Intense Noise Exposure Research Articles

Time Courses of Changes in Phospho- and Total- MAP Kinases in the Cochlea after Intense Noise Exposure

Mitogen-activated protein kinases (MAP kinases) are intracellular signaling kinases activated by phosphorylation in response to a variety of extracellular stimuli. Mammalian MAP kinase pathways are composed of three major pathways: MEK1 (mitogen-activated protein kinase kinase 1)/ERK 1/2 (extracellular signal-regulated kinases 1/2)/p90 RSK (p90 ribosomal S6 kinase), JNK (c-Jun amino (N)-terminal kinase)/c-Jun, and p38 MAPK pathways. These pathways coordinately mediate physiological processes such as cell survival, protein synthesis, cell proliferation, growth, migration, and apoptosis. The involvement of MAP kinase in noise-induced hearing loss (NIHL) has been implicated in the cochlea; however, it is unknown how expression levels of MAP kinase change after the onset of NIHL and whether they are regulated by transient phosphorylation or protein synthesis. CBA/J mice were exposed to 120-dB octave band noise for 2 h. Auditory brainstem response confirmed a component of temporary threshold shift within 0–24 h and significant permanent threshold shift at 14 days after noise exposure. Levels and localizations of phospho- and total- MEK1/ERK1/2/p90 RSK, JNK/c-Jun, and p38 MAPK were comprehensively analyzed by the Bio-Plex® Suspension Array System and immunohistochemistry at 0, 3, 6, 12, 24 and 48 h after noise exposure. The phospho-MEK1/ERK1/2/p90 RSK signaling pathway was activated in the spiral ligament and the sensory and supporting cells of the organ of Corti, with peaks at 3–6 h and independently of regulations of total-MEK1/ERK1/2/p90 RSK. The expression of phospho-JNK and p38 MAPK showed late upregulation in spiral neurons at 48 h, in addition to early upregulations with peaks at 3 h after noise trauma. Phospho-p38 MAPK activation was dependent on upregulation of total-p38 MAPK. At present, comprehensive data on MAP kinase expression provide significant insight into understanding the molecular mechanism of NIHL, and for developing therapeutic models for acute sensorineural hearing loss.

Behavioral Evidence for Possible Simultaneous Induction of Hyperacusis and Tinnitus Following Intense Sound Exposure

Many human subjects suffering from chronic tinnitus also suffer from hyperacusis, a heightened perception of loudness at moderate to intense sound levels. While numerous studies suggest that animals develop chronic tinnitus following intense noise exposure, it is not yet clear whether sound exposure also induces chronic hyperacusis-like responses in animals. We addressed this question by examining the chronic effects of intense sound exposure on the acoustic startle response (ASR) and its suppression by background noise containing brief gaps. We compared startle amplitudes in intense tone-exposed (10 kHz, 115 dB SPL, 4 h) and age-matched controls at 2-28 weeks post-exposure. While both groups showed similar startle thresholds, exposed animals showed a hyperacusis-like augmentation of ASR at high stimulus levels. Addition of background noise had little effect on ASR in controls but had a strong suppressive effect on startle in exposed animals, indicating a sensitization to background noise. When the background noise contained a gap preceding the startle stimulus, ASR was suppressed in control animals, but exposed animals showed a marked weakening of gap-induced suppression of ASR. This weakening of gap-induced startle suppression is consistent with the interpretation that the gap may have been masked by tinnitus. The associated hyper-responsiveness to startle stimuli presented alone and the sensitization to background noise suggest that hyperacusis may have also been induced. The results indicate that noise exposure leads to increases in the gain of auditory responsiveness and may offer a model of the association of hyperacusis with tinnitus.

