Reduced BDNF Expression in Auditory Cortex Contributed to Neonatal Pain Induced Hearing Impairment and Dendritic Pruning Deficiency in Mice

2021 ◽  
Author(s):  
Nanqi Li ◽  
Bing Chen ◽  
Gaogan Jia ◽  
Rui Xu ◽  
Ying Xia ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Auditory Cortex ◽  
Hair Cell ◽  
Hearing Impairment ◽  
Dendritic Spine ◽  
Bdnf Level ◽  
Cochlear Function ◽  
Neonatal Pain ◽  
Brainstem Response ◽  
Spine Pruning

Abstract Hearing loss in children is common especially in NICU with consequences of worse outcomes in speech, language, education, social functioning, cognitive abilities, and quality of life. Whether neonatal pain is link to increase risks for hearing loss remains to be explored. Here, we implemented Complete Freund's adjuvant (CFA) plantar injection and needle prick model to mimic neonatal pain in NICU during critical period of hearing development. Auditory brainstem response (ABR) test was used to determine the hearing threshold at 4w and 8w postnatal. Sufentanil and Oxycodone were used as analgesic to treat neonatal pain. Hair cell and ribbon synapse stanning were performed to detect cochlear function. Golgi-cox staining and BDNF immunofluorescence of auditory cortex were performed to determine dendritic spine pruning in auditory cortex. The dendritic pruning related protein CaMKII and Rac1/2 level were detected by western blot. We found that CFA induced neonatal pain and ABR threshold increased at 4w and 8w postnatal and the impairment were attenuated after analgesic administration. Neither the inner hair cell (IHC) nor the synapse of CFA mice was damaged in cochlear. CFA mice showed increased dendritic spine density at auditory cortex and reduced BDNF level. Furthermore, Rac1/2 and CaMKII might contributed to the disrupt dendritic spine pruning. Our study suggested that neonatal pain could induced hearing impairment in adulthood ascribed to the reduced BDNF level and AC dendritic spine pruning deficiency, optimal analgesic in early-life could beneficial for hearing development.

scholarly journals Prevention of acquired sensorineural hearing loss in mice by in vivo Htra2 gene editing

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xi Gu ◽  
Daqi Wang ◽  
Zhijiao Xu ◽  
Jinghan Wang ◽  
Luo Guo ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Protective Effect ◽  
Hair Cell ◽  
Sensorineural Hearing Loss ◽  
Auditory Brainstem Response ◽  
Gene Editing ◽  
Auditory Brainstem ◽  
Sensorineural Hearing ◽  
Brainstem Response

Abstract Background Aging, noise, infection, and ototoxic drugs are the major causes of human acquired sensorineural hearing loss, but treatment options are limited. CRISPR/Cas9 technology has tremendous potential to become a new therapeutic modality for acquired non-inherited sensorineural hearing loss. Here, we develop CRISPR/Cas9 strategies to prevent aminoglycoside-induced deafness, a common type of acquired non-inherited sensorineural hearing loss, via disrupting the Htra2 gene in the inner ear which is involved in apoptosis but has not been investigated in cochlear hair cell protection. Results The results indicate that adeno-associated virus (AAV)-mediated delivery of CRISPR/SpCas9 system ameliorates neomycin-induced apoptosis, promotes hair cell survival, and significantly improves hearing function in neomycin-treated mice. The protective effect of the AAV–CRISPR/Cas9 system in vivo is sustained up to 8 weeks after neomycin exposure. For more efficient delivery of the whole CRISPR/Cas9 system, we also explore the AAV–CRISPR/SaCas9 system to prevent neomycin-induced deafness. The in vivo editing efficiency of the SaCas9 system is 1.73% on average. We observed significant improvement in auditory brainstem response thresholds in the injected ears compared with the non-injected ears. At 4 weeks after neomycin exposure, the protective effect of the AAV–CRISPR/SaCas9 system is still obvious, with the improvement in auditory brainstem response threshold up to 50 dB at 8 kHz. Conclusions These findings demonstrate the safe and effective prevention of aminoglycoside-induced deafness via Htra2 gene editing and support further development of the CRISPR/Cas9 technology in the treatment of non-inherited hearing loss as well as other non-inherited diseases.

