Auditory Brainstem Response Thresholds Research Articles

Alterations to cognitive abilities and functional networks in rats post broad-band intense noise exposure.

This study aimed to investigate the alterations of cognition and functional connectivity post noise, and find the progress and neural substrates of noise induced hearing loss (NIHL)-associated cognitive impairment. We exposed rats to 122dB broad-band noise for 2h to induce hearing loss and the auditory function was assessed by measuring auditory brainstem response thresholds. Morris water maze test and resting state MRI were computed at 0day, 1, 3, 6months post noise to reveal cognitive ability and neural substrate. The interregional connections in the auditory network and default mode network, as well as the connections using the auditory cortex and cingulate cortex as seeds were also examined addtionally. The deficit in spatial learning/memory was only observed at 6months after noise exposure. The internal connections in the auditory network and default mode network were enhanced at 0day and decreased at 6months post noise. The connectivity using the auditory cortex and cingulate cortex as seeds generally followed the rule of "enhancement-normal-decrease-widely decrease". A new model accounting for arousal, dementia, motor control of NIHL in is proposed. Our study highlights the fundamental flexibility of neural systems, and may also point toward novel therapeutic strategies for treating sensory disorders.

Difference in Thresholds Between Auditory Brainstem Response Test and Pure Tone Audiometry by Frequency

Background and Objectives There is no clear standard for the difference in the thresholds of auditory brainstem response (ABR) and pure tone audiometry (PTA) when using ABR to evaluate the reliability of PTA. Therefore, we assessed the difference in the thresholds of ABR and PTA for each frequency. Consequently, we present here the actual difference values between the two tests that can be used as a reference in the clinic.Subjects and Method We retrospectively assessed the audiometry results of 129 ears. Ears in which the hearing thresholds of each frequency continuously declined were classified as the downward group. We compared the average of differences between the two tests by frequency. The differences were compared for each hearing level from 50 dB or higher.Results For all ears, the appropriate range of difference value was ±5 dB at 2 kHz. At 1 kHz, the ABR threshold was 10 dB higher than PTA, and it was 10 dB less than PTA at 4 kHz. In the downward group, the difference value increased by 10 dB at 1 kHz and 4 kHz. In the subgroups at each hearing level, the difference value showed similar results (p<0.05).Conclusion The difference in the threshold, regardless of the severity or tendency of hearing loss, was the smallest at 2 kHz and the range was ±5 dB. ABR was 10 dB higher at 1 kHz and and 10 dB lower at 4 kHz than PTA. In the downward group, the difference at 1 kHz and 4 kHz increased by 10 dB each.

Metabolomics Analysis Reveals Alterations in Cochlear Metabolic Profiling in Mice with Noise-Induced Hearing Loss.

Noise-induced hearing loss (NIHL) has always been an important occupational hazard, but the exact etiopathogenesis underlying NIHL remains unclear. Herein, we aimed to find metabolic biomarkers involved in the development of NIHL based on a mouse model using a gas chromatography coupled with mass spectrometry (GC-MS) metabolomics technique. We showed that the auditory brainstem response (ABR) thresholds at the frequencies of 4, 8, 12, 16, 24, and 32 kHz were all significantly elevated in the noise-exposed mice. Noise could cause outer hair cell (OHC) loss in the base of the cochlea. A total of 17 differential metabolites and 9 metabolic pathways were significantly affected following noise exposure. Spermidine acting as an autophagy modulator was found to be 2.85-fold higher in the noise-exposed group than in the control group and involved in β-alanine metabolism and arginine and proline metabolism pathways. Additionally, we demonstrated that LC3B and Beclin1 were expressed in the spiral ganglion neurons (SGNs), and their mRNA levels were increased after noise. We showed that SOD activity was significantly decreased in the cochlea of noise-exposed mice. Further experiments suggested that SOD1 and SOD2 proteins in the SGNs were all decreased following noise exposure. The upregulation of spermidine may induce LC3B- and Beclin1-mediated autophagy in the cochlear hair cells (HCs) through β-alanine metabolism and arginine and proline metabolism and be involved in the NIHL. ROS-mediated oxidative damage may be a pivotal molecular mechanism of NIHL. Taken together, spermidine can be regarded as an important metabolic marker for the diagnosis of NIHL.

