Elevation Of Auditory Thresholds Research Articles

Auditory function in humans at high altitude. A scoping review.

High-altitude (HA) affects sensory organ response, but its effects on the inner ear are not fully understood. The present scoping review aimed to collect the available evidence about HA effects on the inner ear with focus on auditory function. The scoping review was conducted following the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis extension for scoping reviews. PubMed, Scopus, and Web of Science electronic databases were systematically searched to identify studies conducted in the last 20 years, which quantified in healthy subjects the effects of HA on auditory function. The systematic search identified 17 studies on a total population of 888 subjects (88.7% male, age: 27.8 ± 4.1 years; median sample size of 15 subjects). Nine studies were conducted in a simulated environment and eight during real expeditions at HA. To quantify auditory function, six studies performed pure tone audiometry, four studies measured otoacoustic emissions (OAE) and eight studies measured auditory evoked responses (AER). Study protocols presented heterogeneity in the spatio-temporal patterns of HA exposure, with highly varying maximal altitudes and exposure durations. Most studies reported a reduction of auditory function with HA in terms of either elevation of auditory thresholds, lengthening of AER latencies, reduction of distortion-product and transient-evoked OAEs. Future studies in larger populations, using standardized protocols and multi-technique auditory function evaluation, are needed to further characterize the spatio-temporal pattern of HA effects along the auditory pathways and clarify the pathophysiological implications and reversibility of the observed changes.

Treatment with the Ferroptosis Inhibitor Ferrostatin-1 Attenuates Noise-Induced Hearing Loss by Suppressing Ferroptosis and Apoptosis.

Hair cell death induced by excessive reactive oxygen species (ROS) has been identified as the major pathogenesis of noise-induced hearing loss (NIHL). Recent studies have demonstrated that cisplatin- and neomycin-induced ototoxicity can be alleviated by ferroptosis inhibitors. However, whether ferroptosis inhibitors have a protective effect against NIHL remains unknown. We investigated the protective effect of the ferroptosis inhibitor ferrostatin-1 (Fer-1) on NIHL in vivo in CBA/J mice and investigated the protective effect of Fer-1 on tert-butyl hydroperoxide (TBHP)-induced hair cell damage in vitro in cochlear explants and HEI-OC1 cells. We observed ROS overload and lipid peroxidation, which led to outer hair cell (OHC) apoptosis and ferroptosis, in the mouse cochlea after noise exposure. The expression level of apoptosis-inducing factor mitochondria-associated 2 (AIFM2) was substantially increased following elevation of the expression of its upstream protein P53 after noise exposure. The ferroptosis inhibitor Fer-1was demonstrated to enter the inner ear after the systemic administration. Administration of Fer-1 significantly alleviated noise-induced auditory threshold elevation and reduced the loss of OHCs, inner hair cell (IHC) ribbon synapses, and auditory nerve fibers (ANFs) caused by noise. Mechanistically, Fer-1 significantly reduced noise- and TBHP-induced lipid peroxidation and iron accumulation in hair cells, alleviating ferroptosis in cochlear cells consequently. Furthermore, Fer-1 treatment decreased the levels of TfR1, P53, and AIFM2. These results suggest that Fer-1 exerted its protective effects by scavenging of ROS and inhibition of TfR1-mediated ferroptosis and P53-AIFM2 signaling pathway-mediated apoptosis. Our findings suggest that Fer-1 is a promising drug for treating NIHL because of its ability to inhibit noise-induced hair cell apoptosis and ferroptosis, opening new avenues for the treatment of NIHL.

Cytokine Levels in Inner Ear Fluid of Young and Aged Mice as Molecular Biomarkers of Noise-Induced Hearing Loss.

