Morphometric Measurements of the Incomplete Partition Type II (IP-II) Cochlea and Implications on Cochlear Implantation.

Hypothesis: The objective of this study is to obtain comprehensive morphometric measurements of the incomplete partition type II (IP-II) cochlea to provide a better understanding of intracochlear anatomy and important considerations for electrode selection and insertion.

Background: IP-II is the most common bony inner ear malformation that often requires cochlear implantation. Currently, there is significant controversy on electrode selection due to a lack of research that can provide reliable, high-resolution measurements.

Expression of TGFβ-1 and CTGF in the Implanted Cochlea and its Implication on New Tissue Formation.

Hypothesis: Transforming growth factor beta-1 (TGFβ-1) and connective tissue growth factor (CTGF) are upregulated in the implanted human cochlea.

Background: Cochlear implantation can lead to insertion trauma and intracochlear new tissue formation, which can detrimentally affect implant performance. TGFβ-1 and CTGF are profibrotic proteins implicated in various pathologic conditions, but little is known about their role in the cochlea.

Single-cell transcriptomic atlas reveals increased regeneration in diseased human inner ear balance organs.

Mammalian inner ear hair cell loss leads to permanent hearing and balance dysfunction. In contrast to the cochlea, vestibular hair cells of the murine utricle have some regenerative capacity. Whether human utricular hair cells regenerate in vivo remains unknown.

Expression of Brain-Derived Neurotrophic Factor in Human Spiral Ganglia Neurons after Cochlear Implantation.

Background: Brain-derived neurotrophic factor (BDNF) is an important factor in the development and neuroprotection of afferent auditory pathways. In this study, we investigated the expression of BDNF in the afferent auditory pathway after cochlear implantation (CI), hypothesizing that electrical stimulation after CI stimulates BDNF expression in the afferent auditory pathway.

Methods: Archival human temporal bones from eight patients with a history of CI and five patients with normal hearing (ages 65-93 years old) were studied.

Dynamic Molecular Markers of Otosclerosis in the Human Cochlea.

Objective: To investigate the role and distribution of various molecular markers using immunohistochemistry and immunofluorescence to further elucidate and understand the pathogenesis of otosclerosis.

Methods: Archival celloidin formalin-fixed 20-micron thick histologic sections from 7 patients diagnosed with otosclerosis were studied and compared to controls. Sections in the mid-modiolar region were immunoreacted with rabbit polyclonal antibodies against nidogen-1, β2-laminin, collagen-IX, BSP, and monoclonal antibodies against TGF β-1 and ubiquitin.

Temporal bone histopathology in revision cochlear implantation.

An increasing number of young infants, as early as six months of age with congenital hearing loss receive cochlear implantation, and it is probable that many of these patients will require revision surgery later in life. The possibility of explantation of the cochlear electrode and reimplantation may cause damage to the cochlea, compromising the speech perception outcome in revision implant is of concern. There is only one prior temporal bone histopathology study to look at the outcome of revision surgery and no prior study evaluating revision cochlear implantation that used the round window approach.

Xenopus Ssbp2 is required for embryonic pronephros morphogenesis and terminal differentiation.

The nephron, functional unit of the vertebrate kidney, is specialized in metabolic wastes excretion and body fluids osmoregulation. Given the high evolutionary conservation of gene expression and segmentation patterning between mammalian and amphibian nephrons, the Xenopus laevis pronephric kidney offers a simplified model for studying nephrogenesis. The Lhx1 transcription factor plays several roles during embryogenesis, regulating target genes expression by forming multiprotein complexes with LIM binding protein 1 (Ldb1).

Emerging Mechanisms in the Pathogenesis of Menière's Disease: Evidence for the Involvement of Ion Homeostatic or Blood-Labyrinthine Barrier Dysfunction in Human Temporal Bones.

Hypothesis: Analysis of human temporal bone specimens of patients with Menière's disease (MD) may demonstrate altered expression of gene products related to barrier formation and ionic homeostasis within cochlear structures compared with control specimens.

