Early Loss of Spiral Ganglion Neurons in the Auditory System after Noise Trauma.

INTRODUCTION: Noise-induced hearing loss is one of the most frequent recognized occupational diseases. The time course of the involved pathologies is still under investigation. Several studies have demonstrated an acute damage of the sensory tissue, but only few experiments investigated the degeneration of (type I) spiral ganglion neurons (SGNs), representing the primary neurons in the auditory system. The aim of the present study was to investigate the time course of SGN degeneration within a 7-day period after traumatic noise exposure starting immediately after trauma. METHODS: Young adult normal hearing mice were noise exposed for 3 h with a broadband noise (5-20 kHz) at 115 dB SPL. Auditory threshold shift was measured by auditory brainstem recordings, and SGN densities were analyzed at different time points during the first week after acoustic trauma. RESULTS: Significant reduction of SGN densities was detected and is accompanied by a significant hearing loss. Degeneration starts within hours after the applied trauma, further progressing within days post-exposure. DISCUSSION: Early neurodegeneration in the auditory periphery seems to be induced by direct overstimulation of the auditory nerve fibers. SGN loss is supposed to be a result of inflammatory responses and neural deprivation, leading to permanent hearing loss and auditory processing deficits.

Electrical Ear Canal Stimulation as a Therapeutic Approach for Tinnitus-A Proof of Concept Study.

Background: Tinnitus-the perception of sound despite the absence of an external source-can be a debilitating condition for which there are currently no pharmacological remedies. Our proof of concept study focused on the immediate effects of non-invasive electrical stimulation through the ear canal on loudness and tinnitus-induced distress. In addition, we aimed to identify variables that may affect the simulation outcomes. Methods: Sixty-six patients (29 women and 37 men, mean age 54.4 ± 10.4) with chronic tinnitus were recruited to the tertiary referral hospital between December 2019 and December 2021. They underwent 10 min of electrical stimulation through the ear canal for three consecutive days. Visual analog scales measured loudness and tinnitus-induced distress immediately before and after stimulation. Results: After three days of electrical stimulation, tinnitus loudness decreased in 47% of patients, 45.5% reported no change, and 7.6% reported worsening. Tinnitus severity decreased in 36.4% of cases, 59.1% of patients reported no change, and 4.5% reported worsening. Women responded positively to therapy earlier than men. In addition, tinnitus distress decreased in patients with compensated tinnitus but not in those with uncompensated tinnitus. Finally, patients with bilateral tinnitus improved earlier than those with unilateral tinnitus, and the age of the patients did not influence the stimulation results. Conclusions: Our proof of concept study confirms the potential of non-invasive electrical stimulation of the ear as a promising screening approach to identifying patients for more advanced electrostimulation treatment, such as an extracochlear anti-tinnitus implant. These findings have practical implications for tinnitus management, offering hope for improved patient care.

Neurodegeneration after repeated noise trauma in the mouse lower auditory pathway.

High intensity noise exposure leads to a permanent shift in auditory thresholds (PTS), affecting both peripheral (cochlear) tissue and the central auditory system. Studies have shown that a noise-induced hearing loss results in significant cell loss in several auditory structures. Degeneration can be demonstrated within hours after noise exposure, particularly in the lower auditory pathway, and continues to progress over days and weeks following the trauma. However, there is limited knowledge about the effects of recurring acoustic trauma. Repeated noise exposure has been demonstrated to increase neuroplasticity and neural activity. Thus, the present study aimed to investigate the influence of a second noise exposure on the cytoarchitecture of key structures of the auditory pathway, including spiral ganglion neurons (SGN), the ventral and dorsal cochlear nucleus (VCN and DCN, respectively), and the inferior colliculus (IC). In the experiments, young adult normal hearing mice were exposed to noise once or twice (with the second trauma applied one week after the initial exposure) for 3 h, using broadband white noise (5 - 20 kHz) at 115 dB SPL. The cell densities in the investigated auditory structures significantly decreased in response to the initial noise exposure compared to unexposed control animals. These findings are consistent with earlier research, which demonstrated degeneration in the auditory pathway within the first week after acoustic trauma. Additionally, cell densities were significantly decreased after the second trauma, but this effect was only observed in the VCN, with no similar effects seen in the SGN, DCN, or IC. These results illustrate how repeated noise exposure influences the cytoarchitecture of the auditory system. It appears that an initial noise exposure primarily damages the lower auditory pathway, but surviving cellular structures may develop resistance to additional noise-induced injury.

