Peak Equivalent Sound Pressure Level Research Articles

Age-related hearing loss was accelerated by apoptosis of spiral ganglion and stria vascularis cells in ApoE KO mice with hyperglycemia and hyperlipidemia.

Age-related hearing loss (ARHL) is associated with diabetes and/or dyslipidemia in humans. However, the detailed mechanism for the development of ARHL by diabetes and/or dyslipidemia has not been elucidated. In this study, we investigated the etiology of ARHL in apolipoprotein E (ApoE)-deficient mice with diabetes and dyslipidemia. The atherosclerotic CD-STZ (mice fed with a control diet and received an STZ injection), WD-con (mice fed with a western diet), and WD-STZ (mice fed with a western diet and received an STZ injection) mice showed a 2.4-, 4.9-, and 6.8-fold larger area, respectively, occupied by lesions throughout the aorta compared with the CD-con mice. A significantly larger area under the curve (AUC) was observed in the STZ-treated groups than in the non-treated groups based on the oral glucose tolerance test (OGTT). At 20 weeks of age, HbA1c levels were significantly higher in the CD-STZ and WD-STZ mice than in the CD-con and WD-con mice. In all the groups, the auditory brainstem response (ABR) thresholds of the 16-week-old mice were significantly higher compared with those of the 8-week-old mice. In particular, in the WD-STZ mice, the ABR thresholds of the left and right ears reached the maximum decibel peak equivalent sound pressure levels (130 dBpeSPL), which is a sign of deafness. The apoptotic spiral ganglion neurons (SGNs) of the WD-STZ mice were significantly increased compared with those of the other three groups, indicating that SGN apoptosis resulted in hearing loss in STZ-induced diabetic ApoE KO mice fed with a WD. A significant loss of the stria vascularis cells was observed in the WD-STZ group compared with the CD-con mice. In the organ of Corti, few apoptotic hair cells were found in all the groups; however, no significant difference was observed. Therefore, we consider that the reduced hearing ability in the STZ-treated and WD-fed groups was attributed to the damage to the SGN and stria vascularis in the cochlea. Thus, our results indicated that ototoxicity by diabetes and/or dyslipidemia accelerated ARHL in ApoE KO mice, thereby suggesting the importance of appropriate treatment of patients with diabetes and/or dyslipidemia to prevent ARHL.

Standardization of the TEOAE Contralateral Suppression Test in Terms of Stimulus Intensity and Contralateral Noise Duration in Individuals with Normal Hearing.

A standard method and parameter study were performed for the contralateral suppression test. Our study aimed to determine the contralateral transient-evoked otoacoustic emission (TEOAE) suppression test method and stimulus-noise parameters that have a standard procedure and will enable the efferent system to be easily evaluated in clinics. This study was conducted in two parts with two different groups of participants as a within-subjects design. In the first part, the signal-to-noise ratio at which maximum suppression obtained was investigated with 29 participants. In the second part, the optimal contralateral noise presentation method (in terms of noise-time or noise-sweep) was examined with 21 participants. In the first part 29 young adults aged between 18 and 32 (23.03 ± 2.84), 20 females and 9 males, and in the second part 21 young adults aged between 19 and 34 years (mean age: 23.71 ± 3.48 years), 16 females and 5 males, participated in the second part. All participants had normal hearing. To obtain maximum OAE suppression, different parameters were tested with the Otodynamics ILO292-II OAE device at both parts of the study in a double-walled audiometric test booths. Multirepeated analysis of variance, pairwise comparison, Friedman test, and Wilcoxon signed-rank tests were used for statistical analysis. In the first part, maximum suppression was achieved at 65 dB peSPL (decibel peak-equivalent sound pressure level) TEOAE stimulus and 65 dB SPL broadband noise. In the second part, maximum suppression was obtained in noise-time method with 30 seconds "duration." To provide standardization in clinics, it can be recommended that the contralateral suppression of OAEs was measured at 65 dB peSPL TEOAE stimulus and 65 dB SPL broadband noise in the linear stimulation mode with Otodynamics ILO 292-II double-probe OAE device. To obtain maximum suppression, the noise-time method with 30 seconds duration can be used.

