Pig models are widely used in otological research. The establishment of common pig and miniature pig animal models has opened up new fields in otological research and is also an ideal large otological animal model. Th...Pig models are widely used in otological research. The establishment of common pig and miniature pig animal models has opened up new fields in otological research and is also an ideal large otological animal model. This article introduces the applications, current status, progress, advantages, and issues of using pigs as otologic animal models. It summarizes current research on pigs in the fields of hearing disorders, otitis, vertigo, cochlea, gene editing, and tissue engineering, among other otologic and audiological areas. These models are valuable for translating basic medical science into clinical applications. Based on this, platforms have been established for studying deafness and vertigo, cochlear implantation experiments, stem cell and gene therapy, and tissue engineering. These serve as ideal experimental models for the prevention and treatment of ear diseases, pointing toward new directions. This will bolster the promotion and application of pig models in the fields of tissue engineering and gene editing in the future.展开更多
Objective: Tinnitus-a common clinical symptom-can be categorized into pulsatile tinnitus(PT) and non-PT. Among these, PT is usually associated with sigmoid sinus symptoms, such as sigmoid sinus wall defect or divertic...Objective: Tinnitus-a common clinical symptom-can be categorized into pulsatile tinnitus(PT) and non-PT. Among these, PT is usually associated with sigmoid sinus symptoms, such as sigmoid sinus wall defect or diverticulum, for which various surgical treatments are available. We have discussed the clinical efficacy of surgery for sigmoid sinus-associated PT via the transmastoid approach in this study.Methods: We conducted a retrospective review of 4 patients who underwent surgery for sigmoid sinusassociated PT via the transmastoid approach at Nanjing Drum Tower Hospital from January to December2020. Of these, 2 patients had sigmoid sinus wall defect and 2 had sigmoid sinus diverticulum. Postoperative tinnitus grading and surgical efficacy were determined.Results: After surgery, PT dissolved in 3 patients, while tinnitus significantly decreased in 1 patient.During the follow-up period of 12-18 months, none of the 4 patients showed complications related to increased intracranial pressure or venous sinus thrombosis, and tinnitus symptoms disappeared in 3patients without recurrence, although 1 patient occasionally developed tinnitus. Postoperative thin-slice CTA of the temporal bone indicated that the sigmoid sinus bone wall defect or diverticulum was completely repaired with a thick soft tissue coverage.Conclusion: Surgical repair of sigmoid sinus-associated PT via the transmastoid approach deserves clinical promotion as it exhibited better efficiency while being relatively less invasive.展开更多
Hereditary hearing loss(HHL),a genetic disorder that impairs auditory function,significantly affects quality of life and incurs substantial economic losses for society.To investigate the underlying causes of HHL and e...Hereditary hearing loss(HHL),a genetic disorder that impairs auditory function,significantly affects quality of life and incurs substantial economic losses for society.To investigate the underlying causes of HHL and evaluate therapeutic outcomes,appropriate animal models are necessary.Pigs have been extensively used as valuable large animal models in biomedical research.In this review,we highlight the advantages of pig models in terms of ear anatomy,inner ear morphology,and electrophysiological characteristics,as well as recent advancements in the development of distinct genetically modified porcine models of hearing loss.Additionally,we discuss the prospects,challenges,and recommendations regarding the use pig models in HHL research.Overall,this review provides insights and perspectives for future studies on HHL using porcine models.展开更多
Odontogenic maxillary sinusitis (OMS) is a subtype of maxillary sinusitis (MS). It is actually inflammation of the maxillary sinus that secondary to adjacent infectious maxillary dental lesion. Due to the lack of uniq...Odontogenic maxillary sinusitis (OMS) is a subtype of maxillary sinusitis (MS). It is actually inflammation of the maxillary sinus that secondary to adjacent infectious maxillary dental lesion. Due to the lack of unique clinical features, OMS is difficult to distinguish from other types of rhinosinusitis. Besides, the characteristic infectious pathogeny of OMS makes it is resistant to conventional therapies of rhinosinusitis. Its current diagnosis and treatment are thus facing great difficulties. The multi-disciplinary cooperation between otolaryngologists and dentists is absolutely urgent to settle these questions and to acquire standardized diagnostic and treatment regimen for OMS. However, this disease has actually received little attention and has been underrepresented by relatively low publication volume and quality. Based on systematically reviewed literature and practical experiences of expert members, our consensus focuses on characteristics, symptoms, classification and diagnosis of OMS, and further put forward multidisciplinary treatment decisions for OMS, as well as the common treatment complications and relative managements. This consensus aims to increase attention to OMS, and optimize the clinical diagnosis and decision-making of OMS, which finally provides evidence-based options for OMS clinical management.展开更多
Tumor resection causes damage in the head and neck which creates problems in swallowing, chewing, articulation, and vision, all of which seriously affect patients' quality of life. In this work, we evaluated the a...Tumor resection causes damage in the head and neck which creates problems in swallowing, chewing, articulation, and vision, all of which seriously affect patients' quality of life. In this work, we evaluated the application of a free medial tibial flap in reconstruction of head and neck defects after tumor resection. We discussed the anatomy, surgical technique, and the advantages and disadvantages of the flap. We found several benefits for the flap, such as, it is especially effective for the defects that require thin-layer epithelium to cover or the separated soft tissue defect; a two-team approach can be used because the donor site is far away from the head and neck; and the flap is easy to integrate because of the subcutaneous fat layer of the free medial tibial flap is thin and the flap is soft. Thus, the medial tibial flap could replace the forearm flap for certain applications.展开更多