[Cochlear implant and tinnitus]. / Cochleaimplantat und Tinnitus.

Cochlear implant (CI) treatment is now established as a successful standard of care for auditory rehabilitation of profoundly deaf or severe hearing loss patients. CI candidates with tinnitus also benefit from improved health-related quality of life (HRQoL) and tinnitus burden. Current CI indications include bilateral (double-sided) profound hearing loss and deafness (DSD), unilateral (single-sided) deafness (SSD), and asymmetric hearing loss (AHL). The new and expanded indications for cochlear implants result in different healthcare situations, which may also be associated with differences in tinnitus burden before and after CI treatment. In this article, we discuss the prevalence of tinnitus in different patient groups and the influence of CI on tinnitus prevalence and severity in these groups. In addition, further therapeutic options for tinnitus suppression based on the CI principle are presented, including the development of an anti-tinnitus implant (proof of concept).

[Prospective comparative analysis of cochlear implant patients with single-sided deafness and asymmetric hearing loss with regard to health-related quality of life, tinnitus distress and psychological comorbidities]. / Prospektive Vergleichsanalyse von CI-Patienten mit einseitiger Taubheit und asymmetrischem Hörverlust hinsichtlich der gesundheitsbezogenen Lebensqualität, Tinnitusbelastung und psychischen Komorbiditäten.

BACKGROUND: Patients with single-sided deafness (SSD) and asymmetric hearing loss (AHL) are increasingly being treated with cochlear implants (CI) due to the demonstrated improvements in auditory abilities and quality of life. To date, there are few published studies in which these two groups are comparatively studied. The aim of the current study was to examine which factors differ between those two patient groups, especially preoperatively. METHODS: A secondary analysis of the previously published raw data of 66 prospectively recruited CI patients (21 SSD/45 AHL) was performed. In addition to the hearing outcome, tinnitus distress (tinnitus questionnaire), health-related quality of life (Nijmegen Cochlear Implant Questionnaire, NCIQ), stress (Perceived Stress Questionnaire, PSQ), and psychological comorbidities (General Depression Scale, ADS­L and Generalized Anxiety Disorder scale, GAD-7) were assessed in SSD and AHL patients pre- and postoperatively. RESULTS: Preoperatively, SSD patients showed significantly higher scores in the NCIQ subdomains "elementary" and "advanced sound perception" than the AHL group. Stress (PSQ) and anxiety symptoms (GAD-7) were significantly higher preoperatively in SSD patients than in AHL patients. After CI, these differences were strongly reduced, with minimal differences being detectable between the groups in the investigated domains postoperatively. CONCLUSION: SSD and AHL patients differ significantly preoperatively in terms of their subjective hearing assessment and psychosocial parameters. In SSD patients, psychological stress factors may have a stronger impact on the quality of life than in AHL patients. These aspects should be taken into account in the preoperative counseling and postoperative rehabilitation.

Short-term overstimulation affects peripheral but not central excitability in an animal model of cochlear implantation.

