Cisplatin, a widely used anticancer drug, damages hair cells in cochlear organotypic cultures at low doses, but paradoxically causes little damage at high doses resulting in a U-shaped dose-response function. To deter...Cisplatin, a widely used anticancer drug, damages hair cells in cochlear organotypic cultures at low doses, but paradoxically causes little damage at high doses resulting in a U-shaped dose-response function. To determine if the cisplatin dose-response function for vestibular hair cells follows a similar pattern, we treated vestibular organotypic cultures with doses of cisplatin ranging from 10 to 1000 μM. Vestibular hair cell lesions progressively increased as the dose of cisplatin increased with maximum damage occurring around 50-100 μM, but the lesions progressively decreased at higher doses resulting in little hair cell loss at 1000 μM. The U-shaped doseresponse function for cisplatin-treated vestibular hair cells in culture appears to be regulated by copper transporters, Ctrl, ATP7A and ATP7B, that dose-dependently regulate the uptake, sequestration and extrusion of cisplatin.展开更多
The imbalance of reactive oxygen species and antioxidants is considered to be an important factor in the cellular injury of the inner ear. At present, great attention has been placed on oxidative stress. However,littl...The imbalance of reactive oxygen species and antioxidants is considered to be an important factor in the cellular injury of the inner ear. At present, great attention has been placed on oxidative stress. However,little is known about fighting oxidative stress. In the current study, we evaluated antioxidant-induced cochlear damage by applying several different additional antioxidants. To determine whether excessive antioxidants can cause damage to cochlear cells, we treated cochlear explants with 50 m M M40403, a superoxide dismutase mimetic, 50 m M coenzyme Q-10, a vitamin-like antioxidant, or 50 m M d-methionine, an essential amino acid and the important antioxidant glutathione for 48 h. Control cochlear explants without the antioxidant treatment maintained their normal structures after incubation in the standard serum-free medium for 48 h, indicating the maintenance of the inherent oxidative and antioxidant balance in these cochlear explants. In contrast, M40403 and coenzyme Q-10-treated cochlear explants displayed significant hair cell damage together with slight damage to the auditory nerve fibers.Moreover, d-methiodine-treated explants exhibited severe damage to the surface structure of hair cells and the complete loss of the spiral ganglion neurons and their peripheral fibers. These results indicate that excessive antioxidants are detrimental to cochlear cells, suggesting that inappropriate dosages of antioxidant treatments can interrupt the balance of the inherent oxidative and antioxidant capacity in the cell.展开更多
Preparation of the temporal bone for light microscopy is an important step in histological studies of the inner ear. Due to the complexity of structures of the inner ear, it is difficult to measure or compare structur...Preparation of the temporal bone for light microscopy is an important step in histological studies of the inner ear. Due to the complexity of structures of the inner ear, it is difficult to measure or compare structures of interest without a commonly accepted standardized measure of temporal bone sections. Therefore, standardization of temporal bone sections is very important for histological assessment of sensory hair cells and peripheral ganglion neurons in the cochlear and vestibular systems. The standardized temporal bone sectioning is oriented to a plane parallel to the outer and internal auditory canals. Sections are collected from the epitympanum to the hypotympanum to reveal layers in the order of the crista ampullaris of the superior and lateral semicircular canals, macula utriculi and macula sacculi, superior vestibular ganglion neurons, macula of saccule and inferior vestibular ganglion neurons, cochlear modiolus, endolymphatic duct and endolymphatic sac, and finally the crista ampullaris of the posterior semicircular canal. Moreover, technical details of preparing for temporal bone sectioning including fixation,decalcification, whole temporal bone staining, embedding penetration, and embedding orientation are also discussed.展开更多
Zebrafish have the potential to regrow injured organs and tissues,but their use as a model for hearing regeneration following blast injury has never been reported.In this study,zebrafish were exposed to a blast wave p...Zebrafish have the potential to regrow injured organs and tissues,but their use as a model for hearing regeneration following blast injury has never been reported.In this study,zebrafish were exposed to a blast wave produced by an underwater blast wave generator.The first peak sound pressures produced by this generator were up to 224dB and 160kPa,measured at 25cm away from the machine.Zebrafish hearing sensitivity was examined by analyzing auditory evoked potentials from 1 to 35 days post blast wave exposure.Cell death and cell proliferation in inner ear organs,including the saccule,lagena,and utricle,were investigated using a terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay,and