Distortion Product Otoacoustic Emission Thresholds Research Articles

Hearing restoration by gene replacement therapy for a multisite-expressed gene in a mouse model of human DFNB111 deafness

Gene therapy has made significant progress in the treatment of hereditary hearing loss. However, most research has focused on deafness-related genes that are primarily expressed in hair cells with less attention given to multisite-expressed deafness genes. MPZL2, the second leading cause of mild-to-moderate hereditary deafness, is widely expressed in different inner ear cells. We generated a mouse model with a deletion in the Mpzl2 gene, which displayed moderate and slowly progressive hearing loss, mimicking the phenotype of individuals with DFNB111. We developed a gene replacement therapy system mediated by AAV-ie for efficient transduction in various types of cochlear cells. AAV-ie-Mpzl2 administration significantly lowered the auditory brainstem response and distortion product otoacoustic emission thresholds of Mpzl2-/- mice for at least seven months. AAV-ie-Mpzl2 delivery restored the structural integrity in both outer hair cells and Deiters cells. This study suggests the potential of gene therapy for MPZL2-related deafness and provides a proof of concept for gene therapy targeting other deafness-related genes that are expressed in different cell populations in the cochlea.

Physiological characterization of a macaque model of presbycusis

Age-related hearing loss (presbycusis) is the leading cause of hearing loss worldwide, but current human studies do not separate this pathology from lifetime noise exposure. Laboratory macaques live in environments with minimal noise-induced hearing trauma and have long lifespans, making them optimal presbycusis models. We describe age-related auditory changes using two clinical, non-invasive physiological measures in aging macaques: distortion product otoacoustic emissions (DPOAEs) and auditory brainstem responses (ABRs). ABRs and DPOAEs were measured in anesthetized young (6–9 years old, n = 36 ears) and aging (26–35 years old, n = 20 ears) Macaca mulatta. ABR and DPOAE thresholds were elevated in aging subjects compared to young macaques at all tested frequencies. ABR thresholds were significantly correlated with age for frequencies >8 kHz, but DPOAE thresholds were not, a pattern likely attributable to a high-frequency ceiling effect for DPOAE measures. For frequencies <8 kHz, DPOAE thresholds showed significant correlation with age. However, this was not observed with ABR thresholds, suggesting differential sensitivity to age-related changes for auditory nerve and brainstem function compared to cochlear outer hair cell function. Ongoing analysis on temporal processing/adaptation metrics will further elucidate age-related changes. Future work will correlate these findings with histological analysis. [Work Supported by NIH R01-DC-015988.]

Study on gene therapy for DPOAE and ABR threshold changes in adult Otof-/- mice

Objective:This study aims to analyze the threshold changes in distortion product otoacoustic emissions（DPOAE） and auditory brainstem response（ABR） in adult Otof-/- mice before and after gene therapy, evaluating its effectiveness and exploring methods for assessing hearing recovery post-treatment. Methods:At the age of 4 weeks, adult Otof-/- mice received an inner ear injection of a therapeutic agent containing intein-mediated recombination of the OTOF gene, delivered via dual AAV vectors through the round window membrane（RWM）. Immunofluorescence staining assessed the proportion of inner ear hair cells with restored otoferlin expression and the number of synapses.Statistical analysis was performed to compare the DPOAE and ABR thresholds before and after the treatment. Results:AAV-PHP. eB demonstrates high transduction efficiency in inner ear hair cells. The therapeutic regimen corrected hearing loss in adult Otof-/- mice without impacting auditory function in wild-type mice. The changes in DPOAE and ABR thresholds after gene therapy are significantly correlated at 16 kHz. Post-treatment,a slight increase in DPOAE was observeds,followed by a recovery trend at 2 months post-treatment. Conclusion:Gene therapy significantly restored hearing in adult Otof-/- mice, though the surgical delivery may cause transient hearing damage. Precise and gentle surgical techniques are essential to maximize gene therapy's efficacy.

