Tympanostomy tube placement for intractable Meniere's disease in the elderly.

BACKGROUND: The treatment of refractory elderly Meniere's disease is a challenge. AIM: To investigate the efficacy of tympanostomy tube placement in elderly patients with Meniere's disease. METHODS: 31 patients over 60 years old with Meniere's disease who had failed medical treatment and underwent tympanostomy tube placement. Vertigo control, hearing level, tinnitus, and ear fullness were recorded and analyzed preoperatively and postoperatively. RESULTS: All patients completed a 6-month follow-up. At 6 months postoperatively,complete control, substantial control and limited control of vertigo were achieved in 10 (32%), 13 (42%), and 6 (19%) patients respectively. Two patients (6%) reported no substantial improvement. Twelve patients completed a 2-year follow-up. At 2 years postoperatively, complete control, substantial control and limited control of vertigo were achieved in 3 (25%), 5 (42%), and 1 (8%) patients respectively. Three (25%) patients showed no significant improvement in vertigo. The majority of patients reported significant improvement in the functional level scale, the Dizziness Handicap Inventory scores, and ear fullness at 6 months and 2 years postoperatively. CONCLUSIONS AND SIGNIFICANCE: Tympanostomy tube placement may reduce vertigo attacks and improved the quality of life in elderly patients with Meniere's disease.

Evaluation of subjective visual vertical and horizontal in patients with acoustic neuroma based on virtual reality.

Objective: To investigate potential differences in absolute deviation values of subjective visual vertical and horizontal between unilateral acoustic neuroma patients and healthy young adults under varying degrees of static head tilt, as well as the impact of proprioception on these values, with the aim of determining the effect of acoustic neuroma on gravity sensory pathway function in patients. Methods: We recruited 22 patients diagnosed with unilateral acoustic neuroma and 25 healthy young adults and employed virtual reality technology to assess the absolute deviation values of subjective visual vertical (SVV) and subjective visual horizontal (SVH) under eight different static tilted head positions (Head centered (0° tilt), PdP, Head tilt 15°, 30°, 45° to the left and right), then compare and analyze intergroup differences. Results: In the Head-centered position, both SVV and SVH absolute deviated values were significantly higher in the AN group compared to healthy young adults. The AN group exhibited significantly higher absolute deviation values of SVV compared to the healthy group when tilting their head 30° left and right. Additionally, when tilting their heads to the right at 15° and 45° the AN group showed significant increases in SVH absolute deviated values compared to healthy adults. The SVV and SVH absolute deviation values of LAN and SAN groups did not reach statistical significance. The results of the SVV test for PDP position did not show any significant differences among all groups. However, the SVH test revealed that the absolute deviation values of the LAN group was significantly higher than that of healthy individuals. Conclusion: Our study shows that the gravity sensing function of patients with unilateral acoustic neuroma is affected to different degrees, however, the degree of gravity sensing function damage of patients has little relationship with tumor size. When acoustic neuroma is larger than 2 cm, the effect of proprioception on patients' SVH outcome is noteworthy. So, we should pay attention to the postoperative follow-up of patients with acoustic neuroma and the evaluation of vestibular rehabilitation effect. Meanwhile, for patients opting for conservative treatment, it is imperative to monitor the dynamic changes in vestibular function and seize timely opportunities for intervention.

Characteristics of tympanogram in symptomatic Eustachian tube dysfunction.

