scholarly journals Progress in protecting vestibular hair cells

Author(s):  
Luoying Jiang ◽  
Zhiwei Zheng ◽  
Yingzi He

AbstractVestibular hair cells are mechanosensory receptors that are capable of detecting changes in head position and thereby allow animals to maintain their posture and coordinate their movement. Vestibular hair cells are susceptible to ototoxic drugs, aging, and genetic factors that can lead to permanent vestibular dysfunction. Vestibular dysfunction mainly results from the injury of hair cells, which are located in the vestibular sensory epithelium. This review summarizes the mechanisms of different factors causing vestibular hair cell damage and therapeutic strategies to protect vestibular hair cells.

1998 ◽  
Vol 79 (4) ◽  
pp. 2235-2239 ◽  
Author(s):  
John S. Oghalai ◽  
Jeffrey R. Holt ◽  
Takashi Nakagawa ◽  
Thomas M. Jung ◽  
Newton J. Coker ◽  
...  

Oghalai, John S., Jeffrey R. Holt, Takashi Nakagawa, Thomas M. Jung, Newton J. Coker, Herman A. Jenkins, Ruth Anne Eatock, and William E. Brownell. Ionic currents and electromotility in inner ear hair cells from humans. J. Neurophysiol. 79: 2235–2239, 1998. The upright posture and rich vocalizations of primates place demands on their senses of balance and hearing that differ from those of other animals. There is a wealth of behavioral, psychophysical, and CNS measures characterizing these senses in primates, but no prior recordings from their inner ear sensory receptor cells. We harvested human hair cells from patients undergoing surgical removal of life-threatening brain stem tumors and measured their ionic currents and electromotile responses. The hair cells were either isolated or left in situ in their sensory epithelium and investigated using the tight-seal, whole cell technique. We recorded from both type I and type II vestibular hair cells under voltage clamp and found four voltage-dependent currents, each of which has been reported in hair cells of other animals. Cochlear outer hair cells demonstrated electromotility in response to voltage steps like that seen in rodent animal models. Our results reveal many qualitative similarities to hair cells obtained from other animals and justify continued investigations to explore quantitative differences that may be associated with normal or pathological human sensation.


1994 ◽  
Vol 110 (4) ◽  
pp. 419-427 ◽  
Author(s):  
Ilsa Schwartz ◽  
Chong-Sun Kim ◽  
See-Ok Shin

Guinea pigs were irradiated with fast neutrons. After a single dose of 2, 6, 10, or 15 Gy was applied, scanning and transmission electron microscopy of the temporal bone was performed to assess the effect of fast neutron irradiation on the cochlea. Outer hair cell damage appeared with neutron irradiation of more than 10 Gy, and Inner hair cell damage with neutron Irradiation of more than 15 Gy. Outer hair cells were more severely damaged than Inner hair cells. No statistically significant differences were found in damage of basal, middle, and apical turns. The second and third rows of outer hair cells were more severely damaged than the first row of outer hair cells. The most significant findings in transmission electron microscopy were clumping of chromatin and extension of the heterochromatin in the nuclei of hair cells. The cytoplasmic changes were sequestration of cytoplasm, various changes of mitochondria, formation of vacuoles, and irregularly arranged stereocilia. The morphologic change in stria vascularis was intercellular and perivascular fluid accumulation. It appeared to be a reversible process.


2020 ◽  
Vol 40 (1) ◽  
pp. 148-157
Author(s):  
YS Chang ◽  
SM Park ◽  
YC Rah ◽  
EJ Han ◽  
SI Koun ◽  
...  

With the ban of conventional cigarettes from public spaces, electronic cigarette (E-cig) liquids have emerged as a nicotine replacement treatment for smoking cessation. However, consumers possess little knowledge of the ingredients and health effects of E-cig liquids following exposure. This study evaluated hair cell damage and developmental toxicities following gestational exposure to E-cig liquids. Zebrafish embryos were exposed to E-cig liquids at different concentrations (0.1%, 0.2%, and 0.4%). Embryonic developmental toxicity and hair cell damage was evaluated at 6 and 7 d, respectively, after fertilization. The average number of hair cells in the anterior lateral line (ALL) and posterior lateral line (PLL) following E-cig exposure was compared to that of the control. Morphological abnormalities and heart rate were evaluated. E-cig liquids significantly damaged the hair cells in the ALL, compared to the control (control; 52.85 ± 5.29 cells, 0.1% E-cig; 49.43 ± 7.70 cells, 0.2% E-cig; 40.68 ± 12.00 cells, 0.4% E-cig; 32.14 ± 20.75%; n = 29–40; p < 0.01). At high concentrations, E-cig liquids significantly damaged the hair cells in the PLL (control; 36.88 ± 5.43 cells, 0.1% E-cig; 33.06 ± 5.21 cells, 0.2% E-cig; 30.95 ± 8.03 cells, 0.4% E-cig; 23.72 ± 15.53%, n = 29–40; p < 0.01). No morphological abnormalities in body shape, somites, notochord, tail, and pectoral fin were observed; however, abnormalities were observed in the dorsal fin and heart rate at high concentrations. Thus, gestational exposure to E-cigs significantly damaged hair cells in a concentration-dependent manner and induced developmental toxicities to the dorsal fin and heart rate at high concentrations.