Zinc deficiency triggers hearing loss by reducing ribbon synapses of inner hair cells in CBA/N mice

Zinc plays a vital role in our metabolism, encompassing antioxidant regulation, immune response, and auditory function. Several studies have reported that zinc levels correlate with hearing loss. We have previously demonstrated that the auditory brainstem response (ABR) threshold increased in mice fed a zinc-deficient diet. However, the effects of zinc deficiency on hearing were not fully elucidated. The present study investigated whether zinc deficiency affects hearing in association with neuronal components or cochlear structures. CBA/N mice were fed a normal or zinc-deficient diet for 8 weeks and assessed for ABR and distortion product otoacoustic emissions (DPOAE). The cochlear sections were stained with hematoxylin and eosin solution. Also, we observed the expression of synaptic ribbons, neurofilaments, and alpha-synuclein (α-Syn). The 8-week zinc-deficient diet mice had an elevated ABR threshold but no changed DPOAE threshold or cochlear structures. A reduced number of synaptic ribbons of inner hair cells (IHCs) and impaired efferent nerve fibers were observed in the zinc-deficient diet mice. The number of outer hair cells (OHCs) and expression of α-Syn remained unchanged. Our results suggest that zinc-mediated hearing loss is associated with the loss of neuronal components of IHCs.

Otologic safety of intratympanic N-acetylcysteine in an animal model.

N-acetylcysteine (NAC) is an anti-oxidant and mucolytic effective against bacterial biofilms, making it useful in the treatment of chronically discharging ears that are unresponsive to traditional treatment methods. The objective of this study was to evaluate the otologic safety of intratympanic NAC combined with Ciprodex® in an animal model. Baseline distortion product otoacoustic emissions (DPOAE) and auditory brainstem response (ABR) measurements were performed for both ears on thirteen guinea pigs from the animal care research facilities of the McGill University Health Center. This was followed by intratympanic administration of control solution (Ciprofloxacin 0.3%/Dexamethasone 0.1%) to the left ear and experimental solution (1.25% NAC/Ciprofloxacin 0.3%/Dexamethasone 0.1%) to the right ear. Three additional intratympanic injections were performed over the next fourteen days. DPOAE and ABR measurements were repeated 3-4 weeks after the initial procedure. Outcome measures included differences in DPOAE and ABR thresholds after intervention, clinical evidence of vestibular dysfunction and histological evidence of ototoxicity. There were no significant differences in the ABR thresholds and DPOAE results of the control and experimental ears at baseline and after intervention. There was neither clinical manifestation of vestibular dysfunction nor histological evidence of ototoxicity. Our study suggests that intratympanic 1.25% NAC with ciprofloxacin and dexamethasone is safe in guinea pigs and support its potential use in the treatment of chronically discharging ears. Further studies in humans are required to analyze its efficacy relative to conventional treatments. Animal Research.

Can Ganciclovir and Quercetin-P188 Ameliorate Cytomegalovirus Induced Hearing Loss?

Determine whether combination therapy with ganciclovir (GCV) and a Quercetin-P188 solution improves hearing outcomes in a murine cytomegalovirus (CMV) model. BALB/c mice were infected with murine CMV on postnatal day 3 (p3). Quercetin was solubilized in saline using P188 (QP188). Treatment groups received either GCV, QP188, GCV and QP188, or P188 delivery vehicle BID at 12-hour intervals via intraperitoneal injection. All treatment groups were treated for 14 days starting at p3. Uninfected controls were treated with the combined regimen, saline or P188 delivery vehicle. Auditory thresholds were assessed using distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) testing at 4, 6, and 8 weeks of age. Temporal bones from separate CMV-infected groups were harvested at p10, and viral load was determined by quantitative polymerase chain reaction. CMV-infected mice receiving combination therapy GCV+QP188 demonstrated statistically significant lower ABR (p < 0.001) and DPOAE thresholds (p < 0.001) compared with mice treated with GCV monotherapy, QP188 monotherapy, and P188 delivery vehicle at 4, 6, and 8 weeks of age. GCV+QP188 combination therapy, GCV monotherapy, and QP188 monotherapy resulted in a nonsignificant reduction in mean viral titers compared to P188 monotherapy (p = 0.08). Combining GCV with the excipients quercetin and P188 effectively ameliorated CMV-induced sensorineural hearing loss in a murine model. This result may be partially explained by a reduction in viral titers in mouse temporal bones that correlate with in vitro studies demonstrating additive antiviral effect in cell culture. NA Laryngoscope, 134:1457-1463, 2024.