scholarly journals Effect of Phlorofucofuroeckol A and Dieckol Extracted from Ecklonia cava on Noise-induced Hearing Loss in a Mouse Model

Marine Drugs ◽  
2021 ◽  
Vol 19 (8) ◽  
pp. 443
Author(s):  
Hyunjun Woo ◽  
Min-Kyung Kim ◽  
Sohyeon Park ◽  
Seung-Hee Han ◽  
Hyeon-Cheol Shin ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Noise Exposure ◽  
Radical Scavenging ◽  
Threshold Shift ◽  
Ecklonia Cava ◽  
Control Group ◽  
Noise Induced Hearing Loss ◽  
Antioxidant Agents ◽  
Brainstem Response

One of the well-known causes of hearing loss is noise. Approximately 31.1% of Americans between the ages of 20 and 69 years (61.1 million people) have high-frequency hearing loss associated with noise exposure. In addition, recurrent noise exposure can accelerate age-related hearing loss. Phlorofucofuroeckol A (PFF-A) and dieckol, polyphenols extracted from the brown alga Ecklonia cava, are potent antioxidant agents. In this study, we investigated the effect of PFF-A and dieckol on the consequences of noise exposure in mice. In 1,1-diphenyl-2-picrylhydrazyl assay, dieckol and PFF-A both showed significant radical-scavenging activity. The mice were exposed to 115 dB SPL of noise one single time for 2 h. Auditory brainstem response(ABR) threshold shifts 4 h after 4 kHz noise exposure in mice that received dieckol were significantly lower than those in the saline with noise group. The high-PFF-A group showed a lower threshold shift at click and 16 kHz 1 day after noise exposure than the control group. The high-PFF-A group also showed higher hair cell survival than in the control at 3 days after exposure in the apical turn. These results suggest that noise-induced hair cell damage in cochlear and the ABR threshold shift can be alleviated by dieckol and PFF-A in the mouse. Derivatives of these compounds may be applied to individuals who are inevitably exposed to noise, contributing to the prevention of noise-induced hearing loss with a low probability of adverse effects.

scholarly journals Concurrent genetic and standard screening test for hearing reduction

2020 ◽  
Vol 66 (2) ◽  
pp. 35-40
Author(s):  
Marina Davcheva Chakar ◽  
Gjorgji Bozhinovski ◽  
Emilija Shukarova Stefanovska ◽  
Dejan Trajkov
Keyword(s):  
Hearing Loss ◽  
Hearing Impairment ◽  
Genetic Screening ◽  
Screening Test ◽  
Screening Program ◽  
Deaf Child ◽  
Hearing Screening ◽  
Pathogenic Variant ◽  
Gjb2 Gene ◽  
Brainstem Response

Reduction of hearing is the most common sensory impairment among newborns with an incidence of 1-3 per 1000 births. Introduction of an Auditory Newborn screening program allows early identification of hearing impairment. Mainly, congenital hearing loss in early childhood is a result of genetic changes. Due to high frequency of GJB2 pathogenic variants, its molecular characterization among sensorineural hearing reduction cases is already conducted as a routine analysis in many countries. The aim of this study is to show our initial results in the effort to determine whether genetic screening along with the standard hearing screening in newborns is justified. Otoacoustic emission (OAE) method was conducted in 223 newborns at risk of hearing impairment. Among them, 7 did not pass the test in both ears while 9 exhibited one-sided hearing loss. In all 7 children with indication of profound bilateral deafness, the diagnosis was confirmed using auditory brainstem response. Genetic screening of GJB2 gene was performed in 6 of them. Genetic analysis of GJB2 revealed homozygous state of the most common pathogenic variant 35delG in 3 (50%) of the analyzed infants. In the remaining 3 no pathogenic variant was determined. The results indicate that performing auditory OAE together with genetic screening is justified. In newborns who have not passed the hearing screening test and have profound hearing loss, without other syndrome traits, screening for mutations of GJB2 gene should be conducted. Genetic screening enables establishment of early definite diagnosis for deafness and helps in conducting adequate therapy providing timely rehabilitation and social inclusion of deaf child. Key words: hearing loss, genetic screening, auditory screening, GJB2 gene

