Transient Threshold Shift Research Articles

The role of GDF15 in attenuating noise-induced hidden hearing loss by alleviating oxidative stress

Noise-induced hidden hearing loss (HHL) is a newly uncovered form of hearing impairment that causes hidden damage to the cochlea. Patients with HHL do not have significant abnormalities in their hearing thresholds, but they experience impaired speech recognition in noisy environments. However, the mechanisms underlying HHL remain unclear. In this study, we developed single-cell transcriptome profiles of the cochlea of mice with HHL, detailing changes in individual cell types. Our study revealed a transient threshold shift, reduced auditory brainstem response wave I amplitude, and decreased number of ribbon synapses in HHL mice. Our findings suggest elevated oxidative stress and GDF15 expression in cochlear hair cells of HHL mice. Notably, the upregulation of GDF15 attenuated oxidative stress and auditory impairment in the cochlea of HHL mice. This suggests that a therapeutic strategy targeting GDF15 may be efficacious against HHL.Graphical HHL mice had a transient threshold shift, reduced ABR wave I amplitude, and decreased number of ribbon synapses.HHL mice's cochlear hair cells exhibited increased oxidative stress and elevated GDF15 expression.Upregulation of GDF15 attenuated oxidative stress and auditory damage in the cochlea of HHL mice, implying that GDF15-targeted treatment techniques may be useful for HHL.

Cochlear Glucocorticoid Receptor and Serum Corticosterone Expression in a Rodent Model of Noise-induced Hearing Loss: Comparison of Timing of Dexamethasone Administration

Glucocorticoid (GC) is a steroid hormone secreted from the adrenal cortex in response to stress, which acts by binding to cytoplasmic glucocorticoid receptors (GRs). Dexamethasone (DEX) is a synthetic GC exhibiting immunosuppressive effects in both human and rodent models of hearing loss. While clinical evidence has shown the effectiveness of DEX for treatment of various inner ear diseases, its mechanisms of action and the optimal timing of treatment are not well understood. In the present study, intergroup comparisons were conducted based on the time point of treatment with DEX: (1) pretreatment; (2) posttreatment; and (3) pre&post-noise. The pre&post DEX treatment group showed a significant improvement in threshold shift at 1 day post-noise exposure as compared to the TTS (transient threshold shift)-only group at 8 and 16 kHz. Both TTS and PTS (permanent threshold shift) significantly reduced cochlear GR mRNA expression and increased serum corticosterone and cochlear inflammatory cytokines. The pre&post DEX treatment group showed a significant decrease in serum corticosterone level as compared to other DEX treatment groups and TTS-treated group at 3 days after acoustic trauma. Our results suggest that the timing of DEX administration differentially modulates systemic steroid levels, GR expression and cochlear cytokine expression.

Behavioral evaluation of auditory function abnormalities in adult rats with normal hearing thresholds that were exposed to noise during early development

Noise-exposed rat pups provide a model of early deprivation of sensory input to the central auditory system, allowing the study of developmental neuroplasticity. Our previous results have demonstrated that a brief exposure of rats to broadband noise (125 dB SPL 8 min, 14th postnatal day) at the onset of hearing resulted in an altered intensity perception and frequency discrimination in adulthood despite normal hearing thresholds. In this study, we assessed the gap-detection ability and possible presence of tinnitus- and hyperacusis-like behavior in adult rats after the same neonatal acoustic trauma, using measurements of the acoustic startle response (ASR) in quiet and noisy environments and its prepulse inhibition by gaps in noise (gap-PPI). A significant deficit in the ability to detect gap was observed in the exposed rats when 55 dB SPL broadband noise was used as background. An increase of noise intensity to 65–75 dB SPL led to strengthening of the gap-PPI in exposed animals, which approached the gap-PPI values of control animals at these levels. Behavioral signs of tinnitus (gap detection deficits in 10 kHz narrow band noise) were found in 25% of exposed rats. An increased sensitivity to continuous noise was manifested in all exposed rats by suppression of the ASR at significantly lower background noise levels than in the controls. This effect was particularly pronounced in rats with tinnitus-like behavior. Our results indicate that neonatal acoustic trauma, producing only a transient threshold shift, may produce permanent abnormalities in suprathreshold auditory functions and the development of tinnitus and hyperacusis-like behavior.

Hearing Thresholds Changes after MRI 1.5T of Head and Neck.

Introduction Exposure to high intensity noise produced by MRI is a cause for concern. This study was conducted to determine the temporary and permanent effects of exposure to noise created by performing MRI on the hearing threshold of the subjects using conventional and extended high frequency audiometry. Methods This semiexperimental study was performed on 35 patients referred to Shahid Rahnemoun Hospital for head and neck MRI due to different clinical conditions. The hearing threshold of patients was measured before, immediately after, and 24 hours after performing 1.5 Tesla MRI using conventional and extended high frequency audiometry. SPSS version 18 was used to compare the mean hearing thresholds before and after MRI using paired T test and repeated measures analysis. Results Comparison of auditory thresholds in conventional and extended high frequencies before and immediately after MRI showed a significant shift at 4 KHz (P = 0.008 and P = 0.08 for right and left ears), 6 KHz (P = 0.03 and P = 0.01 for right and left ears), and 14 KHz (P =0.03 and P = 0.31 for right and left ears). However, there was no significant difference between audiometric thresholds before and 24 hours after MRI. Conclusion Noise due to 1.5 Tesla MRI can only cause transient threshold shift.