Noise-induced hyperactivity in the inferior colliculus: its relationship with hyperactivity in the dorsal cochlear nucleus

Intense noise exposure causes hyperactivity to develop in the mammalian dorsal cochlear nucleus (DCN) and inferior colliculus (IC). It has not yet been established whether the IC hyperactivity is driven by hyperactivity from extrinsic sources that include the DCN or instead is maintained independently of this input. We have investigated the extent to which IC hyperactivity is dependent on input from the contralateral DCN by comparing recordings of spontaneous activity in the IC of noise-exposed and control hamsters before and after ablation of the contralateral DCN. One group of animals was binaurally exposed to intense sound (10 kHz, 115 dB SPL, 4 h), whereas the control group was not. Both groups were studied electrophysiologically 2-3 wk later by first mapping spontaneous activity along the tonotopic axis of the IC to confirm induction of hyperactivity. Spontaneous activity was then recorded at a hyperactive IC locus over two 30-min periods, one with DCNs intact and the other after ablation of the contralateral DCN. In a subset of animals, activity was again mapped along the tonotopic axis after the time course of the activity was recorded before and after DCN ablation. Following recordings, the brains were fixed, and histological evaluations were performed to assess the extent of DCN ablation. Ablation of the DCN resulted in major reductions of IC hyperactivity. Levels of postablation activity in exposed animals were similar to the levels of activity in the IC of control animals, indicating an almost complete loss of hyperactivity in exposed animals. The results suggest that hyperactivity in the IC is dependent on support from extrinsic sources that include and may even begin with the DCN. This finding does not rule out longer term compensatory or homeostatic adjustments that might restore hyperactivity in the IC over time.

Hydrogen-rich saline alleviates experimental noise-induced hearing loss in guinea pigs

Objective. To examine the efficiency of hydrogen-rich saline in the treatment of intensive noise-induced cochlear injury. Materials and methods. Forty guinea pigs were assigned to one of four groups: HS+NOISE (i.p. injection hydrogen-rich saline), NS+NOISE (i.p. injection normal saline), NOISE ALONE (noise control), and NO TREATMENT (normal control) groups. The HS+NOISE, NS+NOISE, and NOISE ALONE groups were exposed to intensive noise (4 h at 115 dB SPL noise of 4000±100 Hz). The auditory brainstem response (ABR) was used to examine the hearing threshold in each group. Distortion product otoacoustic emission (DPOAE) was used to examine outer hair cell function. We also examined cochlear morphology to evaluate inner and outer hair cell trauma induced by noise exposure. Hydrogen-rich saline was administered twice daily for 6 days (2.5 ml/kg, i.p.) 24 h after noise exposure. Results. Baseline ABR thresholds and DPOAE values were normal in all groups at the measured frequencies (2, 4, 8, and 16 kHz) before noise exposure. The ABR threshold shift was 50–55 dB across the frequencies tested, and average DPOAE declined in the NOISE ALONE, NS+NOISE, and HS+NOISE groups 24 h after noise exposure. However, the changes in cochlear parameters were different between groups. The HS+NOISE group showed a significantly decreased ABR threshold value as compared with the NS+NOISE or NOISE ALONE group (P<0.01) on day 7. The mean DPOAE recovered to some extent in the three noise exposure groups, but at most frequencies the HS+NOISE group showed significantly increased DPOAE on day 7 as compared with the NS+NOISE group or NOISE ALONE group (P<0.01). Surface Corti organ preparations stained with succinate dehydrogenase (SDH) showed that most outer hair cells (OHCs) were still dropsical and a few were missing 7 days after noise exposure in the NS+NOISE group. Only a few OHCs were slightly dropsical in the HS+NOISE group. The numbers of missing hair cells 7 days after noise exposure were significantly greater in the NOISE ONLY and NS+NOISE groups than the HS+NOISE group (P<0.01). Conclusions. Hydrogen-rich saline can alleviate experimental noise-induced hearing loss in guinea pigs, partially by preventing the death of cochlear hair cells after intensive noise exposure.

