Dose-dependent effects of ouabain on spiral ganglion neurons and Schwann cells in mouse cochlea

Objective: This study aimed in fully investigating the toxicities of ouabain to mouse cochlea and the related cellular environment, and providing an optimal animal model system for cell transplantation in the treatment of auditory neuropathy (AN) and sensorineural hearing loss (SNHL).

Methods: Different dosages of ouabain were applied to mouse round window. The auditory brainstem responses and distortion product otoacoustic emissions were used to evaluate the cochlear function. The immunohistochemical staining and cochlea surface preparation were performed to detect the spiral ganglion neurons (SGNs), Schwann cells and hair cells.

Results: Ouabain at the dosages of 0.5?mM, 1?mM and 3?mM selectively and permanently destroyed SGNs and their functions, while leaving the hair cells relatively intact. Ouabain at 3?mM resulted in the most severe SGNs loss and induced significant loss of Schwann cells started as early as 7 days and with further damages at 14 and 30 days after ouabain exposure.

Conclusions: The application of ouabain to mouse round window induces damages of SGNs and Schwann cells in a dose- and time-dependent manner, this study established a reliable and accurate animal model system of AN and SNHL.     

A Method for Establishing an Animal Model of Like-Auditary Neuropathy

Objective: To establish an animal model of like-auditory neuropathy in neonatal rat. Methods The ani-mals were injected with phenylhydrazine hydrochloride or saline at 7-day of age. ABR and DPOAE were performed to assess the auditory function. The cochlea basilar membrane stretched preparation and cochlear frozen sections were prepared for immunohistochemical staining to examine the morphological change of hair cells and spiral ganglion cells (SGNs). Results At 7-day age the ABR waveI, III, V, latencies andI-III,I-V IWIs in the experimental group were significantly prolonged compared with those in the control group. The ABR thresholds were also elevated in the experimental group. We found there is no significant differ-ence in DPOAE in phenylhydrazine hydrochloride exposure group compare to control group. The cochlear hair cells showed no signs of loss in both group, but the total number of neurofilaments positive cells in SGNs were significantly reduced in the phenylhydrazine treated animals. Conclusion Our study suggests that phenylhydrazine hydrochloride can change the auditory function and induce peripheral nerve pathology by targeted mainly the SGNs in neonatal rat.     

Maximal number of pre-synaptic ribbons are formed in cochlear region corresponding to middle frequency in mice

Objective: To investigate whether there are more quantitative pre-synaptic ribbons formed in the cochlear region corresponding to middle-frequency in cochlea of mice.

Methods: Counts of pre-synaptic ribbons were performed using immunostaining and laser confocal microscopy. Hearing thresholds and function of ribbon synapses were estimated by auditory brain response (ABR) and compound action potential (CAP). Cochlear mapping has been achieved to match the frequencies and corresponding regions along the cochlear spiral.

Results: The number of pre-synaptic ribbons in per inner hair cell (IHC) has been found to increase gradually from the base turn, the maximal quantity appeared at the region of 50–70% from the apex. Next, ABR thresholds showed that there was the lowest ABR threshold in the frequency around 8–16?kHz, corresponding to the region of 50–70% from the apex according to the cochlear mapping. Further, CAP amplitudes were estimated, and the maximal value identified at the same frequency (8–16?kHz).

Conclusions: Maximal number of pre-synaptic ribbons is formed in the cochlear region of middle frequency in mice, coupling with the lowest ABR threshold and highest CAP amplitudes. Our study shows that the middle frequency (8–16?kHz) could be the most sensitive region to sound stimuli in mice.     