Sensorineural hearing loss (SNHL) is the most common sensory deficit worldwide, frequently caused by noise trauma and aging, with inflammation being implicated in both pathologies. Here, we provide the first direct measurements of proinflammatory cytokines in inner ear fluid, perilymph, of adolescent and 2-year-old mice. The perilymph of adolescent mice exposed to the noise intensity resulting in permanent auditory threshold elevations had significantly increased levels of IL-6, TNF-α, and CXCL1 6 h after exposure, with CXCL1 levels being most elevated (19.3 ± 6.2 fold). We next provide the first immunohistochemical localization of CXCL1 in specific cochlear supporting cells, and its presumed receptor, Duffy antigen receptor for chemokines (DARC), in hair cells and spiral ganglion neurons. Our results demonstrate the feasibility of molecular diagnostics of SNHL using only 0.5 μL of perilymph, and motivate future sub-μL based diagnostics of human SNHL based on liquid biopsy of the inner ear to guide therapy, promote hearing protection, and monitor response to treatment.

Enhancement of the Medial Olivocochlear System Prevents Hidden Hearing Loss.

Cochlear synaptopathy produced by exposure to noise levels that cause only transient auditory threshold elevations is a condition that affects many people and is believed to contribute to poor speech discrimination in noisy environments. These functional deficits in hearing, without changes in sensitivity, have been called hidden hearing loss (HHL). It has been proposed that activity of the medial olivocochlear (MOC) system can ameliorate acoustic trauma effects. Here we explore the role of the MOC system in HHL by comparing the performance of two different mouse models: an α9 nicotinic receptor subunit knock-out (KO; Chrna9 KO), which lacks cholinergic transmission between efferent neurons and hair cells; and a gain-of-function knock-in (KI; Chrna9L9'T KI) carrying an α9 point mutation that leads to enhanced cholinergic activity. Animals of either sex were exposed to sound pressure levels that in wild-type produced transient cochlear threshold shifts and a decrease in neural response amplitudes, together with the loss of ribbon synapses, which is indicative of cochlear synaptopathy. Moreover, a reduction in the number of efferent contacts to outer hair cells was observed. In Chrna9 KO ears, noise exposure produced permanent auditory threshold elevations together with cochlear synaptopathy. In contrast, the Chrna9L9'T KI was completely resistant to the same acoustic exposure protocol. These results show a positive correlation between the degree of HHL prevention and the level of cholinergic activity. Notably, enhancement of the MOC feedback promoted new afferent synapse formation, suggesting that it can trigger cellular and molecular mechanisms to protect and/or repair the inner ear sensory epithelium.SIGNIFICANCE STATEMENT Noise overexposure is a major cause of a variety of perceptual disabilities, including speech-in-noise difficulties, tinnitus, and hyperacusis. Here we show that exposure to noise levels that do not cause permanent threshold elevations or hair cell death can produce a loss of cochlear nerve synapses to inner hair cells as well as degeneration of medial olivocochlear (MOC) terminals contacting the outer hair cells. Enhancement of the MOC reflex can prevent both types of neuropathy, highlighting the potential use of drugs that increase α9α10 nicotinic cholinergic receptor activity as a pharmacotherapeutic strategy to avoid hidden hearing loss.

A case of auditory neuropathy revealed by OTOF gene mutation analysis in a junior high school girl

ObjectiveCongenital auditory neuropathy (AN) affects hearing and speech development. The degree of hearing difficulty in congenital AN varies as a function of pathology at the inner ear hair cell (IHC) synapses or the auditory nerve. We report a case of a Chinese girl with AN revealed by OTOF (otoferlin) gene mutation analysis who had only a mild hearing loss. PatientA 13-year-old Chinese girl was diagnosed as having congenital AN on the basis of OTOF gene mutation analysis. She manifest a mild sensorineural hearing loss with 50% maximum monosyllable speech discrimination rate, normal DPOAEs (distortion product otoacoustic emissions) beyond ambient noise levels, only SPs (summating potentials) evoked during ECoG (electrocochleography) and absent ABRs (auditory evoked brainstem responses) bilaterally to clicks presented at 100 dBnHL. She was able to effectively communicate with others by speech reading owing to her mild hearing loss. Moreover, bilateral hearing aids helped her to communicate. ConclusionsOur patient was demonstrated to have a mutation on the OTOF gene. Nevertheless, she was able to communicate using auditory visual speech reading in spite of a mild auditory threshold elevation probably due to partial pathology at the IHC synapses or in the auditory nerve.