Evaluation of acoustic changes in and the healing outcomes of rat eardrums with pars tensa and pars flaccida perforations.

ObjectivesTo systematically explore the differences in acoustic changes and healing outcomes of tympanic membranes (TMs) with pars flaccida perforation (PFP) and pars tensa perforation (PTP).MethodsWe created PFPs and PTPs of various sizes in Sprague–Dawley rats, and evaluated TM umbo velocity and hearing function using laser Doppler vibrometry and auditory brainstem response (ABR) measurement before and immediately after perforation. Two weeks later, hearing was reevaluated and TMs were investigated by immunohistochemical staining.ResultsSmall PFPs and PTPs did not significantly affect umbo velocity and hearing function. Large PFPs increased umbo velocity loss at low frequency (1.5 kHz) and elevated ABR thresholds within 1–2 kHz. Large PTP caused significant velocity loss at low frequencies from 1.5 to 3.5 kHz and threshold elevations at full frequencies (1–2 kHz). Two weeks after the perforation, the hearing function of rats with healed PFPs recovered completely. However, high‐frequency hearing loss (16–32 kHz) persisted in rats with healed PTPs. Morphological staining revealed that no increase in the thickness and obvious increase in collagen I level of regenerated par flaccida; regenerated pars tensa exhibited obvious increase in thickness and increased collagen I, while the collagen II regeneration was limited with discontinuous and disordered structure in regenerated pars tensa.ConclusionThe hearing loss caused by large PFP limits at low frequencies while large PTP can lead to hearing loss at wide range frequencies. PFP and PTP have different functional outcomes after spontaneous healing, which is determined by the discrepant structure reconstruction and collagen regeneration.

Mild hearing loss in C57BL6/J mice after exposure to antiretroviral compounds during gestation and nursing

Objective There is evidence of ototoxicity from antiretrovirals (ARVs), and ARV therapy in pregnant/nursing mothers can expose offspring to these compounds. The current work modelled whether exposure to ARVs in utero and during nursing altered the functioning of the auditory system in offspring mice. Design The females of seven breeding pairs of C57BL6/J mice were given daily doses of ARVs lamivudine and tenofovir disoproxil fumarate by oral gavage during gestation and nursing. Three breeder females were given equivalent volumes of water as controls. At wean age (3 weeks after birth), the offspring mice were tested with auditory brainstem responses (ABRs). At the conclusion of the experiment, the offspring mice’s cochleae were examined for hair cell counts. Study sample Ten breeder female C57BL6/J mice and 69 offspring mice. Results The offspring mice exposed to ARVs during development showed higher ABR thresholds than the control offspring. No differences were found in supra-threshold ABRs. There was no evidence of missing hair cells. Conclusions Hearing impairment may be a possible consequence of exposure to ARVs during gestation and development. Because the threshold differences were not large, if they are occurring in humans, it is unlikely they would be identified in any hearing screening tests.

Pravastatin Administration Alleviates Kanamycin-Induced Cochlear Injury and Hearing Loss.