Auditory brainstem responses predict auditory nerve fiber thresholds and frequency selectivity in hearing impaired chinchillas

Noninvasive auditory brainstem responses (ABRs) are commonly used to assess cochlear pathology in both clinical and research environments. In the current study, we evaluated the relationship between ABR characteristics and more direct measures of cochlear function. We recorded ABRs and auditory nerve (AN) single-unit responses in seven chinchillas with noise-induced hearing loss. ABRs were recorded for 1-8 kHz tone burst stimuli both before and several weeks after 4 h of exposure to a 115 dB SPL, 50 Hz band of noise with a center frequency of 2 kHz. Shifts in ABR characteristics (threshold, wave I amplitude, and wave I latency) following hearing loss were compared to AN-fiber tuning curve properties (threshold and frequency selectivity) in the same animals. As expected, noise exposure generally resulted in an increase in ABR threshold and decrease in wave I amplitude at equal SPL. Wave I amplitude at equal sensation level (SL), however, was similar before and after noise exposure. In addition, noise exposure resulted in decreases in ABR wave I latency at equal SL and, to a lesser extent, at equal SPL. The shifts in ABR characteristics were significantly related to AN-fiber tuning curve properties in the same animal at the same frequency. Larger shifts in ABR thresholds and ABR wave I amplitude at equal SPL were associated with greater AN threshold elevation. Larger reductions in ABR wave I latency at equal SL, on the other hand, were associated with greater loss of AN frequency selectivity. This result is consistent with linear systems theory, which predicts shorter time delays for broader peripheral frequency tuning. Taken together with other studies, our results affirm that ABR thresholds and wave I amplitude provide useful estimates of cochlear sensitivity. Furthermore, comparisons of ABR wave I latency to normative data at the same SL may prove useful for detecting and characterizing loss of cochlear frequency selectivity.     

Investigation of the ototoxicity of gadoteridol (ProHance) and gadodiamide (Omniscan) in mice

Conclusion: In the mouse, when a tympanic perforation is present, gadoteridol does not seem to cause ototoxicity. Gadodiamide may cause mild ototoxicity other than toxicity to the outer hair cells of the cochlea.

Objectives: Endolymphatic hydrops have been visualized through intra-tympanic injection of gadolinium-based contrast agents (GBCAs) and three-dimensional fluid-attenuated inversion recovery (3-D FLAIR) magnetic resonance imaging. However, reports on the safety of GBCAs are limited. This study aimed to assess ototoxicity of gadoteridol and gadodiamide.

Method: In a prospective, randomized, controlled trial, myringotomies in the left ear were performed in 20 male C57 BL/6 mice. After testing the baseline auditory brainstem response (ABR) (range?=?8–32?kHz), the test solution (gadoteridol, gadodiamide, saline, or cisplatin) was injected into the left ear. ABR testing was repeated 14 days after test solution application. In morphological experiments, images of post-mortem surface preparations were assessed for cochlear hair cell status.

Results: At 14 days following gadoteridol application, there was no significant change in ABR thresholds at 8, 16, or 32?kHz. Gadodiamide application caused a significant change in the ABR threshold at 8?kHz. Apparent cochlear hair cell loss was not observed in the surface preparation after gadoteridol or gadodiamide application.     

Cochlear receptor (microphonic and summating potentials, otoacoustic emissions) and auditory pathway (auditory brain stem potentials) activity in auditory neuropathy

