricles. High concentrations of cisplatin were found in the inner ear after trans-tympanic administration. In comparison, i.v. administration resulted in lower inner ear concentrations. We conclude that trans-tympanic administration provides an easy, reproducible and safe model to study the cochlear and vestibular toxicity of cisplatin in the rat. This route of exposure may be useful to address particular questions on cisplatin induced ototoxicity and to test candidate protective treatments.

The effect of systemic lipoic acid on hearing preservation after cochlear implantation via the round window approach: A guinea pig model

The present study aimed to evaluate the effects of systemic lipoic acid on hearing preservation after cochlear implantation. Twelve Dunkin-Hartley guinea pigs were randomly divided into two groups: the control group and the lipoic acid group. Animals in the lipoic acid group received lipoic acid intraperitoneally for 4 weeks. A sterilised silicone electrode-dummy was inserted through the round window to a depth of approximately 5 mm. The hearing level was measured using auditory brainstem responses (ABRs) prior to electrode-dummy insertion, and at 4 days and 1, 2, 3 and 4 weeks after electrode-dummy insertion. The threshold shift was defined as the difference between the pre-operative threshold and each of the post-operative thresholds. The cochleae were examined histologically 4 weeks after electrode-dummy insertion. Threshold shifts changed with frequency but not time. At 2kHz, ABR threshold shifts were statistically significantly lower in the lipoic acid group than the control group. At 8, 16 and 32kHz, there was no significant difference in the ABR threshold shift between the two groups. Histologic review revealed less intracochlear fibrosis along the electrode-dummy insertion site in the lipoic acid group than in the control group. The spiral ganglion cell densities of the basal, middle and apical turns were significantly higher in the lipoic acid group compared with the control group. Therefore, systemic lipoic acid administration appears to effectively preserve hearing at low frequencies in patients undergoing cochlear implantation. These effects may be attributed to the protection of spiral ganglion cells and prevention of intracochlear fibrosis.

Ick Ciliary Kinase Is Essential for Planar Cell Polarity Formation in Inner Ear Hair Cells and Hearing Function.

Cellular asymmetries play crucial roles in development and organ function. The planar cell polarity (PCP) signaling pathway is involved in the establishment of cellular asymmetry within the plane of a cell sheet. Inner ear sensory hair cells (HCs), which have several rows of staircase-like stereocilia and one kinocilium located at the vertex of the stereocilia protruding from the apical surface of each HC, exhibit a typical form of PCP. Although connections between cilia and PCP signaling in vertebrate development have been reported, their precise nature is not well understood. During inner ear development, several ciliary proteins are known to play a role in PCP formation. In the current study, we investigated a functional role for intestinal cell kinase (Ick), which regulates intraflagellar transport (IFT) at the tip of cilia, in the mouse inner ear. A lack of Ick in the developing inner ear resulted in PCP defects in the cochlea, including misorientation or misshaping of stereocilia and aberrant localization of the kinocilium and basal body in the apical and middle turns, leading to auditory dysfunction. We also observed abnormal ciliary localization of Ift88 in both HCs and supporting cells. Together, our results show that Ick ciliary kinase is essential for PCP formation in inner ear HCs, suggesting that ciliary transport regulation is important for PCP signaling.SIGNIFICANCE STATEMENT The cochlea in the inner ear is the hearing organ. Planar cell polarity (PCP) in hair cells (HCs) in the cochlea is essential for mechanotransduction and refers to the asymmetric structure consisting of stereociliary bundles and the kinocilium on the apical surface of the cell body. We reported previously that a ciliary kinase, Ick, regulates intraflagellar transport (IFT). Here, we found that loss of Ick leads to abnormal localization of the IFT component in kinocilia, PCP defects in HCs, and hearing dysfunction. Our study defines the association of ciliary transport regulation with PCP formation in HCs and hearing function.

Pharmacokinetic Properties of Adenosine Amine Congener in Cochlear Perilymph after Systemic Administration.