Noise levels in a neonatal transport incubator in medically configured aircraft

Objective The purpose of this study was to evaluate exposure of neonates to noise during air medical transport as few commercially available hearing protective devices exist for premature newborns during air medical transport. Methods Sound pressure levels in an infant incubator during actual flight conditions in four common medically configured aircraft were measured. Three noise dosimeters measured time-weighted average noise exposure during flight in each aircraft. One dosimeter was placed in the infant incubator, and the remaining dosimeters recorded noise levels in various parts of the aircraft cabin. Results The incubator provided a 6-dBA decrease in noise exposure from that in the crew cabin. The average noise level in the incubator in all aircraft was close to 80 dB, much higher than the proposed limits of 45 dB for neonatal intensive care unit noise exposure or 60 dB during transport. Conclusions Exposure of neonates to elevated noise levels during transport may be harmful, and steps should be taken to protect the hearing of this patient population.

Noise trauma impairs neurogenesis in the rat hippocampus

The hippocampus, a major site of neurogenesis in the adult brain, plays an important role in memory. Based on earlier observations where exposure to high-intensity noise not only caused hearing loss but also impaired memory function, it is conceivably that noise exposure may suppress hippocampal neurogenesis. To evaluate this possibility, nine rats were unilaterally exposed for 2 h to a high-intensity, narrow band of noise centered at 12 kHz at 126 dB SPL. The rats were also screened for noise-induced tinnitus, a potential stressor which may suppress neurogenesis. Five rats developed persistent tinnitus-like behavior while the other four rats showed no signs of tinnitus. Age-matched sham controls showed no signs of hearing loss or tinnitus. The inner ear and hippocampus were evaluated for sensory hair cell loss and neurogenesis 10 weeks post-exposure. All noise exposed rats showed severe loss of sensory hair cells in the noise-exposed ear, but essentially no damage in the unexposed ear. Frontal sections from the hippocampus were immunolabeled for doublecortin to identify neuronal precursor cells, or Ki67 to label proliferating cells. Noise-exposed rats showed a significant reduction of neuronal precursors and fewer dividing cells as compared to sham controls. However, we could not detect any difference between rats with behavioral evidence of tinnitus versus rats without tinnitus. These results show for the first time that high intensity noise exposure not only damages the cochlea but also causes a significant and persistent decrease in hippocampal neurogenesis that may contribute to functional deficits in memory.

Behavioral consequences of weakened medial olivocochlear efferent noise‐control mechanisms in mice.

The mammalian medial olivocochlear (MOC) efferent feedback system protects the ear from intense noise exposure, aids in cochlear gain control, and improves responses to signals in noise. Unequivocal behavioral effects of eliminating MOC feedback have been difficult to demonstrate. We used an acoustic startle reflex (ASR) modification paradigm to reveal behavioral effects of eliminating MOC feedback in mice. Mice lacking the alpha9 nicotinic acetylcholine receptor subunit showed increased facilitation of the ASR reflex in the presence of background noise, abnormal responses to brief fluctuations in background noise, and abnormal inhibition of the ASR by changes in the location of noise in azimuth and elevation. Abnormal behavioral responses occurred in the absence of cochlear hearing loss. The behavioral effects of weakened MOC feedback may reflect both direct and indirect effects of abnormal cochlear gain control in the presence of noise. The results provide further evidence for a role of MOC efferent feedback in hearing in noise and demonstrate that noise‐related hearing deficits can occur when hearing thresholds are normal.

Intense noise exposure activates JNK signal via generation of nitric oxide in cochlear spiral ligament fibrocytes

Intense noise exposure activates JNK signal via generation of nitric oxide in cochlear spiral ligament fibrocytes

Development of Ebselen, a Glutathione Peroxidase Mimic, for the Prevention and Treatment of Noise-Induced Hearing Loss