OBJECTIVE: To define both auditory nerve and cochlear receptor functions in subjects with auditory neuropathy (AN). DESIGN: We tested 33 AN subjects (66 ears) and compared them with 21 healthy subjects (28 ears). In AN subjects, the average pure-tone (1, 2, and 4 kHz) threshold loss was 57 dB HL. Click stimuli were used to elicit transient evoked otoacoustic emissions (TEOAEs), cochlear microphonics (CMs), and auditory brain stem responses (ABRs). Both cochlear and ABR potentials were recorded from surface electrodes (vertex-ipsilateral mastoid) using averaging procedures. The amplitudes and latencies of CMs and ABRs and the amplitude of the TEOAEs were analyzed. RESULTS: CM amplitudes recorded from normal ears decreased as a function of subject age. CMs recorded from AN subjects fell within the normal age-adjusted range in 60% of the subjects and were >2 SEEs (standard error of estimate) above the age-adjusted normal regression in 40% of the subjects. TEOAEs were absent in 19 (30%) AN ears (bilaterally in eight, and unilaterally in three subjects) and were present in 44 ears. In AN subjects, correlations among CM amplitude, TEOAE amplitude, and pure-tone average thresholds were not significantly related. CM amplitudes were not significantly different whether TEOAEs or ABRs were present or absent. The ABR was present in 21% of AN subjects and consisted of a low-amplitude Wave V without a preceding Wave I. Measures of CM amplitude and PTA hearing loss were not significantly different in those AN ears with a preserved ABR compared with ears with absent ABRs. Summating potentials to transient click stimuli were of small amplitude (<0.1 microV) and detectable in approximately 50% of the AN and healthy control subjects limiting formal analysis of summating potentials. CONCLUSIONS: In a significant proportion of AN subjects, we found abnormalities of cochlear receptor function, including elevated CM amplitudes and absence of TEOAEs. These two abnormalities occurred independently of each other. A low amplitude Wave V of the ABR was found in approximately one-fifth of AN subjects, evidence that neural synchrony can be partially preserved in some subjects with this disorder.     

Effect of hearing loss of cochlear origin on the auditory brain stem response.

Auditory brain stem response (ABR) testing is widely used to detect lesions of the auditory neural pathways. The ABR waves depend not only on the integrity of the neural pathways, but also on the condition of the cochlea. To properly interpret the ABR response, it is necessary to understand the effects of cochlear hearing loss on the ABR wave latencies. We studied two populations of subjects with cochlear hearing loss: one with varying degrees of high-frequency hearing loss and the other with varying degrees of flat configuration hearing loss. The degree of cochlear hearing loss was quantified in several different ways and subjected to one linear and three nonlinear regression analyses to test for accuracy in predicting ABR wave latencies and interpeak intervals (waves I, III, V, I-V, I-III, and III-V) for three click intensities. Hearing loss levels from 2 to 6 kHz, in particular 4 kHz, were superior to other audiometric test frequencies as predictors of ABR wave latencies for the group with the high-frequency losses. No particular characterization was found to be superior for the flat hearing loss configurations. From these results, modeled predictions of wave latencies as a function of degree and configuration of hearing loss were made. The modeled predictions are then used to suggest guidelines for interpretations of ABR results where hearing impaired patients are involved.     

Basic fibroblast growth factor protects auditory neurons and hair cells from glutamate neurotoxicity and noise exposure

Objective To determine the protective effects of basic fibroblast growth factor (bFGF) on cochlear neurons and hair cells in vitro and in vivo.

Material and Methods In Experiment I, cultured spiral ganglion neurons (SGNs) prepared from postnatal Day 3 mice were exposed to 20 mM glutamate for 2 h before the culture medium was replaced with fresh medium containing 0, 25, 50 or 100 ng/ml bFGF. Fourteen days later, all cultures were fixed with 4% paraformaldehyde and stained with 1% toluidine blue. The number of surviving SGNs was counted and the length of the neurites of the SGNs was measured. In Experiment II, in vivo studies were carried out with guinea pigs in which bFGF or normal saline was injected intramuscularly to assess possible protective effects of bFGF on cochlear hair cells and to accelerate the recovery of the auditory brainstem response (ABR). The ABRs were measured before, immediately after and 2 and 4 weeks after exposure to noise.

Results Exposure to 20 mM glutamate for 2 h resulted in an inhibition of neurite outgrowth of SGNs and an increase in cell death. Treatment of the cultures with bFGF led to promotion of neurite outgrowth and an increase in the number of surviving SGNs. In Experiment II, significant (p<0.05) differences in ABR thresholds were observed between the groups injected with bFGF and saline (t=2.689) at 4 weeks after noise exposure. Cochleae were removed and hair cell loss analyzed in surface preparations prepared from all experimental animals. Acoustic trauma caused loss of 240 and 2160 inner hair cells in the groups injected with bFGF and saline, respectively. Similarly, more outer hair cells were lost in the normal saline injection group (99 291) than in the group treated with bFGF (70 377).