cell proliferation assay using 5-ethynyl-20-deoxyuridine,respectively.Significant differences in auditory evoked potential thresholds were observed between exposed and control groups,demonstrating both blast wave-induced hearing loss and recovery of hearing sensitivity.An apoptosis assay revealed significantly increased numbers of terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labelingpositive cells in the inner ear sensory epithelia of exposed groups compared with the control group.However,numbers of 5-ethynyl-20-deoxyuridine-positive cells in the inner ear of exposed groups recovered to a normal level within 10 post blast wave exposure.Furthermore,blast wave exposure caused brain injury with increased cell apoptosis and decreased neurogenesis.Compared with drug or noise-induced zebrafish models,our blast wave-induced model elicited more serious hearing loss phenotypes,which required more time to return to a normal level.Overall,this zebrafish model can provide a reliable animal model for both hearing loss and regeneration research.The study was approved by the Shanghai 6th Hospital Animal Care and Use Committee,China(approval No.2017-0196)on February 28,2017.展开更多
The vestibular system involves high-level sensory and cognitive processes,such as spatial perception,balance control,visual stability,and emotional control.Vestibular dysfunction can induce vertigo,blurred vision,post...The vestibular system involves high-level sensory and cognitive processes,such as spatial perception,balance control,visual stability,and emotional control.Vestibular dysfunction can induce vertigo,blurred vision,postural imbalance,walking instability,and spatial discomfort,which causes serious damage to health.It has long been known that after peripheral vestibular lesion,vestibular dysfunction may spontaneously recover.This is known as vestibular compensation.However,at least 20%to 30%of patients with vestibular disorders cannot yield vestibular compensation and remain with vestibular dysfunction for the rest of their lives.The exploration of the biological characteristics and regulatory factors of the loss and reestablishment of vestibular function will establish a new understanding of the mechanism of vestibular compensation and provide new tools and strategies for promoting vestibular rehabilitation.We aim to comprehensively review the mechanism of vestibular compensation and discuss future directions in this field.展开更多
基金supported in part by a grant from NIOSH(R01OH010235)in part by NIH grant 5ROlDC011808+1 种基金in part by grant NIH ROIDC014437in part by foundation of Science and Technology Commission of Shanghai Municipality(NO 15140900900)
文摘Cisplatin, a widely used anticancer drug, damages hair cells in cochlear organotypic cultures at low doses, but paradoxically causes little damage at high doses resulting in a U-shaped dose-response function. To determine if the cisplatin dose-response function for vestibular hair cells follows a similar pattern, we treated vestibular organotypic cultures with doses of cisplatin ranging from 10 to 1000 μM. Vestibular hair cell lesions progressively increased as the dose of cisplatin increased with maximum damage occurring around 50-100 μM, but the lesions progressively decreased at higher doses resulting in little hair cell loss at 1000 μM. The U-shaped doseresponse function for cisplatin-treated vestibular hair cells in culture appears to be regulated by copper transporters, Ctrl, ATP7A and ATP7B, that dose-dependently regulate the uptake, sequestration and extrusion of cisplatin.
基金supported in part by a grant from NIHR01DC014437in part by the foundation of Science and Technology Commission of Shanghai Municipality (NO 15140900900)
文摘The imbalance of reactive oxygen species and antioxidants is considered to be an important factor in the cellular injury of the inner ear. At present, great attention has been placed on oxidative stress. However,little is known about fighting oxidative stress. In the current study, we evaluated antioxidant-induced cochlear damage by applying several different additional antioxidants. To determine whether excessive antioxidants can cause damage to cochlear cells, we treated cochlear explants with 50 m M M40403, a superoxide dismutase mimetic, 50 m M coenzyme Q-10, a vitamin-like antioxidant, or 50 m M d-methionine, an essential amino acid and the important antioxidant glutathione for 48 h. Control cochlear explants without the antioxidant treatment maintained their normal structures after incubation in the standard serum-free medium for 48 h, indicating the maintenance of the inherent oxidative and antioxidant balance in these cochlear explants. In contrast, M40403 and coenzyme Q-10-treated cochlear explants displayed significant hair cell damage together with slight damage to the auditory nerve fibers.Moreover, d-methiodine-treated explants exhibited severe damage to the surface structure of hair cells and the complete loss of the spiral ganglion neurons and their peripheral fibers. These results indicate that excessive antioxidants are detrimental to cochlear cells, suggesting that inappropriate dosages of antioxidant treatments can interrupt the balance of the inherent oxidative and antioxidant capacity in the cell.
