Blebs in inner and outer hair cells: a pathophysiological hypothesis

2008 ◽  
Vol 122 (11) ◽  
pp. 1151-1155 ◽  
Author(s):  
R Ramírez-Camacho ◽  
J R García-Berrocal ◽  
A Trinidad ◽  
J M Verdaguer ◽  
J Nevado
Keyword(s):  
Hair Cells ◽  
Outer Hair Cell ◽  
Ganglion Cells ◽  
Stria Vascularis ◽  
Spiral Ganglion ◽  
Organ Of Corti ◽  
Outer Hair Cells ◽  
Inner Hair Cells ◽  
Hearing Thresholds

AbstractIntroduction:The ototoxic effects of cisplatin include loss of outer hair cells, degeneration of the stria vascularis and a decrease in the number of spiral ganglion cells. Scanning microscopy has shown balloon-like protrusions (blebs) of the plasma membrane of inner hair cells following cisplatin administration. The present study was undertaken to identify the possible role of inner and outer hair cell blebs in the pathogenesis of cisplatin-induced ototoxicity.Materials and methods:Twenty-five guinea pigs were injected with cisplatin and their hearing tested at different time-points, before sacrifice and examination with scanning electron microscopy.Results and analysis:Seven animals showed blebs in the inner hair cells at different stages. Hearing thresholds were lower in animals showing blebs.Discussion:Cisplatin seems to be able to induce changes in inner hair cells as well as in other structures in the organ of Corti. Blebbing observed in animals following cisplatin administration could play a specific role in the regulation of intracellular pressure.

scholarly journals Caffeine Induces Autophagy and Apoptosis in Auditory Hair Cells via the SGK1/HIF-1α Pathway

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiaomin Tang ◽  
Yuxuan Sun ◽  
Chenyu Xu ◽  
Xiaotao Guo ◽  
Jiaqiang Sun ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cells ◽  
Stria Vascularis ◽  
Spiral Ganglion ◽  
Organ Of Corti ◽  
Spiral Ganglion Neurons ◽  
Auditory Hair Cells ◽  
Qrt Pcr ◽  
Ganglion Neurons

Caffeine is being increasingly used in daily life, such as in drinks, cosmetics, and medicine. Caffeine is known as a mild stimulant of the central nervous system, which is also closely related to neurologic disease. However, it is unknown whether caffeine causes hearing loss, and there is great interest in determining the effect of caffeine in cochlear hair cells. First, we explored the difference in auditory brainstem response (ABR), organ of Corti, stria vascularis, and spiral ganglion neurons between the control and caffeine-treated groups of C57BL/6 mice. RNA sequencing was conducted to profile mRNA expression differences in the cochlea of control and caffeine-treated mice. A CCK-8 assay was used to evaluate the approximate concentration of caffeine. Flow cytometry, TUNEL assay, immunocytochemistry, qRT-PCR, and Western blotting were performed to detect the effects of SGK1 in HEI-OC1 cells and basilar membranes. In vivo research showed that 120 mg/ kg caffeine injection caused hearing loss by damaging the organ of Corti, stria vascularis, and spiral ganglion neurons. RNA-seq results suggested that SGK1 might play a vital role in ototoxicity. To confirm our observations in vitro, we used the HEI-OC1 cell line, a cochlear hair cell-like cell line, to investigate the role of caffeine in hearing loss. The results of flow cytometry, TUNEL assay, immunocytochemistry, qRT-PCR, and Western blotting showed that caffeine caused autophagy and apoptosis via SGK1 pathway. We verified the interaction between SGK1 and HIF-1α by co-IP. To confirm the role of SGK1 and HIF-1α, GSK650394 was used as an inhibitor of SGK1 and CoCl2 was used as an inducer of HIF-1α. Western blot analysis suggested that GSK650394 and CoCl2 relieved the caffeine-induced apoptosis and autophagy. Together, these results indicated that caffeine induces autophagy and apoptosis in auditory hair cells via the SGK1/HIF-1α pathway, suggesting that caffeine may cause hearing loss. Additionally, our findings provided new insights into ototoxic drugs, demonstrating that SGK1 and its downstream pathways may be potential therapeutic targets for hearing research at the molecular level.