Hearing Following Prolonged and Delayed Ganciclovir Treatment in a Murine Cytomegalovirus Model.

Compare hearing outcomes utilizing standard, prolonged and delayed ganciclovir (GCV) therapy in a murine model of cytomegalovirus (CMV). BALB/c mice were inoculated with mouse cytomegalovirus (mCMV) or saline via intracerebral injection on postnatal day 3 (p3). Intraperitoneal GCV or saline was administered at 12 h intervals for the duration of the standard (p3-p17), delayed (p30-p44), or prolonged treatment windows (p3-p31). Auditory thresholds were assessed using distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) testing at 4, 6, and 8 weeks of age. Blood and tissue samples were harvested from mice on p17 and p37 one hour after GCV administration, and their concentrations were assessed via liquid chromatography-mass spectrometry. A delayed course of GCV improved ABR but not DPOAE thresholds in mCMV-infected mice. A prolonged course of GCV did not provide better hearing thresholds than those administered standard treatment. The average GCV concentration in all 17-day-old mice tissue was significantly higher than those in older 37-day-old mice. Delayed GCV treatment provided a hearing benefit on ABR over untreated mCMV infected mice. Prolonged CGV administration showed no benefit compared to a shorter duration GCV treatment. GCV drug concentrations both systemically and in the cochlea are much lower in older mice. These results have potential implications for the clinical management of cCMV infected children. NA Laryngoscope, 134:433-438, 2024.

Longitudinal analysis of auditory dysfunction in Alzheimer’s disease mice 5xFAD

AbstractBackgroundThere is no cure for AD at this moment. All available therapies require accurate diagnosis and staging of AD to ensure proper strategy. Current diagnosis methods rely on high‐cost technologies with radioactive agents, and those are not necessarily included in regular health screenings. Thus, a low‐cost, non‐invasive approach of AD analysis is in great need. The comorbidity between Alzheimer’s disease and hearing loss has been shown to be significant. Beyond hearing loss, AD patients also showed auditory processing disorders. However, it remains unclear if auditory deficits can be a good biomarker for AD analysis, especially for early stages.Method5xFAD animals were bred in CBA/B6 hybrid background to compensate the hearing loss deficits in C57/B6 strain and only F1 animals were used in this study. The auditory features were monitored by Auditory Brainstem Response (ABR) test and Distortion Product Otoacoustic Emission (DPOAE) test at 3, 6, 9 and 12‐month‐old, which correlate to young ‐ middle age of human lifespan. Their anti‐masking ability was evaluated by masking ABR and notched noise ABR in 3 and 12‐month‐old animals. Fluorescent immunostaining was performed to evaluate anatomical change in cochlea.ResultAD animals showed accelerated age‐related hearing loss comparing to their WT littermates. The ABR threshold showed significant change at lower frequencies first, then extended to all testing frequencies. DPOAE threshold did not show significant change at any testing frequency. Aged AD animals showed significantly higher threshold increase in masking ABR and notched‐noise ABR. In addition to the increased hearing threshold, ABR waveform abnormalities were also observed in the AD animals. Longitudinal analysis revealed that ABR waveform abnormalities develop along with the progression of AD. Those abnormalities suggest auditory neuropathy and auditory processing deficits in AD animals. Histology analysis showed no significant change in synapse number or efference morphology.ConclusionAuditory dysfunction is a possible outcome of AD, and more likely reflecting the anatomical changes in central nervous system rather than periphery. Auditory dysfunction is a good candidate as a biomarker for AD progression at early stages.

