THE EFFECTS OF SALICYLATE ON AUDITORY EVOKED POTENTIAL AMPLITWDE FROM THE AUDITORY CORTEX AND AUDITORY BRAINSTEM

Tinnitus has often been studied using salicylate in animal models as they are capable of inducing tempo-rary hearing loss and tinnitus. Studies have recently observed enhancement of auditory evoked responses of the auditory cortex (AC) post salicylate treatment which is also shown to be related to tinnitus like behavior in rats. The aim of this study was to observe if enhancements of the AC post salicylate treatment are also present at structures in the brainstem. Four male Sprague Dawley rats with AC implanted electrodes were tested for both AC and auditory brainstem response (ABR) recordings pre and post 250 mg/kg intraperitone-al injections of salicylate. The responses were recorded as the peak to trough amplitudes of P1-N1 (AC), ABR wave V, and ABR waveⅡ. AC responses resulted in statistically significant enhancement of ampli-tude at 2 hours post salicylate with 90 dB stimuli tone bursts of 4, 8, 12, and 20 kHz. Wave V of ABR re-sponses at 90 dB resulted in a statistically significant reduction of amplitude 2 hours post salicylate and a mean decrease of amplitude of 31%for 16 kHz. WaveⅡamplitudes at 2 hours post treatment were signifi-cantly reduced for 4, 12, and 20 kHz stimuli at 90 dB SPL. Our results suggest that the enhancement chang-es of the AC related to salicylate induced tinnitus are generated superior to the level of the inferior colliculus and may originate in the AC.

AUDITORY BRAINSTEM RESPONSES IN SENILE PRESBYCUSIS PATIENTS OVER 90 YEARS

Objective To analyze the characteristics of auditory brainstem response (ABR) in presbycusis patients el-der than 90 years. Methods Fourteen presbycusis patients elder than 90 years (presbycusis group, 91.1.4 ± 1.3 years, 26 ears) and 9 normal-hearing young adults (control group, 22.7 ± 1.2 years, 18 ears) participated in the study. Alternative click-evoked ABRs were recorded in both groups. The peak latency (PL) of peak I,Ⅲ, and V, and the inter-peak latency (IPI) of I-Ⅲ,Ⅲ-V, and I-V were compared between groups. Results In elder presbycusis patients, the occurrence rate of peak I andⅢwere both 76.9%, and that of peak V was 84.6%. In presbycusis group, the peak latencies of I, Ⅲ, V were significantly longer than that of control group (P<0.001). There was no significant difference between groups in the IPI of peak I-IⅢ (P=0.298, peakⅢ-V (P=0.254) and peak I-V (P=0.364). Conclusions Auditory brainstem responses in presbycusis pa-tients elder than 90 years showed worse wave differentiation.

Effects of glutamate on distortion-product otoacoustic emissions and auditory brainstem responses in guinea pigs

Objectives To investigate changes in evoked potentials and structure of the guinea pig cochleae during whole cochlear perfusion with glutamate. Methods CM, CAP, DPOAE, and ABR were recorded as indicators of cochlear functions during whole cochlear perfusion. The morphology of the cochlea was studied via transmission electron microscopy. Results There were no significant changes in DPOAE amplitude before and after glutamate perfusion. CM I/O function remained nonlinear during perfusion. ABR latencies were delayed following glutamate perfusion. The average CAP threshold was elevated 35 dB SPL following glutamate perfusion.. The OHCs appeared normal, but the IHCs and afferent dendrites showed cytoplasmic blebs after glutamate perfusion. Conclusions While being a primary amino acid neurotransmitter at the synapses between hair cells and spiral ganglion neurons, excessive glutamate is neurotoxic and can destroy IHCs and spiral ganglion neurons. The technique used in this study can also be used to build an animal model of auditory neuropathy.

Universal newborn hearing screening program in Saudi Arabia: Current insight

Newborn hearing screening(NHS) programs are essential to identify hearing loss early in life and to improve outcomes in children. In Saudi Arabia, the national NHS program has been operational since 2016;however, few studies have evaluated its status, and none have covered all provinces across the country. This cross-sectional retrospective study provides an overview of the program's status across all provinces, focusing on screening coverage rates, referral/fail rates, and follow-up procedures. In 2021, 199,034 newborns were screened, with a coverage rate of 92.6% and an overall referral/fail rate of 1.87%. These performance measures provide a foundation for future progress and improvements. This study highlights the importance of ongoing efforts to enhance the program's effectiveness and sustainability.