PURPOSE: To identify the characteristics of tympanogram in symptomatic Eustachian tube dysfunction (SETD) patients. METHODS: One hundred and twenty-four unilateral SETD patients presenting with type A tympanograms who underwent balloon dilation of the Eustachian tube (BDET) were recruited and assigned into effective BDET group and ineffective BDET group based on treatment effect. The unaffected ear in the same patient served as normal control. Fifty-one patients with sudden sensorineural hearing loss (SSHL) and 46 patients with Meniere's disease (MD) were selected for cases of non-ETD ear fullness. Demographics, 7-item Eustachian Tube Dysfunction Questionnaire score (ETDQ-7), and tympanograms were recorded and analyzed preoperatively and postoperatively. RESULTS: Of the 124 SETD patients included in the study 94 (75.8%) showed good response to BDET based on decreased ETDQ-7 scores. There were no significantly differences in the values of tympanometric peak pressure (TPP) between diseased ears and healthy ears in SETD patients, as well as in SSHL and MD patients. Instead, TPP shifts (the difference between two values of TPP obtained under a Valsalva and Toynbee maneuver) were remarkably reduced in affected ears compared with those in unaffected ears in effective BDET group at baseline. Moreover, TPP shifts in these SETD ears significantly raised and reached the levels in healthy ears postoperatively. CONCLUSIONS: This study demonstrated TPP shifts are decreased in a subset of SETD patients presenting with type A tympanograms and these patients are more likely to show good response to BDET.

Comparison between 3D-FLAIR and 3D-real IR MRI sequences with visual classification method in the imaging of endolymphatic hydrops in Meniere's disease.

BACKGROUND: Clinically, the evidence of endolymphatic hydrops (EH) in Meniere's disease (MD) primarily relies on audiological examinations, such as glycerol tests and electrocochleography, to suggest the presence of EH indirectly. However, these techniques lack sensitivity and specificity, and they do not sufficiently assess the degree of EH. This study aims to explore the application of three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) and three-dimensional real inversion recovery (3D-real IR) sequence imaging of EH in MD and to assess the image quality and grading of EH. METHODS: The study included 50 patients with definite MD. The 3D-FLAIR and 3D-real IR sequence images were performed 24 h after bilateral intratympanic injection of gadolinium. The image quality of both sequences was reviewed by two experienced radiologists. The vestibular and cochlear EH grades of both sequences were reviewed by two experienced otologists using a visual grading method. The Cohen's kappa and Pearson tests were used to analyze the data. RESULTS: The reliability of image quality between the two radiologists was excellent (0.7 < kappa < 0.9). There were significant statistical differences in the image quality between the 3D-real IR and 3D-FLAIR sequences (p = 0.023 and p = 0.035, respectively). The reliability for the grading of vestibular and cochlear EH between the two otologists was excellent (0.7 < kappa < 0.9). The 3D-real IR sequence detected more severe hydrops than did the 3D-FLAIR sequence (p < 05). CONCLUSION: The image quality of the 3D-real IR sequence is better than that of the 3D-FLAIR sequence, and there are differences in the vestibular and cochlear EH grades of both sequences. The sensitivity of the 3D-real IR sequence in the cochlea is higher. The method of visual grading can be applied to both technologies when combined with 3D-real IR.

Prognostic Factors Influencing the Tinnitus Improvement After Idiopathic Sudden Sensorineural Hearing Loss Treatment.

PURPOSE: Logistic regression analysis was used to explore the factors that influence tinnitus improvement after idiopathic sudden sensorineural hearing loss (ISSNHL) treatment. MATERIALS AND METHODS: In this retrospective study, 137 ISSNHL patients with tinnitus were recruited at the Sun Yatsen Memorial Hospital of Sun Yat-sen University, China. They underwent audiological examinations, vestibular assessments, tinnitus examinations, a Tinnitus Handicap Inventory (THI) assessment and ISSNHL treatments. Logistic regression analysis was performed to investigate factors that affected tinnitus improvement. RESULTS: Participants were divided into an effective group (73 patients) and noneffective group (64 patients) according to THI scores before and after treatment. The effective group had better averaged hearing threshold than the noneffective group (effective group vs. noneffective group: 74.47 vs. 87.66 dB HL; t = 3.03, p < 0.05). Additionally, before intervention there were significant difference in profound audiogram configuration (effective group vs. noneffective group: 17.81% vs. 46.88%, x2 = 23.63; p < 0.001), mid tinnitus pitch (effective group vs. noneffective group: 19.18% vs. 35.94%, x2 = 6.58; p = 0.037) and mean THI scores (effective group vs. noneffective group: 57.07 ± 22.27 vs. 36.78 ± 24.41, t = -5.09, p < 0.001) between the effective and noneffective tinnitus groups. Logistic regression analysis showed that audiogram configurations (profound audiogram: OR = 0.10, 95% CI 0.01-0.72, p = 0.022), tinnitus pitch (mid tinnitus pitch: OR = 0.16, 95% CI 0.05-0.57, p = 0.004) and THI scores (OR = 1.05, 95% CI 1.03-1.07, p < 0.001) were independent factors associated with tinnitus improvement. CONCLUSION: Audiogram configuration, tinnitus pitch, and THI scores before intervention appear to be predictive of the effectiveness of acute tinnitus improvement following ISSNHL treatment.