Effect of Ascorbic Acid on Noise Induced Hearing Loss in Rats.

After presbycusis, noise-induced hearing loss is the second most common cause of acquired hearing loss. Numerous studies have shown that high-intensity noise exposure increasesfree radical species;therefore, use ofantioxidants to detoxify the free radicals can prevent cellular damage in the cochlea. We studied the potential hearing protective effect of different doses of ascorbic acid administered prior to noise exposure in rats. Twenty-four male albino Wistar rats were randomly allocated into four groups: groups A, B, and C received 1250, 250, and 50 mg/kg/day of ascorbic acid, respectively, and group D acted as the control group. After 14 days of ascorbic acid administration, the rats were exposed to noise (105 dB sound pressure level for 2 h). Distortion product otoacoustic emissions (DPOAE) were recorded prior to starting the ascorbic acid as baseline and 1 h after the noise exposure. The amplitude decrease was 14.99 dB for group A, 16.11 dB for group B, 28.82 dB for group C, and 29.91 dB for the control group. Moderate and high doses of ascorbic acid significantly reduced the transient threshold shift in the rats. The results of present study support the concept of cochlea protection by antioxidant agents. This dose-dependent protective effect was shown through the use of ascorbic acid treatment prior to noise exposure.

Aging after noise exposure: acceleration of cochlear synaptopathy in "recovered" ears.

Cochlear synaptic loss, rather than hair cell death, is the earliest sign of damage in both noise- and age-related hearing impairment (Kujawa and Liberman, 2009; Sergeyenko et al., 2013). Here, we compare cochlear aging after two types of noise exposure: one producing permanent synaptic damage without hair cell loss and another producing neither synaptopathy nor hair cell loss. Adult mice were exposed (8-16 kHz, 100 or 91 dB SPL for 2 h) and then evaluated from 1 h to ∼ 20 months after exposure. Cochlear function was assessed via distortion product otoacoustic emissions and auditory brainstem responses (ABRs). Cochlear whole mounts and plastic sections were studied to quantify hair cells, cochlear neurons, and the synapses connecting them. The synaptopathic noise (100 dB) caused 35-50 dB threshold shifts at 24 h. By 2 weeks, thresholds had recovered, but synaptic counts and ABR amplitudes at high frequencies were reduced by up to ∼ 45%. As exposed animals aged, synaptopathy was exacerbated compared with controls and spread to lower frequencies. Proportional ganglion cell losses followed. Threshold shifts first appeared >1 year after exposure and, by ∼ 20 months, were up to 18 dB greater in the synaptopathic noise group. Outer hair cell losses were exacerbated in the same time frame (∼ 10% at 32 kHz). In contrast, the 91 dB exposure, producing transient threshold shift without acute synaptopathy, showed no acceleration of synaptic loss or cochlear dysfunction as animals aged, at least to ∼ 1 year after exposure. Therefore, interactions between noise and aging may require an acute synaptopathy, but a single synaptopathic exposure can accelerate cochlear aging.

Sustained Release of Triamcinolone Acetonide from an Intratympanically Applied Hydrogel Designed for the Delivery of High Glucocorticoid Doses

The pharmacokinetic properties and tolerability of a triamcinolone acetonide poloxamer 407 hydrogel for intratympanic application were investigated in a guinea pig model. Evaluation of in vivo release kinetics showed very high initial perilymph drug levels, with clinically relevant levels present for a minimum of 10 days. Assessment of auditory brainstem response thresholds showed a minimal, delayed and transient threshold shift, which was apparent on day 3 and resolved by day 10. No relevant histological changes of the middle and inner ear structures were noted, and hair cell counts showed no significant differences between treated and untreated ears. Thus, the triamcinolone-acetonide-loaded poloxamer 407 hydrogel is an effective vehicle for sustained high-dose inner ear glucocorticoid delivery.

Vulnerability to Acoustic Trauma in the Normal Hearing Ear With Contralateral Hearing Loss

We undertook an animal study to investigate the functional and histological changes that occur in the normal hearing ear of following acoustic trauma. As an animal model of unilateral hearing loss, the right ears of CBA mice were deafened by cochlear destruction at 6 weeks of age (SSD group). The control groups included mice that underwent a sham surgery, and mice that were exposed to noise binaurally and monaurally (by plugging the right ear completely). At 10 weeks of age, all mice were exposed to acoustic trauma (110 dB sound pressure level for 1 hour) that induced a transient threshold shift (TTS). Changes in the hearing thresholds of the left ear were assessed over the next 4 weeks by measuring the auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs). Following the noise exposure, the SSD group showed a permanent threshold shift (PTS) of about 10 dB, whereas the other groups showed full recovery from the TTS. The threshold of the DPOAEs of the left ears were increased after noise exposure but returned to normal in all groups, with no significant differences among the groups. Histological evaluation showed no apparent cellular loss or apoptosis in the left ears of all groups, including the SSD group. These results suggest that normal hearing ears are more vulnerable to acoustic trauma following contralateral unilateral cochlear ablation. This increased vulnerability may be due to damaged neural structures.