The effect of statins on aminoglycoside-induced ototoxicity is controversial. This study aimed to explore the role of pravastatin (PV) in kanamycin-induced hearing loss in rats. Adult rats were intraperitoneally treated with 20 mg/kg/day of kanamycin (KM) for 10 days. In the PV- and PV + KM-treated rats, 25 mg/kg/day of PV was intraperitoneally administered for 5 days. The auditory brainstem response (ABR) thresholds were measured before and after drug treatment using a smartEP system at 4, 8, 16, and 32 kHz. Cochlear changes in poly ADP-ribose (PAR) polymerase (PARP), PAR, and caspase 3 were estimated using Western blotting. PV administration did not increase the ABR thresholds. The KM-treated rats showed elevated ABR thresholds at 4, 8, 16, and 32 kHz. The PV + KM-treated rats demonstrated lower ABR thresholds than the KM-treated rats at 4, 8, and 16 kHz. The cochlear outer hair cells and spiral ganglion cells were relatively preserved in the PV + KM-treated rats when compared with that in the KM-treated rats. The cochlear expression levels of PARP, PAR, and caspase 3 were higher in the KM-treated rats. The PV + KM-treated rats showed lower levels of PARP, PAR, and caspase 3 than the KM-treated rats. PV protected cochleae from KM-induced hearing loss in rats. The regulation of autophagy and apoptosis mediated the otoprotective effects of PV.

The Effect of Endolymphatic Hydrops and Mannitol Dehydration Treatment on Guinea Pigs.

BackgroundEndolymphatic hydrops (EH) is considered as the pathological correlate of Menière’s disease (MD) and cause of hearing loss. The mechanism of EH, remaining unrevealed, poses challenges for formalized clinical trials.ObjectiveThis study aims to investigate the development of hearing loss, as well as the effect of dehydration treatment on EH animal models.MethodsIn this study, different severity EH animal models were created. The laser Doppler vibrometer (LDV) and auditory brainstem responses (ABR) were used to study the effects of EH and the dehydration effects of mannitol. The LDV was used to measure the vibration of the round window membrane (RWM) reflecting the changes in inner ear impedance. ABR was used to evaluate the hearing changes. Furthermore, tissue section and scanning electron microscopy (SEM) observations were used to analyze the anatomical change to the cochlea and outer hair cells.ResultsThe RWM vibrations decreased with the severity of EH, indicating an increase in the cochlear impedance. The dehydration therapy lowered the impedance to restore acoustic transduction in EH 10- and 20-day animal models. Simultaneously, the ABR thresholds increased in EH models and were restored after dehydration. Moreover, a difference in the hearing was found between ABR and LDV results in severe EH animal models, and the dehydration therapy was less effective, indicating a sensorineural hearing loss (SNHL).ConclusionEndolymphatic hydrops causes hearing loss by increasing the cochlear impedance in all tested groups, and mannitol dehydration is an effective therapy to restore hearing. However, SNHL occurs for the EH 30-day animal models, limiting the effectiveness of dehydration. Our results suggest the use of dehydrating agents in the early stage of EH.

Determining auditory brain stem response threshold using an adaptive stimulus selection procedure

Auditory brain stem response (ABR) measurements provide a method to determine the hearing threshold of laboratory animals and humans who are unable to provide behavioral responses to auditory stimuli. Determining hearing threshold using ABR typically requires a large number of pre-selected frequency and stimulus levels, which may not be the most efficient method to sample the stimulus space. The goal of the current study is to develop an adaptive procedure that determines in situ the stimulus that will provide the best estimate of the threshold, based on data collected earlier in the procedure. A Gaussian Process model is iteratively fitted after each testlevel, and the subsequent test level is chosen at the interim threshold estimate predicted by the current model fit. Simulations of the adaptive procedure were conducted using previously collected toneburst ABR measurements from mice presented at 5 dB increments from 0 to 80 dB at seven frequencies ranging from 4 to 32 kHz. The thresholds determined by this procedure were compared to those produced by human raters who viewed the response at all stimulus levels. Initial results indicate that the threshold may be accurately estimated utilizing fewer stimuli levels than current methods, thereby reducing the duration of the measurements.

Does N-acetylcysteine Improve Established Hearing Loss in Guinea Pigs?