AIM: To construct functional human full-thickness corneal replacements.METHODS: Acellular porcine corneal matrix(APCM) was developed from porcine cornea by decellulariztion. The biomechanical properties of anterior-AP...AIM: To construct functional human full-thickness corneal replacements.METHODS: Acellular porcine corneal matrix(APCM) was developed from porcine cornea by decellulariztion. The biomechanical properties of anterior-APCM(AAPCM) and posterior-APCM(PAPCM) were checked using uniaxial tensile testing. Human corneal cells were obtained by cell culture. Suspending ring was designed by deformation of an acupuncture needle. MTT cytotoxicity assay was used to check the cytotoxicity of suspending ring soaking solutions. A new three-dimensional organ culture system was established by combination of suspending ring, 48-well plate and medium together. A human full-thickness corneal substitute was constructed from human corneal cells with AAPCM in an organ coculture system. Biochemical marker expression of the construct was measured by immunofluorescent staining and morphological structures were observed using scanning electron microscopy. Pump function and biophysical properties were examined by penetrating keratoplasty and follow-up clinical observations.RESULTS: There were no cells in the AAPCM or PAPCM, whereas collagen fibers, Bowman's membrane, and Descemet's membrane were retained. The biomechanical property of AAPCM was better than PAPCM. Human corneal cells grew better on the AAPCM than on the PAPCM.There was no cytotoxicity for the suspending ring soaking solutions. For the constructed full-depth human corneal replacements keratocytes scattered uniformly throughout the AAPCM and expressed vimentin. The epithelial layer was located on the surface of Bowman's membrane and composed of three or four layers of epithelial cells expressing cytokeratin 3. One layer of endothelial cells covered the stromal surface of AAPCM, expressed Na+/K+ATPase and formed the endothelial layer. The construct was similar to normal human corneas, with many microvilli on the epithelial cell surface, stromal cells with a long shuttle shape, and zonula occludens on the interface of endothelial cells. The construct withstood surgical procedures during penetrating keratoplasty. The corneal transparency increased gradually and was almost completely restored 7 d after surgery.CONCLUSION: AAPCM is an ideal scaffold for constructing full-thickness corneal replacement, and functional human full-thickness corneal replacements are successfully constructed using AAPCM and human corneal cells.展开更多
BACKGROUND： Previous studies have shown that extracellular signal-regulated kinase 1/2 （ERK1/2） and nitric oxide activation play a pivotal role in central sensitization and long-term neuronal plasticity induced by ...BACKGROUND： Previous studies have shown that extracellular signal-regulated kinase 1/2 （ERK1/2） and nitric oxide activation play a pivotal role in central sensitization and long-term neuronal plasticity induced by noxious stimulation. However, their effects on compressive neuralgia formation and maintenance remain poorly understood.OBJECTIVE： To investigate effects of the specific inhibitor of ERK1/2 signal pathway U0126 on neuronal nitric oxide synthase （nNOS） expression in the dorsal horn of the spinal cord in a compressive neuralgia rat model.DESIGN, TIME AND SETTING： A randomized, controlled experiment was performed at the Institute of Otolaryngology, Head and Neck Surgery, First Hospital of Jilin University from July 2008 to March 2009.MATERIALS： U0126 （Bio-Mol, USA） was used in this study.METHODS： A total of 84 rats were randomly assigned to two groups. In the first part of the experiment, 24 rats were used for behavioral testing, and they were randomly assigned to three sub-groups （n =8）： U0126, dimethyl sulfoxide （DMSO） and model control. In the second part of the experiment, 60 rats were used for immunofluorescence and Western blot analysis, and they were randomly assigned to six sub-groups （n = 10）： sham surgery, model control, U0126 post-injection at 0.5, 2, 12 and 24 hours. Neuropathic pain was produced by chronic compression to the dorsal root ganglion in rats from each sub-group. Rats in the U0126 group were administered a 5-ug U0126 intrathecal injection, and rats in the DMSO group were administered a 10-μL 5% DMSO intrathecal injection.MAIN OUTCOME MEASURES： Changes in mechanical and thermal hyperalgesia were observed using von Frey filaments and thermalqia stimular. Thermal and mechanical hyperalgesia were stimulated at different time points following intrathecal injection of U0126. nNOS activation and expression in the spinal cord dorsal horn were determined by immunofluorescence and Western blot analysis.RESULTS： Intrathecal injection of U0126 significantly attenuated chronic compression of dorsal root ganglion-induced mechanical and thermal hyperalgesia. Immunofluorescence staining results demonstrated that, compared to the sham surgery group, the number of nNOS-positive neurons was significantly increased in the injured spinal dorsal horn in the model control group （P〈0.01）. However, compared to the model control group, there were significantly decreasing numbers of nNOS-positive neurons in the U0126 post-injection groups at 0.5-hour, 2-hour, and 12-hour （P〈0.05）. Western blot analysis revealed similar results. CONCLUSION： Decreased activity in the ERK signal pathway resulted in down regulated nNOS expression in the dorsal horn of the spinal cord. These results suggested that ERK is involved in nitric oxide reaction to neuropathic pain.展开更多
Objectives: Facial nerve aberration is the most troublesome situation in congenital malformations of middle ear.The aim of our study is to investigate its imaging and clinical features as well as relevant choice of su...Objectives: Facial nerve aberration is the most troublesome situation in congenital malformations of middle ear.The aim of our study is to investigate its imaging and clinical features as well as relevant choice of surgical techniques for hearing improvement.Methods: A retrospective study involving review of clinical data of 227 patients(256 ears) with congenital middle ear anomaly was undertaken, including preoperative computed tomography(CT) data, surgical records and videos.Results: Aberration involving intratemporal facial nerve was found in 82/256 ears(32.03%) with congenital middle ear anomaly. The most common forms of aberration included overhanging over the oval window(50/82 ears, 60.98%), bifurcation(3/82 ears, 3.66%) and transverse over the promontory(3/82 ears, 3.66%), counting for 68.29%(56/82) of the cases with facial nerve aberration. Concomitant stapes malformation was found in 76/82 ears(92.68%) and atresia or stenosis of the oval window in 27/82 ears(32.93%). In 9/82 ears(10.98%) both stapes and oval window was absent. Elective surgeries for the purpose of hearing improvement included stapodotomy + piston implantation, labyrinthotomy, labyrinthotomy + total ossicular replacement prosthesis(TORP) implantation and Vibrant Soundbridge(VSB) implantation.Conclusion: The majority of facial nerve aberration in congenital malformation of middle ear involves displacement of facial nerve, in addition to concomitant malformations of the stapes and/or oval window, which may influence the choice of surgery for hearing improvement. VSB implantation may be considered as a useful option.展开更多
In medical laboratory animals, the pig is the closest species to human in evolution, except for primates. As an animal model, the pig is highly concerned by many scientists, including comparative biology, developmenta...In medical laboratory animals, the pig is the closest species to human in evolution, except for primates. As an animal model, the pig is highly concerned by many scientists, including comparative biology, developmental biology, medical genetics. Rodents as animal model for human hearing defects has are poor producibility and reliability, due to differences in anatomical structure, evolutionary rate and metabolic rate, but these happens to be the advantages of the pig model. In this paper, we will summarize the application of miniature pig in the study of human hereditary deafness.展开更多