Direct drug application to the round window: A comparative study of ototoxicity in rats

2009 ◽  
Vol 141 (5) ◽  
pp. 584-590 ◽  
Author(s):  
Silvia Murillo-Cuesta ◽  
Fernando García-Alcántara ◽  
Elena Vacas ◽  
Jon Alexander Sistiaga ◽  
Guadalupe Camarero ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Cell Damage ◽  
Round Window ◽  
Drug Application ◽  
Local Drug Delivery ◽  
Saline Control ◽  
Round Window Membrane ◽  
Cochlear Function ◽  
Profound Hearing Loss ◽  
Brainstem Response

Objective: To assess the validity of inducing ototoxicity in rats by applying a sponge soaked in kanamycin and furosemide on the round window. Study Design: Basic, randomized, nonblind experimental study. Setting: Animal models of cochlear damage and reliable methods of local drug delivery are fundamental to study hearing loss and to design new therapies. Subjects and Methods: Four experimental groups of six Wistar rats with different methods of drug administration were used: (1) injection of subcutaneous kanamycin (400 mg/kg) and intravenous furosemide (100 mg/kg); (2) local application of a sponge soaked in saline close to the round window; (3) animals for which the sponge was soaked in a solution containing kanamycin (200 mg/mL) and furosemide (50 mg/mL); and (4) sham-operated rats. The tympanic bulla was exposed using a ventral approach, and a bullostomy was performed to visualize the round window membrane. Cochlear function was assessed by measuring the auditory brainstem response, and hearing thresholds in response to click and tone burst stimuli were determined as peak and interpeak latencies. At the end of the study, cochlear histology was analyzed. Results: Systemic administration of kanamycin and furosemide induced profound hearing loss and severe hair cell damage. Local delivery of these ototoxic drugs caused comparable damage but avoided the systemic side effects of the drug. Sham-operated and saline control animals did not experience functional alterations. Conclusion: Situating a sponge soaked in kanamycin and furosemide on the round window membrane through the ventral approach is a reliable method to provoke local ototoxicity in rats.

scholarly journals Hearing Characteristics of Stroke Patients: Prevalence and Characteristics of Hearing Impairment and Auditory Processing Disorders in Stroke Patients

2017 ◽  
Vol 28 (06) ◽  
pp. 491-505 ◽  
Author(s):  
Nehzat Koohi ◽  
Deborah A. Vickers ◽  
Rahul Lakshmanan ◽  
Hoskote Chandrashekar ◽  
David J. Werring ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hearing Impairment ◽  
Auditory Processing ◽  
Otoacoustic Emissions ◽  
Pure Tone Audiometry ◽  
Stroke Survivors ◽  
Central Auditory Processing ◽  
Hearing Impairments ◽  
Stroke Patients ◽  
Brainstem Response