ObjectiveTo assess whether multiple injections of a powerful antioxidant can improve established sensorineural hearing loss in guinea pigs.Study DesignAnimal study.SettingAnimal science laboratory, University of Manitoba.MethodsA total of 16 guinea pigs were used in our study: 8 underwent unilateral intracochlear neomycin injection, and 8 underwent unilateral saline to serve as controls. After a period of 3 weeks for hearing loss to stabilize, 4 guinea pigs from each group received weekly intraperitoneal injections of N-acetylcysteine (NAC) for 4 weeks. Click auditory brainstem response (ABR) testing was conducted at baseline, weekly after the start of NAC injections, and after the last injection. Pure tone ABR tests were conducted prior to intracochlear injections and at completion of the study.ResultsClick ABR thresholds were significantly worse in ears treated with neomycin (P < .001), as expected, but not significantly different when treated with NAC (P = .664). Thresholds for pure tone ABR were also not statistically different in neomycin-treated ears with or without NAC (P > .99).ConclusionsThe aggressive antioxidant therapy performed in this study was not successful in improving established hearing loss via an antioxidant regimen that is known to change the oxidation-reduction potential in the cochlea.

The voltage-gated Ca2+ channel subunit α2δ-4 regulates locomotor behavior and sensorimotor gating in mice.

Voltage-gated Ca2+ channels are critical for the development and mature function of the nervous system. Variants in the CACNA2D4 gene encoding the α2δ-4 auxiliary subunit of these channels are associated with neuropsychiatric and neurodevelopmental disorders. α2δ-4 is prominently expressed in the retina and is crucial for vision, but extra-retinal functions of α2δ-4 have not been investigated. Here, we sought to fill this gap by analyzing the behavioral phenotypes of α2δ-4 knockout (KO) mice. α2δ-4 KO mice (both males and females) exhibited significant impairments in prepulse inhibition that were unlikely to result from the modestly elevated auditory brainstem response thresholds. Whereas α2δ-4 KO mice of both sexes were hyperactive in various assays, only females showed impaired motor coordination in the rotarod assay. α2δ-4 KO mice exhibited anxiolytic and anti-depressive behaviors in the elevated plus maze and tail suspension tests, respectively. Our results reveal an unexpected role for α2δ-4 in sensorimotor gating and motor function and identify α2δ-4 KO mice as a novel model for studying the pathophysiology associated with CACNA2D4 variants.

Effect of subject state on auditory brainstem response threshold using Kalman-weighted averaging

ObjectivesThis study aims to explore the impact of a subject's testing state on auditory brainstem response (ABR) thresholds using a novel ABR system (Vivosonic Integrity™), which incorporates Kalman-weighted averaging and bluetooth electrical isolation to address the limitation of conventional ABR limitation to obtain a stable result under non-sedated conditions, especially for infants and children. MethodTwenty-four adults (18–34 years old, 48 ears) with normal hearing were enrolled for ABR testing under three different states (lying quietly in the supine position or sleeping—lying; watching silent videos quietly in a seated position—sitting; and writing in a seated position—writing), which simulate the behaviors of young children most often encountered during non-sedated Kalman-weighted ABR testing in clinical practice. The click ABR (cABR) and tone-burst ABR (tbABR) thresholds (0.5, 1, 2, and 4 kHz) of each subject and the time taken to reach the monaural threshold for each kind of stimulus were recorded. Results(1) The cABR and tbABR thresholds were observed to increase in the following order: lying < sitting < writing. Significant threshold differences were found between any two states, except for between the sitting and lying states for the cABR and between sitting and writing for the 0.5 kHz tbABR. (2) The time required for cABR testing in the writing state was significantly longer than that in the lying and sitting states. The time required for 1 and 4 kHz tbABR testing in the lying state was significantly shorter than that in the sitting or writing state. For 2 KHz tbABR, only testing time under writing was significantly longer than that under lying. There were no significant differences in the time used for 0.5 kHz tbABR testing among different states. ConclusionsDifferent testing states have significant impacts on the thresholds of ABRs using Kalman-weighted averaging. A subject's state during ABR testing warrants consideration, and normal levels and correction values to estimate the hearing threshold from the ABR threshold should be determined for different testing states.