Objective To study presynaptic alternations of cochlear ribbons arising from aminoglycoside ototoxic stimuli in C57BL/6J mice. Methods Animals were injected with low dose gentamicin (100 mg/kg/day) for 14 days, From t...Objective To study presynaptic alternations of cochlear ribbons arising from aminoglycoside ototoxic stimuli in C57BL/6J mice. Methods Animals were injected with low dose gentamicin (100 mg/kg/day) for 14 days, From the 14th to 28th days, the mice were maintained free of gentamicin treatment. Immunohisto-chemistry labeling was employed to trace RIBEYE, a major presynaptic componment of ribbon synapses. RIBEYE/CtBP2 expression levels were assessed and compared with hearing threshold shifts. Auditory func-tion was assessed by auditory brainstem responses. The stereocilia of outer hair cells (OHCs) and IHCs was examined by scanning electron microscopy (SEM). Results Hearing thresholds were elevated with peak hearing loss observed on the 7th day after gentamicin exposure, followed by improvement after the 7th day. RIBEYE/CtBP2 expression directly correlated with observed hearing threshold shifts. Strikingly, we did not see any obvious changes in stereocilia in both OHCs and IHCs until the 28th day. Mild changes in stereocil-ia were only observed in OHCs on the 28th day. Conclusions These findings indicate that presynapse co-chlear ribbons, rather than stereocilia, may be sensitive to aminoglycoside ototoxic exposure in mice cochle-ae. A pattern of RIBEYE/CtBP2 expression changes seems to parallel hearing threshold shifts and suggests presynaptic response properties to lower dosage of aminoglycoside ototoxic stimuli.展开更多
Cell-cell junctions in the cochlea are highly complex and well organized. The role of these junctions is to maintain structural and functional integrity of the cochlea. In this review, we describe classification of ce...Cell-cell junctions in the cochlea are highly complex and well organized. The role of these junctions is to maintain structural and functional integrity of the cochlea. In this review, we describe classification of cell junction-associated proteins identified within the cochlea and provide a brief overview of the function of these proteins in adherent junctions, gap junctions and tight junctions. Copyright ? 2016, PLA General Hospital Department of Otolaryngology Head and Neck Surgery. Production and hosting by Elsevier (Singapore) Pte Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).展开更多
The development of auditory synapses is a key process for the maturation of heating function. However, it is still on debate regaralng wnemer the development of auditory synapses is dominated by acquired sound stimula...The development of auditory synapses is a key process for the maturation of heating function. However, it is still on debate regaralng wnemer the development of auditory synapses is dominated by acquired sound stimulations. In this review, we summarize relevant publications in recent decades to address this issue. Most reported data suggest that extrinsic sound stimulations do affect, but not govern the development of periphery auditory synapses. Overall, periphery auditory synapses develop and mature according to its intrinsic mechanism to build up the synaptic connections between sensory neurons and/or interneurons.展开更多
Background:Noise exposure can lead to hearing loss and multiple system dysfunctions.As various forms of noise exist in our living environments,and our auditory organs are very sensitive to acoustic stimuli,it is a cha...Background:Noise exposure can lead to hearing loss and multiple system dysfunctions.As various forms of noise exist in our living environments,and our auditory organs are very sensitive to acoustic stimuli,it is a challenge to protect our hearing system in certain noisy environments.Presentation of the hypothesis:Herein,we propose that our hearing organ could serve as a noise eliminator for high intensity noise and enhance acoustic signal processing abilities by increasing the signal-noise ratio.For suprathreshold signals,the hearing system is capable of regulating the middle ear muscles and other structures to actively suppress the sound level to a safe range.Testing the hypothesis:To test our hypothesis,both mathematic model analyses and animal model studies are needed.Based on a digital 3D reconstructed model,every structure in the auditory system can be analyzed and tested for its contribution to the process of noise reduction.Products manufactured by this bionic method could be used and verified in animal models and volunteers.Implications:By mimicking the noise-reduction effect of the sophisticated structures in the hearing system,we may be able to provide a model that establishes a new active-sound-suppression mode.This innovative method may overcome the limited capabilities of current noise protection options and become a promising possibility for noise prevention.展开更多
ECAPs are the summary of multiple neurons’ spikes which could be recorded by a bidirectional stimulation-recording system via the cochlear implant,with the artifact elimination paradigms of forward-masking subtractio...ECAPs are the summary of multiple neurons’ spikes which could be recorded by a bidirectional stimulation-recording system via the cochlear implant,with the artifact elimination paradigms of forward-masking subtraction paradigm or alternating polarity paradigm.Three kinds of FDA approved cochlear implants support ECAP testing.This article is to summarize the clinical application of ECAP lest.ECAP test after insertion of electrode during implant operation has been widely used during cochlear implant surgery.In recent years.ECAP thresholds are also used to estimate the T levels and C levels helping programming.However,correlation between ECAP thresholds and psychophysical thresholds is affected by many factors.So far,ECAPs cannot yet be a good indicator of post-operative hearing and speech performance.展开更多
Objective To test Calcium ion(Ca2+) flow at the head and end of outer hair cells(OHCs) in resting state and in response to Nimodipine treatment.Methods Non-invasive micro-test techniques were used to study Ca2+ in iso...Objective To test Calcium ion(Ca2+) flow at the head and end of outer hair cells(OHCs) in resting state and in response to Nimodipine treatment.Methods Non-invasive micro-test techniques were used to study Ca2+ in isolated OHCs in adult guinea pigs.Results Four types of Ca2+ transport were identified in OHCs on basilar membrane tissue fragments:influx at the head of with efflux at the bottom(type 1):efflux at the head of OHCs with influx at the bottom(type 2);influx at the both head and bottom(type 3);and efflux at the both head and bottom(type 4).However,only type 1 and type 3 of Ca2+ ion transport were detected in the cochlea.We propose that Ca2+ ion transport exists in adult guinea pig cochlear OHCs in resting state and is variable.Ca2 + flow in OHC can be inhibited by Nimodipine in resting state.展开更多
Objective To study characteristics of hearing loss after exposure to moderate noise exposure in C57BL/6J mice. Methods Male C57BL/6J mice with normal hearing at age of 5-6 weeks were chosen for this study. The mice we...Objective To study characteristics of hearing loss after exposure to moderate noise exposure in C57BL/6J mice. Methods Male C57BL/6J mice with normal hearing at age of 5-6 weeks were chosen for this study. The mice were randomly sclccted to be studied immediately after exposure （Group P0）, or 1 day （Group P1）, 3 days （Group P3）, 7 day （Group P7） or 14 days （P14） after exposure. Their before exposure condition served as the normal control. All mice were exposed to a broad-band white noise at 100 dB SPL for 2 hours, ABR thresholds were used to estimate hearing status at each time point. Results ABR threshold elevation was seen at every tested frequency at P0 （P〈0.01）. Elevation at high-frequencies （16 kHz and 32 kHz） was greater than at lower frequencies （4 kHz and 8 kHz, P〈0.05）. From P1 to P14, ABR thresholds continuously improved, and there was no significant difference between P14 and before exposure （P〉0.05）. Conclusion There is a frequency specific re- sponse to 100 dB SPL broad-band white noise in C57BL/6J mice, with the high-frequency being more susceptible. Hearing loss induced by moderate noise exposure appears reversible in C57BL/6J mice.展开更多