Conclusions Our results demonstrate that bFGF protects SGNs against glutamate neurotoxicity in vitro. In addition, treatment with bFGF protects hair cells from acoustic trauma.     

Atrial natriuretic peptide modulates auditory brainstem response of rat

Conclusion: These findings suggest that Atrial natriuretic peptide (ANP) exhibits an inhibitory effect on auditory brainstem response (ABR) and is involved in the neuromodulation of the auditory nervous system. Objectives: ANP may alter electrophysiological properties of the cochlea and play a role in auditory action. Methods: This study was undertaken to examine and clarify the role of ANP in the rat auditory system using ABR audiometry. The mean ABR thresholds and the latencies for wave II at the ABR threshold altered at given frequencies throughout the study. Results: Intra-arterial infusion of ANP (0.1 mg/kg, 4 mg/kg, and 8 mg/kg; bolus injection) resulted in a significant increase in ABR thresholds. A significant shift in the ABR wave II latency was observed at lower frequency (1 kHz and 2 kHz). There was a little change in latency at 20 kHz. Increased amount of ANP significantly altered the ABR in rats.     

Effects of noise exposure on auditory brainstem response and speech-in-noise tasks: a review of the literature

Abstract

Objective: Short-term noise exposure that induces transient changes in thresholds has induced permanent cochlear synaptopathy in multiple species. Here, the literature was reviewed to gain translational insight into the relationships between noise exposure, ABR metrics, speech-in-noise performance and TTS in humans.

Design: PubMed-based literature search, retrieval and review of full-text articles. Study Sample: Peer-reviewed literature identified using PubMed search.

Results: Permanent occupational noise-induced hearing loss (NIHL) is frequently accompanied by abnormal ABR amplitude and latency. In the absence of NIHL, there are mixed results for relationships between noise exposure and ABR metrics. Interpretation of speech-in-noise deficits is difficult as both cochlear synaptopathy and outer hair cell (OHC) loss can drive deficits. Reductions in Wave I amplitude during TTS may reflect temporary OHC pathology rather than cochlear synaptopathy. Use of diverse protocols across studies reduces the ability to compare outcomes across studies.

Conclusions: Longitudinal ABR and speech-in-noise data collected using consistent protocols are needed. Although speech-in-noise testing may not reflect cochlear synaptopathy, speech-in-noise testing should be completed as part of a comprehensive test battery to provide the objective measurement of patient difficulty.     

C57BL/6J小鼠听力及耳蜗毛细胞活性的年龄相关性研究

目的 建立年龄相关性听力损失(age-related hearing loss,AHL)的小鼠动物模型,探讨C57BL/6J小鼠发生AHL与毛细胞活性变化的关系,并初步对C57BL/6J小鼠AHL模型进行AHL的病理分类.方法 按3、8、9、10、17、18月龄段分6组培育C57BL/6J小鼠,各组分别进行听性脑干反应(ABR)测试,对耳蜗毛细胞行琥珀酸脱氢酶染色并作基底膜硬铺片,观察各年龄段小鼠内外毛细胞线粒体琥珀酸脱氢酶的活性.结果 C57BL/6J小鼠随年龄增大,ABR阈值明显增高,在3月龄到9月龄期间ABR平均反应阈值增大比较缓慢,差异无统计学意义;在10月龄时,出现明显的听力下降,平均阈值比3月龄时约高18～23 dB,差异有统计学意义(click:t=5.78,P＜0.01;6 kHz:t =3.93,P＜0.01;8 kHz:t=3.01,P＜0.05).10月龄后小鼠听力继续下降,21月龄时平均阈值比3月龄时增高约60～68 dB,差异有显著统计学意义(click:t=31.23,P＜0.01;6 kHz:t=30.44,P＜0.01;8 kHz:t=33.83,P＜0.01).琥珀酸脱氰酶染色显示,随年龄增大,毛细胞线粒体活性丧失逐渐加重:先是底回外毛细胞活性下降,接着发生活性消失,并逐渐向顶回发展,最后累及内毛细胞.结论 C57BL/6J小鼠具有典型的年龄相关性听力损失特点,其听力下降的原因早期可能主要足外毛细胞及内毛细胞活性的丧失,晚期可能是由于基底膜结构混乱,导致电生理屏障消失,致耳蜗内电位(EP)不能维持而引起.C57BL/6J小鼠可作为感音型老年性听力损失动物模型.     