Ultrastructural Cochlear Changes following Acoustic Hyperstimulation and Ototoxicity

1976 ◽  
Vol 85 (6) ◽  
pp. 740-751 ◽  
Author(s):  
David J. Lim
Keyword(s):  
Hair Cells ◽  
Sensory Cell ◽  
Ganglion Cells ◽  
Organ Of Corti ◽  
Acoustic Trauma ◽  
Nerve Fibers ◽  
Outer Hair Cells ◽  
Type I ◽  
Cell Degeneration ◽  
Inner Hair Cells

Using guinea pigs and chinchillas as experimental animals, modes and patterns of sensory cell damage by acoustic hyperstimulation and kanamycin intoxication were compared. In general, outer hair cells were more vulnerable to both acoustic trauma and ototoxicity (particularly in the basal turn) than inner hair cells. However, in kanamycin ototoxicity, the inner hair cells were more vulnerable in the apical coil. Nerve endings and nerve fibers generally were resistant to both acoustic trauma and kanamycin intoxication, and their degeneration appears to be secondary to the sensory cell degeneration. A large number of unmyelinated nerve fibers were seen in both the organ of Corti and the osseous spiral lamina even three months after the organ of Corti had been completely degenerated by ototoxicity. The total number of unmyelinated and myelinated nerve fibers in the osseous spiral lamina far exceeded the scanty surviving ganglion cells in Rosenthal's canal, indicating the possibility of regeneration of these fibers following kanamycin intoxication. The remaining few ganglion cells were mainly type II or type III cells, and a majority of the type I ganglion cells appeared to be degenerated. Signs of strial damage were observed in both acoustic trauma and ototoxicity, but their pattern did not correlate well with that of sensory cell degeneration.

scholarly journals Histopathology of the Human Inner Ear in Alström's Syndrome

2015 ◽  
Vol 20 (4) ◽  
pp. 267-272 ◽  
Author(s):  
Joseph B. Nadol Jr ◽  
Jan D. Marshall ◽  
Roderick T. Bronson
Keyword(s):  
Inner Ear ◽  
Autosomal Recessive ◽  
Ganglion Cells ◽  
Stria Vascularis ◽  
Genetic Disorder ◽  
Spiral Ganglion ◽  
Organ Of Corti ◽  
Outer Hair Cells ◽  
Spiral Ligament ◽  
Human Inner Ear

Alström's syndrome is an autosomal recessive syndromic genetic disorder caused by mutations in the ALMS1 gene. Sensorineural hearing loss occurs in greater than 85% of patients. Histopathology of the inner ear abnormalities in the human has not previously been fully described. Histopathology of the inner ear in Alström's syndrome is presented in 2 genetically confirmed cases. The predominant histopathologic correlates of the sensorineural loss were degeneration of the organ of Corti, both inner and outer hair cells, degeneration of spiral ganglion cells, and atrophy of the stria vascularis and spiral ligament.

scholarly journals Induction of Redox-Active Gene Expression by CoCl2 Ameliorates Oxidative Stress-Mediated Injury of Murine Auditory Cells

Antioxidants ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 399 ◽  
Author(s):  
Jhang Ho Pak ◽  
Junyeong Yi ◽  
Sujin Ryu ◽  
In Ki Kim ◽  
Jung-Woong Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ganglion Cells ◽  
Stria Vascularis ◽  
Hypoxia Inducible Factor ◽  
Spiral Ganglion ◽  
Organ Of Corti ◽  
Luciferase Reporter ◽  
Related Factor ◽  
Redox Active

Free radicals formed in the inner ear in response to high-intensity noise, are regarded as detrimental factors for noise-induced hearing loss (NIHL). We reported previously that intraperitoneal injection of cobalt chloride attenuated the loss of sensory hair cells and NIHL in mice. The present study was designed to understand the preconditioning effect of CoCl2 on oxidative stress-mediated cytotoxicity. Treatment of auditory cells with CoCl2 promoted cell proliferation, with increases in the expressions of two redox-active transcription factors (hypoxia-inducible factor 1α, HIF-1α, nuclear factor erythroid 2-related factor 2; Nrf-2) and an antioxidant enzyme (peroxiredoxin 6, Prdx6). Hydrogen peroxide treatment resulted in the induction of cell death and reduction of these protein expressions, reversed by pretreatment with CoCl2. Knockdown of HIF-1α or Nrf-2 attenuated the preconditioning effect of CoCl2. Luciferase reporter analysis with a Prdx6 promoter revealed transactivation of Prdx6 expression by HIF-1α and Nrf-2. The intense immunoreactivities of HIF-1α, Nrf-2, and Prdx6 in the organ of Corti (OC), spiral ganglion cells (SGC), and stria vascularis (SV) of the cochlea in CoCl2-injected mice suggested CoCl2-induced activation of HIF-1α, Nrf-2, and Prdx6 in vivo. Therefore, we revealed that the protective effect of CoCl2 is achieved through distinctive signaling mechanisms involving HIF-1α, Nrf-2, and Prdx6.