Background: Stroke survivors may suffer from a range of hearing impairments that may restrict their participation in postacute rehabilitation programs. Hearing impairment may have a significant impact on listening, linguistic skills, and overall communication of the affected stroke patient. However, no studies sought to systematically characterize auditory function of stroke patients in detail, to establish the different types of hearing impairments in this cohort of patients. Such information would be clinically useful in understanding and addressing the hearing needs of stroke survivors. Purpose: The present study aimed to characterize and classify the hearing impairments, using a detailed audiological assessment test battery, in order to determine the level of clinical need and inform appropriate rehabilitation for this patient population. Research Design: A case–control study. Study Sample: Forty-two recruited stroke patients who were discharged from a stroke unit and 40 control participants matched for age. Data Collection and Analysis: All participants underwent pure-tone audiometry and immittance measurements including acoustic reflex threshold, transient-evoked otoacoustic emissions, auditory-evoked brainstem response, and a central auditory processing assessment battery, performed in a single session. Hearing impairments were classified as peripheral hearing loss (cochlear and neural type), central auditory processing disorder (CAPD), and as a combination of CAPD and peripheral hearing loss. Results: Overall mean hearing thresholds were not significantly different between the control and stroke groups. The most common type of hearing impairment in stroke patients was the combination type, “peripheral and CAPD,” in the 61- to 80-yr-old subgroup (in 55%), and auditory processing deficits in 18- to 60-yr-olds (in 40%), which were both significantly higher than in controls. Conclusions: This is the first study to examine hearing function in detail in stroke patients. Given the importance of hearing for the efficiency of communication, it is essential to identify hearing impairments and differentiate peripheral and central deficits to define an appropriate intervention plan.

scholarly journals Η συμβολή των ωτοακουστικών εκπομπών στη μελέτη της κοχλιακής λειτουργίας σε ασθενείς με υποθυρεοειδισμό

2013 ◽  
Author(s):  
Βασίλειος Ψαλτάκος
Keyword(s):  
Hearing Loss ◽  
Hearing Impairment ◽  
Otoacoustic Emissions ◽  
Pure Tone ◽  
Pure Tone Audiometry ◽  
Otoacoustic Emission ◽  
Upper Respiratory Tract ◽  
Anatomic Site ◽  
Cochlear Function ◽  
Hearing Thresholds

Although several reports exist concerning the occurrence of hearing loss in patients withdisorders of thyroid function, there are still several unsettled issues, such as theincidence and the severity of hearing impairment, the anatomic site of the auditorypathway involved, and the possible pathogenetic mechanisms. Both congenitalhypothyroidism and environmentally based iodine deficiency are established causes ofhearing loss in humans and rodents. Congenital thyroid deficiency in humans can resultin a profound, hearing deficit, which may be prevented by early hormonal replacementtreatment in infants with hypothyroidism. However, the effect of acute or chronichypothyroidism in adults has not been adequately studied, and most information hasbeen obtained from animal experiments, whereas research in humans has been basicallybased on behavioral audiometry. The use of otoacoustic emissions may provide moreinsight into the hearing function of these patients than pure-tone audiometry, since it isconsidered as a sensitive test of the cochlear status. The aim of this study was toevaluate the hearing in a group of patients with acute hypothyroidism, using bothconventional audiometry and transiently evoked otoacoustic emissions (TEOAEs). Material and methods:A group of 52 patients with thyroid carcinoma who underwent total thyroidectomy wasstudied prospectively, All patients were examined before surgery and 6-8 weekspostoperatively. During this period there was no replacement with levothyroxine and themagnitude of thyroxin depletion was monitored by serum thyroid-stimulating hormone levels. On preoperative encounter with each patient, a detailed questionnaire of historyof hearing loss, tinnitus, vertigo, previous ear infections, noise exposure, medications,and recent upper respiratory tract infection was completed. Patients were excluded ifthey were older than 50 years, in order to avoid the phenomenon of presbycusis, or ifthey had a history of cochleovestibular, vascular or neurologic disease, or any other riskfactor for hearing impairment. Pure-tone audiometry, tympanometry and transientlyevoked otoacoustic emissions were performed. A group of healthy volunteers of similarage and sex were used for comparison.Results:(1) Tympanograms were normal, either on initial testing (75%) or on repeat testing(25%).(2) Audiometry showed elevation of all postoperative hearing thresholds, whereas thethresholds varied significantly across frequency.(3) TEOAE testing showed response signal to noise ratios lower in the postoperativesession (hypothyroid state) than in the preoperative session on all measured frequencies.(4) Emission levels varied significantly across frequency, with maximum responseobserved at 2 kHz.(5) Comparison of significant pure-tone and otoacoustic emission shifts for individualears showed more ears affected in otoacoustic emission testing, indicating subclinicalcochlear involvement.(6) Comparison of hearing thresholds and otoacoustic emission levels between patientsand controls showed significant differences on postoperative testing. Conclusions:Acute hypothyroidism in adults causes elevation of hearing thresholds and reducedotoacoustic emissions. The effect on otoacoustic emissions is greater, indicatingsubclinical damage of the cochlear function.