Extensive hearing loss induced by low‐frequency noise exposure

BackgroundWith little attention given to low‐frequency traffic noise and our understanding that cochlear function may be highly susceptible to low‐frequency noise, there is an urgent need to determine traffic noise‐induced hearing loss (NIHL), not only the hearing loss at low frequency but also the possible high‐frequency hearing loss.MethodsThe current study aims to investigate the potential for extensive hearing loss induced by exposure to 0.063 kHz octave band noise (OBN), which is an important component of low‐frequency traffic noise. The threshold of auditory brainstem response (ABR) was used to evaluate hearing function before and after noise exposure. Chinchillas were randomly assigned into seven different groups. Group 63‐3 h/6 h, Group 2 k‐3 h/6 h, and group 4 k‐3 h/6 h were exposed for either 3 or 6 h to 0.063, 2, and 4 kHz OBN at 90 dB SPL, respectively. The control group was not exposed to noise.ResultsSignificant ABR threshold‐shifts (TS) were observed at 0.88, 2, 4, and 5.7 kHz in Group 63‐6 h, and at 2.8 and 4 kHz in Group 2 k‐6 h, and at 5.7 kHz in Group 4 k‐6 h. ABR‐TS were consistent with outer hair cell (OHC) losses, exposure to 0.063 kHz OBN at 90 dB SPL for 6 h induced large‐scale losses of OHC both in low‐ and high‐frequency region.ConclusionsExposure to 0.063 kHz low‐frequency OBN at 90 dB SPL for 6 h leads to significant hearing loss over an extensive range from low to high frequencies.

Beneficial effects of time-restricted feeding on gentamicin cytotoxicity in mouse cochlea and vestibular organs.

ObjectiveTime restricted feeding (TRF), which is an intermittent fasting protocol, has been reported to decrease the toxicity and mortality rate associated with systemic gentamicin (GM) administration. The aim of this study is to evaluate the effect of TRF on GM‐induced vestibular and auditory function in mice.MethodsJapan Central Laboratory for Experimental Animals:Institute of Cancer Research (Jcl:ICR) mice were housed in a light–dark (LD) cycle (12:12) and were divided into three groups: (1) GM treatment at a dose of 220 mg/kg with TRF (feeding time: 8 h [9:00–17:00] during the light phase [7:00–19:00]) (GM + TRF group), (2) GM treatment at a dose of 220 mg/kg without TRF (GM group), and (3) saline injection with TRF (NS + TRF group). GM or saline was injected subcutaneously for 18 days (three courses of 5 days' injection + 2 days' rest, and an additional 3 days' injection). The auditory brainstem response (ABR) and vestibular evoked potential (VsEP) were tested after the treatments. The number of sensory hair cells in the cochlear organs and the vestibular organs were quantified using microscopic images.ResultsAll animals survived until the end of the experiment. One day after the last injection, GM + TRF mice showed significantly lower ABR thresholds at 4 kHz compared to GM mice, and there was no significant difference between the GM + TRF and NS + TRF groups. There was a significant difference of VsEP between GM and GM + TRF mice only in symmetric parabolic waves with linear acceleration and ramps waveform stimulation. GM + TRF mice showed significantly less outer and inner hair cell loss compared to GM mice. GM + TRF mice showed significantly less type II hair cell loss in the utricle and the ampulla compared to GM mice.ConclusionTRF with daytime feeding reduced GM cytotoxicity in the cochlea and vestibular organs of ICR mice.Level of EvidenceNA

Rapamycin ameliorates age-related hearing loss in C57BL/6J mice by enhancing autophagy in the SGNs