Determinants of Occupational Hearing Loss

ISEE-220 Objective: It is essential to study predictive factors of occupational hearing loss. The transient threshold shift (TTS) at high frequencies (4 kHz) after exposure to low frequencies (400 Hz) was hypothesized to predict a higher sensibility of the inner ear. Material and Methods: Starting in 1982, all apprentices at an Austrian steel mill underwent an examination including the determination of the TTS at 4 kHz after a 20-minute exposure to 400 Hz/105 dB. TTS was recorded every 30 seconds from 1.5 till 10 minutes after the exposure. Also, before the experimental noise exposure a Bekesy audiogram was recorded. Among others the difference between “no longer heard” and “heard again” at 4 kHz (diff-dB) was noted. In total, 125 of the apprentices remained in the same enterprise and were exposed to noise at work. In regular follow-up examinations audiometry was performed in this group. Results: Hearing loss (PTS) was significantly influenced by the following parameters: noise-level at the workplace, years of noise exposure (or age, because both were highly correlated with each other), TTS at first examination, diff-dB, and the reported frequency of wearing hearing protection. TTS values at every 30 seconds after exposure were highly correlated. So, only TTS after 2 minutes (that was strongest related to PTS) was kept in the final model. Also diff-dB before and at different intervals after exposure were highly correlated. As the best predictor for PTS, the difference between diff-dB before exposure and 2.5 minutes after exposure (d2.5diff-dB) was chosen for the final model. In this final (multiple regression) model the noise level at the workplace was no longer significant. This is likely due to the high correlation between (adverse) noise level and (protective) frequency of personal protective measures. Conclusions: The importance of personal protective measures was again highlighted in this study. But, in addition, individual (preexisting) factors of susceptibility influence the impact of noise exposure.

Hypoxic changes in the central nervous system of noise-exposed mice

Conclusion. After a noise-induced transient threshold shift, hypoxia occurred in the central nervous system, especially in the auditory cortex, the hippocampus, and the inferior colliculus. Objectives. Noise-induced inner ear hypoxia was shown by measurement of an increase in hypoxia-inducible factor-1 alpha, which is expressed? in the nucleus under hypoxic conditions. This study uses pimonidazole to localize site-specific hypoxic changes occurring in the mouse central auditory pathway during noise-induced auditory threshold shift. Method. BALB/c hybrid mice with normal hearing were exposed to 122 dB SPL white noise for 3 h. Immediately after exposure to the noise, and 7 d after noise exposure, the brains of mice were collected. Brains were cryosectioned into slices 15 µm thick and examined by immunofluorescence after staining with pimonidazole HCl. Results. After 3 h of exposure to 120 dB SPL noise, the hearing thresholds of mice decreased to 51.1±8.6 dB SPL (n =14), but hearing recovered in 7 d. After noise exposure, pimonidazole signal increased in the auditory cortex, the hippocampus, and the inferior colliculus. The pimonidazole signal remained elevated after 7 d. In control mice, pimonidazole did not stain any brain region.

Effects of transient threshold shift and ambient noise on sensitivity and specificity of first screening of special health examination for noise

OBJECT: This study was performed to increase the sensitivity and specificity for screening the examinee of second hearing test.METHODS: Study subjects were 219 workers who exposed more than average 80dB. They were taken the hearing test two times, before noise exposure and at 1 hour to 4 hours after worksite noise exposure. To investigate the ambient noise workers who were taken the hearing test in the test room which ambient noise was less than 45dB were classified Group I and the others were classified Group E. To calculate the sensitivity and specificity we made it gold standard whether worker had noise induced hearing loss.RESULTS: Difference of hearing loss between before and after noise exposure for left and right ear was 11. 4 dB and 11. 7 dB respectively at 500 Hz, 8. 7 dB and 9. 6 dB at 1, 000 Hz, 6. 3 dB and 6. 9 dB at 2, 000 Hz and 6. 9 dB and 7. 4 dB at 4, 000 Hz in Group I. That for left ear and right ear was 5.8 dB and 4.9 dB at 500 Hz respectively, 5.4 dB and 6.4 dB at 1,000 Hz, 6.3 dB and 5.3 dB at 2,000 Hz, and 5.5 dB and 5.8 dB at 4,000 Hz in Group E. The sensitivity was 100 in both Groups and the specificity was increased to 58. 3 and 71. 8 in Group I and Group 3 respectively until 10 dB was deducted from hearing level at 1, 000 Hz and 4, 000 Hz.CONCLUSION: When the screening hearing test was performed at worksite, we might deduct 10 dB from measured hearing level to increase the specificity without reduction of sensitivity.