Objective: Upper current limits (C-levels) are sometimes extremely increased over time since this procedure can enhance speech perception. It should be clarified if a larger amount of electrical stimulation is tolerated by the remaining peripheral and central auditory pathway.Materials and Methods: An animal electrode array was inserted in mechanically deafened guinea pigs. C-levels were adjusted to a mean of approximately 10 CL ('LOS' group), 40 CL ('MOS' group) or 60 CL ('HOS' group) above the electrode specific electrically evoked compound action potential (eCAP) threshold. The stimulation was performed via a sound processor in standardized auditory environment. Implanted and not stimulated animals served as controls.Results: A significant eCAP threshold shift was observed in the 'HOS'-group aftereight hours of stimulation at basal electrodes. Electrically evoked auditory brainstem thresholds were stable over time in all stimulation groups. The ratio between eCAP- and eABR threshold shifts was significantly enhanced in the 'HOS'- group.Conclusion: Even short-time overstimulation reduces the excitability of peripheral but not central auditory structures. The changed relationship between the excitability of spiral ganglion neurons and inferior colliculus neurons seems to indicate an overstimulation. The results are of utmost importance for a safe CI-processor fitting especially in children or non-compliant patients.

Cytomegalovirus Seropositivity as a Potential Risk Factor for Increased Noise Trauma Susceptibility.

Context: Cytomegalovirus (CMV) represents the leading congenital viral infection in humans. Although congenital CMV due to vertically transmitted infections is the main cause of CMV-related diseases, adult CMV infections might still be of clinical significance. It is still discussed how far CMV seropositivity, due to horizontal infection in immunocompetent adults, is able to induce significant dysfunction. The present study investigates in how far CMV seropositivity is an additional risk factor for an increasing susceptibility to sensorineural hearing loss induced by acoustic injury during adulthood in a guinea pig CMV (GPCMV) model of noise-induced hearing loss (NIHL). Methods: Two groups (GPCMV seropositive vs. seronegative) of normal hearing adult guinea pigs were exposed to a broadband noise (5-20 kHz) for 2 hours at 115 dB sound pressure level. Frequency-specific auditory brainstem response recordings for determination of auditory threshold shift were carried out and the number of missing outer hair cells was counted 2 weeks after the noise exposure. Results: The data show a slightly increased shift in auditory thresholds in seropositive animals compared to the seronegative control group in response to noise trauma. However, the observed difference was significant at least at high frequencies. The differences in threshold shift are not correlated with outer hair cell loss between the experimental groups. Conclusion: The results point to potential additional pathologies in a guinea pig NIHL model in correlation to GPCMV seropositivity, which should be taken into account when assessing risks of latent/reactivated CMV infection. Due to the relatively slight effect in the present data, the aim of future studies should be a more detailed consideration (e.g., larger sample size) and to localize possible target structures as well as the significance of the infection route.

Neuroprotective Effect of Near-Infrared Light in an Animal Model of CI Surgery.

INTRODUCTION: The preservation of residual hearing has become an important consideration in cochlear implant (CI) recipients in recent years. It was the aim of the present animal experimental study to investigate the influence of a pretreatment with near-infrared (NIR) light on preservation of sensory hair cells and residual hearing after cochlear implantation. METHODS: NIR was applied unilaterally (15 min, 808 nm, 120 mW) to 8 guinea pigs, immediately before a bilateral scala tympani CI electrode insertion was performed. The nonirradiated (contralateral) side served as control. Twenty-eight days postoperatively, auditory brainstem responses (ABRs) were registered from both ears to screen for hearing loss. Thereafter, the animals were sacrificed and inner hair cells (IHCs) and outer hair cells (OHCs) were counted and compared between NIR-pretreated and control (contralateral) cochleae. RESULTS: There was no IHC loss upon cochlear implantation. OHC loss was most prominent on both sides at the apical part of the cochlea. NIR pretreatment led to a statistically significant reduction in OHC loss (by 39.8%). ABR recordings (across the frequencies 4-32 kHz) showed a statistically significant difference between the 2 groups and corresponds well with the apical structural damage. Hearing loss was reduced by about 20 dB on average for the NIR-pretreated group (p ≤ 0.05). DISCUSSION/CONCLUSION: A single NIR pretreatment in this animal model of CI surgery appears to be neuroprotective for residual hearing. This is in line with other studies where several NIR posttreatments have protected cochlear and other neural tissues. NIR pretreatment is an inexpensive, effective, and noninvasive approach that can complement other ways of preserving residual hearing and, hence, should deserve further clinical evaluation in CI patients.

