Auditory Brainstem Response Thresholds Research Articles

Alpha9alpha10 knockout mice show altered physiological and behavioral responses to signals in masking noise.

Medial olivocochlear (MOC) efferents modulate outer hair cell motility through specialized nicotinic acetylcholine receptors to support encoding of signals in noise. Transgenic mice lacking the alpha9 subunits of these receptors (α9KOs) have normal hearing in quiet and noise, but lack classic cochlear suppression effects and show abnormal temporal, spectral, and spatial processing. Mice deficient for both the alpha9 and alpha10 receptor subunits (α9α10KOs) may exhibit more severe MOC-related phenotypes. Like α9KOs, α9α10KOs have normal auditory brainstem response (ABR) thresholds and weak MOC reflexes. Here, we further characterized auditory function in α9α10KO mice. Wild-type (WT) and α9α10KO mice had similar ABR thresholds and acoustic startle response amplitudes in quiet and noise, and similar frequency and intensity difference sensitivity. α9α10KO mice had larger ABR Wave I amplitudes than WTs in quiet and noise. Other ABR metrics of hearing-in-noise function yielded conflicting findings regarding α9α10KO susceptibility to masking effects. α9α10KO mice also had larger startle amplitudes in tone backgrounds than WTs. Overall, α9α10KO mice had grossly normal auditory function in quiet and noise, although their larger ABR amplitudes and hyperreactive startles suggest some auditory processing abnormalities. These findings contribute to the growing literature showing mixed effects of MOC dysfunction on hearing.

Tone-burst elicited auditory brainstem responses in full-term and pre-term infants

Objective To investigate the reliability of tone-burst auditory brainstem response (TB-ABR) latencies and thresholds in pre-term and full-term infants. Design TB-ABRs to 500 Hz and 4000 Hz tone-burst stimuli were recorded at two-week intervals over the first six weeks of life in a group of full-term infants (40–46 weeks gestational age [GA]) and over ten weeks (36–46 weeks gestation) in a group of preterm infants. Linear mixed model analyses evaluated within-subject changes and the effects of the subject group, age at assessment, and stimulus frequency on ABR latency and threshold. Study sample Twenty-four infants participated. Nine were full-term (GA: 39–41 weeks) and fifteen were healthy pre-term (GA: 28–34 weeks) at birth. Results TB-ABR wave V latencies at 70 dBnHL decreased throughout the study (p < 0.001) in pre-term babies for both test frequencies by approximately 0.5 ms. There were, however, no group or GA (at birth) effects indicating that response latency normalized in these children by the due date. Similarly, TB-ABR threshold levels in the premature group were elevated (p = 0.001) by approximately 5 dB in pre-term evaluation but were equivalent to those of full-term participants in the post-term assessment period. Conclusions In healthy, pre-term infants, tone-burst ABR testing is reliable from 36 weeks gestation.

Audiological Characteristics of Vestibular Schwannoma Patients With Normal Pure-Tone Audiometry.

To investigate the audiological characteristics of vestibular schwannoma (VS) patients with normal pure-tone audiometry (PTA) results. A retrospective study. Forty-two VS patients with normal PTA results from October 2016 to October 2022 were included. Normal PTA was defined when the hearing threshold is ≤25 dB hearing loss (HL) in each test frequency and the PTA is ≤25 dB HL. Results of multiple audiological tests such as the auditory brainstem response (ABR), distortion product otoacoustic emission (DPOAE), multiple auditory steady-state responses threshold (ASSR), and speech discrimination score were retrospectively reviewed. Demographic data of these patients were also been collected. According to our results, the ABR and average ASSR threshold of the affected side were statistically significantly higher in VS patients with normal PTA. ABR waveforms on the affected side also showed more abnormalities. The DPOAE pass rates of the affected side were lower than the unaffected side while the amplitude and signal-to-noise ratio rate was also lower. In addition, we used magnetic resonance imaging 3-dimensional reconstruction images to measure the volume of tumors in these patients. We also found that higher ABR threshold means lager tumor size in patients with normal PTA. VS patients with normal PTA result cannot be assumed to have no impairment of hearing function. ABR, DPOAE, and ASSR results showed the characteristic changes in the affect ear. ABR threshold has the highest sensitivity for hearing abnormalities and is strong relative with tumor size in patients with normal PTA.

Correlation of Grading and Number of Ear Subunits With Auditory Brainstem Response Findings in Children With Microtia.