Object： To identify transcript variants and expression patterns of porcine Mitf. Materials and methods： A pairwise BLAST search at NCBI database was performed to deduce the structure of porcine Mitf gene. Subsequent...Object： To identify transcript variants and expression patterns of porcine Mitf. Materials and methods： A pairwise BLAST search at NCBI database was performed to deduce the structure of porcine Mitf gene. Subsequently, 5＇ RACE and fluorescent quantitative RT-PCR were used to analyze the expression pattern of porcine Mitf in different tissues. Results： Four transcript variants of porcine Mitf, MITF-A, MITF-H, MITF-M and MITF-SUS were identified, all sharing high homology with those in humans, except Mitf-SUS.Conclusion： The sequence of porcine Mitf appear highly homologous to human MITF. However, only 4 transcript variants of porcine Mitf were identified in these minipigs, less than the 9 transcript variants in human MITF.展开更多
Objective To determine the effects of combined administration of furosemide and kanamycin on inner ear structures and the auditory nerve in rats. Methods The rats in the treatment group received intravenous injections...Objective To determine the effects of combined administration of furosemide and kanamycin on inner ear structures and the auditory nerve in rats. Methods The rats in the treatment group received intravenous injections of combined furosemide and kanamycin sulfate, and the rats in the normal control group received no treatment. The auditory brainstem response （ABR） test was carried out 7 days after drug administration to determine the effects of drug administration on hearing. Cochlear slice and cochlear wholcmount were prepared after 7 days of drug treatment. Results After 7 days of drug administration, ABR thresholds were significantly higher in the treatment group than in the control group and neurofilaments were significantly reduced, although the number of spiral ganglia showed no decrease and there were no signs of supporting cell injury. Conclusions Combined administration of furosemide and kanamyein sulfate has an apparent synergistic ototoxic effect. Although spiral ganglion damage may not be apparent within a short time period of drug administration, damage to auditory nerve fibers is obvious.展开更多
Ototoxic drugs can be used to produce a loss of cochlear hair cells to create animal models of deafness. However, to the best of our knowledge, there is no report on the establishment of a rat deafness model through t...Ototoxic drugs can be used to produce a loss of cochlear hair cells to create animal models of deafness. However, to the best of our knowledge, there is no report on the establishment of a rat deafness model through the combined application of aminoglycosides and loop diuretics. The aim of this study was to use single or combined administration of furosemide and kanamycin sulfate to establish rat models of deafness. The rats received intravenous injections of different doses of furosemide and/or intramuscular injections of kanamycin sulfate. The auditory brainstem response was measured to determine the hearing threshold after drug application. Immunocytochemistry and confocal microscopy were performed to evaluate inner ear morphology. In the group receiving combined administration of furosemide and kanamycin, the auditory brainstem response threshold showed significant elevation 3 days after administration, higher than that produced by furosemide or kanamycin alone. The hair cells showed varying degrees of injury, from the apical turn to the basal turn of the cochlea and from the outer hair cells to the inner hair cells. The spiral ganglion cells maintained a normal morphology during the first week after the hair cells completely disappeared, and then gradually degenerated. After 2 months, the majority of spiral ganglion cells disappeared, but a few remained. These findings demonstrate that the combined administration of furosemide and kanamycin has a synergistic ototoxic effect, and that these drugs can produce hair cell loss and hearing loss in rats. These findings suggest that even in patients with severe deafness, electronic cochlear implants may partially restore hearing.展开更多
Glutamate（Glu） is the major afferent excitatory neurotransmitter in the auditory system, and excessive Glu may play an important role in cochlear dysfunction. It is unclear how excessive Glu plays roles in cochlear ...Glutamate（Glu） is the major afferent excitatory neurotransmitter in the auditory system, and excessive Glu may play an important role in cochlear dysfunction. It is unclear how excessive Glu plays roles in cochlear dysfunction in cochlear organotypic cultures. In this study neonatal rat cochlear organotypic cultures were prepared, and then the cochlear tissues were incubated with a new medium containing specific concentrations of Glu（0.1, 0.5, 1, 10 or 20 mmol/L） for 24 h, or incubated with the medium containing a concentration of 20 mmol/L Glu for 6, 12, 24 or 72 h, respectively. It was found that when the cochlear tissues were cultured for 24 h, the inner hair cells（IHCs） were damaged at the concentration of 0.5 mmol/L Glu, and with the increases of the concentrations, the injury was gradually aggravated, and 20 mmol/L Glu resulted in the significant loss of IHCs. In the 20 mmol/L Glu groups, the stereocilia bundles were missing or disarrayed on a few IHCs after culture for 6 h and the damage effect was time-dependent. The missing of IHCs was more significant in the basal turn of the cochlea than in the middle turn of the cochlea under the same concentration of Glu exposure. These results suggest that excessive exogenous Glu affects the morphology of IHCs, but not affects the outer hair cells（OHCs） in cochlear organotypic cultures, and the excitotoxic effects are different on IHCs of different parts of the cochlea under the same concentration of Glu exposure.展开更多
文摘Pig models are widely used in otological research. The establishment of common pig and miniature pig animal models has opened up new fields in otological research and is also an ideal large otological animal model. This article introduces the applications, current status, progress, advantages, and issues of using pigs as otologic animal models. It summarizes current research on pigs in the fields of hearing disorders, otitis, vertigo, cochlea, gene editing, and tissue engineering, among other otologic and audiological areas. These models are valuable for translating basic medical science into clinical applications. Based on this, platforms have been established for studying deafness and vertigo, cochlear implantation experiments, stem cell and gene therapy, and tissue engineering. These serve as ideal experimental models for the prevention and treatment of ear diseases, pointing toward new directions. This will bolster the promotion and application of pig models in the fields of tissue engineering and gene editing in the future.