Frequency-modulated up-chirp stimuli enhance the auditory brainstem response of the killer whale (Orcinus orca).

Previous studies suggested that frequency-modulated tonal stimuli where the frequency sweeps upward (up-chirps) may enhance auditory brainstem response (ABR) amplitudes in mammals. In this study, ABRs were measured in response to up-chirps in three killer whales (Orcinus orca) and compared to ABRs evoked by broadband clicks. Chirp durations ranged from 125 - 2000 μs. Chirp spectral content was either "uncompensated," meaning the spectrum paralleled the transmitting response of the piezoelectric transducer, or "compensated," where the spectral density level was flat (+/-4 dB) across the stimulus bandwidth (10 - 130 kHz). Compensated up-chirps consistently produced higher amplitude ABRs than uncompensated clicks with the same peak equivalent sound pressure level. ABR amplitude increased with up-chirp duration up to 1400 μs, although there was considerable variability between individuals. Results suggest that compensating stimuli for the response of transducers can have a dramatic effect on broadband ABRs, and that compensated up-chirps might be useful for testing whale species where large size makes far-field recording of ABRs at the skin surface difficult.

Is There a Safe Level for Recording Vestibular Evoked Myogenic Potential? Evidence From Cochlear and Hearing Function Tests.

There is a growing concern among the scientific community about the possible detrimental effects of signal levels used for eliciting vestibular evoked myogenic potentials (VEMPs) on hearing. A few recent studies showed temporary reduction in amplitude of otoacoustic emissions (OAE) after VEMP administration. Nonetheless, these studies used higher stimulus levels (133 and 130 dB peak equivalent sound pressure level [pe SPL]) than the ones often used (120 to 125 dB pe SPL) for clinical recording of VEMP. Therefore, it is not known whether these lower levels also have similar detrimental impact on hearing function. Hence, the present study aimed at investigating the effect of 500 Hz tone burst presented at 125 dB pe SPL on hearing functions. True experimental design, with an experimental and a control group, was used in this study. The study included 60 individuals with normal auditory and vestibular system. Of them, 30 underwent unilateral VEMP recording (group I) while the remaining 30 did not undergo VEMP testing (group II). Selection of participants to the groups was random. Pre- and post-VEMP assessments included pure-tone audiometry (250 to 16,000 Hz), distortion product OAE, and subjective symptoms. To simulate the time taken for VEMP testing in group I, participants in group II underwent these tests twice with a gap of 15 minutes. No participant experienced any subjective symptom after VEMP testing. There was no significant interear and intergroup difference in pure-tone thresholds and distortion product OAE amplitude before and after VEMP recording (p > 0.05). Furthermore, the response rate of cervical VEMP was 100% at stimulus intensity of 125 dB pe SPL. Use of 500 Hz tone burst at 125 dB pe SPL does not cause any temporary or permanent changes in cochlear function and hearing, yet produces 100% response rate of cervical VEMP in normal-hearing young adults. Therefore, 125 dB pe SPL of 500 Hz tone burst is recommended as safe level for obtaining cervical VEMP without significantly losing out on its response rate, at least in normal-hearing young adults.

Using Thresholds in Noise to Identify Hidden Hearing Loss in Humans.