[Application of vestibular function examination battery in the staging of vestibular function in Meniere's disease].

Objective:To investigate the staging of vestibular organ damage in Meniere's disease, based on the vestibular function examination battery. Methods:Thirty-nine patients, clinically diagnosed as unilateral Meniere's disease, underwent audiologic test and vestibular function examination battery, including ocular vestibular evoked myogenic potential（oVEMP）, cervical vestibular evoke myogenic potential（cVEMP）, and caloric tests. Based on the results of the vestibular function examination battery, the vestibular function was divided into 4 stages. StageⅠ: oVEMP, cVEMP, and caloric tests were normal; stage Ⅱ: any one test of the three examinations was abnormal; stage Ⅲ: two of the three examinations were abnormal; Stage Ⅳ: All the three examinations were abnormal. Results:According to the vestibular function staging strategy in this study, patients in stage Ⅰ, Ⅱ, Ⅲ, Ⅳ were 7.7%（3/39）, 30.8%（12/39）, 33.3%（13/39）, 28.2%（11/39） respectively in the 39 Meniere's disease patients. However, according to the current clinical staging strategy of Meniere's disease, patients of stage1, 2, 3, 4 were 20.5%（8/39）, 43.6%（17/39）, 28.2%（11/39）, and 7.7%（3/39） respectively. 37.5%（3/8） patients in stage 1 and 64.7%（11/17） patients in stage 2 had two or more abnormal vestibular organs. While all the patients in stage 4 had abnormal semicircular canals, utricle, and saccule. The stage of vestibular function was correlated with the distribution of current clinical staging strategy of Meniere's disease（P<0.05）. Conclusion:The combination of oVEMP, cVEMP and caloric tests can divide the vestibular function into four stages, which can be used as a supplement to the traditional vestibular evaluation and clinical staging based on audiology in Meniere's disease.

Altered Processing of Visual Stimuli in Vestibular Migraine Patients Between Attacks: A Combined VEP and sLORETA Study.

Objective: Vestibular migraine (VM) is one of the most common causes of recurrent vertigo, but the neural mechanisms that mediate such symptoms remain unknown. Since visual symptoms and photophobia are common clinical features of VM patients, we hypothesized that VM patients have abnormally sensitive low-level visual processing capabilities. This study aimed to investigate cortex abnormalities in VM patients using visual evoked potential (VEP) and standardized low-resolution brain electromagnetic tomography (sLORETA) analysis. Methods: We employed visual stimuli consisting of reversing displays of circular checkerboard patterns to examine "low-level" visual processes. Thirty-three females with VM and 20 healthy control (HC) females underwent VEP testing. VEP components and sLORETA were analyzed. Results: Patients with VM showed significantly lower amplitude and decreased latency of P1 activation compared with HC subjects. Further topographic mapping analysis revealed a group difference in the occipital area around P1 latency. sLORETA analysis was performed in the time frame of the P1 component and showed significantly less activity (deactivation) in VM patients in the frontal, parietal, temporal, limbic, and occipital lobes, as well as sub-lobar regions. The maximum current density difference was in the postcentral gyrus of the parietal lobe. P1 source density differences between HC subjects and VM patients overlapped with the vestibular cortical fields. Conclusion: The significantly abnormal response to visual stimuli indicates altered processing in VM patients. These findings suggest that abnormalities in vestibular cortical fields might be a pathophysiological mechanism of VM.