Circadian Rhythm and Intersexual Differences in Auditory Frequency Sensitivity in Emei Music Frogs

In anurans, calling behaviour is strongly seasonal and circadian. Previous studies have revealed that a uditory sensitivity in frogs exhibits seasonal plasticity, and electroencephalographic signals exhibit highly correlated circadian patterns;of which, the circadian rhythm remains unknown. In this study,the circadian rhythm and intersexual differences of auditory sensitivity were tested in the Emei music frog(Nidirana daunchina). This was achieved by comparing thresholds and latencies of auditory brainstem responses(ABRs) evoked by tones and clicks stimuli between male and female frogs during the day and at night,respectively. Our results revealed that both auditory thresholds and latencies had no differences between day and night except the la tencies in 3.5–4.0 kHz frequencies. However, the thresholds of tone pip evoked ABRs differed significantly between male and female frogs from 2.5 to 5.0 kHz. This demonstrated that the auditory sensitivity of Emei music frogs exhibits sexual dimorphism at high frequencies, with female frogs exhibiting greater auditory sensitivity than that of male frogs. Simultaneously, the power spectra of male advertisement calls are matched well with the frequency range of auditory sensitivity in male and female frogs,which supports the matched filter hypothesis. Our study enhances the understanding of circadian plasticity and sexual dimorphism of auditory sensitivity in frogs.

Neurophysiological characteristics in infants and young children with auditory neuropathy

Objective:To analyze neurophysiological characteristics in infants and young children with auditory neuropathy(AN) and explore their clinical significance.Methods: Audiological measurements(acoustic immittance, EOAEs, ABR, CM, MLR and ERPs) and peripheral neurological tests were conducted and evaluated in 13 infants and young children with AN. Six of them received high-resolution temporal bone CT scans and/or cerebral MRI examinations.Results: All of the children showed type “A” tympanograms with abseatation of stapedial reflexes. EOAEs were normal in 12 of 13 subjects. In one child who had a history of anoxia during the birth,the EOAEs were not elicited. Click-evoked ABRs were absent in 12 of 13 subjects when maximum output of the instrument was reached. The CM potentials were presented bilaterally in all individuals,which were independent of the EOAEs and ABR. Of eight cases tested,all had clear MLR and six showed normal ERPs(P300 and MMN). Peripheral neurological tests and radiological findings were within the normal ranges. Conclusion: The diagnosis of AN in infants and young children should focus on analyzing their neurophysiological characteristics,especially on CM,MLR and ERPs. Combined use of EOAEs, ABR and CM was recommended for hearing screening on newborns with high risk factors.

The effect of acupuncture at “Jǐng Jiājǐ”(颈夹脊) on auditory brainstem response threshold of guinea pigs with sensorineural hearing loss

Objective To explore the effect of acupuncture at ＂Jing Jiaji＂ （颈夹背） on sudden hearing loss by observing the changes of the threshold of auditory brainstem response （ABR） of deaf guinea pigs. Methods Sixty healthy guinea pigs were selected, with computer randomization, 20 were randomly divided into a normal control group （group A）, while the rest were randomly and equally divided into a model group （group B） and an acupuncture group （group C） when turned deaf after gentamycin sulfate and furosemide were administered. No treatment was administered for either the group A or the group B, while acupuncture at ＂Jing Jiaji＂ was given for the group C for 30 days. The ABR thresholds of each group were observed and recorded separately after the treatment for 15 days and 30 days. Results The ABR threshold in the group C was lower than that in the group B after the treatment of 15 days （P〈O.05）. After the treatment of 30 days, the ABR threshold in the group C was obviously lower than that in the group B （P〈0.01）, and was obviously lower than that before acupuncture （P〈0.01）. Conclusion Acupuncture at ＂Jing Jiaji＂ has definite effect on improving the hearing of deaf guinea pigs.