The association between microtia severity and hearing function has been thoroughly investigated. This study examined the relationship between microtia grade, number of ear subunits (i.e., helix, antihelix, scapha, triangularis fossa, concha, lobule, tragus, and antitragus) with auditory brainstem response (ABR) findings in children with microtia. A retrospective chart review was employed in this study. We analyzed the ABR test results and photographs of 22 children with 30 microtia ears at Dr. Cipto Mangunkusumo National Hospital, Jakarta. The ABR test results were acquired using click (air conduction only) and 500-Hz tone burst stimuli (air- and bone-conduction). Ear photographs were overlaid with a template of a normal ear to determine the number of ear subunits present and the subsequent microtia grade. Number of ear subunits and ABR results were analyzed using the chi-square, Mann-Whitney U, and Spearman's correlation tests. ABR thresholds for click and 500-Hz tone bursts air-conduction were significantly poorer for ears with a subunit < 5 compared to ears with a subunit ≥ 5. No significant difference was observed in 500 Hz bone-conduction ABR thresholds between these groups. Correlation analysis showed a significant negative correlation between increased ear subunits and click ABR thresholds. No significant correlation was found between ear subunits and 500-Hz air- and bone-conduction ABR thresholds. A higher number of ear subunits are associated with a lower hearing threshold, as assessed using ABR with click stimuli. Therefore, the number of ear subunits and microtia grades can be used to examine the hearing level thresholds in infants and children with microtia. https://doi.org/10.23641/asha.25669440.

Photobiomodulation therapy in improvement of harmful neural plasticity in sodium salicylate-induced tinnitus.

Tinnitus is a common annoying symptom without effective and accepted treatment. In this controlled experimental study, photobiomodulation therapy (PBMT), which uses light to modulate and repair target tissue, was used to treat sodium salicylate (SS)-induced tinnitus in a rat animal model. Here, PBMT was performed simultaneously on the peripheral and central regions involved in tinnitus. The results were evaluated using objective tests including gap pre-pulse inhibition of acoustic startle (GPIAS), auditory brainstem response (ABR) and immunohistochemistry (IHC). Harmful neural plasticity induced by tinnitus was detected by doublecortin (DCX) protein expression, a known marker of neural plasticity. PBMT parameters were 808 nm wavelength, 165 mW/cm2 power density, and 99 J/cm2 energy density. In the tinnitus group, the mean gap in noise (GIN) value of GPIAS test was significantly decreased indicated the occurrence of an additional perceived sound like tinnitus and also the mean ABR threshold and brainstem transmission time (BTT) were significantly increased. In addition, a significant increase in DCX expression in the dorsal cochlear nucleus (DCN), dentate gyrus (DG) and the parafloccular lobe (PFL) of cerebellum was observed in the tinnitus group. In PBMT group, a significant increase in the GIN value, a significant decrease in the ABR threshold and BTT, and also significant reduction of DCX expression in the DG were observed. Based on our findings, PBMT has the potential to be used in the management of SS-induced tinnitus.

Echolocating Bats Have Evolved Decreased Susceptibility to Noise-Induced Temporary Hearing Losses.

Glenis Long championed the application of quantitative psychophysical methods to understand comparative hearing abilities across species. She contributed the first psychophysical studies of absolute and masked hearing sensitivities in an auditory specialist, the echolocating horseshoe bat. Her data demonstrated that this bat has hyperacute frequency discrimination in the 83-kHz range of its echolocation broadcast. This specialization facilitates the bat's use of Doppler shift compensation to separate echoes of fluttering insects from concurrent echoes of non-moving objects. In this review, we discuss another specialization for hearing in a species of echolocating bat that contributes to perception of echoes within a complex auditory scene. Psychophysical and behavioral studies with big brown bats show that exposures to long duration, intense wideband or narrowband ultrasonic noise do not induce significant increases in their thresholds to echoes and do not impair their ability to orient through a naturalistic sonar scene containing multiple distracting echoes. Thresholds of auditory brainstem responses also remain low after intense noise exposures. These data indicate that big brown bats are not susceptible to temporary threshold shifts as measured in comparable paradigms used with other mammals, at least within the range of stimulus parameters that have been tested so far. We hypothesize that echolocating bats have evolved a decreased susceptibility to noise-induced hearing losses as a specialization for echolocation in noisy environments.

