Mitsuya Suzuki

Ebselen prevents noise-induced excitotoxicity and temporary threshold shift.

This investigation tested the hypothesis that a noise-induced temporary threshold shift (TTS) can be attenuated by a peroxynitrite scavenger, ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one). Guinea pigs received an oral dose of the vehicle or 10 mg/kg ebselen 1h before exposure to 115 dB SPL 4-kHz octave band noise for 3 h. In controls, auditory brainstem response (ABR) thresholds increased by 25-45 dB immediately after noise and returned to pre-exposure baseline thresholds 7 days later. Ebselen eliminated this ABR threshold shift following noise exposure. In controls, swelling of the afferent dendrites beneath the inner hair cells was evident immediately after noise, whereas ebselen significantly reduced this pathology. These findings suggest that scavenging peroxynitrite can attenuate noise-induced excitotoxicity and, thereby, TTS.

Novel subtype of idiopathic bilateral vestibulopathy: bilateral absence of vestibular evoked myogenic potentials in the presence of normal caloric responses

To characterize clinical features of those patients who showed an absence of vestibular evoked myogenic potential (VEMP) responses in the presence of normal caloric responses bilaterally, we reviewed clinical records of 1,887 consecutive outpatients who complained of balance problems, and identified three patients, who showed absent VEMPs in the presence of normal caloric responses bilaterally with unknown causes. All three patients had episodes of recurrent vertigo without spontaneous, gaze-evoked, or positional nystagmus at the time of examination. They complained of oscillopsia while moving their body or head and showed positive Romberg’s signs. Drawing on these cases, we underscore the importance of examining the function of the inferior vestibular nerve system, even with no nystagmus and normal caloric findings, in patients complaining of dizziness or oscillopsia during locomotion.

Effect of noise exposure on blood-labyrinth barrier in guinea pigs

The influence of noise exposure on the endothelial transport system in the cochlea was investigated using cationic polyethyleneimine (PEI), since systemically administered PEI passes through the capillary endothelial cell and attaches to basal lamina (BL) anionic sites in the cochlea. Under general anesthesia, all guinea pigs were administered an intravenous injection of 0.5% PEI. Thirty minutes later, five animals were exposed to noise (10 kHz, broad band noise, 105 dB SPL) for 30 min, via speakers inserted into the external auditory canal. The remaining five animals (controls) were left without noise exposure for 1 h following PEI injection. All guinea pigs were then immediately sacrificed, and the bony labyrinths were removed. PEI distribution on the BL was assessed in the stria vascularis, spiral ligament, basilar membrane, spiral limbus and Reissners membrane throughout the cochlea with transmission electron microscopy. Compared to control animals, PEI distribution in the noise-exposed animals was significantly increased in the strial vessels of the basal and second turns and in Reissners membrane of all turns. In the spiral ligament, basilar membrane and spiral limbus, no significant difference in PEI distribution was observed between the control and noise-exposed animals. These findings indicate that noise exposure increases macromolecular transport in the stria vascularis but not in the spiral ligament, spiral limbus and basilar membrane and that systemically administered macromolecules are more readily transported to Reissners membrane by noise exposure.

Effect of vitamin C depletion on age-related hearing loss in SMP30/GNL knockout mice

Using senescence marker protein 30 (SMP30)/gluconolactonase (GNL) knockout (KO) mice, which cannot synthesize vitamin C (VC), we examined whether modulating VC level affects age-related hearing loss (AHL). KO and wild-type (WT) C57BL/6 mice were given water containing 1.5 g/L VC [VC(+)] or 37.5mg/L VC [VC(-)]. At 10 months of age, KO VC(-) mice showed significant reduction in VC level in the inner ear, plasma, and liver, increase in auditory brainstem response (ABR) thresholds, and decrease in the number of spiral ganglion cells compared to WT VC(-), WT VC(+), and KO VC(+) mice. There were no differences in VC level in the inner ear, ABR thresholds, or the number of spiral ganglion cells among WT VC(-), WT VC(+), and KO VC(+) mice. These findings suggest that VC depletion can accelerate AHL but that supplementing VC may not increase VC level in the inner ear or slow AHL in mice.

Changes in cell proliferation in rat and guinea pig cochlea after aminoglycoside-induced damage

Cell proliferation in the cochleae of guinea pigs and rats was investigated after systemic application of kanamycin sulfate (KM) and ethacrynic acid (EA). Bromodeoxyuridine (BrdU) was injected daily for 10 days, after which the number of BrdU-positive cells was counted in paraffin sections of the cochlea. Only a few BrdU-positive cells were present in the spiral ligament and among the acoustic nerve fibers in the non-deafened control animals. Animals treated with KM and EA had profound hearing loss and significant increases in the number of BrdU-positive cells in the spiral ligament and among the acoustic nerve fibers. No BrdU-positive cells were found in the auditory sensory epithelium of any animal. These findings suggest that in the mature mammalian cochlea cell proliferation increases in nonsensory regions after ototoxic damage but may not occur in the auditory sensory epithelium.