基金This study was supported by the National Natural Science Foundation of China(Nos.81870721)the Major Program of National Natural Science Foundation of China(Nos.82192862).
文摘Objective: Tinnitus-a common clinical symptom-can be categorized into pulsatile tinnitus(PT) and non-PT. Among these, PT is usually associated with sigmoid sinus symptoms, such as sigmoid sinus wall defect or diverticulum, for which various surgical treatments are available. We have discussed the clinical efficacy of surgery for sigmoid sinus-associated PT via the transmastoid approach in this study.Methods: We conducted a retrospective review of 4 patients who underwent surgery for sigmoid sinusassociated PT via the transmastoid approach at Nanjing Drum Tower Hospital from January to December2020. Of these, 2 patients had sigmoid sinus wall defect and 2 had sigmoid sinus diverticulum. Postoperative tinnitus grading and surgical efficacy were determined.Results: After surgery, PT dissolved in 3 patients, while tinnitus significantly decreased in 1 patient.During the follow-up period of 12-18 months, none of the 4 patients showed complications related to increased intracranial pressure or venous sinus thrombosis, and tinnitus symptoms disappeared in 3patients without recurrence, although 1 patient occasionally developed tinnitus. Postoperative thin-slice CTA of the temporal bone indicated that the sigmoid sinus bone wall defect or diverticulum was completely repaired with a thick soft tissue coverage.Conclusion: Surgical repair of sigmoid sinus-associated PT via the transmastoid approach deserves clinical promotion as it exhibited better efficiency while being relatively less invasive.
基金supported by the National Key Research and Development Program of China (2021YFA0805902,2022YFF0710703)National Natural Science Foundation of China (32201257)+1 种基金Science and Technology Innovation Project of Xiongan New Area (2022XAGG0121)Young Elite Scientists Sponsorship Program by the China Association for Science and Technology (2019QNRC001)。
文摘Hereditary hearing loss(HHL),a genetic disorder that impairs auditory function,significantly affects quality of life and incurs substantial economic losses for society.To investigate the underlying causes of HHL and evaluate therapeutic outcomes,appropriate animal models are necessary.Pigs have been extensively used as valuable large animal models in biomedical research.In this review,we highlight the advantages of pig models in terms of ear anatomy,inner ear morphology,and electrophysiological characteristics,as well as recent advancements in the development of distinct genetically modified porcine models of hearing loss.Additionally,we discuss the prospects,challenges,and recommendations regarding the use pig models in HHL research.Overall,this review provides insights and perspectives for future studies on HHL using porcine models.
基金project was supported by grants from National Natural Science Foundations of China (Nos. 82025010, 81630023, 81900917)Changjiang Scholars and Innovative Research Team (No. IRT13082)+4 种基金CAMS Innovation Fund for Medical Sciences (No. 2019-I2M-5-022)Beijing Municipal Science and Technology Commision (Nos. Z181100001618002, Z211100002921057)Capital’s Funds for Health Improvement and Research (No.CFH2022-1-1091)Beijing Municipal Administration of Hospitals’ Mission Project (No. SML20150203)Beijing Municipal Administration of Hospitals’ Dengfeng Project (No. DFL20190202)。
文摘Odontogenic maxillary sinusitis (OMS) is a subtype of maxillary sinusitis (MS). It is actually inflammation of the maxillary sinus that secondary to adjacent infectious maxillary dental lesion. Due to the lack of unique clinical features, OMS is difficult to distinguish from other types of rhinosinusitis. Besides, the characteristic infectious pathogeny of OMS makes it is resistant to conventional therapies of rhinosinusitis. Its current diagnosis and treatment are thus facing great difficulties. The multi-disciplinary cooperation between otolaryngologists and dentists is absolutely urgent to settle these questions and to acquire standardized diagnostic and treatment regimen for OMS. However, this disease has actually received little attention and has been underrepresented by relatively low publication volume and quality. Based on systematically reviewed literature and practical experiences of expert members, our consensus focuses on characteristics, symptoms, classification and diagnosis of OMS, and further put forward multidisciplinary treatment decisions for OMS, as well as the common treatment complications and relative managements. This consensus aims to increase attention to OMS, and optimize the clinical diagnosis and decision-making of OMS, which finally provides evidence-based options for OMS clinical management.
文摘Tumor resection causes damage in the head and neck which creates problems in swallowing, chewing, articulation, and vision, all of which seriously affect patients' quality of life. In this work, we evaluated the application of a free medial tibial flap in reconstruction of head and neck defects after tumor resection. We discussed the anatomy, surgical technique, and the advantages and disadvantages of the flap. We found several benefits for the flap, such as, it is especially effective for the defects that require thin-layer epithelium to cover or the separated soft tissue defect; a two-team approach can be used because the donor site is far away from the head and neck; and the flap is easy to integrate because of the subcutaneous fat layer of the free medial tibial flap is thin and the flap is soft. Thus, the medial tibial flap could replace the forearm flap for certain applications.
基金Supported by the Excellent Middle-aged and Yong Scientists Scientific Research Fund of Shandong Province,China(No.BS2014SW034)
文摘AIM: To construct functional human full-thickness corneal replacements.METHODS: Acellular porcine corneal matrix(APCM) was developed from porcine cornea by decellulariztion. The biomechanical properties of anterior-APCM(AAPCM) and posterior-APCM(PAPCM) were checked using uniaxial tensile testing. Human corneal cells were obtained by cell culture. Suspending ring was designed by deformation of an acupuncture needle. MTT cytotoxicity assay was used to check the cytotoxicity of suspending ring soaking solutions. A new three-dimensional organ culture system was established by combination of suspending ring, 48-well plate and medium together. A human full-thickness corneal substitute was constructed from human corneal cells with AAPCM in an organ coculture system. Biochemical marker expression of the construct was measured by immunofluorescent staining and morphological structures were observed using scanning electron microscopy. Pump function and biophysical properties were examined by penetrating keratoplasty and follow-up clinical observations.RESULTS: There were no cells in the AAPCM or PAPCM, whereas collagen fibers, Bowman's membrane, and Descemet's membrane were retained. The biomechanical property of AAPCM was better than PAPCM. Human corneal cells grew better on the AAPCM than on the PAPCM.There was no cytotoxicity for the suspending ring soaking solutions. For the constructed full-depth human corneal replacements keratocytes scattered uniformly throughout the AAPCM and expressed vimentin. The epithelial layer was located on the surface of Bowman's membrane and composed of three or four layers of epithelial cells expressing cytokeratin 3. One layer of endothelial cells covered the stromal surface of AAPCM, expressed Na+/K+ATPase and formed the endothelial layer. The construct was similar to normal human corneas, with many microvilli on the epithelial cell surface, stromal cells with a long shuttle shape, and zonula occludens on the interface of endothelial cells. The construct withstood surgical procedures during penetrating keratoplasty. The corneal transparency increased gradually and was almost completely restored 7 d after surgery.CONCLUSION: AAPCM is an ideal scaffold for constructing full-thickness corneal replacement, and functional human full-thickness corneal replacements are successfully constructed using AAPCM and human corneal cells.