Effects of Cochlear Implantation and Steroids on the Aging Guinea Pig Cochlea.

The objective was to determine the effects of older age on hearing preservation after cochlear implantation (CI), and whether steroids improve hearing preservation in older animals. We hypothesized greater hearing preservation would be observed in (1) young animals compared to older animals and (2) older animals receiving steroids compared to no steroids. The secondary objective was to assess levels of fibrosis utilizing optical coherence tomography (OCT). Experimental Animal Study. Laboratory. Three groups of guinea pigs: young (YCI; 8.5 ± 0.5 weeks; n = 10), old (OCI; 19.1 ± 1.0 months; n = 9) and old + steroids (OCI+S; 19.1 ± 1.0 months; n = 9) underwent CI. The OCI+S group received a steroid taper over 7 days starting 2 days before surgery to 4 days after. Auditory brainstem response (ABR) measurements were performed preoperatively and postoperatively. OCT imaging was performed to assess cochleae for extent of fibrotic tissue growth in the scala tympani. The YCI group had significantly better hearing preservation as measured by smaller increases in ABR thresholds [mean shift: 2.79 ± 0.66] compared to the OCI group [mean shift = 12.44 ± 5.6]. The OCI+S group had significantly better hearing preservation [2.66 ± 1.50] compared to the OCI group. No significant differences was seen in fibrosis across groups. Young animals and older animals that received steroids had better hearing after CI than older animals not given steroids, but hearing preservation was not correlated with the level of fibrosis assessed using OCT. This work is the first to investigate differences in hearing preservation by age in an animal model, and supports the protective effects of steroids on hearing preservation in older individuals.

The relationship between cleft palate repair technique and audiological outcomes: A retrospective cohort study.

Otitis media with effusion is common in children with cleft palates. This study aimed to investigate the link between palatal closure techniques and audiological outcomes. In this retrospective-prospective cohort study, we examined the relationship between palate repair techniques and hearing outcomes in children with cleft palates. From 2017 to 2022, 190 ears of 95 cleft patients were studied at the Cleft Lip and Palate Department of Shiraz University of Medical Sciences. Variables assessed included the surgical technique, cleft severity, auditory brainstem response (ABR) threshold, and tympanometry configuration. The mean ABR improved from a prepalatoplasty value of 39.51(11.62) decibels (dB) to a postpalatoplasty mean of 26.61(11.60) dB (Cohen's d: 1.12 [95% CI; 0.90-1.34]). Initially, 87.9% of the studied ears exhibited abnormal tympanometry, but this significantly decreased to 47% postsurgery (risk ratio: 4.43 [95% CI; 1.20-16.43]). When compared with Sommerlad intravelar veloplasty, the Nadjmi modified Furlow palatoplasty was associated with a notably lower mean ABR (β: -6.58 [95% CI: -10.43 to -2.73], p-value = .001) and a reduced frequency of abnormal tympanometry (odds ratio [OR]: -1.10; 95% CI: -1.85 to -0.36, p-value = .004). Factors like prepalatoplasty ABR, cleft palate severity, gender, and syndromic did not confound these findings. Although the Nadjmi modified Furlow palatoplasty showed better results, our findings indicate a significant improvement in ABR and tympanometry outcomes for both techniques. Future randomized controlled trials are suggested to confirm the influence of palatal closure techniques on audiological outcomes. 3b.

The transcription factor Pou4f3 is essential for the survival of postnatal and adult mouse cochlear hair cells and normal hearing.

Hair cells (HCs) of the cochlea are responsible for sound transduction and hearing perception in mammals. Genetic mutations in the transcription factor Pou4f3 cause non-syndromic autosomal dominant hearing loss in humans (DFNA15) which varies in the age of onset depending on the individual mutation. Mouse models with germline deletion or mutations in Pou4f3 have previously demonstrated its critical role in the maturation and survival of cochlear HCs during embryonic development. However, the role of Pou4f3 in auditory function and in the survival or maintenance of cochlear HCs after birth and during adulthood has not been studied. Therefore, using the inducible CreER-loxP system, we deleted Pou4f3 from mouse cochlear HCs at different postnatal ages, relevant to specific stages of HC maturation and hearing function. Elevated auditory brainstem response thresholds and significant HC loss were detected in mice with Pou4f3 deletion compared to their control littermates, regardless of the age when Pou4f3 was deleted. However, HC loss occurred more rapidly when Pou4f3 was deleted from immature HCs. Additionally, HC loss caused by Pou4f3 deletion did not affect the number of cochlear supporting cells, but caused a delayed loss of spiral ganglion neurons at 4 months after the deletion. In conclusion, Pou4f3 is necessary for the survival of cochlear HCs and normal hearing at all postnatal ages regardless of their maturation state. Our data also suggest that Pou4f3 indirectly regulates the survival of spiral ganglion neurons.