Impact of visual signals on axial segmental control during walking in patients with vestibular disorder and healthy persons.

Head and trunk control during standing in patients with vestibular disorder may depend on intact visual signal to override vestibular disturbance. It is unknown if such process during walking would change. Therefore, the aims of this study were to quantify (1) head and trunk control in healthy participants (HPs) and patients with unilateral vestibular hypofunction (UVH) during walking with and without visual manipulation; and (2) the correlation/association between vestibular function and head/trunk control during walking with visual manipulation in patients. Seventeen UVH patients and 15 HPs completed all the tests. They participated in the caloric test, which was used to examine vestibular function, and walked on a treadmill with and without visual manipulation. Head and trunk angular displacement and velocity were primary outcome measures, deviation of center of mass and step variability were secondary. Head roll angular displacement (7.38° ± 1.38 [mean ± SE] v.s. 12.95° ± 1.48, p = 0.004) and head-trunk correlation (in the pitch/sagittal plane: 0.22 ± 0.05 v.s. 0.38 ± 0.05, roll/frontal plane: 0.35 ± 0.06 v.s. 0.55 ± 0.06, p < 0.05) were significantly lower in patients compared to HPs. Head pitch angular velocity (8.58°/s ± 2.17 v.s. 14.23°/s ± 1.22, p = 0.026) and step width variability (0.075 ± 0.010 v.s. 0.083 ± 0.009, p = 0.04) increased with visual manipulation only in patients. No significant correlation/association was found between vestibular function and head/trunk control. Lower head-trunk correlation in patients suggests an independent head-trunk control strategy in response to vestibular impairment. Visual input could be used by patients to compensate for vestibular disturbance for head control and foot placement. Severe UVH may not lead to worse postural control compared to mild disorder.

Selected Blood Inflammatory and Metabolic Parameters Predicted Successive Bilateral Sudden Sensorineural Hearing Loss.

OBJECTIVES: To explore whether peripheral inflammatory, metabolic, and hemostatic parameters could predict the pathogenesis of successive bilateral sudden sensorineural hearing loss (SSNHL). METHODS: This study reviewed 33 patients with successive bilateral SSNHL and 215 patients with unilateral SSNHL. Clinical characteristics and hematological parameters were compared, including the inflammatory markers (like neutrophil lymphocyte ratio (NLR), monocyte lymphocyte ratio (MLR), and platelet lymphocyte ratio (PLR)) and metabolic features (including hypertension, triglyceridemia, dyslipidemia, and hyperglycemia), as well as hemostatic indices (including prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen). RESULTS: In the successive bilateral SSNHL group, older average onset age (48.67 ± 15.36 vs. 42.71 ± 13.58, p < 0.05), higher male to female ratio (18 : 15 vs. 112 : 103, p > 0.05), and poorer therapeutic efficacy (12% vs. 59%, p < 0.01) were observed than those in the unilateral SSNHL group. Compared to the unilateral SSNHL group, NLR, MLR, and PLR in the successive bilateral SSNHL group were significantly higher (NLR: 5.72 ± 2.23 vs. 4.45 ± 2.82, p = 0.01; MLR: 0.25 ± 0.15 vs. 0.17 ± 0.11, p < 0.01; PLR: 190.70 ± 69.79 vs. 148.18 ± 65.67; p < 0.01); the LDL level was significantly higher; yet, the HDL level was significantly lower (LDL: 3.79 ± 0.53 vs. 3.49 ± 0.74; HDL: 1.33 ± 0.32 vs. 1.44 ± 0.26; p < 0.05 for both); fibrinogen was significantly higher (4.03 ± 0.47 vs. 3.70 ± 0.65; p < 0.01). Logistic regression analysis demonstrated that the risk factors for successive bilateral SSNHL included age, NLR, MLR, PLR, LDL, HDL, diabetes, and fibrinogen. However, only NLR, MLR, PLR, diabetes, LDL, and HDL independently predicted successive bilateral SSNHL. CONCLUSION: Selected blood inflammatory markers combined with metabolic parameters were positively correlated with successive bilateral SSNHL.