Noise-induced hearing loss (NIHL) is a global health problem affecting over 5% of the population worldwide. We have shown previously that acute noise-induced cochlear injury can be ameliorated by administration of drugs acting on adenosine receptors in the inner ear, and a selective A1 adenosine receptor agonist adenosine amine congener (ADAC) has emerged as a potentially effective treatment for cochlear injury and resulting hearing loss. This study investigated pharmacokinetic properties of ADAC in rat perilymph after systemic (intravenous) administration using a newly developed liquid chromatography-tandem mass spectrometry detection method. The method was developed and validated in accordance with the USA FDA guidelines including accuracy, precision, specificity, and linearity. Perilymph was sampled from the apical turn of the cochlea to prevent contamination with the cerebrospinal fluid. ADAC was detected in cochlear perilymph within two minutes following intravenous administration and remained in perilymph above its minimal effective concentration for at least two hours. The pharmacokinetic pattern of ADAC was significantly altered by exposure to noise, suggesting transient changes in permeability of the blood-labyrinth barrier and/or cochlear blood flow. This study supports ADAC development as a potential clinical otological treatment for acute sensorineural hearing loss caused by exposure to traumatic noise.

Application of Curved MPR Algorithm to High Resolution 3 Dimensional T2 Weighted CISS Images for Virtual Uncoiling of Membranous Cochlea as an Aid for Cochlear Morphometry.

With the use of various surgical techniques, types of implants, the preoperative assessment of cochlear dimensions is becoming increasingly relevant prior to cochlear implantation. High resolution CISS protocol MRI gives a better assessment of membranous cochlea, cochlear nerve, and membranous labyrinth. Curved Multiplanar Reconstruction (MPR) algorithm provides better images that can be used for measuring dimensions of membranous cochlea. To ascertain the value of curved multiplanar reconstruction algorithm in high resolution 3-Dimensional T2 Weighted Gradient Echo Constructive Interference Steady State (3D T2W GRE CISS) imaging for accurate morphometry of membranous cochlea. Fourteen children underwent MRI for inner ear assessment. High resolution 3D T2W GRE CISS sequence was used to obtain images of cochlea. Curved MPR reconstruction algorithm was used to virtually uncoil the membranous cochlea on the volume images and cochlear measurements were done. Virtually uncoiled images of membranous cochlea of appropriate resolution were obtained from the volume data obtained from the high resolution 3D T2W GRE CISS images, after using curved MPR reconstruction algorithm mean membranous cochlear length in the children was 27.52 mm. Maximum apical turn diameter of membranous cochlea was 1.13 mm, mid turn diameter was 1.38 mm, basal turn diameter was 1.81 mm. Curved MPR reconstruction algorithm applied to CISS protocol images facilitates in getting appropriate quality images of membranous cochlea for accurate measurements.

Changes in the inner ear structures in cystic fibrosis patients

ObjectiveAlthough prolonged use of antibiotics is very common in cystic fibrosis (CF) patients, no studies have assessed the changes in both cochlear and peripheral vestibular systems in this population. MethodsWe used human temporal bones to analyze the density of vestibular dark, transitional, and hair cells in specimens from CF patients who were exposed to several types of antibiotics, as compared with specimens from an age-matched control group with no history of ear disease or antibiotic use. Additionally, we analyzed the changes in the elements of the cochlea (hair cells, spiral ganglion neurons, and the area of the stria vascularis). Data was gathered using differential interference contrast microscopy and light microscopy. ResultsIn the CF group, 83% of patients were exposed to some ototoxic drugs, such as aminoglycosides. As compared with the control group, the density of both type I and type II vestibular hair cells was significantly lower in all structures analyzed; the number of dark cells was significantly lower in the lateral and posterior semicircular canals. We noted a trend toward a lower number of both inner and outer cochlear hair cells at all turns of the cochlea. The number of spiral ganglion neurons in Rosenthal's canal at the apical turn of the cochlea was significantly lower; furthermore, the area of the stria vascularis at the apical turn of the cochlea was significantly smaller. ConclusionsDeterioration of cochlear and vestibular structures in CF patients might be related to their exposure to ototoxic antibiotics. Well-designed case-control studies are necessary to rule out the effect of CF itself.

Human cochlear hydrodynamics: A high-resolution μCT-based finite element study

Measurements of perilymph hydrodynamics in the human cochlea are scarce, being mostly limited to the fluid pressure at the basal or apical turn of the scalae vestibuli and tympani. Indeed, measurements of fluid pressure or volumetric flow rate have only been reported in animal models. In this study we imaged the human ear at 6.7 and 3-µm resolution using µCT scanning to produce highly accurate 3D models of the entire ear and particularly the cochlea scalae. We used a contrast agent to better distinguish soft from hard tissues, including the auditory canal, tympanic membrane, malleus, incus, stapes, ligaments, oval and round window, scalae vestibule and tympani. Using a Computational Fluid Dynamics (CFD) approach and this anatomically correct 3D model of the human cochlea, we examined the pressure and perilymph flow velocity as a function of location, time and frequency within the auditory range. Perimeter, surface, hydraulic diameter, Womersley and Reynolds numbers were computed every 45° of rotation around the central axis of the cochlear spiral. CFD results showed both spatial and temporal pressure gradients along the cochlea. Small Reynolds number and large Womersley values indicate that the perilymph fluid flow at auditory frequencies is laminar and its velocity profile is plug-like. The pressure was found 102–106° out of phase with the fluid flow velocity at the scalae vestibule and tympani, respectively. The average flow velocity was found in the sub-µm/s to nm/s range at 20–100Hz, and below the nm/s range at 1–20kHz.

