scholarly journals A Simple Model for Inducing Optimal Increase of SDF-1 with Aminoglycoside Ototoxicity

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Hyun Mi Ju ◽  
Sun Hee Lee ◽  
Jin Sil Choi ◽  
Young Joon Seo
Keyword(s):  
Stem Cell ◽  
Mouse Model ◽  
Inner Ear ◽  
Outer Hair Cell ◽  
Stria Vascularis ◽  
Organ Of Corti ◽  
Maximal Increase ◽  
Aminoglycoside Ototoxicity ◽  
Cell Counts ◽  
Hearing Thresholds

Objectives. As a homing factor of stem cell, stromal derived factor-1 (SDF-1) is important for the regenerative research in ototoxicity. Mice models with aminoglycoside ototoxicity have been widely used to study the regeneration capacity of MSCs in repair of cochlear injury. We developed a mouse model with maximal increase in SDF-1 levels in the inner ear, according to the “one-shot” doses of kanamycin and furosemide. Methods. C57BL/6 mice had kanamycin (420, 550, and 600 mg/kg) dissolved in PBS, followed by an intraperitoneal injection of furosemide (130 mg/kg). The injuries of inner ear were measured with hearing thresholds, histology, and outer hair cell counts at 0, 3, 5, 7, 10, and 14 days before the sacrifice. The levels of SDF-1 in the inner ear were tested by real-time RT-PCR and immunohistochemistry. Results. There were a significant reduction in hearing thresholds and a maximal increase of SDF-1 levels in the furosemide 130 mg/kg + kanamycin 550 mg/kg group, but severe hearing deterioration over time was observed in the furosemide 130 mg/kg + kanamycin 600 mg/kg group and four mice were dead. SDF-1 was detected mostly in the stria vascularis and organ of Corti showing the highest increase in expression. Conclusion. We observed optimal induction of the stem cell homing factor in the newly generated aminoglycoside-induced ototoxicity mouse model using a “one-shot” protocol. This study regarding high SDF-1 levels in our mouse model of ototoxicity would play a major role in the development of therapeutic agents using MSC homing.

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 A gap-junction mutation in the mouse cochlea reveals cochlear amplification is driven by outer hair cell extracellular receptor potentials

2021 ◽  
Author(s):  
Snezana Levic ◽  
Victoria A Lukashkina ◽  
Patricio Simoes ◽  
Andrei N Lukashkin ◽  
Ian J Russell
Keyword(s):  
Hair Cell ◽  
Gap Junction ◽  
High Frequency ◽  
Outer Hair Cell ◽  
Stria Vascularis ◽  
Organ Of Corti ◽  
Receptor Potential ◽  
Wild Type ◽  
Hearing Sensitivity ◽  
Cochlear Amplification

Cochlear amplification, whereby cochlear responses to low-to-moderate sound levels are 31 amplified and compressed to loud sounds, is attributed to outer hair cell (OHC) electromotility 32 driven by voltage changes across the OHC basolateral membranes due to sound-induced 33 receptor-current modulation. Cochlear operation at high acoustic frequencies is enigmatic 34 because the OHC intracellular receptor potential (RP) is severely attenuated at these 35 frequencies. Clues to understanding the voltage control of OHC electromotility at different 36 frequencies was provided by measurements from CD-1 mice with an A88V mutation of the 37 gap-junction (GJ) protein connexin 30 (Cx30), which with Cx26, form heterogeneous GJs 38 between supporting cells in the organ of Corti (OoC) and stria vascularis. The A88V mutation 39 results in a smaller GJ conductance which may explain why the resistance across the OoC in 40 CD-1Cx30A88V/A88V mutants is higher compared with wild-type mice. The endocochlear 41 potential, which drives the OHC receptor current and, consequently, the OHC RPs, is smaller 42 in CD-1Cx30A88V/A88V mutants. Even so, their high-frequency hearing sensitivity equals that of 43 wild-type mice. Preservation of high-frequency hearing correlates with similar amplitude of 44 extracellular receptor potentials (ERPs), measured immediately adjacent to the OHCs. ERPs 45 are generated through OHC receptor current flow across the OoC electrical resistance, which 46 is larger in CD-1Cx30A88V/A88V than in wild-type mice. Thus, smaller OHC receptor currents 47 flowing across a larger OoC resistance in CD-1Cx30A88V/A88V mice may explain why their ERP 48 magnitudes are similar to wild-type mice. It is proposed that the ERPs, which are not subject 49 to low-pass electrical filtering, drive high-frequency cochlear amplification.

scholarly journals OHC-TRECK: A Novel System Using a Mouse Model for Investigation of the Molecular Mechanisms Associated with Outer Hair Cell Death in the Inner Ear

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kunie Matsuoka ◽  
Kenta Wada ◽  
Yuki Miyasaka ◽  
Shumpei P. Yasuda ◽  
Yuta Seki ◽  
...  
Keyword(s):  
Cell Death ◽  
Mouse Model ◽  
Hair Cell ◽  
Inner Ear ◽  
Molecular Mechanisms ◽  
Outer Hair Cell ◽  
Hair Cell Death