SIRT1 protects cochlear hair cell and delays age-related hearing loss via autophagy.

Age-related hearing loss (AHL) is typically caused by the irreversible death of hair cells (HCs). Autophagy is a constitutive pathway to strengthen cell survival under normal or stress condition. Our previous work suggested that impaired autophagy played an important role in the development of AHL in C57BL/6 mice, although the underlying mechanism of autophagy in AHL still needs to be investigated. SIRT1 as an important regulator involves in AHL and is also a regulator of autophagy. Thus, we hypothesized that the modulation between SIRT1 and autophagy contribute to HC death and the progressive hearing dysfunction in aging. In the auditory cell line HEI-OC1, SIRT1 modulated autophagosome induction because of SIRT1 deacetylating a core autophagy protein ATG9A. The deacetylation of ATG9A not only affects the autophagosome membrane formation but also acts as a sensor of endoplasmic reticulum (ER) stress inducing autophagy. Moreover, the silencing of SIRT1 facilitated cell death via autophagy inhibition, whereas SIRT1 and autophagy activation reversed the SIRT1 inhibition media cell death. Notably, resveratrol, the first natural agonist of SIRT1, altered the organ of Corti autophagy impairment of the 12-month-old C57BL/6 mice and delayed AHL. The activation of SIRT1 modulates the deacetylation status of ATG9A, which acts as a sensor of ER stress, providing a novel perspective in elucidating the link between ER stress and autophagy in aging. Because SIRT1 activation restores autophagy with reduced HC death and hearing loss, it could be used as a strategy to delay AHL.

The diagnosis and treatment of a variant type of auricular sinus: postauricular sinus.

OBJECTIVES: To make otolaryngologists aware of the variant types of auricular sinus, we have performed a systematic review of patient diagnoses and presented our operative experiences. METHODS: From 2009 to 2013 in Sun Yat-Sen Memorial Hospital, there was a total of 20 children with the variant type of auricular sinuses including the comprehensive group. Postauricular sinuses have pits located posterior to the imaginary vertical line that is tangent to the external auditory canal. Sinuses that penetrate the cartilage and cause postauricular swelling or skin defects characterize type 1 of the variant type, while sinuses that adhere to the cartilage and cause preauricular or auricular swelling or skin defects characterize type 2. Patients with pits both anterior to and posterior to the imaginary vertical line comprise the comprehensive group. The patients who had infected underwent auricular sinusectomy using a dual approach, with accurate fistula tracing and proper cartilage removal. RESULTS: Sixteen children who had infected sinus underwent surgery, while the other four were asymptomatic. Ten children (62.5%) of 16 patients were diagnosed as type 1 of the variant type, 2 (12.5%) as type 2. Four children (25%) were diagnosis as the comprehensive group. The asymptomatic could not be defined as the sinuses location were unknown. Sixteen children (100%) of 16 patients who underwent surgery had a history of misdiagnosis and treatment. These patients did not experience recurrence over a 5-year follow-up period. CONCLUSION: The locations of pits and sinuses help to categorize the different types of auricular sinus. The effective method that we have described should be considered a viable way to reduce recurrence.

Trunk and Head Control During Walking in Patients With Unilateral Vestibular Hypofunction: Effect of Lower Limb Somatosensory Input.