Autophagy plays a pathogenic role in neurodegenerative disease. However, the involvement of autophagy in the pathogenesis of age-related hearing loss (ARHL) remains obscure. Naturally aged C57BL/6J mice were used to identify the role of autophagy in ARHL, and rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, was administered for 34 weeks to explore the potential therapeutic effect of rapamycin in ARHL. We found that the number of autophagosomes and the expression of microtubule-associated protein 1 light chain 3B (LC3B) decreased as the mice aged. The expression of autophagy-related (Atg) proteins, including Beclin1 and Atg5, and the ratio of LC3-II/I was reduced in aged mice, while mTOR activity in aged mice gradually increased. Rapamycin improved the auditory brainstem response (ABR) threshold (at 8, 12, and 24 kHz). Further exploration demonstrated that spiral ganglion neuron (SGN) density was enhanced in response to administration of rapamycin. The rate of apoptosis in the basal turn SGNs was decreased, whereas autophagy activity was increased in the experimental group. Meanwhile, mTOR activity in the experimental group was decreased. Our findings indicate that age-related deficiency in autophagy may lead to increased apoptosis of aged SGNs. Rapamycin enhances autophagy of SGNs by inhibiting mTOR activation, resulting in amelioration of ARHL. Therapeutic strategy targeting autophagy may provide a potential approach for treating ARHL.

Auditory Behavior in Adult-Blinded Mice.

Cross-modal plasticity occurs when the function of remaining senses is enhanced following deprivation or loss of a sensory modality. Auditory neural responses are enhanced in the auditory cortex, including increased sensitivity and frequency selectivity, following short-term visual deprivation in adult mice (Petrus et al. Neuron 81:664-673, 2014). Whether or not these visual deprivation-induced neural changes translate into improved auditory perception and performance remains unclear. As an initial investigation of the effects of adult visual deprivation on auditory behaviors, CBA/CaJ mice underwent binocular enucleation at 3-4weeks old and were tested on a battery of learned behavioral tasks, acoustic startle response (ASR), and prepulse inhibition (PPI) tests beginning at least 2weeks after the enucleation procedure. Auditory brain stem responses (ABRs) were also measured to screen for potential effects of visual deprivation on non-behavioral hearing function. Control and enucleated mice showed similar tone detection sensitivity and frequency discrimination in a conditioned lick suppression test. Both groups showed normal reactivity to sound as measured by ASR in a quiet background. However, when startle-eliciting stimuli were presented in noise, enucleated mice showed decreased ASR amplitude relative to controls. Control and enucleated mice displayed no significant differences in ASR habituation, PPI tests, or ABR thresholds, or wave morphology. Our findings suggest that while adult-onset visual deprivation induces cross-modal plasticity at the synaptic and circuit levels, it does not substantially influence simple auditory behavioral performance.

КОМПЛЕКСНАЯ ДИАГНОСТИКА СЛУХА У ДЕТЕЙ С ЗАБОЛЕВАНИЕМ СПЕКТРА АУДИТОРНЫХ НЕЙРОПАТИЙ В РЕСПУБЛИКЕ БЕЛАРУСЬ

Auditory Neuropathy Spectrum Disorders, ANSD is a state of the auditory system in which the patient has otoacoustic emissions (OAEs) and/or cochlear microphonic potential (CMP), and auditory brainstem responses (ABRs) are absent or significantly reduced. In contrast to sensorineural hearing loss, where the outer and inner hair cells of the cochlea are damaged, in ANSD the outer hair cells are preserved. The complexity of ANSD detection and the variety of clinical symptoms of this disorder make it difficult to differentiate this disease from sensorineural hearing loss. Purpose. Improvement of the differential diagnosis of ANSD and sensorineural hearing loss by defining the main anamnestic and audiological criteria. Materials and methods. The research included 2 groups of patients: the core group - 48 patients with bilateral ANSD and the control group - 30 patients with bilateral chronic sensorineural hearing loss. All patients underwent assessment of the anamnesis data, impedance measurement, tone threshold audiometry, registration of OAE (TEOAE), registration of ABR with allocation of CMP, registration of stationary auditory evoked potentials. Results. In patients with ANSD the incidence of prematurity, low birth weight, and hyperbilirubinemia is significantly higher (p &lt;0.05) than in patients with sensorineural hearing loss. In patients with ANSD the 35delG mutation in the GJB2 gene was not identified, in contrast to patients with sensorineural hearing loss (genetic factor was confirmed in 23.3%) (p &lt;0.05). Newborn hearing screening on both sides was conducted in 15 children (31.3%) with ANSD and only 1 child (3.3%) with sensorineural hearing loss (p &lt;0.05). In 8 patients (16.7%) with ANSD was recorded TEOAE during the initial audiological diagnosis, in contrast to sensorineural hearing loss (TEOAE was not recorded in 100% of patients) (p &lt;0.05). In contrast to sensorineural hearing loss, the ABR thresholds in ANSD did not correspond to the behavioral hearing thresholds. CMP was recorded on the right and left ear in all patients (100%) with ANSD and remained unchanged during the observation process, in contrast to patients with sensorineural hearing loss, in whom CMP was not recorded on both sides (p &lt;0.05). Conclusions. The structure of the main risk factors for hearing loss in children with ANSD and sensorineural hearing loss is different. In the differential diagnosis with sensorineural hearing loss, the possibility of TEOAE disappearance in ANSD should be taken into account. Registration of ABRs with the allocation of CMP is the most informative method of ANSD diagnostics. CMP registration should be conducted for all patients who do not have ABR peaks at the maximum stimulus intensity, regardless of the OAE registration results.

