Cochlear Pathology in Presbycusis

Schuknecht, Harold F.; Gacek, Mark R.

doi:10.1177/00034894931020s101

Cited by 704 publications

(609 citation statements)

References 45 publications

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“…Histopathological evidence exists, from cadaveric evaluation of temporal bones of human patients with presbycusis, that age-related hearing loss can be described by four types of cochlear histopathology: (1) sensory presbycusis involving hair cell loss, (2) neural presbycusis involving loss of spiral ganglion cells and axons, (3) mechanical or conductive presbycusis thought to be conferred by stiffening of the basilar membrane, and (4) metabolic or strial presbycusis, whereby atrophy of the StV is thought to confer hearing loss (Schuknecht and Gacek 1993). Clinically, however, presbycusis is rarely found to present as one specific audiometric pattern correlating to one specific histopathologic process, but it is commonly considered to be an amalgamation of patterns-and hence, a combination of several processes (Shih 1994).…”

Section: Discussionmentioning

confidence: 99%

Conservation of Hearing by Simultaneous Mutation of Na,K-ATPase and NKCC1

Diaz

Vázquez

Dou

et al. 2007

JARO

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Although drug-induced and age-related hearing losses are frequent otologic problems affecting millions of people, their underlying mechanisms remain uncertain. The inner ear is exclusively endowed with a positive endocochlear potential (EP) that serves as the main driving force for the generation of receptor potential in hair cells to confer hearing. Deterioration of EP leads to hearing loss or deafness. The generation of EP relies on the activity of many ion transporters to establish active potassium (K + ) cycling within the inner ear, including K + channels, the Na-K-2Cl co-transporter (NKCC1), and the a 1 and a 2 isoforms of Na,K-ATPase. We show that heterozygous deletion of either NKCC1, a 1 -Na,K-ATPase, or a 2 -Na,K-ATPase independently results in progressive, age-dependent hearing loss with minimal alteration in cochlear morphology. Double heterozygote deletion of NKCC1 with a 1 -Na,K-ATPase also shows a progressive, though delayed, age-dependent hearing loss. Remarkably, double heterozygote deletion of NKCC1 with a 2 -Na,K-ATPase demonstrates a striking preservation of hearing threshold both initially and with age. Measurements of the EP confirm the anticipated drop in potential for genotypes that demonstrate age-dependent hearing loss. The EP generated by the NKCC1 + a 2 -Na,K-ATPase double heterozygote, however, is maintained at a level comparable to that of the control condition, suggesting a potential advantage in this combination of ion transporter modification. These observations provide insight into the detailed mechanisms of EP generation, and results of combination-knockout experiments may have important implications in the future treatment of drug-induced and age-related hearing losses.

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Section: Discussionmentioning

confidence: 99%

Conservation of Hearing by Simultaneous Mutation of Na,K-ATPase and NKCC1

Diaz

Vázquez

Dou

et al. 2007

JARO

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“…Two more categories have subsequently been added: mixed and indeterminate. The latter has been reported to account for 25% of cases [20] and in most cases, a mixture of pathological changes have been noted [21]. Although there is a general consensus that the cochlea is the site of ARHL, otopathologic changes to the inner ear as a direct function of age remain controversial.…”

Section: Pathophysiology Associated With Presbycusismentioning

confidence: 99%

“…Metabolic presbycusis was characterized clinically as showing a flat audiometric pattern [20]. An alteration of endolymph may explain the elevated pure tone thresholds across all frequencies of the auditory spectrum.…”

Section: Ageing and Hearing Loss 191mentioning

confidence: 99%

Ageing and hearing loss

Yan

2007

The Journal of Pathology

278

178

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Although many adults retain good hearing as they age, hearing loss associated with ageing is common among elderly persons. There are a number of pathophysiolological processes underlying age-related changes to functional components in the inner ear. Genetic factors determine the ageing process but are under the influence of intrinsic and environmental factors. It is difficult to distinguish changes of normal ageing from those of other contributing factors. The effects of age-related deafness can have significant physical, functional and mental health consequences. Although a deficit in hearing can be corrected to some degree by a hearing aid or other appropriate amplification devices, hearing-related rehabilitative needs are much more than simply amplifying external sound. Only by better understanding the process of ageing and its effect on the auditory function can we better accommodate elderly people in our day-to-day interactions. We review here the structure and function of the inner ear, pathophysiology associated with age-related hearing loss (ARHL), heritability, allelism and modifier genes of ARHL, and evaluate the genetic analyses for identification of genetic factors that are involved.