Recent animal studies suggest that noise-induced synaptopathy may underlie a phenomenon that has been labeled hidden hearing loss (HHL). Noise exposure preferentially damages low spontaneous-rate auditory nerve fibers, which are involved in the processing of moderate- to high-level sounds and are more resistant to masking by background noise. Therefore, the effect of synaptopathy may be more evident in suprathreshold measures of auditory function, especially in the presence of background noise. The purpose of this study was to develop a statistical model for estimating HHL in humans using thresholds in noise as the outcome variable and measures that reflect the integrity of sites along the auditory pathway as explanatory variables. Our working hypothesis is that HHL is evident in the portion of the variance observed in thresholds in noise that is not dependent on thresholds in quiet, because this residual variance retains statistical dependence on other measures of suprathreshold function. Study participants included 13 adults with normal hearing (≤15 dB HL) and 20 adults with normal hearing at 1 kHz and sensorineural hearing loss at 4 kHz (>15 dB HL). Thresholds in noise were measured, and the residual of the correlation between thresholds in noise and thresholds in quiet, which we refer to as thresholds-in-noise residual, was used as the outcome measure for the model. Explanatory measures were as follows: (1) auditory brainstem response (ABR) waves I and V amplitudes; (2) electrocochleographic action potential and summating potential amplitudes; (3) distortion product otoacoustic emissions level; and (4) categorical loudness scaling. All measurements were made at two frequencies (1 and 4 kHz). ABR and electrocochleographic measurements were made at 80 and 100 dB peak equivalent sound pressure level, while wider ranges of levels were tested during distortion product otoacoustic emission and categorical loudness scaling measurements. A model relating the thresholds-in-noise residual and the explanatory measures was created using multiple linear regression analysis. Predictions of thresholds-in-noise residual using the model accounted for 61% (p < 0.01) and 48% (p < 0.01) of the variance in the measured thresholds-in-noise residual at 1 and 4 kHz, respectively. Measures of thresholds in noise, the summating potential to action potential ratio, and ABR waves I and V amplitudes may be useful for the prediction of HHL in humans. With further development, our approach of quantifying HHL by the variance that remains in suprathreshold measures of auditory function after removing the variance due to thresholds in quiet, together with our statistical modeling, may provide a quantifiable and verifiable estimate of HHL in humans with normal hearing and with hearing loss. The current results are consistent with the view that inner hair cell and auditory nerve pathology may underlie suprathreshold auditory performance.

Click-Evoked Auditory Efferent Activity: Rate and Level Effects.

There currently are no standardized protocols to evaluate auditory efferent function in humans. Typical tests use broadband noise to activate the efferents, but only test the contralateral efferent pathway, risk activating the middle ear muscle reflex (MEMR), and are laborious for clinical use. In an attempt to develop a clinical test of bilateral auditory efferent function, we have designed a method that uses clicks to evoke efferent activity, obtain click-evoked otoacoustic emissions (CEOAEs), and monitor MEMR. This allows for near-simultaneous estimation of cochlear and efferent function. In the present study, we manipulated click level (60, 70, and 80dB peak-equivalent sound pressure level [peSPL]) and rate (40, 50, and 62.5Hz) to identify an optimal rate-level combination that evokes measurable efferent modulation of CEOAEs. Our findings (n = 58) demonstrate that almost all click levels and rates used caused significant inhibition of CEOAEs, with a significant interaction between level and rate effects. Predictably, bilateral activation produced greater inhibition compared to stimulating the efferents only in the ipsilateral or contralateral ear. In examining the click rate-level effects during bilateral activation in greater detail, we observed a 1-dB inhibition of CEOAE level for each 10-dB increase in click level, with rate held constant at 62.5Hz. Similarly, a 10-Hz increase in rate produced a 0.74-dB reduction in CEOAE level, with click level held constant at 80dB peSPL. The effect size (Cohen's d) was small for either monaural condition and medium for bilateral, faster-rate, and higher-level conditions. We were also able to reliably extract CEOAEs from efferent eliciting clicks. We conclude that clicks can indeed be profitably employed to simultaneously evaluate cochlear health using CEOAEs as well as their efferent modulation. Furthermore, using bilateral clicks allows the evaluation of both the crossed and uncrossed elements of the auditory efferent nervous system, while yielding larger, more discernible, inhibition of the CEOAEs relative to either ipsilateral or contralateral condition.