Outcome of Cochlear Implantation in Children with Auditory Neuropathy-A Dual Case Study

Objectives: The aim of this study is to compare the outcome of cochlear implantation in two pediatric auditory neuropathy cases. Methods: Two cases with auditory neuropathy were taken. Case 1 was 10 year old male. Case 2 was 11 year old male. In preoperative assessment both have bilateral severe to profound sensory-neural hearing loss. Case 1 was implanted by MED-EL using sonata Ti100 opus 2 processor. Case 2 was implanted using MED-EL using sonata Ti100 opus 2 processor. Both cases were given auditory verbal therapy. Both cases attended auditory verbal therapy for a period of 2 years. In postoperative assessment for each individual subject, electrically evoked compound action potentials (ECAPs), electrically evoked stapedius reflex threshold (ESRT), and electrically evoked auditory brainstem response (EABR) thresholds were determined. The following questionnaire extended receptive expressive emergent language scale (E-REELS) , Categories of Auditory Performance (CAP) score, Speech Intelligibility Rating (SIR) scale, Meaningful Auditory-Integration Scale (MAIS) and Meaningful Use of Speech Scale (MUSS) are scales were administered. Results: In the postoperative assessment, ECAP, ESRT, EABR, MUSS, MAIS shows that case 1 with auditory neuropathy have better performance than case 2. Conclusion: It is essential that all possible complications and postoperative performance should be considered in cochlear implantation for auditory neuropathy individuals

Alpha-Synuclein Overexpression Causes Mild Hearing Loss and Protection from Noise Trauma

Alpha synuclein (α-Syn) is a small synaptic protein expressed within the central nervous system (CNS). α-Syn has been implicated in the pathogenesis of Parkinson’s disease (PD), and current theory suggests that α-Syn over-expression may lead to some of the CNS changes seen in PD, but the precise function of α-Syn remains elusive. α-Syn has also been identified in the auditory system and it is predominantly localized to the efferent auditory synapses below outer hair cells. In these studies, we studied a transgenic mouse model over-expressing α-Syn to investigate whether over-expression of α-Syn leads to pathologic changes within the cochlea. In the cochleae of wild-type (WT) mice, immunofluorescence using an anti-α-Syn antibody revealed strong labeling only in the base of outer hair cells. In contrast, in mice over-expressing α-Syn, there was robust staining in cells throughout the organ of Corti. Auditory brainstem responses (ABR) showed significant threshold elevations and a significant decrease of the ABR wave I amplitude in the transgenic mice as compared to WT mice. No significant differences were seen between WT and transgenic mice in hair cell counts, morphology or distortion product otoacoustic emissions. Following noise exposure, WT mice demonstrated an ABR threshold shift of 10-20dB whereas transgenic mice showed no significant threshold shift, suggesting a protective effect of α-Syn over-expression against noise-induced hearing loss. Together, these studies demonstrate that α-Syn over-expression causes a mild hearing loss and a protective effect against noise damage with no apparent damage to the cochlear hair cells. These findings suggest that the hearing loss seen with α-Syn over-expression occurs more centrally, while the mechanism of noise protection with over-expression remains unknown.

