Teru Kamogashira

Reactive Oxygen Species, Apoptosis, and Mitochondrial Dysfunction in Hearing Loss

Reactive oxygen species (ROS) production is involved in several apoptotic and necrotic cell death pathways in auditory tissues. These pathways are the major causes of most types of sensorineural hearing loss, including age-related hearing loss, hereditary hearing loss, ototoxic drug-induced hearing loss, and noise-induced hearing loss. ROS production can be triggered by dysfunctional mitochondrial oxidative phosphorylation and increases or decreases in ROS-related enzymes. Although apoptotic cell death pathways are mostly activated by ROS production, there are other pathways involved in hearing loss that do not depend on ROS production. Further studies of other pathways, such as endoplasmic reticulum stress and necrotic cell death, are required.

Noisy galvanic vestibular stimulation induces a sustained improvement in body balance in elderly adults.

Vestibular dysfunction causes postural instability, which is prevalent in the elderly. We previously showed that an imperceptible level of noisy galvanic vestibular stimulation (nGVS) can improve postural stability in patients with bilateral vestibulopathy during the stimulus, presumably by enhancing vestibular information processing. In this study, we investigated the after-effects of an imperceptible long-duration nGVS on body balance in elderly adults. Thirty elderly participants underwent two nGVS sessions in a randomised order. In Session 1, participants received nGVS for 30 min twice with a 4-h interval. In Session 2, participants received nGVS for 3 h. Two-legged stance tasks were performed with eyes closed while participants stood on a foam rubber surface, with and without nGVS, and parameters related to postural stability were measured using posturography. In both sessions, the postural stability was markedly improved for more than 2 h after the cessation of the stimulus and tended to decrease thereafter. The second stimulation in Session 1 caused a moderate additional improvement in body balance and promoted the sustainability of the improvement. These results suggest that nGVS can lead to a postural stability improvement in elderly adults that lasts for several hours after the cessation of the stimulus, probably via vestibular neuroplasticity.

Effect of Noisy Galvanic Vestibular Stimulation on Ocular Vestibular-Evoked Myogenic Potentials to Bone-Conducted Vibration

Objective Galvanic vestibular stimulation (GVS) delivered as zero-mean current noise (noisy GVS) has been shown to improve static and dynamic postural stability probably by enhancing vestibular information. The purpose of this study was to examine the effect of an imperceptible level noisy GVS on ocular vestibular-evoked myogenic potentials (oVEMPs) in response to bone-conducted vibration (BCV). Materials and methods oVEMPs to BCV were measured during the application of white noise GVS with an amplitude ranging from 0 to 300 µA [in root mean square (RMS)] in 20 healthy subjects. Artifacts in the oVEMPs caused by GVS were reduced by inverting the waveforms of noisy GVS in the later half of the stimulus from the one in the early half. We examined the amplitudes of N1 and N1–P1 and their latencies. Results Noisy GVS significantly increased the N1 and N1–P1 amplitudes (p < 0.05) whereas it had no significant effects on N1 or P1 latencies (p > 0.05). Noisy GVS had facilitatory effects in 79% of ears. The amplitude of the optimal stimulus was 127 ± 14 µA, and it increased the N1 and N1–P1 amplitude by 75.9 ± 15% and 47.7 ± 9.1%, respectively, as compared with 0 µA session (p < 0.05). Conclusion Noisy GVS can increase the amplitude of oVEMPs to BCV in healthy subjects probably via stochastic resonance. The results of the present study suggest that noisy GVS may improve static and dynamic postural stability by enhancing the function of the vestibular afferents.

Clinical Characteristics of Patients With Abnormal Ocular/Cervical Vestibular Evoked Myogenic Potentials in the Presence of Normal Caloric Responses

Objective: To investigate the clinical features and vestibular symptoms of patients with abnormal ocular vestibular evoked myogenic potentials (oVEMPs) and/or cervical VEMPs (cVEMPs) in the presence of normal caloric responses. Study Design: Retrospective chart review. Setting: Tertiary referral center. Methods: One thousand five hundred twenty-one consecutive patients with balance problems who underwent the caloric, cVEMP, and oVEMP tests were included, and patients who showed abnormal oVEMPs and/or cVEMPs in the presence of normal caloric responses were selected. Clinical characteristics, diagnoses, and vestibular symptoms of the patients were analyzed. Results: Of the 1521 patients, 227 (15%) were found to have abnormal oVEMPs and/or cVEMP responses with normal caloric responses. Benign paroxysmal positional vertigo (BBPV), Meniere’s disease, and vestibular migraine were the common diagnoses of these patients. Eighty-one patients (36%) could not be diagnosed with a recognizable disease. Multiple episodes of spinning vertigo with a duration of seconds to hours were their most common vestibular symptoms. Conclusion: BPPV, Meniere’s disease, and vestibular migraine are the most frequent diagnoses showing abnormal oVEMP and/or cVEMPs without canal paresis. Apart from these clinical entities, a portion of undiagnosed patients with multiple episodes of vertigo might have a disease that involves the otolith organs only.