Visualization of endolymphatic hydrops after intratympanic injection of Gd-DTPA: a comparison of high resolution three dimensional-real inversion recovery and three dimensional fluid-attenuated inversion recovery with a variable flip angle sequence

Objective To compare the value of high resolution 3D-real inversion recovery(3D-real IR) and 3D fluid-attenuated inversion recovery with a variable flip angle (3D-Flair-VFL) sequence in the visualization of endolymphatic hydrops. Methods 52 ears in 40 patients with Meniere's disease or delayed endolymphatic hydrops were enrolled and performed by axial 3D-real IR and 3D-Flair MRI scans 24 hours after intratympanic injection of eight-fold diluted Gd-DTPA. Signal to noise ratio (SNR) and contrast-to-noise ratio (CNR) of the two sequences were calculated and compared by t test. Whether there were endolymphatic hydrops in the basal turn, middle turn, apical turn of the cochlear and vestibule was further evaluated. Results Both the SNR and CNR of 3D-real IR images were statistically higher than 3D-Flair images (SNR: 28.06±12.71 vs. 17.64±6.38, P<0.05; CNR: 33.79±13.52 vs. 15.40±6.04, P<0.05). Endolymphatic hydrops of the basal turn, second turn, apical turn of the cochlear and vestibule detected by 3D-Flair-VFL images were 33, 37, 10 and 41 cases, respectively, while by 3D-Flair-VFL images were 46, 46, 46 and 49 cases, respectively. There were significant differences between the two sequences in evaluating basal turn, second turn, apical turn of the cochlear except vestibule (P<0.05). Conclusion 3D-real IR images are clearer than 3D-Flair-VFL images and can display endolymphatic hydrops more precisely. Key words: Magnetic resonance imaging; Ear, inner; Meniere disease

Morphofunctional alterations in the olivocochlear efferent system of the genetic audiogenic seizure-prone hamster GASH:Sal.

The genetic audiogenic seizure hamster (GASH:Sal) is a model of a form of reflex epilepsy that is manifested as generalized tonic-clonic seizures induced by external acoustic stimulation. The morphofunctional alterations in the auditory system of the GASH:Sal that may contribute to seizure susceptibility have not been thoroughly determined. In this study, we analyzed the olivocochlear efferent system of the GASH:Sal from the organ of Corti, including outer and inner hair cells, to the olivocochlear neurons, including shell, lateral, and medial olivocochlear (LOC and MOC) neurons that innervate the cochlear receptor. To achieve this, we carried out a multi-technical approach that combined auditory hearing screenings, scanning electron microscopy, morphometric analysis of labeled LOC and MOC neurons after unilateral Fluoro-Gold injections into the cochlea, and 3D reconstruction of the lateral superior olive (LSO). Our results showed that the GASH:Sal exhibited higher auditory brain response (ABR) thresholds than their controls, as well as absence of distortion-product of otoacoustic emissions (DPOAEs) in a wide range of frequencies. The ABR and DPOAE results also showed differences between the left and right ears, indicating asymmetrical hearing alterations in the GASH:Sal. These alterations in the peripheral auditory activity correlated with morphological alterations. At the cochlear level, the scanning electron microscopy analysis showed marked distortions of the stereocilia from basal to apical cochlear turns in the GASH:Sal, which were not observed in the control hamsters. At the brainstem level, MOC, LOC, and shell neurons had reduced soma areas compared with control animals. This LOC neuron shrinkage contributed to reduction in the LSO volume of the GASH:Sal as shown in the 3D reconstruction analysis. Our study demonstrated that the morphofunctional alterations of the olivocochlear efferent system are innate components of the GASH:Sal, which might contribute to their susceptibility to audiogenic seizures. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic".