Near-infrared-light pre-treatment attenuates noise-induced hearing loss in mice.

Noise induced hearing loss (NIHL) is accompanied by a reduction of cochlear hair cells and spiral ganglion neurons. Different approaches have been applied to prevent noise induced apoptosis / necrosis. Physical intervention is one technique currently under investigation. Specific wavelengths within the near-infrared light (NIR)-spectrum are known to influence cytochrome-c-oxidase activity, which leads in turn to a decrease in apoptotic mechanisms. It has been shown recently that NIR can significantly decrease the cochlear hair cell loss if applied daily for 12 days after a noise exposure. However, it is still unclear if a single NIR-treatment, just before a noise exposure, could induce similar protective effects. Therefore, the present study was conducted to investigate the effect of a single NIR-pre-treatment aimed at preventing or limiting NIHL. The cochleae of adult NMRI-mice were pre-treated with NIR-light (808 nm, 120 mW) for 5, 10, 20, 30 or 40 minutes via the external ear canal. All animals were noised exposed immediately after the pre-treatment by broad band noise (5-20 kHz) for 30 minutes at 115 dB SPL. Frequency specific ABR-recordings to determine auditory threshold shift were carried out before the pre-treatment and two weeks after the noise exposure. The amplitude increase for wave IV and cochlear hair cell loss were determined. A further group of similar mice was noise exposed only and served as a control for the NIR pre-exposed groups. Two weeks after noise exposure, the ABR threshold shifts of NIR-treated animals were significantly lower (p < 0.05) than those of the control animals. The significance was at three frequencies for the 5-minute pre-treatment group and across the entire frequency range for all other treatment groups. Due to NIR light, the amplitude of wave four deteriorates significantly less after noise exposure than in controls. The NIR pre-treatment had no effect on the loss of outer hair cells, which was just as high with or without NIR-light pre-exposure. Relative to the entire number of outer hair cells across the whole cochlea, outer hair cell loss was rather negligible. No inner hair cell loss whatever was detected. Our results suggest that a single NIR pre-treatment induces a very effective protection of cochlear structures from noise exposure. Pre-exposure of 10 min seems to emerge as the optimal dosage for our experimental setup. A saturated effect occurred with higher dosage-treatments. These results are relevant for protection of residual hearing in otoneurosurgery such as cochlear implantation.

Acute Noise Exposure Is Associated With Intrinsic Apoptosis in Murine Central Auditory Pathway.

Noise that is capable of inducing the hearing loss (NIHL) has a strong impact on the inner ear structures and causes early and most obvious pathophysiological changes in the auditory periphery. Several studies indicated that intrinsic apoptotic cell death mechanisms are the key factors inducing cellular degeneration immediately after noise exposure and are maintained for days or even weeks. In addition, studies demonstrated several changes in the central auditory system following noise exposure, consistent with early apoptosis-related pathologies. To clarify the underlying mechanisms, the present study focused on the noise-induced gene and protein expression of the pro-apoptotic protease activating factor-1 (APAF1) and the anti-apoptotic B-cell lymphoma 2 related protein a1a (BCL2A1A) in the cochlear nucleus (CN), inferior colliculus (IC) and auditory cortex (AC) of the murine central auditory pathway. The expression of Bcl2a1a mRNA was upregulated immediately after trauma in all tissues investigated, whereas the protein levels were significantly reduced at least in the auditory brainstem. Conversely, acute noise has decreased the expression of Apaf1 gene along the auditory pathway. The changes in APAF1 protein level were not statistically significant. It is tempting to speculate that the acoustic overstimulation leads to mitochondrial dysfunction and induction of apoptosis by regulation of proapoptotic and antiapoptotic proteins. The inverse expression pattern on the mRNA level of both genes might reflect a protective response to decrease cellular damage. Our results indicate the immediate presence of intrinsic apoptosis following noise trauma. This, in turn, may significantly contribute to the development of central structural deficits. Auditory pathway-specific inhibition of intrinsic apoptosis could be a therapeutic approach for the treatment of acute (noise-induced) hearing loss to prevent irreversible neuronal injury in auditory brain structures and to avoid profound deficits in complex auditory processing.