Sound elicits stereotyped facial movements that provide a sensitive index of hearing abilities in mice

Sound elicits rapid movements of muscles in the face, ears, and eyes that protect the body from injury and trigger brain-wide internal state changes. Here, we performed quantitative facial videography from mice resting atop a piezoelectric force plate and observed that broadband sounds elicited rapid and stereotyped facial twitches. Facial motion energy (FME) adjacent to the whisker array was 30 dB more sensitive than the acoustic startle reflex and offered greater inter-trial and inter-animal reliability than sound-evoked pupil dilations or movement of other facial and body regions. FME tracked the low-frequency envelope of broadband sounds, providing a means to study behavioral discrimination of complex auditory stimuli, such as speech phonemes in noise. Approximately 25% of layer 5-6 units in the auditory cortex (ACtx) exhibited firing rate changes during facial movements. However, FME facilitation during ACtx photoinhibition indicated that sound-evoked facial movements were mediated by a midbrain pathway and modulated by descending corticofugal input. FME and auditory brainstem response (ABR) thresholds were closely aligned after noise-induced sensorineural hearing loss, yet FME growth slopes were disproportionately steep at spared frequencies, reflecting a central plasticity that matched commensurate changes in ABR wave 4. Sound-evoked facial movements were also hypersensitive in Ptchd1 knockout mice, highlighting the use of FME for identifying sensory hyper-reactivity phenotypes after adult-onset hyperacusis and inherited deficiencies in autism risk genes. These findings present a sensitive and integrative measure of hearing while also highlighting that even low-intensity broadband sounds can elicit a complex mixture of auditory, motor, and reafferent somatosensory neural activity.

A preliminary study of the mechanism of compound hearing loss caused by ototoxic drugs combined with impulse noise

AbstractBackgroundHearing loss (HL) is becoming increasingly common and is more commonly caused by noise, ototoxic substances, or a combination of ototoxic factors. However, so far, few studies have examined the mechanism by which compound factors cause HL. The only relevant study is about occupational ototoxic substances combined with environmental noise at 85–110 dB SPL. In this study, to address the shortcomings of existing research, we innovatively focused on HL induced by loud noise (impulse noise, &gt;160 dB SPL) combined with common ototoxic drugs. The aim of this study was to establish and validate a mature animal model, and then to compare the characteristics of audiology, pathomorphology and molecular features, and to preliminarily predict pathogenesis in compound HL.Materials and MethodsWe selected guinea pigs to construct in vivo HL model groups for different extents of exposure, including a blank control group, a single‐drug group, a single‐impulse noise group, and a compound group. The animal model of the mature compound HL group was established using gentamicin combined with impulse noise. We then performed audiological and pathological verification. We analyzed the auditory brainstem response (ABR), pathological morphology of the cochlea, and molecules (including important self‐radicals, cytokines, and apoptosis signal transduction pathway proteins in the pathogenesis of drug‐ and noise‐induced HL), compared the effect of different extents of exposure on HL, and preliminarily predict the pathogenic mechanism of compound HL.ResultsFour groups of animal models were established successfully and verified by audiology and pathology. Regarding audiology, there were no significant differences in the ABR thresholds before exposure (p &gt; 0.05), but differences emerged among the groups after exposure. Notably, after 3, 7, and 14 days of exposure, there were significant differences in the ABR thresholds between the compound group and both the drug and noise groups (p &lt; 0.01), and after 14 days, the HL of the compound group was much more severe (greater than the linear sum of single‐factor HL group). Regarding the pathomorphology, compared with the control group, the cochleae were damaged to different degrees in the factor exposure groups. The drug group had the least severe HL, the noise group had serious HL (p &lt; 0.05), and the compound group had the most severe HL (p &lt; 0.01). The compound group's damage was greater than the linear sum of the single‐factor group in many ways, such as the loss and damage of hair cells and cilia, disturbed morphology and arrangement of hair cells, protein metabolism, cell function, and structural defects on the epidermal plate (p &lt; 0.01). From a molecular perspective, the trend was similar to pathology and audiology, and the synergistic effect of ototoxic drugs and impulse noise significantly increased cytokine levels (IL‐6, ICAM‐1,8‐OHDG, IL‐1, and TNF‐α), free radicals Malondialdehyde ([MDA], ▪OH, LPO, O•2ˉ), and the apoptosis signal transduction pathway protein. There were significant differences between the compound group and single‐factor groups (p &lt; 0.05).ConclusionGentamicin, impulse noise, and compound factors were used to induce HL in animal models, which were verified by audiology and pathology, laying a foundation for future studies. After constructing the animal models, we found that 50 mg/kg of gentamicin for 10 days was a subinjury dose, and 50× impulse noise caused partial HL, but the two factors combined had a significant synergistic ototoxicity effect, which increased the level of oxidative stress and the waterfall response of inflammatory cytokines in the cochleae and enhanced the expression of apoptosis‐related proteins, resulting in synergistic pathomorphological and audiological injury. We preliminarily analyzed the pathogenic mechanism of compound HL, establishing the basis for further study of the mechanism, prevention, and treatment of this increasing global problem.