Background: MD represents a challenging otologic disorder for investigation. Despite attempts to define the pathogenesis of MD, there remain many gaps in our understanding, including differences in protein expression within the inner ear.

Ssbp2 is required for embryonic pronephros morphogenesis and terminal differentiation.

The nephron, functional unit of the vertebrate kidney, is specialized in metabolic wastes excretion and body fluids osmoregulation. Given the high evolutionary conservation of gene expression and segmentation patterning between mammalian and amphibian nephrons, the pronephric kidney offers a simplified model for studying nephrogenesis. The Lhx1 transcription factor plays several roles during embryogenesis, regulating target genes expression by forming multiprotein complexes with LIM binding protein 1 (Ldb1).

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

Objective: 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.

Study Design: Histopathologic analysis of cadaveric temporal bones.

Setting: Multi-institutional national temporal bone repository.

Morphometric Analysis and Linear Measurements of the Scala Tympani and Implications in Cochlear Implant Electrodes.

Hypothesis: The objective of this study was to perform detailed height and cross-sectional area measurements of the scala tympani in histologic sections of nondiseased human temporal bones and correlate them with cochlear implant electrode dimensions.

Background: Previous investigations in scala tympani dimensions have used microcomputed tomography or casting modalities, which cannot be correlated directly with microanatomy visible on histologic specimens.

Methods: Three-dimensional reconstructions of 10 archival human temporal bone specimens with no history of middle or inner ear disease were generated using hematoxylin and eosin histopathologic slides.

Immunohistochemical localization of glucocorticoid receptors in the human cochlea.

In the present study we investigated the localization of glucocorticoid receptors (GCR) in the human inner ear using immunohistochemistry. Celloidin-embedded cochlear sections of patients with normal hearing (n = 5), patients diagnosed with MD (n = 5), and noise induced hearing loss (n = 5) were immunostained using GCR rabbit affinity-purified polyclonal antibodies and secondary fluorescent or HRP labeled antibodies. Digital fluorescent images were acquired using a light sheet laser confocal microscope.

Archival Human Temporal Bone: Anatomical and Histopathological Studies of Cochlear Implantation.

Since being FDA approved in 1984, cochlear implantation has been used successfully to restore hearing in those with severe to profound hearing loss with broader applications including single-sided deafness, the use of hybrid electroacoustic stimulation, and implantation at all extremes of age. Cochlear implants have undergone multiple changes in the design aimed at improving the processing technology, while simultaneously minimizing the surgical trauma and foreign body reaction. The following review examines the human temporal bone studies regarding the anatomy of the human cochlea and how the anatomy relates to cochlear implant design, the factors related to complications after implantation, and the predictors of new tissue formation and osteoneogenesis.

Differential Expression of Na/K-ATPase in the Human Saccule of Patients With and Without Otologic Disease.

Hypothesis: Na + , K + -ATPase (Na/K-ATPase) α1 subunit expression in the saccule of patients diagnosed with otologic disease is different compared with normal controls.

Background: We have recently characterized changes in the expression of Na/K-ATPase α1 subunit in the normal and pathological cochlea; however, no studies have determined the distribution Na/K-ATPase α1 subunit in the human saccule. The present study uses archival temporal bones to study the expression Na/K-ATPase α1 subunit in the human saccule.

Endolymphatic Hydrops in the Setting of Vestibular Schwannoma: A Temporal Bone Study.

Hypothesis: Vestibular schwannoma (VS) may be associated with endolymphatic hydrops (EH). EH may account for symptomatology in a subset of patients with VS.

Background: Presenting symptoms of VS and EH overlap, and MRI evaluation of the membranous labyrinth in some patients with VS demonstrates EH.

Histopathologic Analysis of Temporal Bones With Otosclerosis Following Cochlear Implantation.

Objective: Analyze changes in osteoneogenesis and fibrosis following cochlear implant (CI) surgery in patients with otosclerosis and compare differences based on insertion technique.