Apoptosis in the cochlear nucleus and inferior colliculus upon repeated noise exposure.

The time course of apoptosis and the corresponding neuronal loss was previously shown in central auditory pathway of mice after a single noise exposure. However, repeated acoustic exposure is a major risk factor for noise-induced hearing loss. The present study investigated apoptosis by terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling (TUNEL) assay after a second noise trauma in the ventral and dorsal cochlear nucleus and central nucleus of the inferior colliculus. Mice [Naval Medical Research Institute (NMRI) strain] were noise exposed [115 dB sound pressure level, 5-20 kHz, 3 h) at day 0. A double group received the identical noise exposure a second time at day 7 post-exposure and apoptosis was either analyzed immediately (7-day group-double) or 1 week later (14-day group-double). Corresponding single exposure groups were chosen as controls. No differences in TUNEL were seen between 7-day or 14-day single and double-trauma groups. Interestingly, independent of the second noise exposure, apoptosis increased significantly in the 14-day groups compared to the 7-day groups in all investigated areas. It seems that the first noise trauma has a long-lasting effect on apoptotic mechanisms in the central auditory pathway that were not largely influenced by a second trauma. Homeostatic mechanisms induced by the first trauma might protect the central auditory pathway from further damage during a specific time slot. These results might help to understand the underlying mechanisms of different psychoacoustic phenomena in noise-induced hearing loss.

Apoptotic mechanisms after repeated noise trauma in the mouse medial geniculate body and primary auditory cortex.

A correlation between noise-induced apoptosis and cell loss has previously been shown after a single noise exposure in the cochlear nucleus, inferior colliculus, medial geniculate body (MGB) and primary auditory cortex (AI). However, repeated noise exposure is the most common situation in humans and a major risk factor for the induction of noise-induced hearing loss (NIHL). The present investigation measured cell death pathways using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) in the dorsal, medial and ventral MGB (dMGB, mMGB and vMGB) and six layers of the AI (AI-1 to AI-6) in mice (NMRI strain) after a second noise exposure (double-exposure group). Therefore, a single noise exposure group has been investigated 7 (7-day-group-single) or 14 days (14-day-group-single) after noise exposure (3 h, 5-20 kHz, 115 dB SPL peak-to-peak). The double-exposure group received the same noise trauma for a second time 7 days after the initial exposure and was either TUNEL-stained immediately (7-day-group-double) or 1 week later (14-day-group-double) and data were compared to the corresponding single-trauma group as well as to an unexposed control group. It was shown that TUNEL increased immediately after the second noise exposure in AI-3 and stayed upregulated in the 14-day-group-double. A significant increase in TUNEL was also seen in the 14-day-group-double in vMGB, mMGB and AI-1. The present results show for the first time the influence of a repeated noise trauma on cell death mechanisms in thalamic and cortical structures and might contribute to the understanding of pathophysiological findings and psychoacoustic phenomena accompanying NIHL.

Time course of cell death due to acoustic overstimulation in the mouse medial geniculate body and primary auditory cortex.

It has previously been shown that acoustic overstimulation induces cell death and extensive cell loss in key structures of the central auditory pathway. A correlation between noise-induced apoptosis and cell loss was hypothesized for the cochlear nucleus and colliculus inferior. To determine the role of cell death in noise-induced cell loss in thalamic and cortical structures, the present mouse study (NMRI strain) describes the time course following noise exposure of cell death mechanisms for the ventral medial geniculate body (vMGB), medial MGB (mMGB), and dorsal MGB (dMGB) and the six histological layers of the primary auditory cortex (AI 1-6). Therefore, a terminal deoxynucleotidyl transferase dioxyuridine triphosphate nick-end labeling assay (TUNEL) was performed in these structures 24 h, 7 days, and 14 days after noise exposure (3 h, 115 dB sound pressure level, 5-20 kHz), as well as in unexposed controls. In the dMGB, TUNEL was statistically significant elevated 24 h postexposure. AI-1 showed a decrease in TUNEL after 14 days. There was no statistically significant difference between groups for the other brain areas investigated. dMGB's widespread connection within the central auditory pathway and its nontonotopical organization might explain its prominent increase in TUNEL compared to the other MGB subdivisions and the AI. It is assumed that the onset and peak of noise-induced cell death is delayed in higher areas of the central auditory pathway and takes place between 24 h and 7 days postexposure in thalamic and cortical structures.

