Objectives: This study aimed to evaluate the responsiveness of cochlear nerve to electrical stimulation in patients with cochlear nerve deficiency(CND), to compare their results with those measured in implanted children with normal-sized cochlear nerves, and to investigate the characteristics of the cochlear nerve injury of children with CND. Methods: Participants were children who underwent cochlear implantation at Shandong Provincial ENT Hospital from January 2012 to January 2020, including CND group and control group. The CND group included 51 subjects (male:20; female: 31) who were diagnosed with CND and had normal cochlea. For the CND group, four children had been bilaterally implanted, the mean implantation age was (2.7±1.5) years old. The control group included 21 subjects (male:10; femal:11) who had normal-sized cochlear nerve and normal cochlea. For the control group, all children had been unilaterally implanted except one, and the mean implantation age was (3.0±1.9)years old. Three subjects in the CND group used CI422 electrode arrays, and all the other subjects used CI24RECA/CI512 electrode arrays. The electrically evoked compound action potentials (ECAP) had been tried to record for each electrode using Custom Sound EP software (v. 4.3, Cochlear Ltd.) at least six months post first activation. Furthermore, ECAP amplitude growth functions (AGF) were measured at multiple electrode locations across the electrode array. Generalized linear mixed effect models with the subject group and electrode location as the fixed effects and subjects as the random effect were used to compare results of ECAP measurements. Results: In the control group, ECAP could been recorded at all electrodes (100%), but it could only be recorded in 71% (859/1 210) electrodes in the CND group. Additionally, the percentage of electrodes with measurable ECAP decreased from electrode 1 to electrode 22 in the CND group. Compared to the control group, the ECAP thresholds significantly increased, the ECAP amplitudes and AGF slopes significantly decreased, and the ECAP latency significantly increased in the CND group (P<0.01). GLMM showed that the stimulating site had a significant effect on the ECAP threshold, maximum amplitude, and AGF slope (P<0.01), but had no significant effect on the ECAP latency (P>0.05) in the CND group. However, the stimulating site had no significant effects on the ECAP measurements in the control group. Furthermore, the functional status of cochlear nerve varied greatly among CND group. From electrode 1 to electrode 22, the ECAP thresholds gradually increased, the ECAP maximum amplitudes and AGF slopes gradually decreased in the CND group. Conclusion: Compared with patients with normal-sized cochlear nerve, not only the number of residual spinal ganglion neurons reduce,but also the function of spinal ganglion neurons damages in CND patients. The degree of cochlea nerve deterioration varies greatly among CND patients. Generally, the deterioration of cochlear nerve tends to increase from the basal to the apical site of the cochlea.
Child, Preschool ; Female ; Humans ; Infant ; Male ; Cochlea ; Cochlear Implantation/methods* ; Cochlear Implants ; Cochlear Nerve ; Electric Stimulation ; Evoked Potentials, Auditory/physiology*

Mice ; Animals ; Spiral Ganglion/physiology* ; Cochlea/physiology* ; Neurons

Objective: To study the protective effects of metformin on noise-induced hearing loss (NIHL) and its differential protein omics expression profile. Methods: In January 2021, 39 male Wistar rats were randomly divided into control group, noise exposure group and metformin+noise exposure group, with 13 rats in each group. Rats in the noise exposure group and metformin+noise exposure group were continuously exposed to octave noise with sound pressure level of 120 dB (A) and center frequency of 8 kHz for 4 h. Rats in the metformin+noise exposure group were treated with 200 mg/kg/d metformin 3 d before noise exposure for a total of 7 d. Auditory brainstem response (ABR) was used to test the changes of hearing thresholds before noise exposure and 1, 4, 7 d after noise exposure in the right ear of rats in each group. Tandem mass tag (TMT) quantitative proteomics was used to identify and analyze the differentially expressed protein in the inner ear of rats in each group, and it was verified by immunofluorescence staining with frozen sections. Results: The click-ABR thresholds of right ear in the noise exposure group and metformin+noise exposure group were significantly higher than those in the control group 1, 4, 7 d after noise exposure (P<0.05) . The click-ABR threshold of right ear in the metformin+noise exposure group were significantly lower than that in the noise exposure group (P<0.05) . Compared with the noise exposure group, 1035 up-regulated proteins and 1145 down-regulated proteins were differentially expressed in the metformin+noise exposure group. GO enrichment analysis showed that the significantly differentially expressed proteins were mainly involved in binding, molecular function regulation, signal transduction, and other functions. Enrichment analysis of KEGG pathway revealed that the pathways for significant enrichment of differentially expressed proteins included phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) signaling pathway, focal adhesion, diabetic cardiomyopathy, mitogen, and mitogen-activated protein kinase (MAPK) signaling pathway. Immunofluorescence experiments showed that compared with the noise exposure group, the fluorescence intensity of insulin-like growth factor 1 receptor (IGF1R) in the metformin+noise exposure group was increased, and the fluorescence intensity of eukaryotic translation initiation factor 4E binding protein 1 (eIF4EBP1) was decreased. Conclusion: Noise exposure can lead to an increase in rat hearing threshold, and metformin can improve noise-induced hearing threshold abnormalities through multiple pathways and biological processes.
Animals ; Auditory Threshold/physiology* ; Cochlea ; Ear, Inner ; Evoked Potentials, Auditory, Brain Stem/physiology* ; Hearing Loss, Noise-Induced/prevention & control* ; Male ; Metformin/pharmacology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Rats ; Rats, Wistar