用AP-N_1(或ABR波I)潜伏期检测响度重振

本文对50例平坦型感音神经性聋病人用声反射阈以及AP-N_1潜伏期检查响度重振进行了分析,结果显示:声反射阈重振阳性率为76％,纯音听阈与声反射阈阳性率的关系为:随着听阈的增高声反射阈阳性率下降;耳蜗电图在高声强时AP-N_1潜伏期完全在正常范围的占56％,若以患耳与正常耳在同一阈上dB数比较,则100％小于正常耳,显示重振阳性。如果两指标结合检测,响度重振阳性率也明显提高。我们认为用AP-N_1潜伏期检测响度重振方法可行、理论依据充分,且用它检测响度重振的阳性率明显高于声反射阈。

Calpain mediated cisplatin-induced ototoxicity in mice

Ototoxic drug-induced apoptosis of inner ear cells has been shown to be associated with calpain expression. Cisplatin has severe ototoxicity, and can induce cochlear cell apoptosis. This study assumed that cisplatin activated calpain expression in apoptotic cochlear cells. A mouse model of cisplatin-induced ototoxicity was established by intraperitoneal injection with cisplatin （2.5, 3.5, 4.5, 5.5 mg/kg）. Immunofluorescence staining, image analysis and western blotting were used to detect the expression of calpain 1 and calpain 2 in the mouse cochlea. At the same time, the auditory brainstem response was measured to observe the change in hearing. Results revealed that after intraperitoneal injection with cisplatin for 5 days, the auditory brainstem response threshold shifts increased in mice. Calpain 1 and calpain 2 expression significantly increased in outer hair cells, the spiral ganglion and stria vascularis. Calpain 2 protein expression markedly increased with an increased dose of cisplatin. Results suggested that calpain 1 and calpain 2 mediated cisplatin-induced ototoxicity in BALB/c mice. During this process, calpain 2 plays a leading role.

Mechanism of alpha-lipoic acid in attenuating kanamycin-induced ototoxicity

In view of the theory that alpha-lipoic acid effectively prevents cochlear cells from injury caused by various factors such as cisplatin and noise, this study examined whether alpha-lipoic acid can prevent kanamycin-induced ototoxicity. To this end, healthy BALB/c mice were injected subcutaneously with alpha-lipoic acid and kanamycin for 14 days. Auditory brainstem response test showed that increased auditory brainstem response threshold shifts caused by kanamycin were significantly inhibited. Immunohistochemical staining and western blot analysis showed that the expression of phosphorylated p38 mitogen-activated protein kinase and phosphorylated c-Jun N-terminal kinase in mouse cochlea was significantly decreased. The experimental findings suggest that phosphorylated p38 and phosphorylated c-Jun N-terminal kinase mediated kanamycin-induced ototoxic injury in BALB/c mice. AIpha-lipoic acid effectively attenuated kanamycin ototoxicity by inhibiting the kanamycin-induced high expression of phosphorylated p38 and phosphorylated c-Jun N-terminal kinase.

A Model of Spontaneous Chronic Otitis Media with Effusion in Mice with ENU Induced Mutations

Background Chronic otitis media(COM) is a significant clinical problem.Understanding the mechanisms of COM is critical for its control and treatment.However,little is known of the processes leading to COM as a result of lack of animal models of N-ethyl-N-nitrosourea(ENU) induced mutations in otitis media with effusion(OME).Methods Otoscopy and auditory brain response(ABR) evaluation were carried out under sedation in Nmf391nmf/nmf mice of 2,4,6 and 8 months of age.The mice were killed for study of middle and inner ear pathology.Results Tympanic membrane visualization and ABR thresholds in 1-to 8-month-old Nmf391nmf/nmf mice showed spontaneous OME and inner ear diseases in approximately 100% of the animals.The significant elevation of ABR thresholds suggested a sensorineural component in hearing loss in addition to the conductive loss.Middle and inner ear histology showed various degrees of outer hair cells loss and middle ear inflammation in all the mice,but no inflammation cells in the inner ear.The ABR threshold at 32 kHz was significantly elevated.Conclusions This study shows histopathologic changes in the Nmf391nmf/nmf mouse model of COM with effusion that have not been reported in human COM.This ENU induced mutation model of COM will be valuable for the characterization of middle ear inflammation and inner ear disease processes that are induced by middle ear infections.We propose that COM with effusion in this ENU induced mutation model is the cause of the cochlea hair cells damage.

Obstructive Sleep Apnea-Hypopnea Ssyndrome and Hearing in Children

Objective To explore the relationship between hypoxemia and hearing in children with obstructive sleep apnea-hypopnea syndrome. Methods Auditory brainstem responses (ABRs) were recorded in 68 ears and distortion product otoacoustic emissions (DPOAEs) in 60 ears in children with OSAHS and type "A" tym-panograms, and in 30 ears in normal children. Results ABR latencies of waves I, III and V, and I-III, III-V and I-V intervals were not statistically different between OSAHS and normal children. Wave I latency was delayed in children with OSAHS compared to normal children3 (P < 0.05). DPOAE amplitudes in children with mild OSAHS were lower than normal children at 8 kHz (P < 0.05). DPOAEs were lower at 6 kHz and 8 kHz in children with moderate/severe OSAHS than normal children (P < 0.05). Conclusion Cochlear function was affected when AHI was at or greater than 10/hour. ABR and DPOAE can be used to detect early changes in auditory function in children with OSAHS.