Early-Onset Hearing Loss in Mouse Models of Alzheimer's Disease and Increased DNA Damage in the Cochlea.

There is considerable interest in whether sensory deficiency is associated with the development of Alzheimer's disease (AD). Notably, the relationship between hearing impairment and AD is of high relevance but still poorly understood. In this study, we found early-onset hearing loss in two AD mouse models, 3xTgAD and 3xTgAD/Polβ+/-. The 3xTgAD/Polβ+/- mouse is DNA repair deficient and has more humanized AD features than the 3xTgAD. Both AD mouse models showed increased auditory brainstem response (ABR) thresholds between 16 and 32 kHz at 4 weeks of age, much earlier than any AD cognitive and behavioral changes. The ABR thresholds were significantly higher in 3xTgAD/Polβ+/- mice than in 3xTgAD mice at 16 kHz, and distortion product otoacoustic emission signals were reduced, indicating that DNA damage may be a factor underlying early hearing impairment in AD. Poly ADP-ribosylation and protein expression levels of DNA damage markers increased significantly in the cochlea of the AD mice but not in the adjacent auditory cortex. Phosphoglycerate mutase 2 levels and the number of synaptic ribbons in the presynaptic zones of inner hair cells were decreased in the cochlea of the AD mice. Furthermore, the activity of sirtuin 3 was downregulated in the cochlea of these mice, indicative of impaired mitochondrial function. Taken together, these findings provide new insights into potential mechanisms for hearing dysfunction in AD and suggest that DNA damage in the cochlea might contribute to the development of early hearing loss in AD.

Ototoxicity of polystyrene nanoplastics in mice, HEI-OC1 cells and zebrafish.

Polystyrene nanoplastics are a novel class of pollutants. They are easily absorbed by living organisms, and their potential toxicity has raised concerns. However, the impact of polystyrene nanoplastics on auditory organs remains unknown. Here, our results showed that polystyrene nanoplastics entered the cochlea of mice, HEI-OC1 cells, and lateral line hair cells of zebrafish, causing cellular injury and increasing apoptosis. Additionally, we found that exposure to polystyrene nanoplastics resulted in a significant elevation in the auditory brainstem response thresholds, a loss of auditory sensory hair cells, stereocilia degeneration and a decrease in expression of Claudin-5 and Occludin proteins at the blood-lymphatic barrier in mice. We also observed a significant decrease in the acoustic alarm response of zebrafish after exposure to polystyrene nanoplastics. Mechanistic analysis revealed that polystyrene nanoplastics induced up-regulation of the Nrf2/HO-1 pathway, increased levels of malondialdehyde, and decreased superoxide dismutase and catalase levels in cochlea and HEI-OC1 cells. Furthermore, we observed that the expression of ferroptosis-related indicators GPX4 and SLC7A11 decreased as well as increased expression of ACLS4 in cochlea and HEI-OC1 cells. This study also revealed that polystyrene nanoplastics exposure led to increased expression of the inflammatory factors TNF-α, IL-1β and COX2 in cochlea and HEI-OC1 cells. Further research found that the cell apoptosis, ferroptosis and inflammatory reactions induced by polystyrene nanoplastics in HEI-OC1 cells was reversed through the pretreatment with N-acetylcysteine, a reactive oxygen species inhibitor. Overall, our study first discovered and systematically revealed the ototoxicity of polystyrene nanoplastics and its underlying mechanism.