Apical hair cell degeneration causes the increase in the amplitude of summating potential

Conclusion: This study indicates that the lesion of hair cells in the apical turn of the cochlea can cause the change in the summating potential (SP)/Compound potential (CAP) ratio.Objectives: Electrocochleography is a valuable clinic test for diagnosis of cochlear pathologies and the ratio of SP to CAP has been used to identify Meniere’s disease. However, it remains controversial whether the increase of the SP/CAP ratio represents exclusively the endolymphatic hydrops.Method: This study measured the SP and CAP in mice that displayed outer hair cell (OHC) degeneration in the apical section of the cochlea as their age increased.Results: As compared with the mice aged 8–10 months, the 24-month old mice displayed a significant increase in the amplitude of SP at 12–16 kHz. This result suggests that the degeneration of OHCs in the apical turn leads to the increase of the + SP at the middle frequencies. In contrast, the aging mice did not have a significant change in the CAP amplitude at super-threshold levels.

Measurement of Ototoxicity Following Intracochlear Bisphosphonate Delivery.

Assessing the maximum safe dose for local bisphosphonate delivery to the cochlea enables efficient delivery without ototoxicity. Otosclerosis is a disease of abnormal bone metabolism affecting the otic capsule, which can cause conductive hearing loss. Larger otosclerotic lesions involving the cochlear endosteum and spiral ligament can result in sensorineural hearing loss. Bisphosphonates are used to treat patients with metabolic bone diseases, including otosclerosis. Local delivery is the most efficient way of delivery to the cochlea while avoiding systemic side effects. To attain intracochlear bisphosphonate delivery without ototoxicity, the maximum safe dose of bisphosphonates requires definition. In the present study, we tested increasing concentrations of zoledronate, a third-generation bisphosphonate in an intracochlear delivery system. We measured ototoxicity by monitoring distortion product otoacoustic emissions and compound action potentials. Artificial perilymph and increasing molar concentrations of zoledronate were administered to the cochlea in guinea pigs via a cochleostomy. Hearing was measured at multiple time points. A fluorescently labeled zoledronate derivative (6-FAM-ZOL) was coadministered as an internal control for drug delivery. Specimens embedded in the resin blocks were ground to a mid-modiolar section and fluorescent photomicrographs were taken. No significant shift in hearing was observed in animals treated either with artificial perilymph or with 4% of the human systemic zoledronate dose. However, compound action potentials thresholds increased during infusion of 8% of the human systemic zoledronate dose, improved 4 hours later, and then increased again 4 weeks later. Using fluorescent photomicrography, intracochlear bisphosphonate delivery up to the apical cochlear turn was confirmed by visualizing 6-FAM-ZOL. These findings provide reference values for intracochlear bisphosphonate delivery in the treatment of cochlear otosclerosis and describe a useful method for tracking cochlear drug delivery.

A novel missense variant in PRKCB segregates low-frequency hearing loss in an autosomal dominant family with Meniere's disease.

Meniere's Disease (MD) is a complex disorder associated with an accumulation of endolymph in the membranous labyrinth in the inner ear. It is characterized by recurrent attacks of spontaneous vertigo associated with sensorineural hearing loss (SNHL) and tinnitus. The SNHL usually starts at low and medium frequencies with a variable progression to high frequencies. We identified a novel missense variant in the PRKCB gene in a Spanish family with MD segregating low-to-middle frequency SNHL. Confocal imaging showed strong PKCB II protein labelling in non-sensory cells, the tectal cells and inner border cells of the rat organ of Corti with a tonotopic expression gradient. The PKCB II signal was more pronounced in the apical turn of the cochlea when compared with the middle and basal turns. It was also much higher in cochlear tissue than in vestibular tissue. Taken together, our findings identify PRKCB gene as a novel candidate gene for familial MD and its expression gradient in supporting cells of the organ of Corti deserves attention, given the role of supporting cells in K+ recycling within the endolymph, and its apical turn location may explain the onset of hearing loss at low frequencies in MD.

Establishment of a mathematical model for calculating cochlear length

To compare the cochlear length of the miniature pig calculated by 3-dimensional reconstruction technique and an Archimedean spiral model, and to evaluate the feasibility of determining the length of the cochlea using a mathematical model. The temporal bones of three miniature pigs with normal hearing were selected and scanned by micro-CT. The pictures were input into Mimics software, the 3D structure of the inner ear was reconstructed, and the following parameters were determined through Mimics: cochlear length, diameter of each turn, cochlear height, and apical turn angle. The cochlear length was calculated using the Archimedean spiral model. The length of the cochlea was (35.30±0.88)mm based on the three-dimensional reconstruction technique compared to (34.85±0.64)mm based on the Archimedean spiral model. The differences between the two values were not statistically significant. The height of the cochlea is (2.64±0.24)mm. The capsule of the cochlea had 3.67 turns. The three-dimensional reconstruction technique provides accurate and reliable results, but the reconstruction process is time-consuming and is unsuitable for clinical application. The Archimedean spiral model method is simple, feasible, reliable, and therefore suitable for clinical applications, in particular to provide references for cochlear implantation surgeries.