基金Science and Technology Development Project Program of Jilin Province,China,No. 200505195
文摘BACKGROUND： Previous studies have shown that extracellular signal-regulated kinase 1/2 （ERK1/2） and nitric oxide activation play a pivotal role in central sensitization and long-term neuronal plasticity induced by noxious stimulation. However, their effects on compressive neuralgia formation and maintenance remain poorly understood.OBJECTIVE： To investigate effects of the specific inhibitor of ERK1/2 signal pathway U0126 on neuronal nitric oxide synthase （nNOS） expression in the dorsal horn of the spinal cord in a compressive neuralgia rat model.DESIGN, TIME AND SETTING： A randomized, controlled experiment was performed at the Institute of Otolaryngology, Head and Neck Surgery, First Hospital of Jilin University from July 2008 to March 2009.MATERIALS： U0126 （Bio-Mol, USA） was used in this study.METHODS： A total of 84 rats were randomly assigned to two groups. In the first part of the experiment, 24 rats were used for behavioral testing, and they were randomly assigned to three sub-groups （n =8）： U0126, dimethyl sulfoxide （DMSO） and model control. In the second part of the experiment, 60 rats were used for immunofluorescence and Western blot analysis, and they were randomly assigned to six sub-groups （n = 10）： sham surgery, model control, U0126 post-injection at 0.5, 2, 12 and 24 hours. Neuropathic pain was produced by chronic compression to the dorsal root ganglion in rats from each sub-group. Rats in the U0126 group were administered a 5-ug U0126 intrathecal injection, and rats in the DMSO group were administered a 10-μL 5% DMSO intrathecal injection.MAIN OUTCOME MEASURES： Changes in mechanical and thermal hyperalgesia were observed using von Frey filaments and thermalqia stimular. Thermal and mechanical hyperalgesia were stimulated at different time points following intrathecal injection of U0126. nNOS activation and expression in the spinal cord dorsal horn were determined by immunofluorescence and Western blot analysis.RESULTS： Intrathecal injection of U0126 significantly attenuated chronic compression of dorsal root ganglion-induced mechanical and thermal hyperalgesia. Immunofluorescence staining results demonstrated that, compared to the sham surgery group, the number of nNOS-positive neurons was significantly increased in the injured spinal dorsal horn in the model control group （P〈0.01）. However, compared to the model control group, there were significantly decreasing numbers of nNOS-positive neurons in the U0126 post-injection groups at 0.5-hour, 2-hour, and 12-hour （P〈0.05）. Western blot analysis revealed similar results. CONCLUSION： Decreased activity in the ERK signal pathway resulted in down regulated nNOS expression in the dorsal horn of the spinal cord. These results suggested that ERK is involved in nitric oxide reaction to neuropathic pain.
基金supported by Beijing Municipal Science&Technology Commission(No.2171100001017079)for Prof. Shouqin Zhao
文摘Objectives: Facial nerve aberration is the most troublesome situation in congenital malformations of middle ear.The aim of our study is to investigate its imaging and clinical features as well as relevant choice of surgical techniques for hearing improvement.Methods: A retrospective study involving review of clinical data of 227 patients(256 ears) with congenital middle ear anomaly was undertaken, including preoperative computed tomography(CT) data, surgical records and videos.Results: Aberration involving intratemporal facial nerve was found in 82/256 ears(32.03%) with congenital middle ear anomaly. The most common forms of aberration included overhanging over the oval window(50/82 ears, 60.98%), bifurcation(3/82 ears, 3.66%) and transverse over the promontory(3/82 ears, 3.66%), counting for 68.29%(56/82) of the cases with facial nerve aberration. Concomitant stapes malformation was found in 76/82 ears(92.68%) and atresia or stenosis of the oval window in 27/82 ears(32.93%). In 9/82 ears(10.98%) both stapes and oval window was absent. Elective surgeries for the purpose of hearing improvement included stapodotomy + piston implantation, labyrinthotomy, labyrinthotomy + total ossicular replacement prosthesis(TORP) implantation and Vibrant Soundbridge(VSB) implantation.Conclusion: The majority of facial nerve aberration in congenital malformation of middle ear involves displacement of facial nerve, in addition to concomitant malformations of the stapes and/or oval window, which may influence the choice of surgery for hearing improvement. VSB implantation may be considered as a useful option.
基金supported by grants from the National Basic Research Program of China(973 Program)(#2012CB967900),the Major State Basic Research Development Program of China (973 Program)(#2011CBA01000)the National Nature Science Foundation of China(NSFC#81400472)the National Natural Science Foundation of China(NSFC #81271082)
文摘In medical laboratory animals, the pig is the closest species to human in evolution, except for primates. As an animal model, the pig is highly concerned by many scientists, including comparative biology, developmental biology, medical genetics. Rodents as animal model for human hearing defects has are poor producibility and reliability, due to differences in anatomical structure, evolutionary rate and metabolic rate, but these happens to be the advantages of the pig model. In this paper, we will summarize the application of miniature pig in the study of human hereditary deafness.