Assessment of Interaural Attenuation in Infants and Young Children Using Bone-Conducted Auditory Brainstem Response.

In hearing assessment, the term interaural attenuation (IAA) is used to quantify the reduction in test signal intensity as it crosses from the side of the test ear to the nontest ear. In the auditory brainstem response (ABR) testing of infants and young children, the size of the IAA of bone-conducted (BC) stimuli is essential for the appropriate use of masking, which is needed for the accurate measurement of BC ABR thresholds. This study aimed to assess the IAA for BC ABR testing using 0.5 to 4 kHz narrowband (NB) CE-chirp LS stimuli in infants and toddlers with normal hearing from birth to three years of age and to examine the effects of age and frequency on IAA. A total of 55 infants and toddlers with normal hearing participated in the study. They were categorized into three age groups: the young group (n = 31, infants from birth to 3 mo), middle-aged group (n = 13, infants aged 3-12 mo), and older group (n = 11, toddlers aged 12-36 mo). The participants underwent BC ABR threshold measurements for NB CE-chirp LS stimuli at 0.5 to 4 kHz. For each participant, one ear was randomly defined as the "test ear" and the other as the "nontest ear." BC ABR thresholds were measured under two conditions. In both conditions, traces were recorded from the channel ipsilateral to the test ear, whereas masking was delivered to the nontest ear. In condition A, the bone oscillator was placed on the mastoid of the test ear, whereas in condition B, the bone oscillator was placed on the mastoid contralateral to the test ear. The difference between the thresholds obtained under conditions A and B was calculated to assess IAA. The means of IAA (and range) in the young age group for the frequencies 0.5, 1, 2, and 4 kHz were 5.38 (0-15) dB, 11.67 (0-30) dB, 21.15 (10-40) dB, and 23.53 (15-35) dB, respectively. Significant effects were observed for both age and frequency on BC IAA. BC IAA levels decreased with age from birth to 36 mo. In all age groups, smaller values were observed at lower frequencies and increased values were observed at higher frequencies. BC IAA levels were both age and frequency dependent. The study found that the BC IAA values for lower stimulus frequencies were smaller than previously assumed, even in infants younger than 3 mo. These results suggest that masking should be applied in BC ABR threshold assessments for NB CE-chirp LS stimuli at 0.5, 1, and 2 kHz, even in young infants. Masking may not be necessary for testing at 4 kHz if a clear response is obtained at 15 dB normal-hearing level (nHL) in infants younger than 3 mo.

The human OPA1delTTAG mutation induces adult onset and progressive auditory neuropathy in mice

Dominant optic atrophy (DOA) is one of the most prevalent forms of hereditary optic neuropathies and is mainly caused by heterozygous variants in OPA1, encoding a mitochondrial dynamin-related large GTPase. The clinical spectrum of DOA has been extended to a wide variety of syndromic presentations, called DOAplus, including deafness as the main secondary symptom associated to vision impairment. To date, the pathophysiological mechanisms underlying the deafness in DOA remain unknown. To gain insights into the process leading to hearing impairment, we have analyzed the Opa1delTTAG mouse model that recapitulates the DOAplus syndrome through complementary approaches combining morpho-physiology, biochemistry, and cellular and molecular biology. We found that Opa1delTTAG mutation leads an adult-onset progressive auditory neuropathy in mice, as attested by the auditory brainstem response threshold shift over time. However, the mutant mice harbored larger otoacoustic emissions in comparison to wild-type littermates, whereas the endocochlear potential, which is a proxy for the functional state of the stria vascularis, was comparable between both genotypes. Ultrastructural examination of the mutant mice revealed a selective loss of sensory inner hair cells, together with a progressive degeneration of the axons and myelin sheaths of the afferent terminals of the spiral ganglion neurons, supporting an auditory neuropathy spectrum disorder (ANSD). Molecular assessment of cochlea demonstrated a reduction of Opa1 mRNA level by greater than 40%, supporting haploinsufficiency as the disease mechanism. In addition, we evidenced an early increase in Sirtuin 3 level and in Beclin1 activity, and subsequently an age-related mtDNA depletion, increased oxidative stress, mitophagy as well as an impaired autophagic flux. Together, these results support a novel role for OPA1 in the maintenance of inner hair cells and auditory neural structures, addressing new challenges for the exploration and treatment of OPA1-linked ANSD in patients.