Cochlear damage due to germanium-induced mitochondrial dysfunction in guinea pigs

This investigation addressed the effect of germanium dioxide (GeO(2))-induced mitochondrial dysfunction on hearing acuity. Guinea pigs were fed chow that contained 0%, 0.15%, or 0.5% GeO(2). The animals that were fed 0.5% GeO(2) for 2 months developed hearing impairment chiefly due to degeneration of stria vascularis and cochlear supporting cells, which exhibited electron-dense mitochondrial inclusions. Cytochrome c oxidase activity was decreased in the skeletal muscles and kidney, which also exhibited electron-dense mitochondrial inclusions. No apparent pathological changes were observed in the utricle, semicircular canal, or among the vestibular nerve fibers, or in the liver or heart. The untreated animals and those treated with 0.15% GeO(2) did not exhibit hearing impairment or pathological changes in any organs. These findings suggest that administration of 0.5% GeO(2) induces mitochondrial dysfunction in the stria vascularis and supporting cells in the cochlea, as in the skeletal muscles and kidney, thereby causing hearing impairment in the guinea pigs.

Overexpression of ErbB‐2 Protein in Human Middle Ear Cholesteatomas

Objective: The purpose of this study is to verify the hypothesis that ErbB‐2 protein is overexpressed in human middle ear cholesteatomas and to elucidate the relationship between overexpression of ErbB‐2 protein, cell proliferation, and apoptosis.

Time course of apoptotic cell death in guinea pig cochlea following intratympanic gentamicin application.

Conclusions. The present study showed that the molecular signal that promotes the death of cochlear hair cells (HCs) induced by intratympanic gentamicin application is significant before the manifestation of morphological and functional changes. Objectives. The effect of agents that protect the HCs from aminoglycoside ototoxicity is influenced by the timing of their administration. However, morphological, functional and molecular changes in the cochlea in the early stage following aminoglycoside application have rarely been studied. Therefore, we examined the chronological changes in the cochlea following intratympanic gentamicin application. Materials and methods. Small pieces of gelatin sponge soaked with gentamicin (40 mg/ml) were placed on the round window membrane of mature guinea pigs, and the tympanic bulla was filled with gentamicin solution. They were euthanized at 6, 12, 18, 24, and 48 h following gentamicin application. Auditory brainstem responses (ABRs) were measured before gentamicin application and immediately before euthanasia, and the extent of missing and TUNEL-positive HCs was evaluated. Results. ABR thresholds significantly increased 18 h or later following gentamicin application, and the loss of HCs was seen at 24 and 48 h. While functional and morphological changes were not evident until 18 h after gentamicin application, substantial amounts of TUNEL-positive HCs appeared at 12 h.

Transgene expression in mature guinea pig cochlear cells in vitro

Inoculation of adenovirus vectors in vivo has induced transgene expression in a variety of cochlear cells, but not hair cells or supporting cells in most previous studies. Specific hair cell inoculation by viral vectors has not been demonstrated in the mature guinea pig cochlea in vitro. We injected an Adex1CAlacZ into the mature guinea pig cochlear explants, which were incubated for 24-72 h. We found many lacZ-positive cells in a variety of tissues including the spiral ganglion and stria vascularis. Transgene expression was also found in the outer hair cells and supporting cells, such as the Deiters cells and pillar cells. These findings indicate that adenovirus vectors can be transfected into mature guinea pig hair cells and supporting cells in culture.

Audiological Characteristics of Hearing Loss Following Meningitis

Meningitis is one of the leading causes of acquired sensorineural hearing loss in childhood, and many retrospective and prospective studies and case reports have been published. However, they have seldom discussed the nature of postmeningitic hearing loss from the audiological point of view. This study reports the results of audiological examinations performed on 5 patients suffering from hearing loss following meningitis. Extremely poor word discrimination scores as compared with pure-tone audiograms were common in all 5 cases. Type IV Békésy tracings were observed in 2 cases. Discrepancies between pure-tone audiograms and subjective hearing sensation and between pure-tone audiograms and ABR recordings were noted in 2 cases. These results suggest that varying degrees of retrocochlear involvement complicating the inner ear damage are the audiological characteristics of hearing loss following meningitis.