基金supported by grants from the National Basic Research Program of China(973Program)(2012CB9679002012CB967901)+3 种基金Beijing Natural Science Foundation(5122040)supported by grants from the China Postdoctoral Science Foundation(20100377920100470103)the National Natural Science Foundation of China(NSFC)(31040 038)
文摘Objective To study presynaptic alternations of cochlear ribbons arising from aminoglycoside ototoxic stimuli in C57BL/6J mice. Methods Animals were injected with low dose gentamicin (100 mg/kg/day) for 14 days, From the 14th to 28th days, the mice were maintained free of gentamicin treatment. Immunohisto-chemistry labeling was employed to trace RIBEYE, a major presynaptic componment of ribbon synapses. RIBEYE/CtBP2 expression levels were assessed and compared with hearing threshold shifts. Auditory func-tion was assessed by auditory brainstem responses. The stereocilia of outer hair cells (OHCs) and IHCs was examined by scanning electron microscopy (SEM). Results Hearing thresholds were elevated with peak hearing loss observed on the 7th day after gentamicin exposure, followed by improvement after the 7th day. RIBEYE/CtBP2 expression directly correlated with observed hearing threshold shifts. Strikingly, we did not see any obvious changes in stereocilia in both OHCs and IHCs until the 28th day. Mild changes in stereocil-ia were only observed in OHCs on the 28th day. Conclusions These findings indicate that presynapse co-chlear ribbons, rather than stereocilia, may be sensitive to aminoglycoside ototoxic exposure in mice cochle-ae. A pattern of RIBEYE/CtBP2 expression changes seems to parallel hearing threshold shifts and suggests presynaptic response properties to lower dosage of aminoglycoside ototoxic stimuli.
基金supported by grants from the National Basic Research Program of China (973 Program) (#2012CB967900)the Major State Basic Research Development Program of China (973 Program) (#2011CBA01000)+1 种基金the National Nature Science Foundation of China (NSFC#81400472)the National Natural Science Foundation of China (NSFC #81271082)
文摘Cell-cell junctions in the cochlea are highly complex and well organized. The role of these junctions is to maintain structural and functional integrity of the cochlea. In this review, we describe classification of cell junction-associated proteins identified within the cochlea and provide a brief overview of the function of these proteins in adherent junctions, gap junctions and tight junctions. Copyright ? 2016, PLA General Hospital Department of Otolaryngology Head and Neck Surgery. Production and hosting by Elsevier (Singapore) Pte Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
基金supported by grants from the National Basic Research Program of China(973Program)(2012CB9679002012CB967901)+3 种基金Beijing Natural Science Foundation(5122040)supported by grants from the China Postdoctoral Science Foundation(20100377920100470103)the National Natural Science Foundation of China(NSFC)(31040038)
文摘The development of auditory synapses is a key process for the maturation of heating function. However, it is still on debate regaralng wnemer the development of auditory synapses is dominated by acquired sound stimulations. In this review, we summarize relevant publications in recent decades to address this issue. Most reported data suggest that extrinsic sound stimulations do affect, but not govern the development of periphery auditory synapses. Overall, periphery auditory synapses develop and mature according to its intrinsic mechanism to build up the synaptic connections between sensory neurons and/or interneurons.
基金supported by a Major Project of Twelfth Five-Year Plan(BWS14J045)a Major Project of the National Ministry of Science and Technology(2014ZX09J14101-06C)+3 种基金the National Natural Science Foundation of China(NSFC)(81528005,81470700)the National Key Basic Research Development Program(973 Program)(2012CB967900)the Hundred Leading Talent Project of High-Tech Beijinga Fostering Fund of the Beijing Science and Technology Commission on Frontier Technology in Life Sciences.
文摘Background:Noise exposure can lead to hearing loss and multiple system dysfunctions.As various forms of noise exist in our living environments,and our auditory organs are very sensitive to acoustic stimuli,it is a challenge to protect our hearing system in certain noisy environments.Presentation of the hypothesis:Herein,we propose that our hearing organ could serve as a noise eliminator for high intensity noise and enhance acoustic signal processing abilities by increasing the signal-noise ratio.For suprathreshold signals,the hearing system is capable of regulating the middle ear muscles and other structures to actively suppress the sound level to a safe range.Testing the hypothesis:To test our hypothesis,both mathematic model analyses and animal model studies are needed.Based on a digital 3D reconstructed model,every structure in the auditory system can be analyzed and tested for its contribution to the process of noise reduction.Products manufactured by this bionic method could be used and verified in animal models and volunteers.Implications:By mimicking the noise-reduction effect of the sophisticated structures in the hearing system,we may be able to provide a model that establishes a new active-sound-suppression mode.This innovative method may overcome the limited capabilities of current noise protection options and become a promising possibility for noise prevention.
基金supported by grants from the National Basic Research Program of China(973 Program)(#2012CB967900)Science and Technology Innovation Nursery Foundation of PLA General Hospital(13KMM14)Clinical Research Supporting Foundation of PLA General Hospital(2012FC-TSYS-3056)
文摘ECAPs are the summary of multiple neurons’ spikes which could be recorded by a bidirectional stimulation-recording system via the cochlear implant,with the artifact elimination paradigms of forward-masking subtraction paradigm or alternating polarity paradigm.Three kinds of FDA approved cochlear implants support ECAP testing.This article is to summarize the clinical application of ECAP lest.ECAP test after insertion of electrode during implant operation has been widely used during cochlear implant surgery.In recent years.ECAP thresholds are also used to estimate the T levels and C levels helping programming.However,correlation between ECAP thresholds and psychophysical thresholds is affected by many factors.So far,ECAPs cannot yet be a good indicator of post-operative hearing and speech performance.
文摘Objective To test Calcium ion(Ca2+) flow at the head and end of outer hair cells(OHCs) in resting state and in response to Nimodipine treatment.Methods Non-invasive micro-test techniques were used to study Ca2+ in isolated OHCs in adult guinea pigs.Results Four types of Ca2+ transport were identified in OHCs on basilar membrane tissue fragments:influx at the head of with efflux at the bottom(type 1):efflux at the head of OHCs with influx at the bottom(type 2);influx at the both head and bottom(type 3);and efflux at the both head and bottom(type 4).However,only type 1 and type 3 of Ca2+ ion transport were detected in the cochlea.We propose that Ca2+ ion transport exists in adult guinea pig cochlear OHCs in resting state and is variable.Ca2 + flow in OHC can be inhibited by Nimodipine in resting state.