Sensorineural Hearing Loss due to Cochlear Otospongiosis: Theoretical Considerations of Etiology

1975 ◽  
Vol 84 (4) ◽  
pp. 544-551 ◽  
Author(s):  
Fred H. Linthicum ◽  
Roberto Filipo ◽  
Sidney Brody
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Inner Ear ◽  
Basilar Membrane ◽  
Stria Vascularis ◽  
Organ Of Corti ◽  
Sensorineural Hearing ◽  
Toxic Substances ◽  
Theoretical Considerations

Several theories have been advanced to explain the sensorineural hearing loss that occurs in patients with otospongiosis: toxic substances produced by the otospongiotic focus; vascular shunts between the inner ear vessels and the otospongiotic focus; and atrophy of the organ of Corti and stria vascularis due to unknown causes. Presented here is yet another theory: impingement upon the cochlear walls by the otospongiotic focus, causing a narrowing of the lumen of the cochlea and distortion of the basilar membrane.

scholarly journals Selective Ablation of Cochlear Hair Cells Promotes Engraftment of Human Embryonic Stem Cells-derived Progenitors in The Mouse organ of Corti

2020 ◽  
Author(s):  
Hiroki Takeda ◽  
Anna Dondzillo ◽  
Jessica A. Randall ◽  
Samuel P. Gubbels
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Inner Ear ◽  
Hair Cells ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Organ Of Corti ◽  
Human Stem Cells ◽  
Cochlear Hair Cells ◽  
Mouse Organ

Abstract Backgroud: Hearing loss affects 25% of the population at ages 60–69 years. Loss of the hair cells of the inner ear commonly underlies deafness and once lost this cell type cannot spontaneously regenerate in higher vertebrates. As a result there is a need for the development of regenerative strategies to replace hair cells once lost. Stem cell-based therapies are one such strategy and offer promise for cell replacement in a variety of tissues. A number of investigators have previously demonstrated successful implantation, and certain level of regeneration of hair and supporting cells in both avian and mammalian models using rodent pluripotent stem cells. However, the ability of human stem cells to engraft and generate differentiated cell types in the inner ear is not well understood. Methods: We differentiate human pluripotent stem cells to the pre-placodal stage in vitro then transplant them into the mouse cochlea after selective and complete lesioning of the endogenous population of hair cells. Results: We demonstrate that hair cell ablation prior to transplantation leads to increased engraftment in the auditory sensory epithelium, the organ of Corti, as well as differentiation of transplanted cells into hair and supporting cell immunophenotypes. Conclusion: We have demonstrated the feasibility of human stem cell engraftment into an ablated mouse organ of Corti.

Connexin 26 Immunohistochemistry in Temporal Bones With Cochlear Otosclerosis

2018 ◽  
Vol 127 (8) ◽  
pp. 536-542 ◽  
Author(s):  
Mia E. Miller ◽  
Ivan A. Lopez ◽  
Fred H. Linthicum ◽  
Akira Ishiyama
Keyword(s):  
Hearing Loss ◽  
Stria Vascularis ◽  
Organ Of Corti ◽  
Connexin 26 ◽  
Spiral Ligament ◽  
Mixed Hearing Loss ◽  
Cell Counts ◽  
Normal Hair ◽  
Connexin 30 ◽  
Temporal Bones

Hypothesis: Connexin-26 (Cx26) expression is diminished in the spiral ligament of subjects with hearing loss and cochlear otosclerosis (CO). Background: Human temporal bone (HTB) studies have demonstrated that CO is associated with hyalinization of the spiral ligament. We hypothesize that hyalinization is associated with a loss of fibrocytes with a consequent decline in Cx26 expression. Cx26 and Connexin-30 (Cx30) encode gap junction proteins expressed in supporting cells of the organ of Corti, the spiral limbus, stria vascularis, and in fibrocytes of the spiral ligament. These gap junctions are critical for potassium recycling and maintenance of the endocochlear potential. Diminished expression of these proteins would likely be associated with hearing dysfunction. Methods: Histopathology and clinical characteristics of 45 HTB specimens with CO and spiral ligament hyalinization were reviewed. Those with sensorineural or mixed hearing loss but normal or near-normal hair cell counts were analyzed with light microscopy, and Cx26-immunoreactive (IR) signal was qualitatively assessed. Results: H&E staining demonstrated hyalinization in the spiral ligament and loss of type II and type III fibrocytes. Cx26-IR was diminished throughout the cochlea affected with CO compared with normal controls. Conclusions: Cx26-IR reduction in the spiral ligament of subjects with CO likely plays a role in hearing loss.

Endotoxic damage to the stria vascularis: the pathogenesis of sensorineural hearing loss secondary to otitis media?