scholarly journals The Role of Prestin in the Generation of Electrically Evoked Otoacoustic Emissions in Mice

2008 ◽  
Vol 99 (4) ◽  
pp. 1607-1615 ◽  
Author(s):  
Markus Drexl ◽  
Marcia M. Mellado Lagarde ◽  
Jian Zuo ◽  
Andrei N. Lukashkin ◽  
Ian J. Russell
Keyword(s):  
Hair Cells ◽  
Otoacoustic Emissions ◽  
Temporal Structure ◽  
Organ Of Corti ◽  
Outer Hair Cells ◽  
Tectorial Membrane ◽  
Wild Type ◽  
Short Delay ◽  
Delay Component

Electrically evoked otoacoustic emissions are sounds emitted from the inner ear when alternating current is injected into the cochlea. Their temporal structure consists of short- and long-delay components and they have been attributed to the motile responses of the sensory-motor outer hair cells of the cochlea. The nature of these motile responses is unresolved and may depend on either somatic motility, hair bundle motility, or both. The short-delay component persists after almost complete elimination of outer hair cells. Outer hair cells are thus not the sole generators of electrically evoked otoacoustic emissions. We used prestin knockout mice, in which the motor protein prestin is absent from the lateral walls of outer hair cells, and Tecta ΔENT/ΔENT mice, in which the tectorial membrane, a structure with which the hair bundles of outer hair cells normally interact, is vestigial and completely detached from the organ of Corti. The amplitudes and delay spectra of electrically evoked otoacoustic emissions from Tecta ΔENT/ΔENT and Tecta +/+ mice are very similar. In comparison with prestin +/+ mice, however, the short-delay component of the emission in prestin −/− mice is dramatically reduced and the long-delay component is completely absent. Emissions are completely suppressed in wild-type and Tecta ΔENT/ΔENT mice at low stimulus levels, when prestin-based motility is blocked by salicylate. We conclude that near threshold, the emissions are generated by prestin-based somatic motility.

scholarly journals Static length changes of cochlear outer hair cells can tune low-frequency hearing

2017 ◽  
Author(s):  
Nikola Ciganović ◽  
Rebecca L. Warren ◽  
Batu Keçeli ◽  
Stefan Jacob ◽  
Anders Fridberger ◽  
...  
Keyword(s):  
Inner Ear ◽  
Hair Cells ◽  
Organ Of Corti ◽  
Outer Hair Cells ◽  
Frequency Selectivity ◽  
Apical Region ◽  
Low Frequencies ◽  
Inner Hair Cells ◽  
Length Changes ◽  
The Brain

AbstractThe cochlea not only transduces sound-induced vibration into neural spikes, it also amplifies weak sound to boost its detection. Actuators of this active process are sensory outer hair cells in the organ of Corti, whereas the inner hair cells transduce the resulting motion into electric signals that propagate via the auditory nerve to the brain. However, how the outer hair cells modulate the stimulus to the inner hair cells remains unclear. Here, we combine theoretical modeling and experimental measurements near the cochlear apex to study the way in which length changes of the outer hair cells deform the organ of Corti. We develop a geometry-based kinematic model of the apical organ of Corti that reproduces salient, yet counter-intuitive features of the organ’s motion. Our analysis further uncovers a mechanism by which a static length change of the outer hair cells can sensitively tune the signal transmitted to the sensory inner hair cells. When the outer hair cells are in an elongated state, stimulation of inner hair cells is largely inhibited, whereas outer hair cell contraction leads to a substantial enhancement of sound-evoked motion near the hair bundles. This novel mechanism for regulating the sensitivity of the hearing organ applies to the low frequencies that are most important for the perception of speech and music. We suggest that the proposed mechanism might underlie frequency discrimination at low auditory frequencies, as well as our ability to selectively attend auditory signals in noisy surroundings.Author summaryOuter hair cells are highly specialized force producers inside the inner ear: they can change length when stimulated electrically. However, how exactly this electromotile effect contributes to the astonishing sensitivity and frequency selectivity of the inner ear has remained unclear. Here we show for the first time that static length changes of outer hair cells can sensitively regulate how much of a sound signal is passed on to the inner hair cells that forward the signal to the brain. Our analysis holds for the apical region of the inner ear that is responsible for detecting the low frequencies that matter most in speech and music. This shows a mechanisms for how frequency-selectivity can be achieved at low frequencies. It also opens a path for the efferent neural system to regulate hearing sensitivity.