A fluorescent photoimmunoconjugate for imaging of cholesteatoma

Cholesteatoma is a potentially serious complication of chronic ear infections and requires surgical intervention for definitive management. Long-term complications include a frequent need for repeat surgical intervention for disease recurrence, and techniques to improve efficacy of single-stage surgery are an important area of continued research. This study investigates a novel application of the photosensitizer immune conjugate (PIC) cetuximab-benzoporphyrin derivative (Cet-BPD) for in vitro localization of human cholesteatoma tissue, coupled with an in vivo safety study for middle ear application of Cet-BPD in a murine model. In fresh human cholesteatoma tissues, Cet-BPD demonstrates selective localization to the hyperplastic squamous cell tissue associated with cholesteatoma, without localizing to other tissues such as middle ear mucosa. Applied to the murine middle ear, Cet-BPD does not demonstrate any deleterious effect on murine hearing when assessed by any of auditory brainstem response (ABR) thresholds, distortion product otoacoustic emission thresholds, or ABR wave I amplitudes. These findings demonstrate the technical promise and encouraging safety profile for the use of PICs for intraoperative localization and treatment of cholesteatoma.

Optimized AAV Vectors for TMC1 Gene Therapy in a Humanized Mouse Model of DFNB7/11.

Gene therapy for genetic hearing loss is an emerging therapeutic modality for hearing restoration. However, the approach has not yet been translated into clinical application. To further develop inner-ear gene therapy, we engineered a novel mouse model bearing a human mutation in the transmembrane channel-1 gene (Tmc1) and characterized the auditory phenotype of the mice. TMC1 forms the mechanosensory transduction channel in mice and humans and is necessary for auditory function. We found that mice harboring the equivalent of the human p.N199I mutation (p.N193I) had profound congenital hearing loss due to loss of hair cell sensory transduction. Next, we optimized and screened viral payloads packaged into AAV9-PHP.B capsids. The vectors were injected into the inner ears of Tmc1Δ/Δ mice and the new humanized Tmc1-p.N193I mouse model. Auditory brainstem responses (ABRs), distortion product otoacoustic emissions (DPOAEs), cell survival, and biodistribution were evaluated in the injected mice. We found broad-spectrum, durable recovery of auditory function in Tmc1-p.N193I mice injected with AAV9-PHP.B-CB6-hTMC1-WPRE. ABR and DPOAE thresholds were equivalent to those of wild-type mice across the entire frequency range. Biodistribution analysis revealed viral DNA/RNA in the contralateral ear, brain, and liver but no overt toxicity. We conclude that the AAV9-PHP.B-CB6-hTMC1-WPRE construct may be suitable for further development as a gene therapy reagent for treatment of humans with genetic hearing loss due to recessive TMC1 mutations.

The influence of self-reported noise exposure on 2ƒ1-ƒ2 distortion product otoacoustic emission level, fine structure, and components in a normal-hearing population.

Distortion product otoacoustic emissions (DPOAEs) offer an outcome measure to consider for clinical detection and monitoring outer hair cell dysfunction as a result of noise exposure. This investigation detailed DPOAE characteristics and behavioral hearing thresholds up to 20 kHz to identify promising metrics for early detection of cochlear dysfunction. In a sample of normal-hearing individuals with and without self-reported noise exposure, the DPOAE and hearing threshold measures, as assessed by two questions, were examined. The effects on various auditory measures in individuals aged 10-65 years old with clinically normal/near-normal hearing through 4 kHz were evaluated. Individuals reporting occupational noise exposures (n = 84) and recreational noise exposures (n = 46) were compared to age-matched nonexposed individuals. The hearing thresholds and DPOAE level, fine structure, and component characteristics for the full frequency bandwidth were examined. The data suggest that the DPOAE levels measured using a range of stimulus levels hold clinical utility while fine structure characteristics offer limited use. Under carefully calibrated conditions, the extension to frequencies beyond 8 kHz in combination with various stimulus levels holds clinical utility. Moreover, this work supports the potential utility of the distortion product place component level for revealing differences in cochlear function due to self-reported, casual noise exposure that are not observable in behavioral hearing thresholds.

Hearing Recovery Induced by DNA Demethylation in a Chemically Deafened Adult Mouse Model.