1994 ◽  
Vol 108 (4) ◽  
pp. 310-313 ◽  
Author(s):  
Yangchun Guo ◽  
Yiqin Wu ◽  
Wenlie Chen ◽  
Jizhen Lin
Keyword(s):  
Inner Ear ◽  
Otitis Media ◽  
Stria Vascularis ◽  
Animal Experiments ◽  
Organ Of Corti ◽  
Control Group ◽  
Structural Evaluation ◽  
Ion Imbalance ◽  
Secondary Lysosomes ◽  
Perilymphatic Space

AbstractThis study presents animal experiments on endotoxin (lipopolysaccharides: LPS) damage to the inner ear with special reference to the stria vascularis. The experimental group animals (albino guinea pigs) were injected with LPS into the perilymphatic space. Pyrogen-free saline (PFS) was injected into the control group. Strial structural evaluation and hearing tests were carried out before and one, three and five days after treatment. In PFS-treated (control) ears, no significant change was found either in hearing or structure. However, thresholds of Nl/Pl were elevated and latencies prolonged in LPS-treated ears. They had severe strial damage mainly to the cellular organelles. The mitochondria became swollen with a disordered, broken, degenerated or absent crest. Secondary lysosomes and autophagosomes increased in number with the presence of medulative inclusions. Na+-K+-ATPase reactant was obviously diminished. It is concluded that LPS-induced strial ototoxicityproduces ion imbalance, causing changesin endolymph composition and energy failure in the organ of Corti and is also responsible for the pathogenesis of inner ear sequelae secondary to otitis media.

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 Selective ablation of cochlear hair cells promotes engraftment of human embryonic stem cell-derived progenitors in the mouse organ of Corti

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hiroki Takeda ◽  
Anna Dondzillo ◽  
Jessica A. Randall ◽  
Samuel P. Gubbels
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Inner Ear ◽  
Hair Cells ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Organ Of Corti ◽  
Human Stem Cells ◽  
Cochlear Hair Cells ◽  
Mouse Organ

Abstract Background Hearing loss affects 25% of the population at ages 60–69 years. Loss of the hair cells of the inner ear commonly underlies deafness and once lost this cell type cannot spontaneously regenerate in higher vertebrates. As a result, there is a need for the development of regenerative strategies to replace hair cells once lost. Stem cell-based therapies are one such strategy and offer promise for cell replacement in a variety of tissues. A number of investigators have previously demonstrated successful implantation, and certain level of regeneration of hair and supporting cells in both avian and mammalian models using rodent pluripotent stem cells. However, the ability of human stem cells to engraft and generate differentiated cell types in the inner ear is not well understood. Methods We differentiate human pluripotent stem cells to the pre-placodal stage in vitro then transplant them into the mouse cochlea after selective and complete lesioning of the endogenous population of hair cells. Results We demonstrate that hair cell ablation prior to transplantation leads to increased engraftment in the auditory sensory epithelium, the organ of Corti, as well as differentiation of transplanted cells into hair and supporting cell immunophenotypes. Conclusion We have demonstrated the feasibility of human stem cell engraftment into an ablated mouse organ of Corti. Graphical abstract

scholarly journals Circulating Serum miRNA-205 as a Diagnostic Biomarker for Ototoxicity in Mice Treated with Aminoglycoside Antibiotics

2018 ◽  
Vol 19 (9) ◽  
pp. 2836 ◽  
Author(s):  
Sun Lee ◽  
Hyun Ju ◽  
Jin Choi ◽  
Yeji Ahn ◽  
Suhun Lee ◽  
...  
Keyword(s):  
Mouse Model ◽  
Hearing Impairment ◽  
Stria Vascularis ◽  
Organ Of Corti ◽  
Kidney Injury ◽  
Serum Levels ◽  
Circulating Micrornas ◽  
Injury Model ◽  
Ototoxic Drugs ◽  
Inner Ear Damage

Background: To confirm levels and detection timing of circulating microRNAs (miRNAs) in the serum of a mouse model for diagnosis of ototoxicity, circulating miR-205 in the serum was evaluated to reflect damages in the cochlear microstructure and compared to a kidney injury model. Method: A microarray for miRNAs in the serum was performed to assess the ototoxic effects of kanamycin-furosemide. Changes in the levels for the selected miRNAs (miR-205, miR-183, and miR-103) were compared in the serum and microstructures of the cochlea (stria vascularis, organ of Corti, and modiolus) between the ototoxicity and normal mouse groups. An acute kidney injury (AKI) mouse model was used to assess changes in miR-205 levels in the kidney by ototoxic drugs. Results: In the mouse model for ototoxicity, the serum levels of circulating miR-205 peaked on day 3 and were sustained from days 7–14. Furthermore, miR-205 expression was highly expressed in the organ of Corti at day 5, continued to be expressed in the modiolus at high levels until day 14, and was finally also in the stria vascularis. The serum miR-205 in the AKI mice did not change significantly compared to the normal group. Conclusions Circulating miR-205 from the cochlea, after ototoxic damage, migrates through the blood vessels to organs, which is then finally found in blood. In conditions of hearing impairment with ototoxic medications, detection of circulating miR-205 in the blood can be used to determine the extent of hearing loss. In the future, inner ear damage can be identified by simply performing a blood test before the hearing impairment due to ototoxic drugs.

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