The miR-34a/Bcl-2 Pathway Contributes to Auditory Cortex Neuron Apoptosis in Age-Related Hearing Loss

2017 ◽  
Vol 22 (2) ◽  
pp. 96-103 ◽  
Author(s):  
Qiuhong Huang ◽  
Yongkang Ou ◽  
Hao Xiong ◽  
Haidi Yang ◽  
Zhigang Zhang ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Auditory Cortex ◽  
Molecular Mechanisms ◽  
Primary Auditory Cortex ◽  
Auditory Brainstem ◽  
Hearing Ability ◽  
Age Related ◽  
Brainstem Response ◽  
The Central Nervous System ◽  
Age Related Hearing Loss

Hypothesis: The miR-34a/Bcl-2 signaling pathway may play a role in the mechanisms related to age-related hearing loss (AHL) in the auditory cortex. Background: The auditory cortex plays a key role in the recognition and processing of complex sound. It is difficult to explain why patients with AHL have poor speech recognition, so increasing numbers of studies have focused on its central change. Although micro (mi)RNAs in the central nervous system have recently been increasingly reported to be associated with age-related diseases, the molecular mechanisms of AHL in the auditory cortex are not fully understood. Methods: The auditory brainstem response was used to assess the hearing ability of C57BL/6 mice, and q-PCR, immunohistochemistry, and Western blotting were used to detect the expression levels of miR-34a and Bcl-2 in the mouse auditory cortex. TUNEL and DNA fragmentation were adopted to detect the apoptosis of neurons in the auditory cortex. To verify the relationship of miR-34a and Bcl-2, we transfected an miR-34a mimic or miR-34a inhibitor into primary auditory cortex neurons. Results: In this study, miR-34a/Bcl-2 signaling was examined in auditory cortex neurons during aging. miR-34a and apoptosis increased in the auditory cortex neurons of C57BL/6 mice with aging, whereas an age-related decrease in Bcl-2 was determined. In the primary neurons of the auditory cortex, miR-34a overexpression inhibited Bcl-2, leading to an increase in apoptosis. Moreover, miR-34a knockdown increased Bcl-2 expression and diminished apoptosis. Conclusion: Our results support a link between age-related apoptosis in auditory cortex neurons and miR-34a/Bcl-2 signaling, which may serve as a potential mechanism of the expression of AHL in the auditory cortex.

scholarly journals Hearing Assessment of Neonates at Risk for Hearing Loss at a Hearing Health High Complexity Service: An Electrophysiological Assessment

2018 ◽  
Vol 23 (02) ◽  
pp. 157-164
Author(s):  
Flavia Mara Reis ◽  
Claudia Gonçalves ◽  
Juliana Conto ◽  
Milena Iantas ◽  
Débora Lüders ◽  
...  
Keyword(s):  
At Risk ◽  
Hearing Loss ◽  
Risk Factor ◽  
Hearing Impairment ◽  
Public Service ◽  
Auditory Brainstem ◽  
Public Hospitals ◽  
Brainstem Response ◽  
Hearing Assessment ◽  
Hearing Health