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“…Consistent with this is our observation of rough equivalence between the anatomical correlates of noise exposure and aging and recent reports that Ahl impacts the hearing phenotype associated with at least three other loci Zheng and Johnson 2001;Kozel et al 2002). Schuknecht also noted the similarity and possibility of overlap between the histopathology of noise injury and sensory ARHL (Schuknecht 1974;Schuknecht and Gacek 1993), so that some ARHL categories, or subsets of these, may represent cumulative injury. All published reports to date implicate Ahl in pathology of some combination of organ of Corti, spiral ganglion, spiral ligament, stria vascularis, and spiral limbus.…”

Section: Mouse Ahl As a Model For Human Arhlmentioning

confidence: 99%

“…Its causes remain poorly understood because of the dif®culty of separating genetic and environmental contributors (Schuknecht 1974;Willott 1991;Li 1992b). Schuknecht (1974;Schuknecht and Gacek 1993) proposed categories for human ARHL, de®ned according to the degeneration that best accounted for the observed hearing performance. In the majority of cases ( 60%), overall hearing ability appeared best explained by degeneration of organ of Corti (sensory ARHL), spiral ganglion cells (neural), stria vascularis (strial), or a combination of these (mixed).…”

Section: Introductionmentioning

confidence: 99%

Reduction in Sharpness of Frequency Tuning but not Endocochlear Potential in Aging and Noise-Exposed BALB/cJ Mice

Ohlemiller

2002

JARO - Journal of the Association for Research in Otolaryngolog

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Schuknecht proposed categories for human age-related hearing loss (ARHL) based upon whether the primary degeneration involves the organ of Corti (sensory ARHL), spiral ganglion cells (neural), stria vascularis (strial), or a combination of these (mixed). Genetically standardized mouse ARHL models can help validate Schuknecht's framework and clarify the underlying cellular processes. Much recent work has focused on the mouse Ahl locus, which promotes both ARHL and noise-induced hearing loss. On the C57BL/6 inbred background, Ahl has been associated with degeneration of organ of Corti, afferent neurons, and stria vascularis/spiral ligament, suggesting that it promotes mixed (sensory/neural/strial) ARHL. Some cochlear degeneration in C57BL/6 mice could be caused by genes other than Ahl, however. The question of what constitutes Ahl-related pathology can be addressed by comparing C57BL/6 mice with other strains that carry the same allele, including BALB/c substrains. We examined the effects of aging and broadband noise exposure in inbred BALB/cJ mice (1.5±13.0 mos) using measures of frequency tuning (compound action potential tuning curves) (CAPTCs), strial function (endocochlear potential recording, EP), and light microscopy. Aging and noise led to generally similar physiological and anatomical changes. Reductions in sensitivity and sharpness of frequency tuning were not consistently linked to hair cell loss, reduction in the EP, or changes in the lateral wall. Instead they appeared best explained by alterations in supporting cells in the basal half of the cochlear and in the spiral limbus in the apex. These results emphasize the importance of cell types other than hair cells in cochlear pathology. They also indicate that Ahl does not necessarily promote a strial form of ARHL.

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Cochlear Pathology in Presbycusis

Cited by 704 publications

References 45 publications

Conservation of Hearing by Simultaneous Mutation of Na,K-ATPase and NKCC1

Conservation of Hearing by Simultaneous Mutation of Na,K-ATPase and NKCC1

Ageing and hearing loss

Reduction in Sharpness of Frequency Tuning but not Endocochlear Potential in Aging and Noise-Exposed BALB/cJ Mice

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