Central Nervous Activity upon Systemic Salicylate Application in Animals with Kanamycin-Induced Hearing Loss--A Manganese-Enhanced MRI (MEMRI) Study.

This study investigated the effect of systemic salicylate on central auditory and non-auditory structures in mice. Since cochlear hair cells are known to be one major target of salicylate, cochlear effects were reduced by using kanamycin to remove or impair hair cells. Neuronal brain activity was measured using the non-invasive manganese-enhanced magnetic resonance imaging technique. For all brain structures investigated, calcium-related neuronal activity was increased following systemic application of a sodium salicylate solution: probably due to neuronal hyperactivity. In addition, it was shown that the central effect of salicylate was not limited to the auditory system. A general alteration of calcium-related activity was indicated by an increase in manganese accumulation in the preoptic area of the anterior hypothalamus, as well as in the amygdala. The present data suggest that salicylate-induced activity changes in the auditory system differ from those shown in studies of noise trauma. Since salicylate action is reversible, central pharmacological effects of salicylate compared to those of (permanent) noise-induced hearing impairment and tinnitus might induce different pathophysiologies. These should therefore, be treated as different causes with the same symptoms.

Bilateral Changes of Spontaneous Activity Within the Central Auditory Pathway Upon Chronic Unilateral Intracochlear Electrical Stimulation.

OBJECTIVES: In recent years, cochlear implants have been applied successfully for the treatment of unilateral hearing loss with quite surprising benefit. One reason for this successful treatment, including the relief from tinnitus, could be the normalization of spontaneous activity in the central auditory pathway because of the electrical stimulation. The present study, therefore, investigated at a cellular level, the effect of a unilateral chronic intracochlear stimulation on key structures of the central auditory pathway. DESIGN: Normal-hearing guinea pigs were mechanically single-sided deafened through a standard HiFocus1j electrode array (on a HiRes 90k cochlear implant) being inserted into the first turn of the cochlea. Four to five electrode contacts could be used for the stimulation. Six weeks after surgery, the speech processor (Auria) was fitted, based on tNRI values and mounted on the animal's back. The two experimental groups were stimulated 16 hours per day for 90 days, using a HiRes strategy based on different stimulation rates (low rate (275 pps/ch), high rate (5000 pps/ch)). The results were compared with those of unilateral deafened controls (implanted but not stimulated), as well as between the treatment groups. All animals experienced a standardized free field auditory environment. RESULTS: The low-rate group showed a significantly lower average spontaneous activity bilaterally in the dorsal cochlear nucleus and the medial geniculate body than the controls. However, there was no difference in the inferior colliculus and the primary auditory cortex. Spontaneous activity of the high-rate group was also reduced bilaterally in the dorsal cochlear nucleus and in the primary auditory cortex. No differences could be observed between the high-rate group and the controls in the contra-lateral inferior colliculus and medial geniculate body. The high-rate group showed bilaterally a higher activity in the CN and the MGB compared with the low-rate group, whereas in the IC and in the AC a trend for an opposite effect could be determined. CONCLUSIONS: Unilateral intracochlear electrical stimulation seems to facilitate the homeostasis of the network activity, since it decreases the spontaneous activity that is usually elevated upon deafferentiation. The electrical stimulation per se seems to be responsible for the bilateral changes described above, rather than the particular nature of the electrical stimulation (e.g., rate). The normalization effects of electrical stimulation found in the present study are of particular importance in cochlear implant recipients with single-sided deafness.