Characteristics of vertigo and the affected vestibular nerve systems in idiopathic bilateral vestibulopathy

Abstract Conclusion: Vertigo attacks in IBV patients involving both the superior and inferior vestibular nerve systems were significantly more severe than vertigo attacks in patients with selective involvement of the inferior vestibular nerve system alone. Objective: To investigate the relationship between the frequency and duration of vertigo and the affected vestibular nerve system in idiopathic bilateral vestibulopathy (IBV). Methods: This study categorized 44 IBV patients into the following three sub-groups according to the affected vestibular nerve system: superior, inferior, and mixed type. These patients were also categorized into the following three sub-groups according to their clinical time course: progressive type showing no episodes of vertigo, sequential type showing recurrent vertigo attacks and single-attack type showing a single episode of vertigo. Results: Ten, 11 and 23 patients were classified as the superior, the inferior, and the mixed type, respectively. Seventeen, 23, and four patients were classified as the progressive, the sequential, and the single-attack type, respectively. For the patients having one or more vertigo attacks, the duration of the vertigo attack was longer than 24 h in 69% of the mixed type, and the duration of vertigo in the mixed type was significantly longer than that in the inferior type (p < 0.05).

Power spectral analysis of postural sway during foam posturography in patients with peripheral vestibular dysfunction.

Objective To assess the frequency-domain characteristics of postural instability caused by peripheral vestibular dysfunction by performing a power spectral analysis of the center of pressure (COP) sway during foam posturography. Methods Data were obtained from 78 patients and 163 controls. Two-legged stance tasks were performed in 4 conditions: eyes open with and without foam rubber, and eyes closed with and without foam rubber. We estimated the power spectrum of the acceleration signal using the maximum entropy method. The areas under the curve (AUCs) of power spectral density of the COP were calculated across low-frequency (0.02 to 0.1 Hz, LF-AUC), middle-frequency (0.1 to 1Hz, MF-AUC), and high-frequency (1 to 10 Hz, HF-AUC) ranges. We performed binomial logistic regression analyses to see whether the AUCs of selected bandwidths of COP have a stronger association with the presence of peripheral vestibular dysfunction in comparison with the velocity and area in the eyes closed/foam rubber condition. Results In both the controls and patients, the MF-AUC was significantly larger than the LF-AUC or HF-AUC in the eyes closed/foam rubber condition. In this condition, the presence of peripheral vestibular dysfunction had a significantly positive relationship with MF-AUC and HF-AUC (p < 0.05) and the MF-AUC of the anterior-posterior axis showed a stronger association with the presence of peripheral vestibular dysfunction than area. Conclusion An increase in activity at middle frequency movements could be characteristic of peripheral vestibular dysfunction when standing on foam rubber with the eyes closed.

Manganese superoxide dismutase influences the extent of noise-induced hearing loss in mice

Reactive oxygen species (ROS) generation is one of the mechanisms underlying noise-induced hearing loss (NIHL). Manganese superoxide dismutase (Mn-SOD), an antioxidant enzyme acting within the mitochondria, converts toxic superoxide to hydrogen peroxide. We investigated the role of Mn-SOD in NIHL by examining the extent of hearing loss and hair cell damage after noise exposure in C57BL/6 wild-type (WT) mice and Mn-SOD heterozygous knockout (HET) mice (n=6 each). Both HET and WT mice were exposed to 120dB sound pressure level at 4kHz octave band noise for 4h. Auditory brainstem responses (ABRs) were used to evaluate hearing thresholds before noise exposure, and at 1h, and 1, 3, 7, and 14days after exposure. The mice were euthanized 14days after noise exposure for examination of the cochlear pathology. Mean ABR thresholds were similarly elevated at all frequencies in both groups 1h after noise exposure, but were significantly worse, particularly at 4kHz, on post-noise exposure days 7 and 14 in HET mice compared with WT mice. Outer hair cell damage was significantly greater in all cochlear turns in HET mice compared with WT mice. Collectively, these findings suggest that Mn-SOD plays an important role in protecting the cochlea from noise-induced damage.