2015 ◽  
Vol 112 (47) ◽  
pp. 14723-14727 ◽  
Author(s):  
Chang Liu ◽  
Elisabeth Glowatzki ◽  
Paul Albert Fuchs

In the mammalian cochlea, acoustic information is carried to the brain by the predominant (95%) large-diameter, myelinated type I afferents, each of which is postsynaptic to a single inner hair cell. The remaining thin, unmyelinated type II afferents extend hundreds of microns along the cochlear duct to contact many outer hair cells. Despite this extensive arbor, type II afferents are weakly activated by outer hair cell transmitter release and are insensitive to sound. Intriguingly, type II afferents remain intact in damaged regions of the cochlea. Here, we show that type II afferents are activated when outer hair cells are damaged. This response depends on both ionotropic (P2X) and metabotropic (P2Y) purinergic receptors, binding ATP released from nearby supporting cells in response to hair cell damage. Selective activation of P2Y receptors increased type II afferent excitability by the closure of KCNQ-type potassium channels, a potential mechanism for the painful hypersensitivity (that we term “noxacusis” to distinguish from hyperacusis without pain) that can accompany hearing loss. Exposure to the KCNQ channel activator retigabine suppressed the type II fiber’s response to hair cell damage. Type II afferents may be the cochlea’s nociceptors, prompting avoidance of further damage to the irreparable inner ear.


Author(s):  
Melanie Holmgren ◽  
Michael E. Ravicz ◽  
Kenneth E. Hancock ◽  
Olga Strelkova ◽  
Artur A. Indzhykulian ◽  
...  

AbstractNoise exposure damages sensory hair cells, resulting in loss of synaptic connections with auditory nerves and hair-cell death. The cellular mechanisms underlying noise-induced hair-cell damage and subsequent repair are not completely understood. Hair cells in neuromasts (NMs) of larval zebrafish are structurally and functionally comparable to mammalian hair cells but undergo robust regeneration following damage. We therefore developed a model for noise-induced hair-cell damage in this highly tractable system. Free swimming larvae exposed to strong water current for 2 hours displayed damage to NMs, including synapse loss, afferent neurite retraction, damaged hair bundles, and reduced mechanotransduction. Overstimulation also elicited an inflammatory response and macrophage recruitment. Remarkably, NM morphology and function appeared to fully recover within 2 days following exposure. Our results reveal morphological and functional changes in mechanically overstimulated lateral-line NMs that are analogous to changes observed in noise-exposed mammalian ear yet are rapidly and completely repaired.


eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Eric D Thomas ◽  
David W Raible

Mechanosensory hair cells of the zebrafish lateral line regenerate rapidly following damage. These renewed hair cells arise from the proliferation of surrounding support cells, which undergo symmetric division to produce two hair cell daughters. Given the continued regenerative capacity of the lateral line, support cells presumably have the ability to replenish themselves. Utilizing novel transgenic lines, we identified support cell populations with distinct progenitor identities. These populations show differences in their ability to generate new hair cells during homeostasis and regeneration. Targeted ablation of support cells reduced the number of regenerated hair cells. Furthermore, progenitors regenerated after targeted support cell ablation in the absence of hair cell damage. We also determined that distinct support cell populations are independently regulated by Notch signaling. The existence of independent progenitor populations could provide flexibility for the continued generation of new hair cells under a variety of conditions throughout the life of the animal.


2018 ◽  
Author(s):  
Eric D. Thomas ◽  
David W. Raible

ABSTRACTMechanosensory hair cells of the zebrafish lateral line regenerate rapidly following damage. These renewed hair cells arise from the proliferation of surrounding support cells, which undergo symmetric division to produce two hair cell daughters. Given the continued regenerative capacity of the lateral line, support cells presumably have the ability to replenish themselves. Utilizing novel transgenic lines, we identified support cell populations with distinct progenitor identities. These populations show differences in their ability to generate new hair cells during homeostasis and regeneration. Targeted ablation of support cells reduced the number of regenerated hair cells. Furthermore, progenitors regenerated after targeted support cell ablation in the absence of hair cell damage. We also determined that distinct support cell populations are independently regulated by Notch signaling. The existence of independent progenitor populations could provide flexibility for the continued generation of new hair cells under a variety of conditions throughout the life of the animal.