Characterization of Lgr5+ progenitor cell transcriptomes in the apical and basal turns of the mouse cochlea.

Lgr5+ supporting cells (SCs) are enriched hair cell (HC) progenitors in the cochlea, and several studies have shown a difference in the proliferation and HC regeneration ability of SCs between the apical and basal turns. However, the detailed differences between the transcriptomes of the apical and basal Lgr5+ SCs have not yet been investigated. We found that when isolated by FACS, Lgr5+ cells from the apex generated significantly more HCs and had significantly higher proliferation and mitotic HC regeneration ability compared to those from the base. Next, we used microarray analysis to determine the transcriptome expression profiles of Lgr5+ progenitors from the apex and the base. We first analyzed the genes that were enriched and differentially expressed in Lgr5+ progenitors from the apex and the base. Then we analyzed the cell cycle genes and the transcription factors that might regulate the proliferation and differentiation of Lgr5+ progenitors. Lastly, to further analyze the role of differentially expressed genes and to gain an overall view of the gene network in cochlear HC regeneration, we created a protein-protein interaction network. Our datasets suggest the possible genes that might regulate the proliferation and HC regeneration ability of Lgr5+ progenitors, and these genes might provide new therapeutic targets for HC regeneration in the future.

Minimally Invasive Surgery for Intracochlear Schwannoma Removal and Simultaneous Cochlear Implantation.

Introduction Hearing preservation has not yet been reported in patients undergoing resection of intracochlear schwannomas. This study describes a minimally invasive procedure for intracochlear schwannoma resection with simultaneous cochlear implantation that resulted in good hearing.Objective This study aims to describe a minimally invasive procedure for intracochlear schwannoma resection with simultaneous cochlear implantation.Data Synthesis The technique described in this study was developed for a 55-year-old male with a 20-year history of bilateral progressive hearing loss and tinnitus that had a mass in the left apical turn of the cochlea measuring 0.3 cm. Surgery accessed the apical turn of the cochlea. We performed mastoidectomy and posterior tympanotomy and removed incus and tensor tympani muscle to expose the cochlear apex. The tumor was identified and completely resected. After the cochlea was anatomically preserved, it was implanted with a straight electrode via round window insertion. The histopathological examination confirmed intracochlear schwannoma. Speech perception test revealed 100% speech recognition with closed sentences and the average audiometric threshold (500 to 2000 Hz) was 23 dB.Conclusion Our technique led to rehabilitation of the patient and improved hearing without damaging the intracochlear structure, making it possible to perform CI in the same procedure with good results.

Intracochlear Drug Delivery Through the Oval Window in Fresh Cadaveric Human Temporal Bones.

Drug delivered to the oval window can diffuse to the apex of the human cochlea. We have previously demonstrated that zoledronate, a nitrogen-containing bisphosphonate, can arrest the sensorineural hearing loss in cochlear otosclerosis. We have also shown that, in animals, delivery of bisphosphonate into the cochlea can dramatically increase delivery efficiency. Intracochlear drug delivery has the potential to increase local concentration of drug while decreasing the risk of systemic toxicity. In the present study, a fluorescently labeled bisphosphonate compound (6-FAM-ZOL) was introduced into the human cochlea through the oval window and its distribution within the temporal bone was quantified. In three fresh human temporal bones, we introduced 6-FAM-ZOL via the oval window. We compared these specimens to control specimens treated with artificial perilymph alone. Specimens were then processed, embedded into methyl methacrylate, and ground to the mid-modiolar axis. We quantified the fluorescence in confocal images. We found 6-FAM-ZOL to be distributed up to the apical cochlear turn. In specimens treated with 6-FAM-ZOL, we identified a strong baso-apical gradient of fluorescent signal along the lateral cochlear wall and the modiolus both in the scala vestibuli and in the scala tympani. Bisphosphonate introduced via the oval window in the human cochlea can be delivered up to the apical cochlear turn. Interscalar communication is likely to play an important role in determining patterns of drug delivery in the inner ear.