Dolphin auditory brainstem responses to frequency-modulated “chirps.”

Previous studies have demonstrated that increasing-frequency chirp (up-chirp) stimuli can enhance auditory brainstem response (ABR) amplitudes by compensating for temporal dispersion occurring along the cochlear partition. In this study, ABRs were measured in two bottlenose dolphins in response to 5-µs, spectrally “white” clicks, up-chirps, and decreasing-frequency chirps (down-chirps). For all stimuli, bandwidth was constant (10 to 180 kHz) and peak-equivalent sound pressure levels (peSPLs) were 115, 125, or 135 dB re 1 μPa. Chirp durations varied from 125 to 2000 μs. Up-chirps with durations less than ~1000 μs generally increased ABR peak amplitudes compared to clicks with the same peSPL or energy flux spectral density level, while down-chirps with durations above ~250 to 500 μs decreased ABR amplitudes relative to clicks. Increases in ABR amplitude occurred with up-chirps having a broad range of durations. The findings parallel those from human studies and suggest that the use of chirp stimuli may be an effective way to enhance broadband ABR amplitudes in larger marine mammals. [Work supported by US Navy Living Marine Resources Program.]

Relating Click-Evoked Auditory Brainstem Response Waveforms to Hearing Loss in the Bottlenose Dolphin (Tursiops truncatus)

Hearing sensitivity in captive Atlantic bottlenose dolphins was assessed using a portable electrophysiologic data collection system, a transducer attached to the pan region of the mandible, and non-invasive recording electrodes. The auditory steady-state response (ASSR) was evoked using sinusoidal amplitude-modulated tones at half octave steps from 20–160 kHz and utilized to determine the upper frequency limit of hearing (i.e., the frequency at which threshold was ≤ 120 dB re 1 μPa). An auditory brainstem response (ABR) was then recorded to a moderate-amplitude click (peak-equivalent sound pressure level of 122 dB re 1 μPa) and examined to determine if relationships existed between the upper frequency limit of hearing and the waveform characteristics of the click-evoked ABR. The ASSR and click-evoked ABR were measured in 6 bottlenose dolphins with varying hearing sensitivity and frequency range of hearing. A significant relationship existed between click-evoked ABR wave amplitudes and the upper frequency limit of hearing. Test times for assessment using frequency-specific ASSR and click-evoked ABR were ∼45 minutes and 1 minute, respectively. With further definition of normative data, measurement of click-evoked ABRs could form the basis of an expedited electrophysiologic method for hearing screening in marine mammals.

On the Relationship Between Musicianship and Contralateral Suppression of Transient-Evoked Otoacoustic Emissions.

The medial olivocochlear (MOC) efferent reflex that modulates outer hair cell function has been shown to be more robust in musicians versus nonmusicians as evidenced in greater contralateral suppression of transient-evoked otoacoustic emissions (TEOAEs). All previous research comparing musical ability and MOC efferent strength has defined musicianship dichotomously (i.e., high-level music students or professional classical musicians versus nonmusicians). The objective of the study was to further explore contralateral suppression of TEOAEs among adults with a full spectrum of musicianship ranging from no history of musicianship to professional musicians. Musicianship was defined by both self-report and with an objective test to quantify individual differences in perceptual music skills. A single-factor between-subjects and correlational research designs were employed. Forty-five normal-hearing young adults participated. Participants completed a questionnaire concerning their music experience and completed the Brief Profile of Music Perception Skills (PROMS) to quantify perceptual musical skills across multiple musical domains (i.e., accent, melody, tempo, and tuning). TEOAEs were evaluated with 60 dB peak equivalent sound pressure level click stimuli with and without a contralateral 65 dB sound pressure level white noise suppressor. TEOAE suppression was expressed in two ways, absolute TEOAE suppression in dB and a normalized index of TEOAE suppression (i.e., percentage of suppression). Participants who considered themselves musicians scored significantly higher on all subscales and total Brief PROMS score (p < 0.05). There was no statistically significant difference between musicians and nonmusicians in absolute TEOAE suppression or percentage of TEOAE suppression (p > 0.05). There were no statistically significant correlations or linear predictive relationships between subscale or total Brief PROMS scores with absolute and percentage of TEOAE suppression (p > 0.05). The findings do not support the notion of a graded enhancement of MOC efferent suppression among adults with varied degrees of musicianship from nonmusicians to professional musicians.