Effect of 2.45 GHz Microwave Radiation on the Inner Ear: A Histopathological Study on 2.45 GHz Microwave Radiation and Cochlea.

The present study aims to determine the possible low dose-dependent adverse effects of 2.45 GHz microwave exposure and Wi-Fi frequency on the cochlea. Twelve pregnant female rats (n=12) and their male newborns were exposed to Wi-Fi frequencies with varying electric field values of 0.6, 1.9, 5, 10 V/m, and 15 V/m during the 21-day gestation period and 45 days after birth, except for the control group. Auditory brainstem response testing was performed before exposure and sacrification. After removal of the cochlea, histopathological examination was conducted by immunohistochemistry methods using caspase (cysteine-aspartic proteases, cysteine aspartates, or cysteine-dependent aspartate-directed proteases)-3, -9, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Kruskal-Wallis and Wilcoxon tests and multivariate analysis of variance were used. Auditory brainstem response thresholds in postexposure tests increased statistically significantly at 5 V/m and above doses. When the number of apoptotic cells was compared in immunohistochemistry examination, significant differences were found at 10 V/m and 15 V/m doses (F(5,15)=23.203, P=.001; Pillai's trace=1.912, η2=0.637). As the magnitude of the electric field increased, all histopathological indicators of apoptosis increased. The most significant effect was noted on caspase-9 staining (η2 c9=0.996), followed by caspase-3 (η2 c3=0.991), and TUNEL staining (η2 t=0.801). Caspase-3, caspase-9, and TUNEL-stained cell densities increased directly by increasing the electric field and power values. Apoptosis and immune activity in the cochlea depend on the electric field and power value. Even at low doses, the electromagnetic field in Wi-Fi frequency damages the inner ear and causes apoptosis.

Audiogram Estimation by Auditory Brainstem Response with NB CE-Chirp LS stimulus in Normal Hearing Infants.

Introduction NB CE-Chirp LS was developed to improve the audiogram estimation by auditory brainstem response (ABR) thresholds during audiological assessment of infants and difficult to test children. However, before we know how the stimulus behaves in several types of hearing loss, it is important we know how the stimulus behaves in normal hearing infants. Objective To describe ABR thresholds with NB CE-Chirp LS stimulus for 500, 1,000, 2,000, and 4,000 Hz, as well as the amplitude and absolute latency for ABR thresholds. Methods Auditory brainstem response thresholds were evaluated with the Eclipse EP25 system. NB CE-Chirp LS was presented using an ER-3A insert earphone. EEG filter was 30 Hz high-pass and 1,500 Hz low-pass. The ABR threshold was defined as the lowest intensity capable of clearly evoke wave V, accompanied by an absent response 5 dB below. Results Eighteen normal hearing infants were evaluated. The mean and standard deviation (SD) of the ABR threshold (dB nHL) were: 23.8 (±4.2); 14.4 (±5.7); 6.0 (±5.0); and 7.0 (±5.9). The mean and SD of the absolute latency (ms) were: 8.86 (±1.12); 9.21 (±0.95); 9.44 (±0.78); and 9.64 (±0.52). The mean amplitude (nV) and SD were: 0.123 (±0.035); 0.127 (±0.039); 0.141 (±0.052); and 0.105 (±0.028), respectively, for 500, 1,000, 2,000 and 4,000 Hz. Conclusion Auditory brainstem response threshold with NB CE-Chirp LS reaches low levels, in special for high frequencies. It provides absolute latencies similar between frequencies with robust amplitude. The results obtained brings to the examiner more confidence in the results registered.