Age-dependent changes of calcium related activity in the central auditory pathway.

Age-related hearing loss (ARHL) represents one of the most common chronic health problems that faces an aging population. In the peripheral auditory system, aging is accompanied by functional loss or degeneration of sensory as well as non-sensory tissue. It has been recently described that besides the degeneration of cochlear structures, the central auditory system is also involved in ARHL. Although mechanisms of central presbycusis are not well understood, previous animal studies have reported some signs of central neurodegeneration in the lower auditory pathway. Moreover, changes in neurophysiology are indicated by alterations in synaptic transmission. In particular, neurotransmission and spontaneous neuronal activity appear to be affected in aging animals. Therefore, it was the aim of the present study to determine the neuronal activity within the central auditory pathway in aging mice over their whole lifespan compared to a control group (young adult animals, ~3months of age) using the non-invasive manganese-enhanced MRI technique. MRI signal strength showed a comparable pattern in most investigated auditory brain areas. An increase in activity was particularly pronounced in the middle-aged groups (13 or 18 months), with the largest effect in the dorsal and ventral cochlear nucleus. In higher auditory structures, namely the inferior colliculus, medial geniculate body and auditory cortex, the enhancement was much less expressed; while a decrease was detected in the superior olivary complex. Interestingly, calcium-dependent activity reduced to control levels in the oldest animals (22 months) in the cochlear nucleus and was significantly reduced in higher auditory structures. A similar finding was also found in the hippocampus. The observed changes might be related to central neuroplasticity (including hyperactivity) as well as neurodegenerative mechanisms and represent central nervous correlates of the age-related decline in auditory processing and perception.

Acute and long-term effects of noise exposure on the neuronal spontaneous activity in cochlear nucleus and inferior colliculus brain slices.

Noise exposure leads to an immediate hearing loss and is followed by a long-lasting permanent threshold shift, accompanied by changes of cellular properties within the central auditory pathway. Electrophysiological recordings have demonstrated an upregulation of spontaneous neuronal activity. It is still discussed if the observed effects are related to changes of peripheral input or evoked within the central auditory system. The present study should describe the intrinsic temporal patterns of single-unit activity upon noise-induced hearing loss of the dorsal and ventral cochlear nucleus (DCN and VCN) and the inferior colliculus (IC) in adult mouse brain slices. Recordings showed a slight, but significant, elevation in spontaneous firing rates in DCN and VCN immediately after noise trauma, whereas no differences were found in IC. One week postexposure, neuronal responses remained unchanged compared to controls. At 14 days after noise trauma, intrinsic long-term hyperactivity in brain slices of the DCN and the IC was detected for the first time. Therefore, increase in spontaneous activity seems to develop within the period of two weeks, but not before day 7. The results give insight into the complex temporal neurophysiological alterations after noise trauma, leading to a better understanding of central mechanisms in noise-induced hearing loss.

Apoptotic cascades in the central auditory pathway after noise exposure.

Noise exposure leads to dramatic physiological and anatomical changes within the central auditory pathway in addition to the well-known cochlear damage. Our group previously described a significant loss of neurons in different central auditory structures upon acoustic overstimulation. The aim of the present study was to investigate if declined neuronal cell density is caused by apoptotic mechanisms. Mice were noise-exposed (3 h, 5-20 kHz) at 115 dB SPL under anesthesia and investigated immediately after, and at 6 h, 24 h, or 7 days after the exposure (n=16). Unexposed animals were used as controls (n=5). Apoptotic cells were detected by fluorescence microscopy after terminal deoxynucleotidyl transferase dUTP nick-end labeling assay (TUNEL). TUNEL-positive cells were compared to cell density (diamidino phenylindole, DAPI) within the dorsal and ventral cochlear nucleus (VCN), and the central nucleus of the inferior colliculus (ICC). In all investigated auditory areas, TUNEL-positive cells were significantly increased after acoustic overstimulation. In the acute, 6-h, and 24-h groups, their numbers were significantly increased in the VCN, as well as in the 6-h, 24-h, and 7-day groups in the dorsal cochlear nucleus (DCN). In the ICC, TUNEL-positive cells were significantly increased in all exposed mice. In the VCN, the number of TUNEL-positive cells of the same grid size was three times the numbers in the ICC. Our results show that noise exposure induces apoptosis-related pathophysiological changes within the central auditory pathway in a time-dependent manner. This may represent potential therapeutic targets, and helps clarify the complex psychoacoustic phenomena of noise-induced hearing loss.