Hair cell synaptic dysfunction, auditory fatigue and thermal sensitivity in otoferlin Ile515Thr mutants.

The multi-C2 domain protein otoferlin is required for hearing and mutated in human deafness. Some OTOF mutations cause a mild elevation of auditory thresholds but strong impairment of speech perception. At elevated body temperature, hearing is lost. Mice homozygous for one of these mutations, OtofI515T/I515T, exhibit a moderate hearing impairment involving enhanced adaptation to continuous or repetitive sound stimulation. In OtofI515T/I515T inner hair cells (IHCs), otoferlin levels are diminished by 65%, and synaptic vesicles are enlarged. Exocytosis during prolonged stimulation is strongly reduced. This indicates that otoferlin is critical for the reformation of properly sized and fusion-competent synaptic vesicles. Moreover, we found sustained exocytosis and sound encoding to scale with the amount of otoferlin at the plasma membrane. We identified a 20 amino acid motif including an RXR motif, presumably present in human but not in mouse otoferlin, which reduces the plasma membrane abundance of Ile515Thr-otoferlin. Together, this likely explains the auditory synaptopathy at normal temperature and the temperature-sensitive deafness in humans carrying the Ile515Thr mutation.

Acoustic alterations of ultrasonic vocalization in rat pups induced by perinatal hypothyroidism

Perinatal hypothyroidism causes serious damage to auditory functions that are essential for vocalization development. In rat pups, perinatal hypothyroidism potentially affects the development of ultrasonic vocalization (USV) as a result of hearing deficits. This study examined the effect of perinatal hypothyroidism on the development of USVs in rat pups. Twelve pregnant rats were divided into three groups and treated with the anti-thyroid drug methimazole (MMI) via drinking water, from gestational day 15 to postnatal day (PND) 21. The MMI concentration (w/v) was 0% (control group), 0.01% (low-dose group), or 0.015% (high-dose group). After birth, the pups were individually separated from the dam and littermates on PNDs 5, 10, 15, and 20, and their USVs were recorded for 5min. On PNDs 5 and 10, compared with the control group, the low- and high-dose groups exhibited reductions of both frequency-modulated and downward USVs. On PND 15, however, the low- and high-dose groups displayed increases in number, duration, and amplitude of USVs compared with those in the control group. Lower body weights were observed for the low- and high-dose groups than for the control group. Total thyroxine concentrations in plasma were dose-dependently reduced. The onset of auditory functions appeared on PNDs 11–14. Thus, the rat pups were unable to hear externally produced USVs before PND 11. USVs emitted on PNDs 5 and 10 might have been spontaneous and independent of the pups’ own or littermate-emitted USVs. The developmental retardation of vocalization-related organs or muscles might underlie the acoustic alterations of USVs on PNDs 5 and 10. The greater number, duration, and amplitude of USVs on PND 15, after which the hearing onset occurred, suggested that the elevation of auditory thresholds occurred as a result of hearing deficits in the low- and high-dose groups. Perinatal hypothyroidism appears to have caused acoustic alterations in the USV development.

Loss of auditory sensitivity from inner hair cell synaptopathy can be centrally compensated in the young but not old brain

A dramatic shift in societal demographics will lead to rapid growth in the number of older people with hearing deficits. Poorer performance in suprathreshold speech understanding and temporal processing with age has been previously linked with progressing inner hair cell (IHC) synaptopathy that precedes age-dependent elevation of auditory thresholds. We compared central sound responsiveness after acoustic trauma in young, middle-aged, and older rats. We demonstrate that IHC synaptopathy progresses from middle age onward and hearing threshold becomes elevated from old age onward. Interestingly, middle-aged animals could centrally compensate for the loss of auditory fiber activity through an increase in late auditory brainstem responses (late auditory brainstem response wave) linked to shortening of central response latencies. In contrast, old animals failed to restore central responsiveness, which correlated with reduced temporal resolution in responding to amplitude changes. These findings may suggest that cochlear IHC synaptopathy with age does not necessarily induce temporal auditory coding deficits, as long as the capacity to generate neuronal gain maintains normal sound-induced central amplitudes.