A Comparative Study on Efficacy of Fludrocortisones versus Glucocorticoids and Vasodilators in the Treatment of Idiopathic Sensorineural Cochlear Hearing Loss

Introduction and Objectives: The idiopathic sensorineural cochlear hearing loss is one of the most frequent human sensory deficits and there is no specific drug therapy for it. The possible hearing recovery is related with the reestablishment of normal ionic homeostasis of the endolymph controlled by the mineralocorticoid as could be demonstrate experimentally. The purpose of this clinical trial was to confirm the efficacy of mineralocorticoids to the recovery of hearing level in patients suffering idiopathic sensorineural hearing loss (SNHL) against the glucocorticoids and vasodilator drugs. Material and Methods: The research lasted three months and involved 90 patients allocated into four different groups: Placebo group, consisted of 20 patients (10 men and 10 women);the group consisting of 22 patients treated with glucocorticoid therapy (12 men and 10 female);the group treated with mineralocorticoid therapy encompassed 26 patients (13 males and 13 females) and the group of vasodilators formed by 22 patients (12 men and 10 women). The level of hearing loss was estimated by the tests Liminal Tone Audiometry (LTA) and Auditory Brainstem Response (ABR). Results: The main features in this research were overall better response in improving the hearing level with the mineralocorticoid therapy. This improvement in hearing levels was greater in women than in men, and a higher response was found in the left ear regardless of patient’s gender. Conclusions: The hearing gain was significantly superior in the mineralocorticoids group followed by the glucocorticoids group whereas the response to vasodilators was lesser and with no statistical significance.

A METHOD FOR ESTABLISHING AN ANIMAL MODEL OF LIKE-AUDITARY NEUROPATHY

Objective: To establish an animal model of like-auditory neuropathy in neonatal rat. Methods The ani-mals were injected with phenylhydrazine hydrochloride or saline at 7-day of age. ABR and DPOAE were performed to assess the auditory function. The cochlea basilar membrane stretched preparation and cochlear frozen sections were prepared for immunohistochemical staining to examine the morphological change of hair cells and spiral ganglion cells (SGNs). Results At 7-day age the ABR waveI, III, V, latencies andI-III,I-V IWIs in the experimental group were significantly prolonged compared with those in the control group. The ABR thresholds were also elevated in the experimental group. We found there is no significant differ-ence in DPOAE in phenylhydrazine hydrochloride exposure group compare to control group. The cochlear hair cells showed no signs of loss in both group, but the total number of neurofilaments positive cells in SGNs were significantly reduced in the phenylhydrazine treated animals. Conclusion Our study suggests that phenylhydrazine hydrochloride can change the auditory function and induce peripheral nerve pathology by targeted mainly the SGNs in neonatal rat.

Acoustic Trauma of Guinea Pigs Caused by ^(60) Cobalt γ-Ray

Auditory cortical cvokod rcsponse(ACER) and auditory brainstom cvoked response (ABR) were recorded in guinea pigs before and after irradiation of ^(60)Co γ-ray. A single dose of irradiation on head was 90Gy and 70Gy in two groups, respectively. Two h after irradiation. the threshold shift was 12. 5 dB and 9 dB, and the ACER post-irradiation amplitude ex- ceeded the maximum pre-irradiation value by 20% and 37%. Six h after irradiation, the threshold shift increased to 37 dB and the maximum amplitnde decreased to the level of pre-irradiation in 70Gy-group. In another group, right auditory bulla arca was irradiated with a total dose of 45Gy in a course of six fractions/two weeks. Fourteen d after irradiation, the threshold shift of ABR was 118 dB and the latency of wave I was longer. The amplitude-intensity curve was after irradiation. Histological observation using scanning showed that only outer hair- cells in the basal coil of the cochlea were 6 h after irrdiation 50Gy-group. Bul 16 h later, outer, hair cells in all coils of the cochlea were found to be destroyed extensively and inner cells were destroyed slightly. In 45Gy-group, 14 d after irradiation, outer hair cells in all coils of the cochlea were damaged and no inmer hair cell was injured severely.