Relating click-evoked auditory brainstem response waveforms to hearing loss in the bottlenose dolphin (Tursiops truncatus)

Hearing sensitivity in captive Atlantic bottlenose dolphins was assessed using a portable electrophysiologic data collection system, a transducer attached to the pan region of the mandible, and non-invasive recording electrodes. The auditory steady-state response (ASSR) was evoked using sinusoidal amplitude-modulated tones at half octave steps from 20–160 kHz and utilized to determine the upper frequency limit of hearing (i.e., the frequency at which threshold was ≤ 120 dB re 1 μPa). An auditory brainstem response (ABR) was then recorded to a moderate-amplitude click (peak-equivalent sound pressure level of 122 dB re 1 μPa) and examined to determine if relationships existed between the upper frequency limit of hearing and the waveform characteristics of the click-evoked ABR. The ASSR and click-evoked ABR were measured in 6 bottlenose dolphins with varying hearing sensitivity and frequency range of hearing. A significant relationship existed between click-evoked ABR wave amplitudes and the upper frequency limit of hearing. Test times for assessment using frequency-specific ASSR and click-evoked ABR were ∼45 minutes and 1 minute, respectively. With further definition of normative data, measurement of click-evoked ABRs could form the basis of an expedited electrophysiologic method for hearing screening in marine mammals.

Further tests of the local nonlinear interaction-based mechanism for simultaneous suppression of tone burst-evoked otoacoustic emissions

Tone burst-evoked otoacoustic emission (TBOAE) components measured in response to a 1 kHz tone burst (TB1) are suppressed by the simultaneous presence of an additional tone burst (TB2). This “simultaneous suppression of TBOAEs” has been explained in terms of a mechanism based on local nonlinear interactions between the basilar membrane (BM) travelling waves caused by TB1 and TB2. A test of this local nonlinear interaction (LNI)-based mechanism, as a function of the frequency separation (Δf, expressed in kHz) between TB1 and TB2, has previously been reported by Killan et al. (2012) using a simple mathematical model [Killan et al., Hear. Res. 285, 58–64 (2012)]. The two experiments described in this paper add additional data on the extent to which the LNI-based mechanism can account for simultaneous suppression, by testing two further hypotheses derived from the model predictions. Experiment I tested the hypothesis that TBOAE suppression is directly linked to TBOAE amplitude nonlinearity where ears that exhibit a higher degree of amplitude nonlinearity yield greater suppression than more linear ears, and this relationship varies systematically as a function of Δf. In order to test this hypothesis simultaneous suppression at a range of values of Δf at 60 dB peak-equivalent sound pressure level (p.e. SPL) and TBOAE amplitude nonlinearity from normal human ears was measured. In Experiment II the hypothesis that suppression will also increase progressively as a function of increasing tone burst level was tested by measuring suppression for a range of Δf and tone burst levels at 40, 50, 60 and 70 dB p.e. SPL. The majority of the findings from both experiments provide support for the LNI-based mechanism being primarily responsible for simultaneous suppression. However, some data were inconsistent with this view. Specifically, a breakdown in the relationship between suppression and TBOAE amplitude nonlinearity at Δf = 1 (i.e. when TB2 was reasonably well separated from, and had a higher frequency than TB1) and unexpected level-dependence, most notably at Δf = 1, but also where Δf = −0.5, was observed. Either the LNI model is too simple or an alternative explanation, involving response components generated at basal regions of the basilar membrane, is required to account for these findings.