Functional hair cell regeneration in the adult mammalian inner ear remains challenging. This study aimed to study the function of new hair cells induced by a DNA demethylating agent 5-azacytidine. Adult mice were deafened chemically, followed by injection of 5-azacytidine or vehicle into the inner ear. Functionality of regenerated hair cells was evaluated by expression of hair cell proteins, auditory brainstem response (ABR), and distortion-product otoacoustic emission (DPOAE) tests for 6 weeks. In the vehicle-treated group, no cells expressed the hair cell-specific protein myosin VIIa in the cochlea, whereas numerous myosin VIIa-expressing cells were found in the 5-azacytidine-treated cochlea, suggesting the regeneration of auditory hair cells. Moreover, regenerated hair cells were co-labeled with functional proteins espin and prestin. Expression of ribbon synapse proteins suggested synapse formation between new hair cells and neurons. In hearing tests, progressive improvements in ABR [5–30 dB sound pressure level (SPL)] and DPOAE (5–20 dB) thresholds were observed in 5-azacytidine-treated mice. In vehicle-treated mice, there were <5 dB threshold changes in hearing tests. This study demonstrated the ability of 5-azacytidine to promote the functional regeneration of auditory hair cells in a mature mouse model via DNA demethylation, which may provide insights into hearing regeneration using an epigenetic approach.

Individualized Cochlear Models Based on Distortion Product Otoacoustic Emissions.

Auditory models have been adopted for years to simulate characteristics of the human auditory processing for normal and hearing-impaired listeners. However, individual differences due to varying degrees of frequency-dependent hearing damage hinders the simulation of auditory processing on an individualized basis. Here, with a view on precise auditory profiling, recorded distortion product otoacoustic emission (DPOAE) metrics are used to determine individual parameters of cochlear non-linearity to yield individualized human cochlear models, which can be used as pre-processors for hearing-aid and machine-hearing applications. We test whether individualized cochlear models based on DPOAE measurements can simulate the measured DPOAEs and audiograms of normal-hearing and hearing-impaired listeners. Results showed that cochlear models individualized based on DPOAE-grams measured at low stimulus levels or DPOAE thresholds, yield the smallest simulation errors.

Sensorineural Hearing Loss and Mitochondrial Apoptosis of Cochlear Spiral Ganglion Neurons in Fibroblast Growth Factor 13 Knockout Mice.

Deafness is known to occur in more than 400 syndromes and accounts for almost 30% of hereditary hearing loss. The molecular mechanisms underlying such syndromic deafness remain unclear. Furthermore, deafness has been a common feature in patients with three main syndromes, the BÖrjeson-Forssman-Lehmann syndrome, Wildervanck syndrome, and Congenital Generalized Hirsutism, all of which are characterized by loss-of-function mutations in the Fgf13 gene. Whether the pathogenesis of deafness in these syndromes is associated with the Fgf13 mutation is not known. To elucidate its role in auditory function, we generated a mouse line with conditional knockout of the Fgf13 gene in the inner ear (Fgf13 cKO). FGF13 is expressed predominantly in the organ of Corti, spiral ganglion neurons (SGNs), stria vascularis, and the supporting cells. Conditional knockout of the gene in the inner ear led to sensorineural deafness with low amplitude and increased latency of wave I in the auditory brainstem response test but had a normal distortion product otoacoustic emission threshold. Fgf13 deficiency resulted in decreased SGN density from the apical to the basal region without significant morphological changes and those in the number of hair cells. TUNEL and caspase-3 immunocytochemistry assays showed that apoptotic cell death mediated the loss of SGNs. Further detection of apoptotic factors through qRT-PCR suggested the activation of the mitochondrial apoptotic pathway in SGNs. Together, this study reveals a novel role for Fgf13 in auditory function, and indicates that the gene could be a potential candidate for understanding deafness. These findings may provide new perspectives on the molecular mechanisms and novel therapeutic targets for treatment deafness.

A Wirelessly Controlled Scalable 3D-Printed Microsystem for Drug Delivery.

Here we present a 3D-printed, wirelessly controlled microsystem for drug delivery, comprising a refillable microreservoir and a phase-change peristaltic micropump. The micropump structure was inkjet-printed on the back of a printed circuit board around a catheter microtubing. The enclosure of the microsystem was fabricated using stereolithography 3D printing, with an embedded microreservoir structure and integrated micropump. In one configuration, the microsystem was optimized for murine inner ear drug delivery with an overall size of 19 × 13 × 3 mm3. Benchtop results confirmed the performance of the device for reliable drug delivery. The suitability of the device for long-term subcutaneous implantation was confirmed with favorable results of implantation of a microsystem in a mouse for six months. The drug delivery was evaluated in vivo by implanting four different microsystems in four mice, while the outlet microtubing was implanted into the round window membrane niche for infusion of a known ototoxic compound (sodium salicylate) at 50 nL/min for 20 min. Real-time shifts in distortion product otoacoustic emission thresholds and amplitudes were measured during the infusion, demonstrating similar results with syringe pump infusion. Although demonstrated for one application, this low-cost design and fabrication methodology is scalable for use in larger animals and humans for different clinical applications/delivery sites.