Diaphanous homolog 3 (Diap3) Overexpression Causes Progressive Hearing Loss and Inner Hair Cell Defects in a Transgenic Mouse Model of Human Deafness

We previously demonstrated that a mutation in the 5′ untranslated region of Diaphanous homolog 3 (DIAPH3) results in 2 to 3-fold overexpression of the gene, leading to a form of delayed onset, progressive human deafness known as AUNA1 (auditory neuropathy, nonsyndromic, autosomal dominant, 1). To investigate the mechanism of deafness, we generated two lines of transgenic mice overexpressing Diap3, the murine ortholog of DIAPH3, on an FVB/NJ background. Line 771 exhibits a relatively mild 20 dB hearing loss at 12 kHz at 4 and 8 weeks of age, progressing to 40 dB and 60 dB losses at 16 and 24 weeks, respectively, at 12 and 24 kHz. Line 924 shows no hearing loss at 4 or 8 weeks, but manifests 35 and 50 dB threshold shifts at 16 and 24 weeks, respectively, at both 12 and 24 kHz. Notably, mice from the two transgenic lines retain distortion product otoacoustic emissions, indicative of normal cochlear outer hair cell (OHC) function despite elevation of auditory thresholds. Scanning electron microscopy of the organ of Corti demonstrates striking anomalies of the inner hair cell (IHC) stereocilia, while OHCs are essentially intact. Over time, IHCs of both lines develop elongated stereocilia that appear fused with neighboring stereocilia, in parallel to the time course of hearing loss in each line. Furthermore, we observe significant reduction in the number of IHC ribbon synapses over 24 weeks in both lines, although this reduction does not correlate temporally with onset and progression of hearing loss or stereociliary anomalies. In summary, overexpression of wild-type Diap3 in two lines of transgenic mice results in hearing loss that recapitulates human AUNA1 deafness. These findings suggest an essential role of Diap3 in regulating assembly and/or maintenance of actin filaments in IHC stereocilia, as well as a potential role at the IHC ribbon synapse.

The effects of pegylated interferon/lamivudine therapy on auditory functions in patients with chronic hepatitis B

Objectives The aim of this study was to assess the effects of pegylated interferon monotherapy and pegylated interferon + lamivudine combination therapy on auditory functions in patients with chronic hepatitis B (CHB) infection. Methods A total of 54 patients with a diagnosis of CHB were grouped into four treatment groups: patients in Group 1 received pegylated interferon-alpha 2a; patients in Group 2 received pegylated interferon-alpha 2a + lamivudine; patients in Group 3 received pegylated interferon-alpha 2b, and patients in Group 4 received pegylated interferon-alpha 2b + lamivudine treatment. The auditory system (using standard and high frequency audiometry) and the vestibulocochlear adverse effects including otalgia, tinnitus, vertigo and imbalance were assessed immediately before the onset of the study, and at the 12th, 24th, and 48th weeks of the study. Results A mean elevation of auditory threshold of 1–10 dB was found in all treatment groups when the thresholds at the onset of the study and the thresholds at the 12th, 24th, and 48th weeks were compared. However, the elevations were not significant. The elevations were mostly at high frequencies (10,000, 12,000 and 16,000 Hz). The most common vestibulocochlear adverse effects related to treatment were tinnitus, vertigo, imbalance, and otalgia, respectively. Tinnitus was the most common adverse effect in Group 2, vertigo was the most common in Group 3, imbalance was at equal frequency in Group 2 and 3, and otalgia was the most common adverse effect in Group 2 ( p > 0.05). Conclusion There were no significant auditory adverse effects in the treatment groups. We think that it may be beneficial to monitor the auditory functions in patients receiving PEG-IFN treatment because of the mild elevation in the auditory thresholds (although not significant).