In-Air Evoked Potential Audiometry of Grey Seals (Halichoerus grypus) from the North and Baltic Seas

In-air anthropogenic sound has the potential to affect grey seal (Halichoerus grypus) behaviour and interfere with acoustic communication. In this study, a new method was used to deliver acoustic signals to grey seals as part of an in-air hearing assessment. Using in-ear headphones with adapted ear inserts allowed for the measurement of auditory brainstem responses (ABR) on sedated grey seals exposed to 5-cycle (2-1-2) tone pips. Thresholds were measured at 10 frequencies between 1–20 kHz. Measurements were made using subcutaneous electrodes on wild seals from the Baltic and North Seas. Thresholds were determined by both visual and statistical approaches (single point F-test) and good agreement was obtained between the results using both methods. The mean auditory thresholds were ≤40 dB re 20 µPa peak equivalent sound pressure level (peSPL) between 4–20 kHz and showed similar patterns to in-air behavioural hearing tests of other phocid seals between 3 and 20 kHz. Below 3 kHz, a steep reduction in hearing sensitivity was observed, which differed from the rate of decline in sensitivity obtained in behavioural studies on other phocids. Differences in the rate of decline may reflect influence of the ear inserts on the ability to reliably transmit lower frequencies or interference from the structure of the distal end of the ear canal.

Ultrasonic courtship song of the yellow peach moth, Conogethes punctiferalis (Lepidoptera: Crambidae)

Although generation of ultrasound during courtship has been reported for an increasing number of moth species, the effect of the ultrasound on mating remains uncertain in many cases because of a lack of proper verification. Here we report that males of the yellow peach moth Conogethes punctiferalis (Crambidae) sexually communicate with females by emitting loud ultrasound (103 dB peak equivalent sound pressure level at 1 cm; dominant frequency 82 kHz) before attempting copulation. The male ultrasound consists of consecutive clicks (pulses) in the early phase of the sound train and consecutive pulses (burst) in the late phase. When females were deafened by puncturing the abdominal tympanic membranes, copulation never occurred. We found that deafened females did not assume the wing-raising posture, which, for normal pairs, always precedes successful copulation. Our findings indicate that male courtship ultrasound evokes wing-raising as an acceptance behavior from females, which in turn evokes a copulation attempt by a male.

Toneburst-evoked auditory brainstem response in a leopard seal, Hydrurga leptonyx

Toneburst-evoked auditory brainstem responses (ABRs) were recorded in a captive subadult male leopard seal. Three frequencies from 1 to 4 kHz were tested at sound levels from 68 to 122 dB peak equivalent sound pressure level (peSPL). Results illustrate brainstem activity within the 1-4 kHz range, with better hearing sensitivity at 4 kHz. As is seen in human ABR, only wave V is reliably identified at the lower stimulus intensities. Wave V is present down to levels of 82 dB peSPL in the right ear and 92 dB peSPL in the left ear at 4 kHz. Further investigations testing a wider frequency range on seals of various sex and age classes are required to conclusively report on the hearing range and sensitivity in this species.

Up-regulation of hypoxia-inducible factor-1 alpha by cobalt chloride prevents hearing loss in noise-exposed mice

Since hypoxia-inducible factor-1α (HIF-1α) is the key transcription factor that enables cells to survive in hypoxia, we have investigated whether an upregulation of HIF-1α prevents the noise-induced hearing loss in BALB/c hybrid mice, which were intraperitoneally injected with CoCl 2 (a HIF-1α inducer) and exposed to white band noise with 120 dB peak equivalent sound pressure level for 3 h once daily for 3 days. In the CoCl 2 treatment group, HIF-1α was found to be up-regulated in the cochlear tissues and the hearing loss was largely prevented. Histologically, the loss of sensory hair cells was also significantly lower in the CoCl 2 treatment group than the Control group. However, YC-1 (a HIF-1α inhibitor) attenuated the preventive effect of CoCl 2 on the noise-induced hearing loss. These results suggest that HIF-1α plays a crucial role in the prevention against noise trauma in the inner ear.