The protective effect of astaxanthin on cisplatin-induced ototoxicity.

Promising studies have been conducted with many substances to reduce the ototoxic effects of cisplatin, but there is no treatment that completely eliminates the ototoxic effect. To determine the effectiveness of astaxanthin (ASX) as a protective agent against cisplatin-induced ototoxicity. Thirty-six rats were randomly divided into 6 groups. Group 1 received no drug injections except for anesthetics; group 2 received intraperitoneal (IP) olive oil only for 8 days; group 3 received only IP ASX 75 mg/kg dissolved in olive oil for 8 days; group 4 received a single dose of only IP 16 mg/kg cisplatin on the 5th day; group 5 received 25 mg/kg ASX IP daily for 8 days and a single 16 mg/kg dose of cisplatin on the 5th day; group 6 received 75 mg/kg ASX IP daily for 8 days and a single 16 mg/kg dose of cisplatin on the 5th day. The animals were tested for distortion product otoacoustic emissions (DPOAE) before and 3 days after cisplatin treatment. The animals in all groups were sacrificed under anesthesia on the 10th day. Before sacrifice, inferior vena cava blood samples were drawn into commercial tubes for biochemical analysis and their cochlea were prepared for histological analysis. The ASX+cisplatin groups demonstrated significantly higher DPOAE thresholds when compared to the cisplatin-only group (p < 0.05). The ASX 25 mg/kg/day+cisplatin group showed a significant increase in total antioxidant capacity compared to the cisplatin-only group, whereas the ASX 75 mg/kg/day+cisplatin group had significantly lower total oxidative stress and oxidative stress index. Histologic results showed that the cortical organ was better preserved in the ASX+cisplatin groups compared to the cisplatin-only group, and the degeneration in the spiral ganglion and inner and outer hair cells was less visible in the ASX groups. Astaxanthin can protect hearing from cisplatin-induced ototoxicity, prevent cellular degeneration and significantly reduce oxidative stress.

Effect of Oral Allylnitrile Administration on Cochlear Functioning in Mice Following Comparison of Different Anesthetics for Hearing Assessment.

Background: Allylnitrile is a compound found in cruciferous vegetables and has the same lethality and toxic effects as the other nitriles. In 2013, a viable allylnitrile ototoxicity mouse model was established. The toxicity of allylnitrile was limited through inhibition of CYP2E1 with trans-1,2-dichloroethylene (TDCE). The allylnitrile intoxication model has been extensively tested in the 129S1 mouse strain for vestibular function, which showed significant HC loss in the vestibular organ accompanied by severe behavioral abnormalities. However, the effect of allylnitrile on auditory function remains to be evaluated. Commonly used anesthetics to conduct hearing measurements are isoflurane and ketamine/xylazine anesthesia but the effect of these anesthetics on hearing assessment is still unknown. In this study we will evaluate the otovestibular effects of oral allylnitrile administration in mice. In addition, we will compare the influence of isoflurane and ketamine/xylazine anesthesia on hearing thresholds.Methods and Materials: Fourteen Coch+/– CBACa mice were randomly allocated into an allylnitrile (n = 8) and a control group (n = 6). Baseline measurements were done with isoflurane and 1 week later under ketamine/xylazine anesthesia. After baseline audiovestibular measurements, mice were co-administered with a single dose of allylnitrile and, to reduce systemic toxicity, three intraperitoneal injections of TDCE were given. Hearing loss was evaluated by recordings of auditory brainstem responses (ABR) and distortion product otoacoustic emissions (DPOAE). Specific behavioral test batteries for vestibular function were used to assess alterations in vestibular function.Results: Hearing thresholds were significantly elevated when using isoflurane anesthesia compared to ketamine/xylazine anesthesia for all frequencies of the ABR and the mid-to-high frequencies in DPOAE. Allylnitrile-treated mice lacked detectable ABR thresholds at each frequency tested, while DPOAE thresholds were significantly elevated in the low-frequency region of the cochlea and completely lacking in the mid-to high frequency region. Vestibular function was not affected by allylnitrile administration.Conclusion: Isoflurane anesthesia has a negative confounding effect on the measurement of hearing thresholds in mice. A single oral dose of allylnitrile induced hearing loss but did not significantly alter vestibular function in mice. This is the first study to show that administration of allylnitrile can cause a complete loss of hearing function in mice.