High level noise can damage cochlear hair cells, auditory nerve and synaptic connections between cochlear hair cells and auditory nerve, resulting in noise-induced hearing loss (NIHL). Recent studies have shown that animal cochleae have circadian rhythm, which makes them different in sensitivity to noise throughout the day. Cochlear circadian rhythm has a certain relationship with brain-derived neurotrophic factor and glucocorticoids, which affects the degree of hearing loss after exposure to noise. In this review, we summarize the research progress of the regulation of cochlear sensitivity to noise by circadian rhythm and prospect the future research direction.
Animals ; Auditory Threshold ; Circadian Rhythm ; Cochlea ; Evoked Potentials, Auditory, Brain Stem/physiology* ; Hair Cells, Auditory ; Hearing Loss, Noise-Induced ; Noise/adverse effects*

More than 80% of all cases of deafness are related to the death or degeneration of cochlear hair cells and the associated spiral ganglion neurons, and a lack of regeneration of these cells leads to permanent hearing loss. Therefore, the regeneration of lost hair cells is an important goal for the treatment of deafness. Atoh1 is a basic helix-loop-helix (bHLH) transcription factor that is critical in both the development and regeneration of cochlear hair cells. Atoh1 is transcriptionally regulated by several signaling pathways, including Notch and Wnt signalings. At the post-translational level, it is regulated through the ubiquitin-proteasome pathway. In vitro and in vivo studies have revealed that manipulation of these signaling pathways not only controls development, but also leads to the regeneration of cochlear hair cells after damage. Recent progress toward understanding the signaling networks involved in hair cell development and regeneration has led to the development of new strategies to replace lost hair cells. This review focuses on our current understanding of the signaling pathways that regulate Atoh1 in the cochlea.
Basic Helix-Loop-Helix Transcription Factors/physiology* ; Cell Differentiation ; Cochlea/physiology* ; Hair Cells, Auditory/physiology* ; Hearing Loss/etiology* ; Humans ; Proteasome Endopeptidase Complex/physiology* ; Signal Transduction/physiology* ; Transcription Factors/physiology* ; Ubiquitin/metabolism* ; Wnt Signaling Pathway ; beta Catenin/physiology*

Bone morphogenetic proteins (BMPs) are the largest subfamily of the transforming growth factor-β superfamily, and they play important roles in the development of numerous organs, including the inner ear. The inner ear is a relatively small organ but has a highly complex structure and is involved in both hearing and balance. Here, we discuss BMPs and BMP signaling pathways and then focus on the role of BMP signal pathway regulation in the development of the inner ear and the implications this has for the treatment of human hearing loss and balance dysfunction.
Body Patterning ; Bone Morphogenetic Protein Receptors/physiology* ; Bone Morphogenetic Proteins/physiology* ; Cell Differentiation ; Cochlea/embryology* ; Ear, Inner/embryology* ; Hedgehog Proteins/physiology* ; Humans ; Signal Transduction/physiology* ; Smad Proteins/physiology* ; Vestibule, Labyrinth/embryology* ; Wnt Signaling Pathway