文摘Preparation of the temporal bone for light microscopy is an important step in histological studies of the inner ear. Due to the complexity of structures of the inner ear, it is difficult to measure or compare structures of interest without a commonly accepted standardized measure of temporal bone sections. Therefore, standardization of temporal bone sections is very important for histological assessment of sensory hair cells and peripheral ganglion neurons in the cochlear and vestibular systems. The standardized temporal bone sectioning is oriented to a plane parallel to the outer and internal auditory canals. Sections are collected from the epitympanum to the hypotympanum to reveal layers in the order of the crista ampullaris of the superior and lateral semicircular canals, macula utriculi and macula sacculi, superior vestibular ganglion neurons, macula of saccule and inferior vestibular ganglion neurons, cochlear modiolus, endolymphatic duct and endolymphatic sac, and finally the crista ampullaris of the posterior semicircular canal. Moreover, technical details of preparing for temporal bone sectioning including fixation,decalcification, whole temporal bone staining, embedding penetration, and embedding orientation are also discussed.
基金the State Key Program of National Natural Science Foundation of China(No.81530029 to SY)International Cooperation and Exchange of the National Natural Science Foundation of China(No.8171001156 to SY)+1 种基金National Natural Science Foundation of China(No.81771007 to JW)the Major Program of Shanghai Committee of Science and Technology of China(No.14DJ1400202 to SY).
文摘Zebrafish have the potential to regrow injured organs and tissues,but their use as a model for hearing regeneration following blast injury has never been reported.In this study,zebrafish were exposed to a blast wave produced by an underwater blast wave generator.The first peak sound pressures produced by this generator were up to 224dB and 160kPa,measured at 25cm away from the machine.Zebrafish hearing sensitivity was examined by analyzing auditory evoked potentials from 1 to 35 days post blast wave exposure.Cell death and cell proliferation in inner ear organs,including the saccule,lagena,and utricle,were investigated using a terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay,and cell proliferation assay using 5-ethynyl-20-deoxyuridine,respectively.Significant differences in auditory evoked potential thresholds were observed between exposed and control groups,demonstrating both blast wave-induced hearing loss and recovery of hearing sensitivity.An apoptosis assay revealed significantly increased numbers of terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labelingpositive cells in the inner ear sensory epithelia of exposed groups compared with the control group.However,numbers of 5-ethynyl-20-deoxyuridine-positive cells in the inner ear of exposed groups recovered to a normal level within 10 post blast wave exposure.Furthermore,blast wave exposure caused brain injury with increased cell apoptosis and decreased neurogenesis.Compared with drug or noise-induced zebrafish models,our blast wave-induced model elicited more serious hearing loss phenotypes,which required more time to return to a normal level.Overall,this zebrafish model can provide a reliable animal model for both hearing loss and regeneration research.The study was approved by the Shanghai 6th Hospital Animal Care and Use Committee,China(approval No.2017-0196)on February 28,2017.
基金supported by the Shanghai Leadership Talent Training Plan(No.2017062)Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(No.20152233)Multicenter Clinical Research Plan of Medical College of Shanghai Jiao Tong University(No.DLY201823).
文摘The vestibular system involves high-level sensory and cognitive processes,such as spatial perception,balance control,visual stability,and emotional control.Vestibular dysfunction can induce vertigo,blurred vision,postural imbalance,walking instability,and spatial discomfort,which causes serious damage to health.It has long been known that after peripheral vestibular lesion,vestibular dysfunction may spontaneously recover.This is known as vestibular compensation.However,at least 20%to 30%of patients with vestibular disorders cannot yield vestibular compensation and remain with vestibular dysfunction for the rest of their lives.The exploration of the biological characteristics and regulatory factors of the loss and reestablishment of vestibular function will establish a new understanding of the mechanism of vestibular compensation and provide new tools and strategies for promoting vestibular rehabilitation.We aim to comprehensively review the mechanism of vestibular compensation and discuss future directions in this field.