OBJECTIVES: The aim of the study was to investigate (a) postural control, especially trunk and head control, in patients with unilateral vestibular hypofunction and healthy controls during walking on firm and foam surface and (b) the difference between the impact of left and right unilateral vestibular hypofunction, and correlation between trunk/head control and vestibular function in the patients. DESIGN: Thirteen patients and 13 healthy controls were recruited. Vestibular function was examined based on the canal paresis value. Participants walked on a treadmill on firm and foam surface. Peak-to-peak trunk (Troll and Tpitch) and head roll and pitch angle (Hroll and Hpitch) were calculated as primary outcome measures. RESULTS: In the unilateral vestibular hypofunction group but not healthy controls, Troll was significantly higher on foam than firm surface (P = 0.03). Tpitch was significantly higher on foam than firm surface in both groups (P = 0.02). Patients had significantly lower Hroll (P = 0.03) and Hpitch (P = 0.02) and lower head-trunk correlation in both medio-lateral (P = 0.05) and anteroposterior direction (P = 0.03) than those in the healthy control group. CONCLUSIONS: Patients with unilateral vestibular hypofunction seemed to rely more on lower limb somatosensory input for trunk control especially in the medio-lateral direction compared with healthy controls. Lower head sway and head-trunk correlation may suggest a more independent and successful head control strategy in patients.

Clinical Findings in Patients With Persistent Positional Nystagmus: The Designation of "Heavy and Light Cupula".

Objective: Direction-changing positional nystagmus (DCPN) had been observed as persistent horizontal apogeotropic and was considered as "cupulolithiasis or heavy cupula. " Recently, the concept of "light cupula" exhibiting persistent geotropic DCPN has been introduced. However, the light cupula is not systematically described, while the identification and diagnosis of "light cupula" should be improved. Here we investigated the underlying characteristics and therapeutic options designed to the "light" and "heavy" cupula, respectively; and summarized the clinical characteristics and therapeutic effect in the two groups. Methods: A total of 359 cases with vertigo and bilateral DCPN were found in the supine roll test. Only 25 patients with persistent DCPN were enrolled and followed up. According to the direction of nystagmus, we further divided the patients into "heavy cupula" (apogeotropic) and "light cupula" (geotropic) groups. We compared the incidence, characteristics of nystagmus and the efficacy of repositioning maneuver in the two groups. Results: Nine patients with persistent horizontal geotropic DCPN were confirmed as "light cupula," other 16 patients with persistent horizontal ageotropic DCPN were confirmed as heavy cupula. All 25 patients had null plane; the mean value and standard deviation of the null plane in light cupula and heavy cupula was 25.67 ± 9.31° and 27.06 ± 6.29°, respectively. The mean value and standard deviation of the termination plane in light cupula was 28.78 ± 10.00°, and 30.25 ± 6.53° in heavy cupula. There was no statistical significance between the two groups. We found that the direction of evoked nystagmus in the supine position was toward the intact side in light cupula, while in heavy cupula, it was toward the lesion side. The null plane appeared on the lesion side. For light cupula patients, the effect was not obvious at Day-7 after the treatment, however, treatment for most heavy cupula patients were effective. All patients recovered after 30 days of treatment. Conclusion: The null plane is crucial in determining the lesion side for light or heavy cupula. Although the short-term therapeutic effect of the light cupula is not as promising as the effect seen in heavy cupula, the long-term prognosis in both groups is comparable; with all patients recovered after 30 days of treatment. Study design: This is a retrospective cohort study.

Sirtuin 1 and Autophagy Attenuate Cisplatin-Induced Hair Cell Death in the Mouse Cochlea and Zebrafish Lateral Line.

