Erik G. Nelson

Presbycusis: a human temporal bone study of individuals with downward sloping audiometric patterns of hearing loss and review of the literature.

Objective: The purpose of this retrospective case review was to identify patterns of cochlear element degeneration in individuals with presbycusis exhibiting downward sloping audiometric patterns of hearing loss and to correlate these findings with those reported in the literature to clarify conflicting concepts regarding the association between hearing loss and morphologic abnormalities.

Quantification of the mitochondrial DNA common deletion in presbycusis

This study was conducted to evaluate the association between the mitochondrial DNA (mtDNA) common deletion (CD) level in cochlear tissue and the severity of hearing loss in individuals with presbycusis.

Presbycusis: A human temporal bone study of individuals with flat audiometric patterns of hearing loss using a new method to quantify stria vascularis volume

Objective: The purpose of this study was to determine the prevalence of stria vascularis atrophy in individuals with presbycusis and flat audiometric patterns of hearing loss. Individuals with presbycusis have historically been categorized by the shape of their audiograms, and flat audiometric thresholds have been reported to be associated with atrophy of the stria vascularis. Stria vascularis volume was not measured in these studies. Study Design: Retrospective case review. Methods: Archival human temporal bones from individuals with presbycusis were selected on the basis of strict audiometric criteria for flat audiometric thresholds. Six temporal bones that met these criteria were identified and compared with 10 temporal bones in individuals with normal hearing. A unique quantitative method was developed to measure the stria vascularis volume in these temporal bones. The hair cell and spiral ganglion cell populations also were quantitatively evaluated. Results: Only one of the six individuals with presbycusis and flat audiometric thresholds had significant atrophy of the stria vascularis. This individual with stria vascularis atrophy also had reduced inner hair cell, outer hair cell, and ganglion cell populations. Three of the individuals with presbycusis had spiral ganglion cell loss, three individuals had inner hair cell loss, and all six individuals had outer hair cell loss. Conclusions: The results of this investigation suggest that individuals with presbycusis and flat audiometric patterns of hearing loss infrequently have stria vascularis atrophy. Outer hair cell loss alone or in combination with inner hair cell or ganglion cell loss may be the cause of flat audiometric thresholds in individuals with presbycusis.

Aplasia of the cochlear nerve: a temporal bone study.

Objective The purpose of this study was to evaluate the temporal bone findings in individuals with cochlear nerve aplasia. Study Design Retrospective case review. Methods Two individuals with unilateral profound deafness caused by aplasia of the cochlear nerve were identified. The temporal bones were processed, and the cochlear elements were quantified. Results Histopathologic study of the temporal bones from these individuals demonstrate that a fully formed cochlea and normal-appearing organ of Corti can occur in the absence of the spiral ganglion and cochlear nerve. Cochlear nerve aplasia can occur in both a narrow or a normal-sized internal auditory canal. Conclusion These findings suggest that the development of the cochlea and organ of Corti are not dependent on the presence of the cochlear nerve and spiral ganglion. The entity of cochlear nerve aplasia in the presence of a normally formed cochlea must be considered when evaluating individuals as candidates for cochlear implantation.

Questioning the Relationship between Cochlear Otosclerosis and Sensorineural Hearing Loss: A Quantitative Evaluation of Cochlear Structures in Cases of Otosclerosis and Review of the Literature

Background: The literature provides conflicting information regarding the prevalence and cause of sensorineural hearing loss (HL) in individuals with otosclerosis.

Aminoglycoside ototoxicity: a human temporal bone study.

Objective Hearing loss after aminoglycoside administration has been thought to result primarily from hair cell injury. The purpose of the study was to determine the potential for direct injury of spiral ganglion cells and hair cells in cases of documented human aminoglycoside ototoxicity.

Major arc mitochondrial DNA deletions in cytochrome c oxidase-deficient human cochlear spiral ganglion cells

Abstract Conclusions: This study suggests that cytochrome c oxidase subunit 3 (COX 3) expression is diminished in spiral ganglion cells from individuals with presbycusis. In addition to the mitochondrial DNA (mtDNA) common deletion (CD), other deletions involving the mtDNA major arc contribute to the observed deficit in COX 3 expression. Objectives: To assess COX 3 deficiency in spiral ganglion cells from individuals with presbycusis and to determine whether deletions other than the CD contribute to this deficiency. Methods: COX 3 immunofluorescence staining of archival human temporal bone tissue sections from individuals with presbycusis and from age-matched normal-hearing individuals was performed and the intensity of spiral ganglion cell immunostaining was measured. Single COX 3-deficient spiral ganglion cells were isolated by laser microdissection (LMD) and the DNA was analyzed with duplex real-time PCR assays to assess the CD level and the total mtDNA major arc deletion level. Results: A statistically significant difference (p = 0.021) in the mean intensity of COX 3 immunofluorescence staining of spiral ganglion cells was observed between individuals with presbycusis and normal-hearing controls. The total mtDNA major arc deletion level was greater than the CD level in COX 3-deficient spiral ganglion cells.

Technical report : Immunofluorescence and TUNEL staining of celloidin embedded human temporal bone tissues

The large archival human temporal bone collections of the world have been fixed in formalin and embedded in celloidin. These treatments have created challenges to the use of contemporary probes, which are routinely used in the evaluation of fresh and frozen tissues, for the analysis of archival temporal bone tissues. Formalin alters the configuration of proteins and can obscure antigens by modifying the epitopes recognized by antibodies. Celloidin embedding provides superior support of the delicate membranous structures of the inner ear to maintain tissue integrity during sectioning, however, inadequate removal of celloidin may limit tissue permeability resulting in poor penetration of large molecules. Methods are described in this manuscript that have allowed reproducible immunofluorescence and TUNEL (terminal deoxynucleotidyl transferase mediated dUTP nick end labeling) staining results in these archival tissues. To our knowledge, successful immunofluorescence staining of type I collagen, immunofluorescence staining of cytochrome c oxidase subunit III (COX III), and TUNEL staining in archival human temporal bone tissues with confocal microscopy has not been previously reported. These results demonstrate the utility of developing techniques to evaluate the existing collections of archival temporal bones which remain our greatest source of tissue for investigating the causes of ear diseases.

Cochlear nucleus neuron analysis in individuals with presbycusis

The aim of this study was to analyze the cochlear nucleus neuron population in individuals with normal hearing and presbycusis.

Technical report: laser microdissection of cochlear structures from celloidin embedded human temporal bone tissues and detection of the mitochondrial DNA common deletion using real time PCR.

Laser microdissection (LMD) has been used to isolate groups of cells and single cells from numerous tissues. In this study, we describe a technique for isolating cochlear structures and individual spiral ganglion cells from archival celloidin embedded human temporal bone sections. The specimens isolated are suitable for quantifying the mitochondrial DNA (mtDNA) common deletion (CD) within these tissues using a real time polymerase chain reaction (PCR) assay. The results presented in this manuscript demonstrate the feasibility of using this LMD technique to study the accumulation of mtDNA deletions in diseases of the ear. To our knowledge, this approach to analyzing archival human temporal bone tissues has not been previously reported.