Fine Structure Histopathology of Labyrinthitis Ossificans in the Gerbil Model

2005 ◽  
Vol 114 (2) ◽  
pp. 161-166 ◽  
Author(s):  
Steven P. Tinling ◽  
Vishad Nabili ◽  
Hilary A. Brodie
Keyword(s):  
Connective Tissue ◽  
Ganglion Cells ◽  
Stria Vascularis ◽  
Spiral Ganglion ◽  
Organ Of Corti ◽  
Spiral Ligament ◽  
Otic Capsule ◽  
Dense Connective Tissue ◽  
Labyrinthitis Ossificans ◽  
End Stage

Labyrinthitis ossificans (LO) is the pathological deposition of new bone within the lumen of the cochlea and labyrinth. This process occurs most commonly as a result of infection or inflammation affecting the otic capsule. Trauma and vascular compromise can also lead to neo-ossification within the otic capsule. The mechanism that regulates this process remains unestablished. This study details the end-stage histopathology in high-resolution plastic thin sections. Twenty Mongolian gerbils were infected by intrathecal injection of Streptococcus pneumoniae type 3 followed by subcutaneous penicillin G procaine (8 days) and were painlessly sacrificed 3 months later. The cochleas were serially divided and sectioned for light and electron microscopy. Sixteen of 20 animals (27 of 40 cochleas) demonstrated LO. Cochlear damage was most extensive in the vestibule and basal turn and decreased toward the apex, which often appeared normal. The histopathologic findings consisted of 1) new bone, calcospherites, osteoid, and fibrosis without dense connective tissue or osteoblasts extending from the endosteal wall into the lumen of the vestibule and scala tympani; 2) areas of dense connective tissue and osteoid enclosed by epithelial cells conjoined with the organ of Corti, stria vascularis, spiral ligament, and vestibular (Reissner's) membrane; and 3) partial to complete loss of the organ of Corti, spiral ligament cell bodies, stria vascularis, and spiral ganglion cells. Osteoblastic activity was not demonstrated in end-stage ossification in LO in the gerbil model. Neoossification appears to occur by calcospherite deposition along collagen-like fibrils within osteoid. The destruction of the organ of Corti, spiral ganglion cells, stria vascularis, and cells of Reissner's membrane and the spiral ligament occurs even in the absence of ossification of the cochlear duct.

scholarly journals NTPDase1 and NTPDase2 Immunolocalization in Mouse Cochlea: Implications for Regulation of P2 Receptor Signaling

2002 ◽  
Vol 50 (11) ◽  
pp. 1435-1441 ◽  
Author(s):  
Srdjan M. Vlajkovic ◽  
Peter R. Thorne ◽  
Jean Sévigny ◽  
Simon C. Robson ◽  
Gary D. Housley
Keyword(s):  
Hair Cells ◽  
Spiral Ganglion ◽  
Organ Of Corti ◽  
Nerve Fibers ◽  
Outer Hair Cells ◽  
Spiral Ligament ◽  
Receptor Signaling ◽  
P2 Receptor ◽  
Efferent Nerve ◽  
Root Region

Cellular, molecular, and physiological studies have demonstrated an important signaling role for ATP and related nucleotides acting via P2 receptors in the cochlea of the inner ear. Signal modulation is facilitated by ectonucleotidases, a heterologous family of surface-located enzymes involved in extracellular nucleotide hydrolysis. Our previous studies have implicated CD39/NTPDase1 and CD39L1/NTPDase2, members of the ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) family, as major ATP-hydrolyzing enzymes in the tissues lining the cochlear endolymphatic and perilymphatic compartments. NTPDase1 hydrolyzes both nucleoside triphosphates and diphosphates. In contrast, NTPDase2 is a preferential nucleoside triphosphatase. This study characterizes expression of these E-NTPDases in the mouse cochlea by immunohistochemistry. NTPDase1 can be immunolocalized to the cochlear vasculature and neural tissues (primary auditory neurons in the spiral ganglion). In contrast, NTPDase2 immunolabeling was principally localized to synaptic regions of the sensory inner and outer hair cells, stereocilia and cuticular plates of the outer hair cells, supporting cells of the organ of Corti (Deiters’ cells and inner border cells), efferent nerve fibers located in the intraganglionic spiral bundle, and in the outer sulcus and root region of the spiral ligament. This differential expression of NTPDase1 and 2 in the cochlea suggests spatial regulation of P2 receptor signaling, potentially involving different nucleotide species and hydrolysis kinetics.

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