2005 ◽  
Vol 24 (6) ◽  
pp. 443-449 ◽  
Author(s):  
J. P. Carey ◽  
T. Cooper ◽  
G. I. Jallo ◽  
B. S. Carson ◽  
M. Guarnieri

Ototoxicity is a common side effect of platinum-based chemotherapy. Intratumoral drug delivery theoretically could reduce the ototoxic effects of systemic drug infusions. However, local delivery to central nervous system (CNS) tumors might promote ototoxicity through drug release into cerebrospinal fluid (CSF). This report describes an examination of the cytoarchitecture of vestibular cells of cynomolgus monkeys that had chronic brainstem infusions with the maximum tolerated dose (MTD) of carboplatin. The brainstems of adult monkeys were infused for 30 days at 0.42 μl/h with 0.025 to 0.25 mg/kg (MTD) of carboplatin. The vestibular sensory epithelia of eight drug-treated animals were isolated for microscopic examination of vestibular hair cells and support cells. Local infusions produced chronic elevated CSF levels of platinum, neurological symptoms, and radiographic evidence of pontine injury. Histology revealed significant cell damage at the infusion sites. Microscopic examinations of vestibular support cells and hair cells demonstrate a small reduction in cell counts in the drug-treated monkeys compared to a noninfused control animal. Parametric and nonparametric tests show no effect of dose in predicting the vestibular cell counts. In this single study of eight monkeys, a dose-dependent reduction of vestibular hair cells or support cells was not observed in animals infused with brainstem infusions of 0.025 to 0.25 mg/kg of carboplatin.


2021 ◽  
Author(s):  
Jing-cui Qi ◽  
Qing-qing Jiang ◽  
Long Ma ◽  
Shuo-long Yuan ◽  
Wei Sun ◽  
...  

Abstract Background:. Pathological changes of the cochlea and hearing loss have been well addressed in Waardenburg syndrome (WS). However, the vestibular organ malformation in WS is still largely unknown. In this study, the differentiation and development of vestibular sensory epithelium and vestibular function caused by SOX10 mutation, a critical gene induces WS, has been studied in minature pig model. Results: Degeneration of vestibular hair cells was found in this Sox10 mutation porcine model. Inner ear phenotype of the SOX10+/R109W miniature pigs showed cochlear abnormalities as well as saccular hypofunction. In the mutant pigs, no prominent dissimilarity was shown in the bone structure of the semicircular canals. However, the saccular membrane was collapsed and the infusion of stereocilia of the hair cells were observed. There was no dark cells in the uticules in th mutant pigs. The density of the utricular hair cells was also significantly lower in the mutant pigs compared to the wild type. Conclusions: Our study demonstrated that the SOX10 gene and melanocytes play important roles in the vestibular organ development. Sox10 mutation disrupts the KIT-DCT signaling pathway, affects the development of melanocytes and leads to vestibule morphogenesis.


2015 ◽  
Vol 34 (11) ◽  
pp. 1043-1052 ◽  
Author(s):  
SK Lee ◽  
KH Oh ◽  
AY Chung ◽  
HC Park ◽  
SH Lee ◽  
...  

Background and objectives: The aim of this study was to evaluate the protective effects of quercetin on cisplatin-induced hair cell damage in transgenic zebrafish embryos. Materials and methods: Five days postfertilization zebrafish embryos were exposed to 1 mM cisplatin and quercetin at 10, 50, 100, or 200 μM for 4 h. Hair cells within neuromasts of the supraorbital, otic, and occipital lateral lines were analyzed by fluorescent microscopy ( n = 10). Survival of hair cells was calculated as the average number of hair cells in the control group that were not exposed to cisplatin. Ultrastructural changes were evaluated using scanning electron microscopy. Results: Hair cell damage in neuromasts was decreased by co-treatment of quercetin and cisplatin (quercetin 100 μM: 8.6 ± 1.1 cells; 1 mM cisplatin only: 5.0 ± 0.5 cells; n = 10, p < 0.05); apoptosis of hair cells examined by special stain was also decreased by quercetin. The ultrastructure of hair cells within neuromasts was preserved in zebrafish by the combination of quercetin (100 μM) and cisplatin (1 mM). Conclusion: In conclusion, quercetin showed protective effects against cisplatin-induced toxicity in a zebrafish model. The results of this study suggest the possibility of a protective role of quercetin against cisplatin-induced apoptotic cell death in zebrafish.


Sign in / Sign up

Export Citation Format

Share Document