The development of therapeutics for the prevention and treatment of sensorineural hearing loss remains an elusive goal for auditory scientists and clinicians worldwide. While much research has focused on the histopathology associated with exposure to intense noise or ototoxins (i.e., loss of hair cells), the biochemical and genetic mechanisms that evoke or mediate hair cell death and dysfunction are still under investigation and debate. Many have observed an early oxidative burst in the cochlea that leads to an increase in lipoperoxidation and the activation of cell death pathways, ultimately resulting in apoptosis. In support of this hypothesis, many have protected the cochlea and preserved auditory function by injecting high doses of antioxidants or inhibitors of cell death activation prior to intense noise or ototoxin exposure. Here we discuss a compound currently in Phase II clinical testing for the prevention and treatment of noise-induced hearing loss. This article will review the historic background and pertinent preclinical and clinical data available for ebselen, a novel drug that mimics the activity of glutathione peroxidase, a catalytic antioxidant enzyme that is essential for the peripheral auditory system.

Visualization of inner ear disorders with MRI in vivo: from animal models to human application

Conclusion: The inner ear membranous permeability and leakiness and endolymphatic hydrops can be visualized using gadolinium-enhanced MRI in both rodents and man. Intratympanic administration of contrast agent gives greater perilymphatic loading of gadolinium. Objectives: Visualization of different types of inner ear dysfunction in MRI with intravenous or intratympanic administration of contrast agent. Materials and methods: In the animal study, gadolinium was administered intravenously or intratympanically and imaged with 4.7 T MRI. In man, gadolinium was delivered intratympanically and studied with 1.5 T or 3 T MRI. Results: In the animals, intravenous delivery of gadolinium demonstrated uptake in the perilymph of normal inner ears. The cochlear modiolus appeared to be a critical site for the secretion of perilymph and the location of fluid communication between the perilymphatic scalae. Intense noise exposure and immune reaction caused cochlear injury and accelerated gadolinium passage through the blood–perilymph and blood–endolymph barriers. In man, perilymphatic uptake of gadolinium was only observed in the impaired inner ear when administered intravenously. However, the signal-to-noise ratio of images was improved when gadolinium was delivered intratympanically. MRI demonstrated endolymphatic hydrops in both animal models and patients with Meniere's disease.

Heme oxygenase-1 expression in the guinea pig cochlea induced by intense noise stimulation

Conclusion: These results suggest that noise induces free radical formation in the cochlea and that, in the guinea pig, heme oxygenase-1 (HO-1) may play an important role in the recovery from noise trauma in the organ of Corti. Objective: Free radicals are involved in noise-induced hearing loss. It has been demonstrated that the induction of HO-1 may protect cells exposed to oxidative challenge. The present study was designed to investigate the effect of intense noise exposure on HO-1 induction. Materials and methods: A total of 25 adult guinea pigs (body weight 200–300 g) with a normal Preyers's reflex were used as subjects. Based on preliminary tests, the appropriate intensities and durations of noise were determined that were adequate to induce apparent threshold shifts and lead to various recovery patterns to initial thresholds. The sound was routed through a power amplifier to a speaker, which was positioned directly over the animals in a sound chamber. Auditory brainstem response (ABR) testing, Western blot analysis for HO-1, and immunohistochemical testing were done. Results: Exposure of the guinea pigs to 115 dB SPL octave band noise for 5 h induced HO-1 expression in the organ of Corti. In the organ of Corti, HO-1 expression increased mainly in the outer hair cells. Some expression of HO-1 was observed before and after noise exposure in the supporting cells. HO-1 expression in the organ of Corti was definitely increased in guinea pigs with an intense noise exposure which causes a temporary threshold shift.

Using auditory evoked potentials to measure marine mammal hearing.