Structural and Ultrastructural Changes to Type I Spiral Ganglion Neurons and Schwann Cells in the Deafened Guinea Pig Cochlea

Sensorineural hearing loss is commonly caused by damage to cochlear sensory hair cells. Coinciding with hair cell degeneration, the peripheral fibres of type I spiral ganglion neurons (SGNs) that normally form synaptic connections with the inner hair cell gradually degenerate. We examined the time course of these degenerative changes in type I SGNs and their satellite Schwann cells at the ultrastructural level in guinea pigs at 2, 6, and 12 weeks following aminoglycoside-induced hearing loss. Degeneration of the peripheral fibres occurred prior to the degeneration of the type I SGN soma and was characterised by shrinkage of the fibre followed by retraction of the axoplasm, often leaving a normal myelin lumen devoid of axoplasmic content. A statistically significant reduction in the cross-sectional area of peripheral fibres was evident as early as 2 weeks following deafening (p < 0.001, ANOVA). This was followed by a decrease in type I SGN density within Rosenthal’s canal that was statistically significant 6 weeks following deafening (p < 0.001, ANOVA). At any time point examined, few type I SGN soma were observed undergoing degeneration, implying that once initiated, soma degeneration was rapid. While there was a significant reduction in soma area as well as changes to the morphology of the soma, the ultrastructure of surviving type I SGN soma appeared relatively normal over the 12-week period following deafening. Satellite Schwann cells exhibited greater survival traits than their type I SGN; however, on loss of neural contact, they reverted to a non-myelinating phenotype, exhibiting an astrocyte-like morphology with the formation of processes that appeared to be searching for new neural targets. In 6- and 12-week deafened cochlea, we observed cellular interaction between Schwann cell processes and residual SGNs that distorted the morphology of the SGN soma. Understanding the response of SGNs, Schwann cells, and the complex relationship between them following aminoglycoside deafening is important if we are to develop effective therapeutic techniques designed to rescue SGNs.     

Apical hair cell degeneration causes the increase in the amplitude of summating potential

Conclusion: This study indicates that the lesion of hair cells in the apical turn of the cochlea can cause the change in the summating potential (SP)/Compound potential (CAP) ratio.

Objectives: Electrocochleography is a valuable clinic test for diagnosis of cochlear pathologies and the ratio of SP to CAP has been used to identify Meniere’s disease. However, it remains controversial whether the increase of the SP/CAP ratio represents exclusively the endolymphatic hydrops.

Method: This study measured the SP and CAP in mice that displayed outer hair cell (OHC) degeneration in the apical section of the cochlea as their age increased.

Results: As compared with the mice aged 8–10 months, the 24-month old mice displayed a significant increase in the amplitude of SP at 12–16?kHz. This result suggests that the degeneration of OHCs in the apical turn leads to the increase of the?+?SP at the middle frequencies. In contrast, the aging mice did not have a significant change in the CAP amplitude at super-threshold levels.     