Analysis of potential protective effects of caffeic acid phenethyl ester against gentamicin ototoxicity: An experimental study

Objective(s):In this study, it is aimed to investigate the potential protective effect of caffeic acid phenethyl ester (CAPE) on ototoxicity caused by gentamicin in a rat model.Materials and Methods:Thirty Wistar albino rats were divided into 3 groups. Group I was selected as the control group. Gentamicin was administered intraperitoneally in group II, gentamicin and CAPE in group III. Audiological assessment was performed by the distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) measurements before and after treatment of each group. At the end of the study all rats were decapitated, cochlea was removed and electron microscopic examination was performed. Results:In group II post-treatment DPOAE levels were found to be lower than pretreatment DPOAE levels (P<0.05). However, in group III, there is no significant difference between pre- and post-treatment DPOAE levels (P>0.05). Except for Group I, ABR thresholds increased after the procedure and this increase was statistically significant (P<0.0001). According to histological examination by transmission electron microscopy, CAPE has a cellular protective effect against gentamicin ototoxicity. Conclusion:CAPE may ameliorate hearing deterioration caused by gentamicin ototoxicity and protect the cochlear cells from apoptosis due to the strong antioxidant effect.

Preloaded D-methionine protects from steady state and impulse noise-induced hearing loss and induces long-term cochlear and endogenous antioxidant effects.

ObjectiveDetermine effective preloading timepoints for D-methionine (D-met) otoprotection from steady state or impulse noise and impact on cochlear and serum antioxidant measures.DesignD-met started 2.0-, 2.5-, 3.0-, or 3.5- days before steady-state or impulse noise exposure with saline controls. Auditory brainstem response (ABRs) measured from 2 to 20 kHz at baseline and 21 days post-noise. Samples were then collected for serum (SOD, CAT, GR, GPx) and cochlear (GSH, GSSG) antioxidant levels.Study sampleTen Chinchillas per group.ResultsPreloading D-met significantly reduced ABR threshold shifts for both impulse and steady state noise exposures but with different optimal starting time points and with differences in antioxidant measures.For impulse noise exposure, the 2.0, 2.5, and 3.0 day preloading start provide significant threshold shift protection at all frequencies. Compared to the saline controls, serum GR for the 3.0 and 3.5 day preloading groups was significantly increased at 21 days with no significant increase in SOD, CAT or GPx for any impulse preloading time point. Cochlear GSH, GSSG, and GSH/GSSG ratio were not significantly different from saline controls at 21 days post noise exposure.For steady state noise exposure, significant threshold shift protection occurred at all frequencies for the 3.5, 3.0 and 2.5 day preloading start times but protection only occurred at 3 of the 6 test frequencies for the 2.0 day preloading start point. Compared to the saline controls, preloaded D-met steady-state noise groups demonstrated significantly higher serum SOD for the 2.5–3.5 day starting time points and GPx for the 2.5 day starting time but no significant increase in GR or CAT for any preloading time point. Compared to saline controls, D-met significantly increased cochlear GSH concentrations in the 2 and 2.5 day steady-state noise exposed groups but no significant differences in GSSG or the GSH/GSSG ratio were noted for any steady state noise-exposed group.ConclusionsThe optimal D-met preloading starting time window is earlier for steady state (3.5–2.5 days) than impulse noise (3.0–2.0). At 21 days post impulse noise, D-met increased serum GR for 2 preloading time points but not SOD, CAT, or GpX and not cochlear GSH, GSSG or the GSH/GSSG ratio. At 21 days post steady state noise D-met increased serum SOD and GPx at select preloading time points but not CAT or GR. However D-met did increase the cochlear GSH at select preloading time points but not GSSG or the GSH/GSSG ratio.