Stereological estimation of total cell numbers in the young human utricular macula

Severinsen, Stig Åvall; Sørensen, Mads Sølvsten; Kirkegaard, Mette; Nyengaard, Jens Randel

doi:10.3109/00016480903397694

Cited by 5 publications

(5 citation statements)

References 17 publications

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“…Similar to other outward conductances described above, initially, G K,L is small and likely to increase in amplitude during development as has been observed in developing mouse vestibular hair cells (Geleoc et al 2004). Our results also suggest that this physiological differentiation, as determined by the expression of G K,L , precedes morphological differentiation, as a recent study could not unambiguously distinguish type I and type II hair cells at 16 WG (Severinsen et al 2010). …”

Section: Discussionsupporting

confidence: 63%

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Preliminary Characterization of Voltage-Activated Whole-Cell Currents in Developing Human Vestibular Hair Cells and Calyx Afferent Terminals

Lim

Drury

Camp

et al. 2014

JARO

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We present preliminary functional data from human vestibular hair cells and primary afferent calyx terminals during fetal development. Whole-cell recordings were obtained from hair cells or calyx terminals in semi-intact cristae prepared from human fetuses aged between 11 and 18 weeks gestation (WG). During early fetal development (11–14 WG), hair cells expressed whole-cell conductances that were qualitatively similar but quantitatively smaller than those observed previously in mature rodent type II hair cells. As development progressed (15–18 WG), peak outward conductances increased in putative type II hair cells but did not reach amplitudes observed in adult human hair cells. Type I hair cells express a specific low-voltage activating conductance, GK,L. A similar current was first observed at 15 WG but remained relatively small, even at 18 WG. The presence of a “collapsing” tail current indicates a maturing type I hair cell phenotype and suggests the presence of a surrounding calyx afferent terminal. We were also able to record from calyx afferent terminals in 15–18 WG cristae. In voltage clamp, these terminals exhibited fast inactivating inward as well as slower outward conductances, and in current clamp, discharged a single action potential during depolarizing steps. Together, these data suggest the major functional characteristics of type I and type II hair cells and calyx terminals are present by 18 WG. Our study also describes a new preparation for the functional investigation of key events that occur during maturation of human vestibular organs.

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Section: Discussionsupporting

confidence: 63%

“…A recent study estimated there were 36,000 hair cells in both fetal (16 WG) and adult human utricle (Severinsen et al 2010). This is almost an order of magnitude greater (36,000 versus.…”

Section: Discussionmentioning

confidence: 99%

Preliminary Characterization of Voltage-Activated Whole-Cell Currents in Developing Human Vestibular Hair Cells and Calyx Afferent Terminals

Lim

Drury

Camp

et al. 2014

JARO

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“…During embryonic and postnatal development, hair cells in any particular region display various states of morphological and electrophysiological maturation, suggesting that maturation might not be regionally synchronized [26, 30, 64]. It should be noted that hair cell formation appears to be restricted to embryogenesis in humans [65], in contrast to rats and mice.…”

Section: Developmentmentioning

confidence: 99%

Development and regeneration of vestibular hair cells in mammals

Burns

Stone

2017

Seminars in Cell & Developmental Biology

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Vestibular sensation is essential for gaze stabilization, balance, and perception of gravity. The vestibular receptors in mammals, Type I and Type II hair cells, are located in five small organs in the inner ear. Damage to hair cells and their innervating neurons can cause crippling symptoms such as vertigo, visual field oscillation, and imbalance. In adult rodents, some Type II hair cells are regenerated and become re-innervated after damage, presenting opportunities for restoring vestibular function after hair cell damage. This article reviews features of vestibular sensory cells in mammals, including their basic properties, how they develop, and how they are replaced after damage. We discuss molecules that control vestibular hair cell regeneration and highlight areas in which our understanding of development and regeneration needs to be deepened.