Multiple auditory steady-state responses in children and adults with normal hearing, sensorineural hearing loss, or auditory neuropathy

OBJECTIVES: We tested the clinical effectiveness of multiple auditory steady-state responses (ASSRs) for the objective assessment of hearing thresholds in patients with and without hearing loss, candidates for cochlear implants, and children with auditory neuropathy. METHODS: The study sample included 29 subjects with sensorineural hearing loss (SNHL), 18 candidates for cochlear implants, 11 subjects with auditory neuropathy, and 18 subjects with normal hearing thresholds. Behavioral hearing thresholds and ASSRs to carrier frequencies of 0.5, 1, 2, and 4 kHz were obtained. Special care was taken to minimize possible aliasing and high-intensity multiple stimulation effects. Differences and correlations between the ASSRs and the behavioral thresholds were determined. RESULTS: The ASSR estimation of behavioral thresholds in the normal-hearing group was elevated, whereas very close predictions were found for the SNHL group. The correlations between the two measures ranged from 0.86 at 0.5 kHz carrier frequency to 0.94 at 2 kHz. In the cochlear implant candidates and the auditory neuropathy group, the ASSR thresholds generally overestimated the behavioral audiogram. In these groups the number of detected ASSRs was higher than the number of behavioral responses, especially for the high-frequency carrier stimuli. CONCLUSIONS: Multiple ASSRs may reliably predict the behavioral threshold in subjects with SNHL and may serve as a valuable objective measure for assessing the hearing threshold across different frequencies in candidates for cochlear implants and children with auditory neuropathy.     

听神经病的听功能状态分析

目的 :探讨听神经病的听功能状态及病损部位。方法 :分析 6 5例听神经病患者的临床资料、纯音测听、声导抗测试、听性脑干反应 (ABR)、4 0Hz听觉相关电位及OAE检查结果。结果 :听神经病的低频听力损失源于蜗后的传入、传出神经及听性脑干受损 ,表现为声反射、传出抑制、ABR异常及诱发性OAE与纯音听阈不呈平行关系 ,与之相对应 ,低频区的外毛细胞处于失抑制的超常活动状态 ,表现为低频区SOAE增强、TEOAE反应幅值及DPOAE幅值升高 ;听神经病的高频听力损失源于耳蜗的外毛细胞损害 ,表现为高频区DPOAE幅值与纯音听阈呈一致性下降 ;听神经病的中频听力损失最轻或接近正常 ,表现为 2kHz附近的纯音听阈和DPOAE幅值均接近于正常。结论 :听神经病的传入、传出系统及耳蜗水平均有不同程度的功能障碍 ,其病损部位主要在耳蜗传入、传出神经 ,向上可侵及脑干 ,向下可侵及耳蜗     

Cochlear microphonics in sensorineural hearing loss: lesson from newborn hearing screening

The diagnostic dilemma surrounding the presence of cochlear microphonics (CM) coupled with significantly elevated auditory brainstem response (ABR) thresholds in babies failing the newborn hearing screening is highlighted. A case report is presented where initial electo-diagnostic assessment could not help in differentiating between Auditory Neuropathy/Auditory Dys-synchrony (AN/AD) and sensorineural hearing loss (SNHL). In line with the protocol and guidelines provided by the national Newborn Hearing Screening Programme in the UK (NHSP) AN/AD was suspected in a baby due to the presence of CM at 85 dBnHL along with click evoked ABR thresholds of 95 dBnHL in one ear and 100 dBnHL in the other ear. Significantly elevated thresholds for 0.5 and 1kHz tone pip ABR fulfilled the audiological diagnostic criteria for AN/AD. However, the possibility of a SNHL could not be ruled out as the 85 dBnHL stimuli presented through inserts for the CM would have been significantly enhanced in the ear canals of the young baby to exceed the threshold level of the ABR that was carried out using headphones. SNHL was eventually diagnosed through clinical and family history, physical examination and imaging that showed enlarged vestibular aqueducts. Presence of CM in the presence of very high click ABR thresholds only suggests a pattern of test results and in such cases measuring thresholds for 0.5 and 1 kHz tone pip ABR may not be adequate to differentiate between SNHL and other conditions associated with AN/AD. There is a need for reviewing the existing AN/AD protocol from NHSP in the UK and new research to establish parameters for CM to assist in the differential diagnosis. A holistic audiological and medical approach is essential to manage babies who fail the newborn hearing screening.     