The use of auditory evoked potential (AEP) measurements for examining the hearing of marine mammals was accelerated by the need to rapidly test hearing following sound exposures during temporary threshold shift experiments. AEP measures have allowed quick measurements of hearing following intense noise exposures of sounds ranging from filtered white noise to 53‐C sonars. The refinement of AEP hearing measurements with envelope following response measures leads to comparisons between behavioral and AEP hearing thresholds. These comparisons have allowed an expansion of basic hearing measurements including measures of new species such as the white‐beaked dolphin and polar bear, measures of increased numbers of the same species in order to better examine population audiogram estimates and variability, and testing of hearing of animals in the field. AEP measures have also allowed the measurement of hearing during echolocation. A false killer whale has been shown to hear its own outgoing signal 40 dB down from the same sort of signal presented directly in front of it, actively control the level of its hearing of echolocation returns in an automatic gain control of hearing, and hear sounds other than echolocation sounds 20 dB differently when it is echolocating depending on target condition.

GFAP aggregates in the cochlear nerve increase the noise vulnerability of sensory cells in the organ of Corti in the murine model of Alexander disease

Outer hair cell (OHC) loss in the auditory sensory epithelium is a primary cause of noise-induced sensory-neural hearing loss (SNHL). To clarify the participation of glial cells in SNHL, we used an Alexander disease (AxD) mouse model. These transgenic mice harbor the AxD causal mutant of the human glial fibrillary acidic protein (GFAP) under the control of the mouse GFAP promoter. It is thought that GFAP aggregates compromise the function of astrocytes. In the auditory pathway, the formation of GFAP aggregates was observed only in GFAP-positive cells of the cochlear nerve. The presence of GFAP aggregates did not change auditory function at the threshold level. To assess the change in vulnerability to auditory excitotoxicity, both transgenic and control mice were treated with intense noise exposure. Auditory threshold shifts were assessed by auditory brainstem responses (ABR) at 1 and 4 weeks after noise exposure, and OHC damage was analyzed by quantitative histology at 4 weeks after exposure. Transgenic mice showed more severe ABR deficits and OHC damage, suggesting that cochlear nerve glial cells with GFAP aggregates play a role in noise susceptibility. Thus, we should focus more on the roles of cochlear nerve glial cells in SNHL.

Chronologic Changes of Nitric Oxide Concentration in the Cochlear Lateral Wall and Its Role in Noise‐Induced Permanent Threshold Shift

The objective of this study was to investigate the chronologic changes of nitric oxide (NO) concentration in the cochlear lateral wall and to explore its possible role in permanent threshold shift (PTS) after intense noise exposure. Seventeen guinea pigs were subjected to a single continuous exposure to broadband white noise at 105 +/- 2 dB sound pressure level (SPL) for 40 hours and were divided into four groups according to various postnoise recovery periods. Another 12 guinea pigs were not exposed to noise and served as controls. The hearing status of all animals was evaluated with auditory brainstem responses (ABR) evoked by condensation "click" sounds. ABR were recorded both prior to noise exposure and immediately before killing the animal. After death, NO concentration in the cochlear lateral wall was directly measured with an NO/ozone chemiluminescence technique. An approximately 1.7-fold increase in NO concentration was observed immediately postnoise exposure, which persisted for up to 28 days. The threshold of ABR elevation (mean, 30 dB SPL) peaked immediately after cessation of noise exposure and gradually resolved to a PTS (mean, 14.5 dB SPL) 56 days after noise exposure when NO concentration had returned to its prenoise exposure level. Noise-induced threshold shift, which resolved to a mild PTS, can be partially attributed to NO elevation in the cochlear lateral wall. Our results revealed a nonlinear correlation between ABR recovery and depletion of NO, indicating that the mechanisms of NO changes in the cochlear lateral wall may be more complicated than previously conceived and that other pathophysiologic mechanisms may also play important roles in noise-induced PTS.