Temporal characteristics of the cochlear response after noise exposure

The effect of intense noise on cochlear sensitivity has been extensively studied, but its influence on the temporal characteristics of the cochlear response is still unclear. This study investigated the effects of noise exposure on the latency of cochlear response and cochlear forward masking. Rats were exposed to an octave band noise (8–16 kHz) at 90 dB SPL for 5 days. Cochlear compound action potentials (CAPs) induced by single- and double-tone stimuli and distortion product otoacoustic emissions (DPOAE) were recorded 1 day or 2 months after the noise exposure. The latency of the CAP and its forward masking were compared between the noise-exposed rats and normal control rats. The noise exposure significantly reduced DPOAE and elevated CAP threshold in the noise band region, but not in the other areas. Even in the noise band area, the noise did not reduce CAP-amplitude at the high stimulation level (80 dB SPL). Correspondingly, about one-third of the outer hair cells (OHC) in the noise band area disappeared, while the inner hair cells (IHC) did not. However, the noise exposure in the frequency range of 4–24 kHz significantly prolonged CAP latency and increased its variability, while the CAP forward masking effect was significantly enhanced in the frequency range of 16–30 kHz. The frequency-dependent changes in CAP latency and forward masking after noise exposure may reflect different types of synaptic subinjury in the cochlea, which may lead to psychophysical consequences of sound localization and speech recognition.

Esketamine may be an ideal substitute for ketamine during cochlear function measurement

The mixture of ketamine and xylazine is widely used for the auditory brainstem response (ABR) measurement. Esketamine is twice as potent as ketamine. Our objective was to assess the influence of esketamine in mice undergoing cochlear function measurement including ABR and distortion product otoacoustic emission (DPOAE) measurement. C57Bl/6J mice were treated with an equivalent dose of analgesia and received either a single intraperitoneal (ip) injection of 100 mg/kg ketamine and 25 mg/kg xylazine or 50 mg/kg esketamine and 25 mg/kg xylazine. Hearing thresholds, peak latencies of waves I and V, and DPOAE thresholds were recorded. Time to loss of righting and time to regain righting were also assessed. We found that hearing thresholds, the peak latencies of waves I and V, and DPOAE thresholds were similar between the two groups (all P>0.05). Time to regain righting was significantly shorter in the esketamine group (P<0.001) than in the ketamine group. We concluded that when using equivalent doses of analgesia, esketamine may be an ideal substitute for ketamine during cochlear function test.

Comparative Study on Method of Threshold Estimation: Distortion Product Threshold Test versus Pure Tone Threshold Test

Abstract Introduction Distortion product otoacoustic emissions (DPOAEs) can be helpful in estimating the hearing thresholds by extrapolating the DPOAE input/output function with the help of scissor paradigm, and thus the following study aims at assessing its reliability by comparing DPOAE thresholds with those obtained by behavioral responses at pure tones on various frequencies. Materials and Methods Fifty participants having normal hearing sensitivity were included in the study. Pure tone (PT) audiometry was carried out on all participants to determine PT thresholds in both ears. DPOAE threshold test was administered and thresholds at 1, 2, 4, and 8 kHz were compared accordingly. Results The result indicated significant difference between the two methods of threshold estimation where the mean difference was found to be 3 decibel (dB) and 4 dB for left and right ears, respectively. Shapiro-Wilk test revealed normal distribution (p &gt; 0.05) of the data. Hence, parametric paired t-test was performed, which revealed significant difference between PT and distortion product thresholds. Conclusion Study concludes as having good clinical applicability in assessing neonates and infants.