Background: When advanced otosclerotic disease extends to the otic capsule, severe and profound sensorineural hearing loss necessitates consideration of a cochlear implant. Histopathological analysis of the human temporal bone after implantation in the patient with otosclerosis may reveal important variables that predict CI success.

Cisplatin ototoxicity histopathology.

This study investigates the histopathological changes of the cochlea and vestibular end organs of a patient who received cisplatin for Hodgkin's lymphoma. He experienced acute high-frequency sensorineural hearing loss and tinnitus after receiving treatment. Using histopathological analysis of his temporal bones after he unfortunately succumbed to his disease, we found that the ototoxic effect of cisplatin is primarily within the cochlea, with significant damage located at the organ of Corti at the base-hook region, consistent with findings in animal models.

Corrigendum: Characterizing Adult Cochlear Supporting Cell Transcriptional Diversity Using Single-Cell RNA-Seq: Validation in the Adult Mouse and Translational Implications for the Adult Human Cochlea.

[This corrects the article DOI: 10.3389/fnmol.2020.

Identification of a genetic variant underlying familial cases of recurrent benign paroxysmal positional vertigo.

Benign paroxysmal positional vertigo (BPPV) is the most common cause of vertigo in humans, yet the molecular etiology is currently unknown. Evidence suggests that genetic factors may play an important role in some cases of idiopathic BPPV, particularly in familial cases, but the responsible genetic variants have not been identified. In this study, we performed whole exome sequencing [including untranslated regions (UTRs)] of 12 families and Sanger sequencing of additional 30 families with recurrent BPPV in Caucasians from the United States (US) Midwest region, to identify the genetic variants responsible for heightened susceptibility to BPPV.

Predictors of Fibrotic and Bone Tissue Formation With 3-D Reconstructions of Post-implantation Human Temporal Bones.

Hypothesis: Years of implantation, surgical insertion approach, and electrode length will impact the volume of new tissue formation secondary to cochlear implantation.

Background: New tissue formation, fibrosis, and osteoneogenesis after cochlear implantation have been implicated in increasing impedance and affecting performance of the cochlear implant.

Methods: 3-D reconstructions of 15 archival human temporal bones from patients with a history of cochlear implantation (CI) were generated from H&E histopathologic slides to study factors which affect volume of tissue formation.

Immunohistochemical location of Na, K-ATPase α1 subunit in the human inner ear.

Na, K-ATPase (Na,K-ATPase) is an ubiquitous enzyme in the inner ear and a key factor in the maintenance of the osmotic gradient of the endolymph. This study uses Na,K-ATPase α1 subunit immunoreactivity (IR) to identify cellular structures in the normal and disease human cochlea. Formalin-fixed celloidin-embedded (FFCE) human temporal bone sections were immunoreacted with mouse monoclonal antibodies against Na,K-ATPase α1 subunit.

Mouse Models of Human Pathogenic Variants of Associated with Non-Syndromic Deafness DFNB86 and DFNA65 and Syndromes Involving Deafness.

Human pathogenic variants of are associated with clinically heterogeneous phenotypes, including recessive nonsyndromic deafness DFNB86, dominant nonsyndromic deafness DFNA65, seizure accompanied by deafness, a variety of isolated seizure phenotypes and DOORS syndrome, characterized by deafness, onychodystrophy, osteodystrophy, intellectual disability and seizures. Thirty-five pathogenic variants of human associated with deafness have been reported. However, functions of TBC1D24 in the inner ear and the pathophysiology of TBC1D24-related deafness are unknown.

Immune Response of Macrophage Population to Cochlear Implantation: Cochlea Immune Cells.

Hypothesis: The presence and distribution of ionized calcium binding adaptor 1 and CD68 macrophages in the human cochlea is altered in cochlear implantation (CI) compared with the normative or nonimplanted cochlea.

Background: It has been hypothesized that CI induces an immunological response in macrophages leading to implant failure or reduced hearing. Macrophages are resident immune cells in human cochlea and have been shown to phagocytize implant material.