The role of cochlear neurotransmitters in tinnitus

Pathologic changes in the cochlear neurotransmission, e.g. as a result of intensive noise exposure or ototoxic drugs, can be a factor in the development of tinnitus. The efficiency of inhibitory and excitatory neurotransmitters may then be modulated at the switching points. Glutamate is the most important afferent neurotransmitter within the inner ear. A massive glutamate release induced by cochlear damage may result in excitotoxicity and irrevocable cell death. Efferent cochlear neurotransmitters include dopamine, gamma aminobutyric acid (GABA), acetylcholine (ACH) and serotonin. Dopamine and GABA are inhibitory transmitters that may protect the cochlea from excitotoxicity. ACH, like GABA, reduces the stiffness of the outer hair cells and increases their motility. Serotonin is a neuromodulator of the cholinergic and GABAergic innervation within the cochlea and can inhibit glutamatergic impulses. Our understanding of neurotransmission in the cochlea has been extended by advances in molecular biology, which has given rise to new approaches in the treatment of tinnitus. As there are several types of tinnitus, differing in aetiology and development, our present challenge is to achieve precise identification of the cause in individual cases of tinnitus.

Acoustic overstimulation facilitates the expression of glutamate–cysteine ligase catalytic subunit probably through enhanced DNA binding of activator protein-1 and/or NF-κB in the murine cochlea

Glutamate–cysteine ligase (GCL), previously known as γ-glutamylcysteine synthetase, is the rate-limiting enzyme for GSH synthesis. The expression of GCL is mediated by activator protein-1 (AP-1) and nuclear factor-kappa B (NF-κB), which are known to participate in stress-induced apoptotic pathways in neuronal cells. In this study, we investigated the changes in the level of these transcription factors as well as of GCL catalytic subunit in the cochlea in response to acoustic overstimulation. Nuclear extracts were prepared from the cochlear at various time points after intense noise exposure (4 kHz octave band, 125 dB sound pressure level, 5 h), and then determined DNA binding activity of the transcription factors. AP-1 DNA binding was markedly increased 2–12 h after the noise exposure, with a peak at 2 h after the exposure. NF-κB DNA binding was also increased immediately after the exposure. Semi-quantitative RT-PCR revealed that the catalytic subunit of GCL mRNA was elevated in the cochlea 2–24 h post the exposure. Further immunohistochemical study revealed that increased level of GCL catalytic subunit observed at least in the spiral ganglion cells after the exposure. These results suggest that intense noise exposure facilitates the expression of GCL catalytic subunit in the cochlea possibly through the activation of transcription factors including AP-1 and NF-κB.

Administration of amitriptyline attenuates noise-induced hearing loss via glial cell line-derived neurotrophic factor (GDNF) induction

Antidepressant treatments have been described to induce neurotrophic factors (NTFs) and reverse the cell loss observed in rodent stress models. Amitriptyline (AT), a tricyclic antidepressant agent, has been reported in recent studies to induce glial cell line-derived neurotrophic factor (GDNF) synthesis and release in rat C6 glioblastoma cells. GDNF has shown protection against acoustic trauma in previous studies. Therefore, we investigated whether AT could induce GDNF synthesis in the cochlea and attenuate cochlea damage against acoustic trauma. We used Hartley guinea pigs and injected AT (30 mg/kg) or saline into the peritoneum. Subjects were exposed to 117 dB SPL octave band noise centered at 4 kHz for 24 h. Noise-induced hearing loss (NIHL) was assessed with auditory brain stem response (ABR) at 4, 8 and 16 kHz measured prior to the injection, 3 days and 7 days after noise exposure. For histological assessment, we observed the sensory epithelium using a surface preparation technique and assessed the quantitative hair cell (HC) damage. We evaluated GDNF synthesis with or without intense noise exposure at 3, 12 and 24 h after the administration of AT in the cochlea using Western blot analysis. GDNF expression was shown 3 h and 12 h after the injection without noise, whereas with noise the GDNF expression lasted for 24 h. The AT-administrated group showed significantly reduced ABR threshold shift and less HC damage than the saline-administrated group. These findings suggest that the administration of AT-induced GDNF levels in the cochlea and attenuated cochlea damage from NIHL.