Differential ablation of sensory receptors underlies ototoxin‐induced shifts in auditory thresholds of the goldfish (Carassius auratus)

In recent years, fish models have become popular for investigations of ototoxic agents. However, the vast majority of such studies have focused on anatomical changes in lateral line hair cells after drug administration. Using the goldfish (Carassius auratus), we confirm that the acquisition of auditory evoked potentials offers a rapid and non-invasive method for quantifying ototoxin-induced changes in hearing sensitivity. Gentamicin (100 mg ml(-1)) was the drug of choice as it is a well-studied human ototoxin. Auditory threshold elevation was observed between 300 and 600 Hz and was accompanied by significant reductions in hair cell ciliary bundle densities in specific regions of the utricle and saccule. The correlations between structure and function suggest that differential susceptibility of sensory hair cells to acute gentamicin treatment underlies the frequency-specific elevation of auditory thresholds. We propose that fish auditory systems should be used alongside the lateral line, for the assessment of ototoxicity in new-developed drugs.

Safety and efficacy of carbomethylcellulose foam in guinea pig middle ear surgery

Objective Carbomethylcellulose (CMC) foam has been widely adopted to promote hemostasis and healing in sinus surgery. There has been interest in the use of CMC in middle ear surgery. The purpose of this study was to evaluate the safety and efficacy of CMC foam for use in middle ear surgery. Study Design Prospective, controlled. Setting Academic research laboratory. Subjects and Methods Adult guinea pigs underwent experimental tympanoplasty followed by packing of the middle ear (n = 19 per group) with CMC, hyaluronic acid (HA), or gelatin sponge (GS). Auditory evoked brainstem response testing and otomicroscopy were performed before and serially for eight weeks after surgery. Tympanic membrane healing, hemostasis, and retention of packing material were assessed. Results All tympanic membranes treated with CMC healed by week eight. Less postoperative bleeding was observed with CMC than with HA or GS. Surgery elevated auditory thresholds, at least temporarily, in all groups. However, CMC was associated with greater auditory threshold elevation (15-25 dB) at eight weeks across all test frequencies relative to HA or GS ( P < 0.01). Residual CMC and scarring were not found in the middle ear, indicating that the hearing loss was sensorineural. No head tilt posturing suggestive of vestibulopathy was seen. Conclusion CMC was associated with hearing loss and may be ototoxic. Therefore, CMC should not be used in human middle ears given the presence of several nontoxic alternative materials.

Physiological dimensions of ototoxic responses in a model fish species

Pharmaceutical agents known to be toxic to the human auditory system also impair sensory hair cells of teleosts, and this supports the use of fish models for the screening of such compounds. However, previous investigations have focused almost exclusively on anatomical changes after drug administration without assessing macro-level physiological effects. Using the goldfish ( Carassius auratus), we demonstrate that the acquisition of auditory evoked potentials offers a rapid and non-invasive means for tracking ototoxin-induced shifts in auditory thresholds. Gentamicin (100 mg/mL) was the agent of choice as it is an extensively-studied human ototoxin. Significant shifts ( p < 0.05) in hearing sensitivity were observed between 300 Hz and 600 Hz and these shifts depended on acoustic pressure, but not particle motion. This differential elevation of auditory thresholds may be caused by impairment of specific populations of auditory sensory hair cells.

Prevention of noise- and drug-induced hearing loss with d-methionine

A number of otoprotective agents are currently being investigated. Various types of agents have been found in animal studies to protect against hearing loss induced by cisplatin, carboplatin, aminoglycosides, or noise exposure. For over a decade we have been investigating d-methionine ( d-met) as an otoprotective agent. Studies in our laboratory and others around the world have documented d-met’s otoprotective action, in a variety of species, against a variety of ototoxic insults including cisplatin-, carboplatin-, aminoglycoside- and noise-induced auditory threshold elevations and cochlear hair cell loss. For cisplatin-induced ototoxicity, protection of the stria vascularis has also been documented. Further d-met has an excellent safety profile. d-Met may act as both a direct and indirect antioxidant. In this report, we provide the results of three experiments, expanding findings in d-met protection in three of our translational research areas: protection from platinum based chemotherapy-, aminoglycoside- and noise-induced hearing loss. These experiments demonstrate oral d-met protection against cisplatin-induced ototoxicity, d-met protection against amikacin-induced ototoxicity, and d-met rescue from permanent noise-induced hearing loss when d-met is initiated 1 h after noise exposure. These studies demonstrate some of the animal experiments needed as steps to translate a protective agent from bench to bedside.