Abnormal Cochlear Potentials from Deaf Patients with Mutations in the Otoferlin Gene

Otoferlin is involved in neurotransmitter release at the synapse between inner hair cells (IHCs) and auditory nerve fibres, and mutations in the OTOF gene result in severe to profound hearing loss. Abnormal sound-evoked cochlear potentials were recorded with transtympanic electrocochleography from four children with otoferlin (OTOF) mutations to evaluate physiological effects in humans of abnormal neurotransmitter release from IHCs. The subjects were profoundly deaf with absent auditory brainstem responses and preserved otoacoustic emissions consistent with auditory neuropathy. Two children were compound heterozygotes for mutations c.2732_2735dupAGCT and p.Ala964Glu; one subject was homozygous for mutation p.Phe1795Cys, and one was compound heterozygote for two novel mutations c.1609delG in exon 16 and c.1966delC in exon 18. Cochlear potentials evoked by clicks from 60 to 120 dB peak equivalent sound pressure level were compared to recordings obtained from 16 normally hearing children. Cochlear microphonic (CM) was recorded with normal amplitudes from all but one ear. After cancelling CM, cochlear potentials were of negative polarity with reduced amplitude and prolonged duration compared to controls. These cochlear potentials were recorded as low as 50-90 dB below behavioural thresholds in contrast to the close correlation in controls between cochlear potentials and behavioural threshold. Summating potential was identified in five out of eight ears with normal latency whilst auditory nerve compound action potentials were either absent or of low amplitude. Stimulation at high rates reduced amplitude and duration of the prolonged potentials, consistent with neural generation. This study suggests that mechano-electrical transduction and cochlear amplification are normal in patients with OTOF mutations. The low-amplitude prolonged negative potentials are consistent with decreased neurotransmitter release resulting in abnormal dendritic activation and impairment of auditory nerve firing.

Auditory Function After a Prolonged Course of Ciprofloxacin-Dexamethasone Otic Suspension in a Murine Model

To test for ototoxicity after prolonged ototopical fluoroquinolone use in the middle ear space using a murine model. Nonrandomized controlled trial. Twelve CBA/J mice. The mice received daily intratympanic injections of ciprofloxacin-dexamethasone otic suspension for 21 days. The contralateral ear received daily intratympanic injections of sterile isotonic sodium chloride solution (saline) as a control. Click-evoked auditory brainstem response (ABR) thresholds were obtained before injection and 10 days and 3 months after injection. Mean (SEM) preinjection ABR thresholds were 47.17 (2.74) dB peak equivalent sound pressure level (peSPL) in ciprofloxacin-dexamethasone-treated ears and 45.08 (1.56) dB peSPL in saline-treated ears (P = .38). Mean (SEM) postinjection ABR thresholds in ciprofloxacin-dexamethasone-treated ears were 44.25 (1.25) dB peSPL after 10 days and 43.00 (1.51) dB peSPL after 3 months. Mean (SEM) postinjection ABR thresholds in saline-treated ears were 48.00 (1.51) dB peSPL after 10 days and 45.92 (1.79) dB peSPL after 3 months. There were no significant differences in ABR thresholds for ciprofloxacin-dexamethasone-treated ears (P = .29, P = .10) or saline-treated ears (P = .07, P = .59). Ciprofloxacin-dexamethasone suspension did not cause either immediate or delayed ototoxicity after 21 days of intratympanic administration in the CBA/J mouse model.