基金supported by grants from the Liaoning Science and Technology Project(No.2011225017,2012225021)the National Basic Research Program of China(973 Program)(2012CB967900,2012CB967901)+2 种基金supported by the grants from the Beijing Natural Science Foundation(5122040)the China Postdoctoral Science Foundation(201003779,20100470103)the National Natural Science Foundation of China(NSFC,31040038)
文摘Objective To study characteristics of hearing loss after exposure to moderate noise exposure in C57BL/6J mice. Methods Male C57BL/6J mice with normal hearing at age of 5-6 weeks were chosen for this study. The mice were randomly sclccted to be studied immediately after exposure （Group P0）, or 1 day （Group P1）, 3 days （Group P3）, 7 day （Group P7） or 14 days （P14） after exposure. Their before exposure condition served as the normal control. All mice were exposed to a broad-band white noise at 100 dB SPL for 2 hours, ABR thresholds were used to estimate hearing status at each time point. Results ABR threshold elevation was seen at every tested frequency at P0 （P〈0.01）. Elevation at high-frequencies （16 kHz and 32 kHz） was greater than at lower frequencies （4 kHz and 8 kHz, P〈0.05）. From P1 to P14, ABR thresholds continuously improved, and there was no significant difference between P14 and before exposure （P〉0.05）. Conclusion There is a frequency specific re- sponse to 100 dB SPL broad-band white noise in C57BL/6J mice, with the high-frequency being more susceptible. Hearing loss induced by moderate noise exposure appears reversible in C57BL/6J mice.
基金supported by grants from the Major State Basic Research Development Program of China(973 Program)(#2011CBA01000)the National Basic Research Program of China(973 Program)(#2012CB967900)the National Natural Science Foundation of China(81400472)
文摘Object： To identify transcript variants and expression patterns of porcine Mitf. Materials and methods： A pairwise BLAST search at NCBI database was performed to deduce the structure of porcine Mitf gene. Subsequently, 5＇ RACE and fluorescent quantitative RT-PCR were used to analyze the expression pattern of porcine Mitf in different tissues. Results： Four transcript variants of porcine Mitf, MITF-A, MITF-H, MITF-M and MITF-SUS were identified, all sharing high homology with those in humans, except Mitf-SUS.Conclusion： The sequence of porcine Mitf appear highly homologous to human MITF. However, only 4 transcript variants of porcine Mitf were identified in these minipigs, less than the 9 transcript variants in human MITF.
基金supported by grants from the Major State Basic Research Development Program of China(973 Program)(#2011CBA01000)National Hi-Tech Research and Development Program of China(863 Program)(#2007AA02Z150)to SMY+1 种基金the National Natural Science Foundation of China(NSFC)(#30871398,30730040,30628030)to SMYNational Eleventh Scientific Program(2008BAI50B08,2007BAI18B12,2007BAI18B14)to SMY
文摘Objective To determine the effects of combined administration of furosemide and kanamycin on inner ear structures and the auditory nerve in rats. Methods The rats in the treatment group received intravenous injections of combined furosemide and kanamycin sulfate, and the rats in the normal control group received no treatment. The auditory brainstem response （ABR） test was carried out 7 days after drug administration to determine the effects of drug administration on hearing. Cochlear slice and cochlear wholcmount were prepared after 7 days of drug treatment. Results After 7 days of drug administration, ABR thresholds were significantly higher in the treatment group than in the control group and neurofilaments were significantly reduced, although the number of spiral ganglia showed no decrease and there were no signs of supporting cell injury. Conclusions Combined administration of furosemide and kanamyein sulfate has an apparent synergistic ototoxic effect. Although spiral ganglion damage may not be apparent within a short time period of drug administration, damage to auditory nerve fibers is obvious.
基金supported by grants from the National Program on Key Basic Research Project of China(973 Program),No.2011CBA01000,2012CB967900
文摘Ototoxic drugs can be used to produce a loss of cochlear hair cells to create animal models of deafness. However, to the best of our knowledge, there is no report on the establishment of a rat deafness model through the combined application of aminoglycosides and loop diuretics. The aim of this study was to use single or combined administration of furosemide and kanamycin sulfate to establish rat models of deafness. The rats received intravenous injections of different doses of furosemide and/or intramuscular injections of kanamycin sulfate. The auditory brainstem response was measured to determine the hearing threshold after drug application. Immunocytochemistry and confocal microscopy were performed to evaluate inner ear morphology. In the group receiving combined administration of furosemide and kanamycin, the auditory brainstem response threshold showed significant elevation 3 days after administration, higher than that produced by furosemide or kanamycin alone. The hair cells showed varying degrees of injury, from the apical turn to the basal turn of the cochlea and from the outer hair cells to the inner hair cells. The spiral ganglion cells maintained a normal morphology during the first week after the hair cells completely disappeared, and then gradually degenerated. After 2 months, the majority of spiral ganglion cells disappeared, but a few remained. These findings demonstrate that the combined administration of furosemide and kanamycin has a synergistic ototoxic effect, and that these drugs can produce hair cell loss and hearing loss in rats. These findings suggest that even in patients with severe deafness, electronic cochlear implants may partially restore hearing.
基金supported by grants from National Natural Science Foundation of China(No.30872858)Research Fund for Doctoral Program of Higher Education of China(No.200800250006)Beijing Municipal Natural Science Foundation of China(No.7082024)
文摘Glutamate（Glu） is the major afferent excitatory neurotransmitter in the auditory system, and excessive Glu may play an important role in cochlear dysfunction. It is unclear how excessive Glu plays roles in cochlear dysfunction in cochlear organotypic cultures. In this study neonatal rat cochlear organotypic cultures were prepared, and then the cochlear tissues were incubated with a new medium containing specific concentrations of Glu（0.1, 0.5, 1, 10 or 20 mmol/L） for 24 h, or incubated with the medium containing a concentration of 20 mmol/L Glu for 6, 12, 24 or 72 h, respectively. It was found that when the cochlear tissues were cultured for 24 h, the inner hair cells（IHCs） were damaged at the concentration of 0.5 mmol/L Glu, and with the increases of the concentrations, the injury was gradually aggravated, and 20 mmol/L Glu resulted in the significant loss of IHCs. In the 20 mmol/L Glu groups, the stereocilia bundles were missing or disarrayed on a few IHCs after culture for 6 h and the damage effect was time-dependent. The missing of IHCs was more significant in the basal turn of the cochlea than in the middle turn of the cochlea under the same concentration of Glu exposure. These results suggest that excessive exogenous Glu affects the morphology of IHCs, but not affects the outer hair cells（OHCs） in cochlear organotypic cultures, and the excitotoxic effects are different on IHCs of different parts of the cochlea under the same concentration of Glu exposure.