Potenciales evocados auditivos de estado estable en el estudio de dos pacientes con neuropatía auditiva

IntroductionWe described the results of the auditory multiple steady state response (MSSR) technique in the assessment of two patients with auditory neuropathy (AN). The aim of this study was to corroborate the correspondence between the MSSR generators elicited by amplitude modulated tones ranging between 80-100 Hz, with the generators of auditory brain stem response (ABR). Moreover, we would also try to demonstrate the validity of the MSSR in the diagnosis of AN in children. Material and MethodsTwo children diagnosed of hyperbilirrubinemia, aged, 18 months and 10 years have been studied with MSSR (500, 1000, 2000 and 4000Hz); ABR with clicks; OAE; behavioural audiometry; MRI and acoustic reflexes. ResultsA difference between electrophysiological and behavioural audiogram in both cases diagnosed with auditory neuropathy have been found. The auditory thresholds were similar using the two types of evoked potentials (MSSR and ABR). Both techniques showed an increment of auditory threshold congruous with a severe auditory impairment, while behavioural audiometry showed only a mild elevation of auditory threshold. We can also see how the threshold differed between frequencies using behavioral audiometry and MSSR. ConclusionIt is concluded that our findings are in agreement with previous studies and they sustain the theory about the coincidence of MSSR at fast rate (80-110 Hz) and ABR generators. Also, we demonstrate the usefulness of the MSSR as an objetive electroaudiometric tool in patients with auditory neuropathy as ABR. This technique is thus a recommendable test to complete the audiological study in infants with AN, to establish a more precise treatment.

Succinate dehydrogenase (SDH) activity in hair cells: a correlate for permanent threshold elevations

Hair cell loss is often used as a histological correlate of hearing loss. However, the histological and the physiological data are not always well correlated. This paper investigates the use of succinate dehydrogenase (SDH) activity in the hair cells as a marker of cellular dysfunction and so the loss of auditory sensitivity. In our previous studies, potentiation of noise-induced auditory threshold elevation by carbon monoxide (CO) was observed [Chen and Fechter, 1999; Chen et al., 1999]. However, its histological basis is still unclear. In this study, rats were exposed to 100-dB octave-band noise (center frequency=13.6 kHz, 2 h) or to the combination of the noise and CO (1200 ppm). Threshold elevation of compound action potential (CAP) and cochlear histological changes were assessed 4 weeks after exposure. The noise alone caused CAP threshold elevations with little if any or without hair cell loss. However, the SDH activity in the hair cells decreased after the exposure. The SDH reduction, especially in the inner hair cells, was well related to the loss of auditory sensitivity. The combined exposure to noise and CO caused more severe CAP threshold elevation and SDH activity reduction than did the noise alone and it also caused significant outer hair cell loss. However, across all the test frequencies, neither the hair cell loss nor the SDH reduction alone had good correlation to the reduction of the auditory sensitivity. Under this situation, CAP threshold elevation seemed to follow OHC loss at high frequencies and to follow SDH reductions in the IHCs at low frequencies, where no hair cell loss occurred.

Steroid-responsive cochlear dysfunction in the MRL/lpr autoimmune mouse

Corticosteroids historically have been used to treat autoimmune sensorineural hearing loss, although little is known of how steroids restore normal inner ear function. Therefore, to identify a potential model for this field of research, this study examined the effects of prednisolone on auditory brain stem response thresholds in the MRL/ lpr mouse model of autoimmune sensorineural hearing loss. Mice treated with prednisolone after auditory threshold elevations demonstrated significant improvement and stabilization of thresholds compared with untreated controls. MRL/ lpr mice treated with steroids before the onset of autoimmune disease and cochlear dysfunction demonstrated decreased serum immune complexes, higher survival rates, and lower auditory thresholds compared with untreated controls. These positive results suggest the autoimmune mouse may be useful for studies of steroid-responsive mechanisms of the cochlea in autoimmune sensorineural hearing loss, as well as any hearing disorder in which steroid therapy is currently used. (Otolaryngol Head Neck Surg 1999;121:344-7.)