Prestin gene expression in the rat cochlea following intense noise exposure

Noise-induced permanent loss of cochlear amplification was observed previously with the majority of outer hair cells (OHCs) still surviving in the cochlea and even with a normal OHC receptor potential, indicated by CM (cochlear microphonics) recording [Chen, G.D., Fechter, L.D., 2003. The relationship between noise-induced hearing loss and hair cell loss in rats. Hear. Res. 177(1–2), 81–90; Chen, G.D., Liu, Y., 2005. Mechanisms of noise-induced hearing loss potentiation by hypoxia. Hear. Res. 200, 1–9]. This study focused on effects of an intense noise exposure (10–20 kHz at a level of 110 dB SPL for 4 h) on the OHC motor protein (prestin) and structural proteins in the OHC membrane skeleton. The noise exposure significantly disrupted CM and CAP (cochlear compound action potential). The injured CM recovered after 1-week resting period. The impaired CAP at frequencies lower than the noise band also recovered. However, the CAP recovery at frequencies of the noise band stopped at a linear line one week after the noise exposure, indicating a permanent loss of cochlear amplification. Gene expression of prestin, β-spectrin, and β-actin was significantly up-regulated after the noise exposure. The elevated gene expression peaked at the 3rd post-exposure day and returned to baseline 4 weeks after the noise exposure. The up-regulated gene expression may be in response to injury of the proteins, which may be responsible for the loss of cochlear amplification.

Effects of intense noise exposure on the outer hair cell plasma membrane fluidity

Outer hair cells (OHCs) play an important role in cochlear amplification via their length changes (electromotility). A noise-induced cochlear amplification loss leading to a permanent threshold shift (PTS) was observed without a significant hair cell loss in rats [Chen, G.D., Liu, Y., 2005. Mechanisms of noise-induced hearing loss potentiation by hypoxia. Hear. Res. 200, 1–9.]. Since motor proteins are inserted in the OHC lateral membrane, any change in the OHC plasma membrane may result in a loss of OHC electromotility, leading to a loss of cochlear amplification. In this study, the lateral diffusion in the OHC plasma membrane was determined in vitro in guinea pigs by fluorescent recovery after photobleaching (FRAP) after an in vivo noise exposure. The lateral diffusion in the OHC plasma membrane demonstrated a length-dependence, which increased as OHC length increased. A reduction in the lateral diffusion was observed in those OHCs with lengths of 50–70 μm after exposure to an 8-kHz octave band noise at 110 dB SPL for 3 h. This membrane fluidity change was associated with the selective PTS at frequencies around 8 kHz. The reduction of the lateral diffusion in the OHC lateral wall indicated that noise could impair the micromechanics of the OHC lateral wall and might consequently impair OHC electromotility to induce threshold shift.

Nuclear factor-kappa B nuclear translocation in the cochlea of mice following acoustic overstimulation

There is increasing evidence to suggest that the expression of many molecules in the lateral wall of the cochlea plays an important role in noise-induced stress responses. In this study, activation of the nuclear transcription factor nuclear factor-kappa B (NF-κB) was investigated in the cochlea of mice treated with intense noise exposure (4 kHz, octave band, 124 dB, for 2 h). The present noise exposure led to remarkable auditory brainstem response threshold shifts and cochlear damage on surface preparations. To assess the effects of noise exposure on NF-κB/DNA binding activity in the cochlea, we prepared nuclear extracts from the cochlea at different time points after noise exposure and carried out an electrophoretic mobility shift assay using a probe specific to NF-κB. NF-κB/DNA binding was significantly enhanced in the cochlea 2–6 h after noise exposure and returned to basal levels after 12 h. Supershift analysis using antibodies against p65 and p50 proteins, which are components of NF-κB, demonstrated that enhancement of NF-κB/DNA binding was at least in part due to nuclear translocation of p65. An immunohistochemical study also showed that nuclear translocation of both p65 and p50 was observed in the lateral wall after noise exposure and that there may be a possible close association between p65 and enhanced inducible nitric oxide synthase expression. These results suggest that NF-κB may have a detrimental role in the response to acoustic overstimulation in the cochlea of mice.