Cisplatin-induced ototoxicity is one of the major adverse effects in cisplatin chemotherapy, and hearing protective approaches are unavailable in clinical practice. Recent work unveiled a critical role of autophagy in cell survival in various types of hearing loss. Since the excessive activation of autophagy can contribute to apoptotic cell death, whether the activation of autophagy increases or decreases the rate of cell death in CDDP ototoxicity is still being debated. In this study, we showed that CDDP induced activation of autophagy in the auditory cell HEI-OC1 at the early stage. We then used rapamycin, an autophagy activator, to increase the autophagy activity, and found that the cell death significantly decreased after CDDP injury. In contrast, treatment with the autophagy inhibitor 3-methyladenine (3-MA) significantly increased cell death. In accordance with in vitro results, rapamycin alleviated CDDP-induced death of hair cells in zebrafish lateral line and cochlear hair cells in mice. Notably, we found that CDDP-induced increase of Sirtuin 1 (SIRT1) in the HEI-OC1 cells modulated the autophagy function. The specific SIRT1 activator SRT1720 could successfully protect against CDDP-induced cell loss in HEI-OC1 cells, zebrafish lateral line, and mice cochlea. These findings suggest that SIRT1 and autophagy activation can be suggested as potential therapeutic strategies for the treatment of CDDP-induced ototoxicity.

Characterizing Patients with Unilateral Vestibular Hypofunction Using Kinematic Variability and Local Dynamic Stability during Treadmill Walking.

Here, we aimed to compare the unstable gait caused by unilateral vestibular hypofunction (UVH) with the normal gait. Twelve patients with UVH and twelve age-matched control subjects were enrolled in the study. Thirty-four markers were attached to anatomical positions of each participant, and a three-dimensional (3D) motion analysis system was used to capture marker coordinates as the participants walked on a treadmill. The mean standard deviation of the rotation angles was used to represent gait variability. To explore gait stability, local dynamic stability was calculated from the trunk trajectory. The UVH group had wider step width and greater variability of roll rotation at the hip than the control group (P < 0.05). Also, the UVH group had lower local dynamic stability in the medial-lateral (ML) direction than the control group (P < 0.05). By linear regression analysis, we identified a linear relationship between the short-term Lyapunov exponent and vestibular functional asymmetry. The result implies that UVH-induced asymmetry can increase posture variability and gait instability. This study demonstrates the potential for using kinematic parameters to quantitatively evaluate the severity of vestibular functional asymmetry. Further studies will be needed to explore the clinical effectiveness of such approaches.

The miR-34a/Bcl-2 Pathway Contributes to Auditory Cortex Neuron Apoptosis in 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.

miR-34a/Bcl-2 signaling pathway contributes to age-related hearing loss by modulating hair cell apoptosis.

MicroRNAs, such as miR-34, have been reported to influence age-related diseases. In this study, we explored the role of the miR-34a/Bcl-2 signaling pathway in age-related hearing loss (AHL). Using an AHL mouse model (C57BL/6), we found that the expression of miR-34a in the cochlea increased with age, whereas expression of Bcl-2 decreased. Increasing the amount of a miR-34a mimetic in a mouse auditory cell line (HEI-OC1) inhibited Bcl-2, leading to enhanced apoptosis; in contrast, miR-34a inhibition produced the opposite effect. Our results support a link between age-related cochlear hair cell apoptosis and miR-34a/Bcl-2 signaling. The latter may thus serve as a potential target for AHL therapy.

Resveratrol Promotes Recovery of Hearing following Intense Noise Exposure by Enhancing Cochlear SIRT1 Activity.

The sirtuin SIRT1 is a highly conserved nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylase known to have protective effects against a wide range of neurological disorders. In the present study, we discovered that C57BL/6 mice fed a long-term diet supplemented with high-dose resveratrol exhibited increased cochlear SIRT1 activity and presented a better recovery of hearing and less loss of hair cells after intense noise exposure compared with those fed a standard chew. Moreover, resveratrol attenuated cochlear SIRT1 decrease and reduced oxidative stress in the cochlea after noise exposure. These results suggest a considerable therapeutic potential of resveratrol for the treatment of noise-induced hearing loss.