Introduction Hearing is the main sensory access in the first years of life. Therefore, early detection and intervention of hearing impairment must begin before the first year of age. Objective To analyze the results of the electrophysiological hearing assessment of children at risk for hearing loss as part of the newborn hearing screening (NHS). Methods This is a cross-sectional study held at a hearing health public service clinic located in Brazil, with 104 babies at risks factors for hearing loss referred by public hospitals. A questionnaire was applied to parents, and the auditory brainstem response (ABR) test was held, identifying those with alterations in the results. The outcome of the NHS was also analyzed regarding risk factor, gestational age and gender. Results Among the 104 subjects, most of them were male (53.85%), and the main risk factor found was the admission to the neonatal intensive care unit (NICU) for a period longer than 5 days (50.93%). Eighty-five (81.73%) subjects were screened by NHS at the maternity and 40% of them failed the test. Through the ABR test, 6 (5.77%) infants evidenced sensorineural hearing loss, 4 of them being diagnosed at 4 months, and 2 at 6 months of age; all of them failed the NHS and had family history and admission at NICU for over 5 days as the most prevalent hearing risks; in addition, family members of all children perceived their hearing impairment. Conclusion Advances could be observed regarding the age of the diagnosis after the implementation of the NHS held at the analyzed public service clinic.

scholarly journals Hidden hearing loss is associated with loss of ribbon synapses of cochlea inner hair cells

2021 ◽  
Author(s):  
Feng Song ◽  
Bin Gan ◽  
Na Wang ◽  
Zhe Wang ◽  
An-ting Xu
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Noise Exposure ◽  
Repeated Exposure ◽  
Ribbon Synapse ◽  
Intensity Noise ◽  
Auditory Function ◽  
Ribbon Synapses ◽  
Brainstem Response ◽  
Hidden Hearing Loss

This study aimed to observe the changes in the cochlea ribbon synapses after repeated exposure to moderate-to-high intensity noise. Guinea pigs received 95 dB SPL white noise exposure 4 hours a day for consecutive 7 days (we regarded it a medium-term and moderate-intensity noise, or MTMI noise). Animals were divided into 4 groups: Control, 1DPN (1-day post noise), 1WPN (1-week post noise), and 1MPN (1-month post noise). Auditory function analysis by ABR and CAP recordings, as well as ribbon synapse morphological analyses by immunohistochemistry (Ctbp2 and PSD95 staining) were performed one day, one week, and one month after noise exposure. After MTMI noise exposure, the amplitudes of auditory brainstem response (ABR) I and III waves were suppressed. The compound action potential (CAP) threshold was elevated, and CAP amplitude was reduced in the 1DPN group. No apparent changes in hair cell shape, arrangement or number were observed, but the number of ribbon synapse was reduced. The 1WPN and 1MPN groups showed that part of ABR and CAP changes recovered, as well as the synapse number. The defects in cochlea auditory function and synapse changes were observed mainly in the high-frequency region. Together, repeated exposure in MTMI noise can cause hidden hearing loss, which is partially reversible after leaving the noise environment; and MTMI noise induced hidden hearing loss is associated with inner hair cell ribbon synapses.

Absence of Sensorineural Hearing Loss in Treated Infants and Children with Congenital Toxoplasmosis

1992 ◽  
Vol 106 (1) ◽  
pp. 75-80 ◽  
Author(s):  
Therese McGee ◽  
Cheryl Wolters ◽  
Laszlo Stein ◽  
Nina Kraus ◽  
Daniel Johnson ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Hearing Impairment ◽  
Congenital Toxoplasmosis ◽  
Auditory Brainstem ◽  
Sensorineural Hearing ◽  
Infants And Children ◽  
Auditory Function ◽  
Serial Testing ◽  
Brainstem Response

Educationally significant hearing loss has been reported in 10% to 15% of children with congenital toxoplasmosis. As part of a pilot study to assess feasibility and safety of prolonged therapy for congenital toxoplasmosis, 30 congenially infected infants and children were evaluated for auditory function. Serial testing, beginning within 2 months of birth, was performed. Availability of auditory brainstem response (ABR) testing made evaluation at an earlier age than previously possible. Six (20%) of the 30 infants had mild to moderate conductive type hearing loss associated with otitis media. No infant or child had sensorineural hearing loss. The better outcome we observed compared to previous reports of a 15% to 26% incidence of sensorineural hearing loss and 10% to 15% incidence of educationally significant, bilateral hearing impairment may be related to early initiation and/or prolonged institution of antimicrobial therapy. Continued followup to exclude progressive hearing impairment and study of larger numbers of children are needed to verify these preliminary findings.

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