Aminoglycoside-Induced Degeneration of Adult Spiral Ganglion Neurons Involves Differential Modulation of Tyrosine Kinase B and p75 Neurotrophin Receptor Signaling

Aminoglycoside antibiotics induce sensorineural hearing loss by destroying hair cells of the organ of Corti, causing progressive secondary degeneration of primary auditory or spiral ganglion neurons (SGNs). Recent studies show that the p75 neurotrophin receptor (NTR) is aberrantly up-regulated under pathological conditions when the neurotrophin receptor tyrosine kinases (Trks) are presumptively down-regulated. We provide in vivo evidence demonstrating that degenerating SGNs induced an augmented p75NTR expression and a coincident reduction of TrkB expression in their peripheral processes. Nuclear transcription factors c-Jun and cyclic AMP response element-binding protein phosphorylated by p75NTR- and TrkB-activated signal pathways, respectively, also showed a corresponding differential modulation, suggesting an activation of apoptotic pathways, coupled to a loss of pro-survival neurotrophic support. Our findings identified brain-derived neurotrophic factor (BDNF) expression in hair and supporting cells of the adult cochlea, and its loss, specifically the mature form, would impair TrkB-induced signaling. The precursor of BDNF (pro-BDNF) is differentially cleaved in aminoglycoside-deafened cochleae, resulting in a predominant up-regulation of a truncated form of pro-BDNF, which colocalized with p75NTR-expressing SGN fibers. Together, these data suggest that an antagonistic interplay of p75NTR and TrkB receptor signaling, possibly modulated by selective BDNF processing, mediates SGN death in vivo.

Calibration of acoustic transients

This article reviews the appropriate stimulus parameters (click duration, toneburst envelope) that should be used when eliciting auditory brainstem responses from mice. Equipment specifications required to calibrate these acoustic transients are discussed. Several methods of calibrating the level of acoustic transients are presented, including the measurement of peak equivalent sound pressure level (peSPL) and peak sound pressure level (pSPL). It is hoped that those who collect auditory brainstem response thresholds in mice will begin to use standardized methods of acoustic calibration, so that hearing thresholds across mouse strains obtained in different laboratories can more readily be compared.

Investigation of ototoxic effects of Taxol on a mice model

To investigate the effects of taxol on the inner ear in a mice model. This study was performed on 112 ears of 56 albino Swiss mice. All animals underwent baseline auditory brainstem response (ABR) testing bilaterally and baseline Peak Equivalent Sound Pressure Levels (PESPLs) were obtained. The mice were randomly assigned to seven groups consisting of one control and six study groups. The control group received no medications while the mice in groups 1-6 received 1 x 60, 1 x 20, 2 x 20, 3 x 20, 4 x 20 and 5 x 20 mg/kg taxol intraperitoneally. Control ABR assessments were performed 3 weeks after the last dose. The animals were then sacrificed while still anaesthetised and the bullae (cochleae included) were dissected from their temporal bones. Haematoxylin-eosin and Masson's trichrome stains were used to demonstrate connective tissue, and periodic acid Schiff (PAS) stain was used to highlight epithelial elements. Significant decreases in the hearing levels were observed in all the groups which received taxol. No correlation was observed between the dose given and the degree of hearing loss. The sections from the control group showed no histopathologic abnormalities while the sections from the study groups demonstrated vacuolisation in the epithelial cells of the spiral limbus, and the stria vascularis, vacuolisation of the fibroblasts and decreasing the number of the fibroblasts in the spiral limbus. Taxol causes mild to moderate sensorineural hearing loss in mice. Histopathologically, there were degenerative changes in the cochlea resembling the ones that take place in salisylate and interferon alpha 2a ototoxicity which are thought to be reversible. There was no sensory cell loss. The hearing loss begins with doses less than or equal to 20mg/kg and is not dose dependent after this dose. Hearing monitorisation with audiologic evaluation is strongly recommended before and during the use of the drug in human subjects.