GRP78 protein metabolism in obese and diabetic rats: a study of its role in metabolic disorders

ObjectiveThis study aimed to compare and analyze the expression and significance of the GRP78 protein in cochlear cell injury induced by a high glucose and high-fat diet in obese and diabetic rats.MethodsMale SD rats were randomly divided into two groups: normal (NC) and high-fat (HF) groups. The NC group was fed a standard diet for eight weeks, while the HF group received a high-glucose, high-fat diet. The HF group was further categorized into the obesity group (OB group) and the type II diabetes mellitus group (T2DM group). To induce a type II diabetes mellitus (T2DM) model, the T2DM group received an intraperitoneal injection of a small dose of STZ (45 mg/kg). After four weeks on the original diet, body weight, blood glucose, blood lipid levels, and auditory brainstem response (ABR) thresholds were measured. The cochlea was dissected, and its morphology was observed using HE staining. Immunohistochemistry and western blotting were utilized to examine the expression level of the GRP78 protein in the cochlea.Results(1) The ABR threshold demonstrated a statistically significant difference between the T2DM group and the OB group (P < 0.05), as well as between the OB group and the NC group (P < 0.05). (2) Based on morphological comparisons from HE-stained sections, the T2DM group exhibited the most significant alterations in the number of cells in the spiral ganglion, the organ of Corti, and the stria vascularis of the cochlea. (3) The expression level of the GRP78 protein in the cochlea was higher in the T2DM group compared to the OB group (P < 0.05) and higher in the OB group compared to the NC group (P < 0.05).ConclusionThe findings indicate that the GRP78 protein plays a role in hearing loss caused by T2DM and hyperlipidemia. Moreover, T2DM is more likely than hyperlipidemia to be associated with hearing impairment.

Study on gene therapy for DPOAE and ABR threshold changes in adult Otof-/- mice

Objective:This study aims to analyze the threshold changes in distortion product otoacoustic emissions（DPOAE） and auditory brainstem response（ABR） in adult Otof-/- mice before and after gene therapy, evaluating its effectiveness and exploring methods for assessing hearing recovery post-treatment. Methods:At the age of 4 weeks, adult Otof-/- mice received an inner ear injection of a therapeutic agent containing intein-mediated recombination of the OTOF gene, delivered via dual AAV vectors through the round window membrane（RWM）. Immunofluorescence staining assessed the proportion of inner ear hair cells with restored otoferlin expression and the number of synapses.Statistical analysis was performed to compare the DPOAE and ABR thresholds before and after the treatment. Results:AAV-PHP. eB demonstrates high transduction efficiency in inner ear hair cells. The therapeutic regimen corrected hearing loss in adult Otof-/- mice without impacting auditory function in wild-type mice. The changes in DPOAE and ABR thresholds after gene therapy are significantly correlated at 16 kHz. Post-treatment,a slight increase in DPOAE was observeds,followed by a recovery trend at 2 months post-treatment. Conclusion:Gene therapy significantly restored hearing in adult Otof-/- mice, though the surgical delivery may cause transient hearing damage. Precise and gentle surgical techniques are essential to maximize gene therapy's efficacy.

Genetic characteristic analysis of slight-to-moderate sensorineural hearing loss in children

Objective:To analyze genetic factors and phenotype characteristics in pediatric population with slight-to-moderate sensorineural hearing loss. Methods:Children with slight-to-moderate sensorineural hearing loss of and their parents, enrolled from the Chinese Deafness Genome Project, were studied. Hearing levels were assessed using pure tone audiometry, behavioral audiometry, auditory steady state response（ASSR）, auditory brainstem response（ABR） thresholds, and deformed partial otoacoustic emission（DPOAE）. Classification of hearing loss is according to the 2022 American College of Medical Genetics and Genomics（ACMG） Clinical Practice Guidelines for Hearing Loss. Whole exome sequencing（WES） and deafness gene Panel testing were performed on peripheral venous blood from probands and validations were performed on their parents by Sanger sequencing. Results:All 134 patients had childhood onset, exhibiting bilateral symmetrical slight-to-moderate sensorineural hearing loss, as indicated by audiological examinations. Of the 134 patients, 29（21.6%） had a family history of hearing loss, and the rest were sporadic patients. Genetic causative genes were identified in 66（49.3%） patients. A total of 11 causative genes were detected, of which GJB2 was causative in 34 cases（51.5%）, STRC in 10 cases（15.1%）, MPZL2 gene in six cases（9.1%）, and USH2A in five cases（7.6%）.The most common gene detected in slight-to-moderate hearing loss was GJB2, with c. 109G>A homozygous mutation found in 16 cases（47.1%） and c. 109G>A compound heterozygous mutation in 9 cases（26.5%）. Conclusion:This study provides a crucial genetic theory reference for early screening and detection of mild to moderate hearing loss in children, highlighting the predominance of recessive inheritance and the significance of gene like GJB2, STRC, MPZL2, USH2A.