Development of auditory skills after cochlear implantation in children with inner ear malformations

Abstract Conclusions: CI improves hearing thresholds and auditory skills in children with most types of inner ear malformations. However, the development of sound detection skills is not as good as it is in children without inner ear malformations. Objectives: To investigate the influence of inner ear malformations on development of auditory skills after cochlear implantation (CI). Methods: Records of 20 children with inner ear malformations who underwent cochlear implantation before 4 years of age and followed up for more than 2 years were retrospectively reviewed. Hearing thresholds, the Meaningful Auditory Integration Scale (MAIS), and Meaningful Use of Speech Scale (MUSS) scores before and after CI were analyzed and compared with 20 age-matched deaf children who underwent CI. Results: The children with inner ear malformations showed significant improvements in hearing thresholds and the MAIS and MUSS scores 1 year after CI (p < 0.01). However, their development of the MAIS scores was significantly delayed compared to children without inner ear malformations (p < 0.05), while there was no significant difference in development of the MUSS scores between them. Significant improvements in hearing thresholds and the MAIS and MUSS scores were observed in cochlear hypoplasia and incomplete partition (p < 0.05).

Functionally and morphologically damaged mitochondria observed in auditory cells under senescence-inducing stress

We aimed at determining the mitochondrial function in premature senescence model of auditory cells. Short exposure to H2O2 (1 h, 0.1 mM) induced premature cellular senescence in House Ear Institute-Organ of Corti 1 auditory cells. The transmission electron microscopy analysis revealed that damaged mitochondria and autophagosomes containing dense organelles appeared in the auditory cells after short exposure to H2O2. The branch and junction parameters of the skeletonized image of the mitochondria were found to decrease significantly in H2O2-treated cells. A branched reticulum of tubules was poorly formed, featuring coexistence of numerous tiny clusters along with few relatively large entities in the H2O2-treated cells. In terms of bioenergetics, H2O2-treatment led to the dose-dependent decrease in mitochondrial membrane potential in the auditory cells. The fragmented mitochondria (fusion < fission) were in a low potential. In addition, the potential of hyperfused mitochondria (fusion > fission) was slightly lower than the control cells. The short-time exposure of live auditory cells to H2O2 damaged the mitochondrial respiratory capacity without any effect on the baseline ATP production rates. The vulnerability of the mitochondrial membrane potential to the uncoupling reagent was increased after H2O2 treatment. Our findings indicated that the mitochondrial dysfunction due to the decline in the O2 consumption rate should be the first event of premature senescence process in the auditory cells, resulting in the imbalance of mitochondrial fusion/fission and the collapse of the mitochondrial network.Auditory system senescence: Mitochondrial dynamics and respirationThe mitochondrial morphology and physiology could influence the process of age-related hearing loss. Prof. Tatsuya Yamasoba’s research group at the University of Tokyo has examined the functional changes of mitochondria in terms of its respiratory function, membrane potential and morphology under premature senescence induced by oxidative stress in an auditory cell line. The morphological and functional mitochondrial damage were observed as the respiratory capacity deficiency and the fluctuation of the fusion/fission balance. Their results provide evidence of the fundamental interdependence between mitochondrial metabolic activity and its network structure in premature senescence process of auditory cells. This is a pioneer study to indicate the influence of mitochondrial dynamics and respiratory system on the premature senescence process of auditory cells. Further studies into inter cellular communication including cytoskeleton and nucleus can help us understand the etiology underlying age-related hearing loss.

Prediction of Intraoperative CSF Gusher and Postoperative Facial Nerve Stimulation in Patients with Cochleovestibular Malformations Undergoing Cochlear Implantation Surgery

OBJECTIVE To determine parameters in computed tomography (CT) of the temporal bone that would be useful for prediction of cerebrospinal fluid (CSF) gusher during cochlear implantation (CI) surgery and postoperative facial nerve stimulation (FNS) in patients with inner ear malformations. STUDY DESIGN Retrospective study. SETTING Tertiary referral center. PATIENTS Three hundred seventy-five cases who had undergone CI surgery including 54 inner ear malformation cases were analyzed. MAIN OUTCOME MEASURES The diameters of the cochlea modiolar base and porus of the internal auditory canal (IAC), length of IAC, diameter of the vestibular aqueduct (VA) at the operculum, and presence or absence of the modiolus of the cochlea were evaluated by using CT. RESULTS CSF gusher occurred in 12 (22%) cases, in whom the diameters of the cochlea modiolar base (2.7 ± 0.6 mm, p < 0.01) and widths of VA (1.5 ± 1.0 mm, p < 0.05) were significantly greater compared with those without gusher. The modiolus was significantly less formed (8%) in cases with gusher compared with those without gusher (p < 0.01). FNS occurred in 10 (19%) cases, and the widths of VA and lengths of IAC were significantly shorter in these cases compared with those without FNS (p < 0.05). CONCLUSION The absence of the modiolus, larger cochlea modiolar base, and wider VA in CT images were important predictors of CSF gusher during CI surgery. The width of VA was also an important factor in predicting FNS.