Distortion product otoacoustic emissions in the C57BL/6J mouse model of age-related hearing loss

One of the earliest histopathological changes associated with age-related hearing loss appears to be the disruption of outer hair cells (OHCs). To evaluate age-related changes in OHC function, distortion product otoacoustic emissions (DPOAEs) were recorded in the young and aging C57BL/6J mouse. Starting in young adulthood, the C57 mouse displays age-related elevation of auditory brainstem response thresholds, beginning in the high frequencies and progressing toward lower frequencies. The 2f 1-f 2 DPOAEs of mice between 2 and 20 months of age were examined for f 2s between 8 and 16 kHz. In this octave region, the features of 2f 1-f 2 DPOAEs in the 2-month-old C57 mouse were comparable to those described for non-murine rodents in the literature in terms of optimum f 2 f 1 ratio, optimum primary level difference, input/output (I/O) function features and microstructure. It was determined that f 2 f 1 = 1.2 and L 1−L 2 = 20 dB were optimal stimulus parameters for investigation of the effects of age on C57 DPOAEs. Age-related changes in DPOAE I/O functions consisted of a right shift (i.e. increased DPOAE detection thresholds), disappearance of ‘notches’ and shallowing of the slopes after 8 months of age. As DPOAE I/O functions continued to shift to the right and DPOAE levels decreased with age, the appearance of I/O functions became complex to include regions of steep or shallow slopes and plateaus. The present results suggest that the age-related elevation of auditory thresholds in the C57 mice is associated with substantial progressive changes in OHC function.

Pathophysiological mechanisms of hearing loss.

An understanding of auditory transduction in the ear can contribute to a better comprehension of the pathophysiological mechanisms which give rise to hearing loss. The incoming sound sets up a mechanical traveling wave which begins at the base and progresses along the basilar membrane, reaching a point of maximal displacement. The region of maximal displacement is a function of stimulus frequency. The mechanical displacement, by directly opening ion channels in the stereocilia of the hair cells, induces changes in the electrical potential of the hair cells. This initial stage is called mechano-electrical transduction, and in the normal ear, is followed by a stage of electro-mechanical transduction based on the ability of the outer hair cells to respond to the electrical changes induced in them with a change in their length. This "electromotility" presumably provides mechanical feedback to the basilar membrane, augmenting its mechanical displacement. This is called the cochlear amplifier, providing the ear with improved sensitivity and frequency discrimination. Most forms of sensori-neural hearing losses (affecting the inner ear) are due to a lesion to some part of this cochlear amplifier (e.g. noise induced hearing loss, ototoxic drugs) and are therefore characterized by auditory threshold elevations and poorer frequency discrimination.

Morphologic changes in the anteroventral cochlear nucleus of acoustically-deprived gerbil

Microcystic lesions are reported as a neurodegenerative disorder in the cochlear nucleus of the Mongolian gerbil. These lesions resemble the spongioform degeneration. Such lesions are large holes, cavities or vacuoles and are also known as the microcysts. The microcysts develop in the neuropil or appear in the neuronal perikarya, degenerated axons and dendrites. The number and size of the microcysts is greatly reduced either by the elevation of auditory thresholds or by the conductive hearing loss induced by ligation of the external auditory canal. Furthermore, absence of the microcysts is found in the old deaf animals. This study was to investigate the morphologic changes in the anteroventral cochlear nucleus (AVCN) of the acoustically-deprived gerbil following the sequence of time courses after ligation of the external auditory canal during postnatal development.The mongolian gerbil, Meriones unguiculatus, had been acoustically deprived on the right side by a surgical ligation of the external auditory canal at postnatal day 12-14.