Degeneration of stria vascularis in age-related hearing loss; a corrosion cast study in a mouse model

Conclusion With age, in a mouse model, degenerative changes to the capillaries of the stria vascularis are observed. These range from a narrowing of vessel lumen to complete degeneration of strial vessels. Other vascular beds in the cochlea are relatively unchanged with age. Strial capillaries at the cochlear base are significantly more affected than those in mid-apical turns.

Objectives Previous work suggests that age-related hearing loss is associated with degenerative changes to cochlear vasculature; the term strial presbyacusis is often cited. This study reports on vascular changes observed in a murine model of presbyacusis, analyzed using corrosion cast techniques.

Methods A novel corrosion cast technique was developed to compare cochlear vasculature in control mice (non-presbycusic, CD1) and old (>?6 months) C57BL/6 animals. ABR measures indicated a significant age-related threshold elevation in the C57BL/6 mice. Cochlear vascular casts were imaged using scanning electron microscopy, and vessel degeneration was quantified by measuring capillary diameters.

Results Corrosion casts of cochlear vasculature in 6–12 month old C57BL/6 mice reveal significant degeneration of stria vascularis. Other capillary beds (spiral ligament and the spiral limbus) appear unchanged. Comparison of strial capillary diameters reveals significantly more damage in basal/lower-turn regions compared with the cochlear mid-turn.     

Elevated auditory brainstem response thresholds in mice with Connexin36 gene ablation

Conclusion: Expression of connexin36 (Cx36) and electrical synapses formed by Cx36-containing gap junctions contribute to normal auditory brainstem response thresholds in mice. Objectives: Electrical synaptic transmission mediated by gap junctions has not been intensively studied in the auditory system. This study used transgenic mice with knockout of the gene coding for the major protein that forms neuronal gap junctions in mammalian brain (Cx36) to evaluate the role of Cx36 in murine hearing. Methods: Auditory brainstem response (ABR) thresholds and distortion product otoacoustic emissions (DPOAEs) were measured in 26 wild-type and 26 Cx36 knockout mice. ABR thresholds were used to assess auditory brainstem function at four frequencies. DPOAEs were delivered for seven frequency pairs to assess cochlear function. Results: The magnitudes of the 2f1–f2 distortion products were not different between Cx36 knockout and wild-type mice, suggesting similar cochlear function in the two groups. ABR thresholds were significantly elevated in the Cx36 knockout compared with the wild-type groups, suggesting impaired function in the auditory brainstem. The results suggest that electrical synapses formed by Cx36-containing gap junctions contribute to auditory sound processing and function at the level of the brainstem, not the cochlea. These findings may be important for understanding human auditory pathology.     

Cochlear implantation in children with auditory neuropathy: outcomes and rationale

CONCLUSION: Children with auditory neuropathy (AN) obtain considerable benefit from cochlear implantation. Their performance outcomes are as good as those of implanted children with sensorineural hearing loss (SNHL). The neural status of children with AN would be comparable to that of children with SNHL and be suitable for cochlear implantation. OBJECTIVE: The purpose of this study was to evaluate the outcomes of cochlear implantation in children with AN and to assess the status of auditory nerve in these patients. SUBJECTS AND METHODS: Nine children with AN who underwent cochlear implantation were included. Their performance outcomes which were measured by Categories of Auditory Performance (CAP), Monosyllabic Word (MW) test for phonemes, and Common Phrases test were compared with those of matched implanted children with SNHL. To assess the status of auditory nerve in children with AN, the slopes of amplitude growth functions of electrically evoked compound action potentials (ECAPs) in implanted children with AN were compared to those of implanted children with SNHL. RESULTS: There were no statistically significant differences between two groups in performance outcomes (CAP, p=0.1200; MW test, p=0.5768; Common Phrases test, p=0.3337). No significant difference was found in the slopes of ECAP amplitude growth functions (p=0.970) between two groups, which shows that spiral ganglion cell populations may be comparable in these two groups.