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“…While less rigorous than the dissector stereological technique (Sterio 1984), its accuracy has been validated in multiple studies of archived human temporal bones that underwent sectioning and processing using techniques similar to those employed in this study (Merchant 1999;Richter 1980;Rauch et al 2001), and yielded results similar to more labor-intensive stereological methods (Lopez et al 2005). Moreover, although optical (Severinsen et al 2010) and physical dissector techniques (Lysakowski and Goldberg 2008) have been employed with success in other studies, pilot studies in our specimens indicated that the slice thickness we employed (10 μm) was too thin for optical sectioning and too thick for physical dissector techniques, relative to the average size of an HC (5 μm). The typical nucleus size was measured in each section and found to be comparable across all tissues examined, minimizing the effect of varying nucleus size on cell estimates.…”

Section: Effects Of Hair Cell Counting Techniquementioning

confidence: 70%

Histopathologic Changes of the Inner ear in Rhesus Monkeys After Intratympanic Gentamicin Injection and Vestibular Prosthesis Electrode Array Implantation

Sun

Lehar

Dai

et al. 2015

JARO

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Bilateral vestibular deficiency (BVD) due to gentamicin ototoxicity can significantly impact quality of life and result in large socioeconomic burdens. Restoring sensation of head rotation using an implantable multichannel vestibular prosthesis (MVP) is a promising treatment approach that has been tested in animals and humans. However, uncertainty remains regarding the histopathologic effects of gentamicin ototoxicity alone or in combination with electrode implantation. Understanding these histological changes is important because selective MVP-driven stimulation of semicircular canals (SCCs) depends on persistence of primary afferent innervation in each SCC crista despite both the primary cause of BVD (e.g., ototoxic injury) and surgical trauma associated with MVP implantation. Retraction of primary afferents out of the cristae and back toward Scarpa's ganglion would render spatially selective stimulation difficult to achieve and could limit utility of an MVP that relies on electrodes implanted in the lumen of each ampulla. We investigated histopathologic changes of the inner ear associated with intratympanic gentamicin (ITG) injection and/or MVP electrode array implantation in 11 temporal bones from six rhesus macaque monkeys. Hematoxylin and eosin-stained 10-μm temporal bone sections were examined under light microscopy for four treatment groups: normal (three ears), ITG-only (two ears), MVP-only (two ears), and ITG + MVP (four ears). We estimated vestibular hair cell (HC) surface densities for each sensory neuroepithelium and compared findings across end organs and treatment groups. In ITG-only, MVP-only, and ITG + MVP ears, we observed decreased but persistent ampullary nerve fibers of SCC cristae despite ITG treatment and/or MVP electrode implantation. ITG-only and ITG + MVP ears exhibited neuroepithelial thinning and loss of type I HCs in the cristae but little effect on the maculae. MVP-only and ITG + MVP ears exhibited no signs of trauma to the cochlea or otolith end organs except in a single case of saccular injury due to over-insertion of the posterior SCC electrode. While implanted electrodes reached to within 50-760 μm of the target cristae and were usually ensheathed in a thin fibrotic capsule, dense fibrotic reaction and osteoneogenesis were each observed in only one of six electrode tracts examined. Consistent with physiologic studies that have demonstrated directionally appropriate vestibulo-ocular reflex responses to MVP electrical stimulation years after implantation in these animals, histologic findings in t h e p r e s e n t s t u d y i n d i c a t e t h a t a l t h o u g h intralabyrinthine MVP implantation causes some inner

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Stereological estimation of total cell numbers in the young human utricular macula

Cited by 5 publications

References 17 publications

Preliminary Characterization of Voltage-Activated Whole-Cell Currents in Developing Human Vestibular Hair Cells and Calyx Afferent Terminals

Preliminary Characterization of Voltage-Activated Whole-Cell Currents in Developing Human Vestibular Hair Cells and Calyx Afferent Terminals

Development and regeneration of vestibular hair cells in mammals

Histopathologic Changes of the Inner ear in Rhesus Monkeys After Intratympanic Gentamicin Injection and Vestibular Prosthesis Electrode Array Implantation

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