The possible impact of noise-induced Ca2+-dependent activity in the central auditory pathway: a manganese-enhanced MRI study.

Noise exposure at high intensities leads to a temporary shift of hearing thresholds (TTS) and is followed by a permanent threshold shift (PTS). Permanent threshold shift is not only associated with cochlear damage as the primary site-of-lesion, but also with subsequent structural and functional changes within the central auditory pathway. The aim of the present study was to monitor neuronal activity within central auditory structures in mice after noise exposure at different time intervals using manganese-enhanced magnetic resonance imaging (MEMRI). The results demonstrate for the first time that calcium-dependent activity patterns are modified in several structures of the central auditory system as the result of a noise-induced hearing loss (NIHL). The MEMRI data demonstrate that temporary threshold shift is correlated with an activity increase in hierarchically lower structures of the auditory pathway. This seems to be indicative of a direct noise impact at the first stage of central auditory processing. However, noise-dependent changes of higher auditory structures were found as well in the phase of PTS. Repeated noise exposure was found to induce an additional elevation of calcium-dependent activity in all investigated auditory structures - without a significant shift in auditory thresholds. Sustained manganese accumulation was present in the auditory brainstem after moderate acoustic stimulation as well without PTS induction. The long-lasting enhancement of MEMRI signals suggests a noise-induced activity increase of various calcium-dependent processes of different origin (such as neuroprotective mechanisms). The present findings could be helpful to better understand the time-course of different symptoms in NIHL and the individual susceptibility to noise.

Differential impact of temporary and permanent noise-induced hearing loss on neuronal cell density in the mouse central auditory pathway.

Although acoustic overstimulation has a major pathophysiological influence on the inner ear, central components of the auditory pathway can also be affected by noise-induced hearing loss (NIHL). The present study investigates the influence of a noise-induced temporary threshold shift (TTS) and/or permanent threshold shift (PTS) on neuronal cell densities in key structures of the central auditory pathway. Mice were noise-exposed (3 h, 5-20 kHz) at 115 dB sound pressure level (SPL) under anesthesia, and were investigated immediately (TTS group, n = 5) after the exposure, or 1 week later (PTS group, n = 6). Unexposed animals were used as controls (n = 7). Frequency-specific auditory brainstem responses (ABR) were recorded to examine auditory thresholds. Cell density was determined within the dorsal (DCN) and ventral (VCN) cochlear nucleus; the central nucleus of the inferior colliculus (ICC); the dorsal, ventral, and medial subdivisions of the medial geniculate body (MGBd, MGBv, and MGBm); and layer I to VI of the primary auditory cortex (AI I-VI). ABR thresholds were significantly elevated in the TTS group (52-69 dB SPL) and in the PTS group (33-42 dB SPL) compared to controls. There was a significant decrease in cell density only in the VCN of the TTS group (-10%), most likely induced by the acute overstimulation of neurons. Cell density was significantly reduced in all investigated auditory structures at 1 week post-exposure (PTS group), except in layer II of the AI (VCN: -30% and DCN: -30% (high-frequency); -39% (low-frequency); ICC: -31%; MGBd: -31%; MGBm: -28%; MGBv: -31%; AI: -10 to 14%). Thus there were dramatic changes within the neuronal cytoarchitecture of the central auditory pathway following a single noise exposure. The present findings should help clinicians to better understand the complex psychoacoustic phenomena of NIHL.