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

Background:Hearing 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,>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 Methods:We 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 audio-logical 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 trans-duction 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.Results:Four groups of animal models were established successfully and verified by audiology and pathology.Regarding audiology,there were no sig-nificant differences in the ABR thresholds before exposure(p>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<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 patho-morphology,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<0.05),and the compound group had the most severe HL(p<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<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<0.05).Conclusion:Gentamicin,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 syn-ergistic 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.

Effects of delayed brain-derived neurotrophic factor application on cochlear pathology and auditory physiology in rats

Background The development and maintenance of spiral ganglion cells （SGCs） appear to be supported by neurotrophins Removal of this support leads to their gradual degeneration. Intracochlear infusion with neurotrophins can provide trophic support to SGCs in animal deafness models if given shortly after deafening. However, it is not known whether delayed intervention will provide similar protection, which might be clinically relevant. The present research was conducted to determine the effects of brain-derived neurotrophic factor （BDNF） administration on the capacity of the peripheral processes to resprout. Methods The left cochlea of 20 profoundly deafened rats, which were divided into 2 groups equally, was implanted with an electrode and drug-delivery system 30 days after deafening. Either BDNF or artificial perilymph （AP） was delivered continuously for 28 days. Electrically evoked auditory brainstem responses （EABRs） were recorded during the period. SGC body and peripheral process density were measured. Results The EABR thresholds of AP increase continually. Those of BDNF increase slowly at the beginning then decrease, and were significantly less than those of the AP group from day 14 to 28 （P 〈0.01）. In terms of SGC and peripheral process density, the difference between the treated and control ears of BDNF group was clearly significant （P 〈0.01）, but not in AP group （P 〉0.05）. Analysis of the left cochlea between the two groups demonstrated that SGC/peripheral process density of the BDNF group was significantly greater than that of the AP group. Finally, a functional formula was developed relating the last EABR threshold and SGC density and process density, which was as follows： T= 466.184-2.71 （F.B.L）. Conclusions Under the conditions of delayed intervention following 30 days after deafening in rats, it can be concluded that BDNF enhances SGC bodies and peripheral processes survival after differentiation and so improves auditory sensitivity. SGC peripheral processes influence the auditory sensitivity.

Screening strategy and time points for newborn hearing re-screening with high risk factors

Objective: To compare and analyze the pass rate and screening strategy of hearing rescreening for newborns with high risk factors.Methods: Retrospective chart review of high-risk newborns who failed their initial newborn hearing screen and subsequently underwent secondary hearing tests from June 2011 to June 2018 in Guangzhou Women and Children’’s Medical Center were performed.Results: Eight hundred and sixty-eight newborns with high risk factors were included in the study. The 57-70 days (83.5%) and 71-84 days (83.4%) group had the highest pass rate compared with 42-56 days (75.8%) and < 42 days (68.3%) group. As for different screening strategies, the pass rate of OAE(otoacoustic emissions), AABR (auto auditory brainstem response) and OAE + AABR was the highest in 57-70 days group and 71-84 days group, respectively. The OAE + AABR had the lowest pass rate compared to the other two modalities. When the pass rate was compared as different risk factors, the 57-70 days and 71-84 days group also had the highest pass rate compared with 42-56 days and < 42 days group and the pass rate had no significant differences among various risk factors group.Conclusion: Our results showed that all the pass rate of OAE, AABR and OAE+ AABR was the highest in 57-70 days group and 71-84 days group with significant difference, suggesting that the delayed screening time (>57 days) may increase the re-screening pass rate and reduce anxiety of parents, which is of great significance for clinical work.

Frequency Following Response of Speech-ABR by Instantaneous Energy Spectrum

A frequency following response(FFR) of speech auditory brainstem response(speech-ABR) elicited by the speech syllable/da/contains three distinct waves named as D, E and F, corresponding to the structure of the stimulus sound. The detection and characterization of FFRs are critical in the study and application of speech-ABRs. Conventional methods detect the latencies of the waves in time domain by measuring the maximal amplitudes of the waveform in the preset windows, which suffers the problem of low quality of FFR waves. In this paper, we defined an instantaneous energy(IE) spectrum based on empirical mode decomposition(EMD)method(EMD-IE method) to detect FFR and measured the latencies of the waves. The results reveal that the FFRs are mostly evident on the second layer of the IE spectra,which would benefit the detection and measurement of the FFRs in clinic.