OBJECTIVE: To investigate the feasibility of the round window stimulation electrical evoked auditory brainstem response (EABR) test, and optimize the parameters of recording and stimulation electrodes positions. METHOD: Ten healthy Hartley guinea pigs (20 ears) were used for the EABR test. The positive stimulation electrodes were placed into the round window niche, the animals were divided into three group according to the negative electrodes position, group A: the electric field was parallel with the projection of cochlear modiolus on the tympanic membrane, group B: the electric field was perpendicular to modiolus projection toward to the mastoid, group C: the electric field was perpendicular to modiolus projection toward to the zygomatic process. A series of optimized recording and stimulation parameters were uesed to reduce the electrical artifact. RESULT: All the 20 ears were normal in the ABR testing, and EABR waves were stable and well-differentiated in the EABR tests out of cochlea. But EABR waves of group A were more stable and differentiated than those of group B and C. In group A, the threshold of EABR was (0.54 ± 0.11) mA, and latency of wave III was (1.71 ± 0.05) ms when the stimulus intensity was 0.8 mA. In group B, the threshold of EABR was (0.62 ± 0.12) mA, and latency of wave III was (1.77 ± 0.03) ms. In group C, the threshold of EABR was (0.70 ± 0.14) mA, and latency of wave III was (1.86 ± 0.04)ms. The threshold of EABR and latency of wave III were significantly different among the three groups by statistic analysis. CONCLUSION EABR waves were stable and well-differentiated in the EABR tests out of cochlea. The EABR waves were recorded more stably and differentiated when the stimulating electrode and recording electrode were paralleled with the projection of modiolus on the tympanic membrane.
Animals ; Cochlea ; physiology ; Electric Stimulation ; Electrodes ; Evoked Potentials, Auditory, Brain Stem ; Guinea Pigs ; Round Window, Ear ; Tympanic Membrane

OBJECTIVE: To study the relationship of distortion product in cochlea with cochlear activity and hearing. METHOD: Time variances of distortion product of basilar membrane vibration in vitro guineapig cochlea were observed by laser interferometry. RESULT: Within half hour after a cochlea was isolated from a guineapig, distortion product accompanied with two-tone inhibition in cochlea, can be observed. As time passed, distortion product and two-tone inhibition effect disappeared at the same time. After that, the membrane contiune vibrating in response to the sound stimulus, but the vibration amplitude decreased obviously and continued decreasing until it disappeared completely. CONCLUSION Distortion product in cochlea is a symbol of cochlear activity which makes the membrane respond in large amplitude vibration to sound stimulus and exhibit two-tone inhibition. The former makes the hearing highly sensitive to sound stimulus, the later makes the hearing perform information abstract well.
Acoustic Stimulation ; Animals ; Basilar Membrane ; physiology ; Cochlea ; physiology ; Guinea Pigs ; Hearing ; physiology ; Hearing Tests ; Interferometry ; Sound

OBJECTIVETo establish a mechanical simulation model for studying the relationship between the characteristic frequency and feature location of the basilar membrane of the cochlea.

METHODSMacro-mechanical methods were used to simplify the details of the model. With simulation tools, the basilar membrane vibration frequency characteristics were analyzed based on the box model.

RESULTSThe basilar membrane had obvious frequency-selective properties, and the basilar membrane from the stapes was sensitive to high frequencies while the farther membrane was sensitive to low frequencies.

CONCLUSIONThe frequency characteristics of the basilar membrane of the cochlea is mainly a result of the longitudinal variations of the geometric dimensions and material properties and is not related with other structures within the cochlea corti.

OBJECTIVE: The purpose of this study is to report surgical skills for CI cases with modiolus ossification and to investigate the relation between post-operational electroneurophysilogical test result and speech recognition result. Further more, we also attempt to confirm indications for CI in this specific population. METHOD: Based on temporal bone HRCT, 7 subjects were identified as modiolus ossification from 101 cases with cochlear ossification. Modiolus ossification is confirmed by CT scan if CT value in modiolus reaches or exceeds 900 HU with the exception of congenital modiolus ossification or modiolus seal off. Electroneurophysiological test was conducted intra- and pos-operationally speech tests were applied for 7 subjects. RESULT: Normal impedance value was observed by intro-operational measurement in 7 subjects. EABR test was conducted and negtive response was observed in only 1 subject, while other 6 subjects were confirmed with atypical EABR waves which were observed in apical and middle turn region. Hearing threshold test (in sound field) was applied, no auditory response was recorded for the subject without EABR waveform, while hearing threshold in average for the other 6 subjects was 75 dB. Results of speech tests (Mandarin) were followed as 0 for the one without EABR wave, while 100% (simple finals test) and 30% (simple initials test) for the other 6 subjects. CONCLUSION Optimal multichannel CI surgery that inserting and locating electrode array spirally is very frequently interrupted by ossification,which was indentified with atypical EABR wave and relative poor speech recognition results, especially in modiolus ossification case. A post-operative negative EABR response may indicate surgical failure following cochlear implantation.
Adolescent ; Adult ; Child ; Child, Preschool ; Cochlea ; pathology ; Cochlear Implantation ; Evoked Potentials, Auditory, Brain Stem ; physiology ; Female ; Humans ; Infant ; Male ; Middle Aged ; Ossification, Heterotopic ; surgery ; Postoperative Period ; Young Adult