Mototane Komeda

Direct inner ear infusion of dexamethasone attenuates noise-induced trauma in guinea pig

The protective effect of dexamethasone (DEX) against noise-induced trauma, as reflected in hair cell destruction and elevation in auditory brainstem response (ABR) sensitivity, was assessed in guinea pigs. The animals were administered DEX (1, 10, 100, and 1000 ng/ml) or artificial perilymph (AP) via a mini-osmotic pump directly into scala tympani and, on the fourth day after pump implantation, exposed to 120 dB SPL octave band noise, centered at 4 kHz, for 24 h. Animals receiving DEX demonstrated a dose-dependent reduction in noise-induced outer hair cell loss (significant at 1, 10 and 100 ng/ml DEX animals compared to AP control animals) and a similar attenuation of the noise-induced ABR threshold shifts, observed 7 days following exposure (significant at 100 ng/ml DEX animals compared to AP control animals). These physiological and morphological results indicate that direct infusion of DEX into the perilymphatic space has protective effects against noise-induced trauma in the guinea pig cochlea.

Intra-cochlear administration of dexamethasone attenuates aminoglycoside ototoxicity in the guinea pig

This study demonstrates the attenuation of aminoglycoside ototoxicity by cochlear infusion of dexamethasone (Dex) using a microcannulation-osmotic pump delivery system. The results indicate that treating the cochlea with Dex both before and after kanamycin administration was more effective in preventing ototoxicity than Dex treatment only after kanamycin administration. A concentration of 1 ng/ml Dex showed the greatest protective effect on both kanamycin-induced threshold shift of the auditory brainstem response and outer hair cell survival. These results show that the Dex treatment attenuates both functional and structural damage of the inner ear from aminoglycoside toxicity.

The influence of interleukin-1 receptor antagonist transgene on spiral ganglion neurons

The cytokine interleukin-1beta (IL-1) has been shown to induce the secretion of NGF and GDNF in several types of neuronal populations. IL-1 has also been shown to mediate immune response following trauma or presence of foreign antigens. We investigated the influence of an IL-1 antagonist on the survival of spiral ganglion neurons in inner ears in which hair cells have been eliminated. We used a replication-deficient adenoviral vector containing the human IL-1 receptor antagonist (IL-1ra) cDNA. Guinea pigs were bilaterally deafened with ototoxic drugs. One week later their left cochleae were inoculated with the IL-1ra vector, designated Ad.IL-1ra. The vector was delivered by injection through the cochlear round window. IL-1ra protein levels within the perilymph of Ad.IL-1ra-injected animals were measured with ELISA and found to be significantly elevated compared to our controls. Spiral ganglion cell counts in experimental ears revealed a lower density of neurons after Ad.IL-1ra inoculation. Taken together, the data suggest that the Ad.IL-1ra-infected cochlear cells synthesized the transgenic human IL-1ra protein, which was then secreted by the cells into the perilymph, resulting in an accelerated neuronal degeneration in hair cell-depleted ears.

Glutamate-induced intracellular Ca2+ elevation in isolated spiral ganglion cells of the guinea pig cochlea.

Intracellular calcium concentrations ([Ca2+]i) in acutely isolated spiral ganglion cells (SGCs) of the guinea pig cochlea were measured using digital imaging microscopy and the Ca(2+)-sensitive fluorescence dye fura-2. L-glutamate increased [Ca2+]i in SGCs with neuritic processes but did not lead to an increase in [Ca2+]i in SGCs without neuritic processes. The depolarization induced by high K+ (150 mM) solution increased [Ca2+]i in both SGCs, with and without neuritic processes. The L-glutamate-induced [Ca2+]i elevation was abolished in the absence of extracellular Ca2+. We thus propose that the increase of [Ca2+]i during L-glutamate stimulation is mainly related to an influx of extracellular Ca2+. The excitatory amino acids, probably L-glutamate, may function as a neurotransmitter of the hair cell-afferent nerve synapse in the guinea pig cochlea.

Hearing results for ossicular reconstruction using a cartilage-connecting hydroxyapatite prosthesis with a spearhead.

Objective: Assessment of the efficacy of ossicular reconstruction using a cartilage-connecting hydroxyapatite prosthesis designed with a spearhead to reduce extrusion and dislocation of the implant. Patients: All patients undergoing ossicular reconstruction after chronic ear surgery, connecting the cartilage to the prosthesis, with a minimum of 1 year of postoperative follow-up. Main Outcome Measures: Postoperative change in pure-tone averages. Air-bone gap closures, and implant extrusion rates. Results: Overall mean pure-tone averages improved by 12.2 dB (ranged between −40 and 60 dB). In total, 68.4% of the patients achieved an air-bone gap less than 20 dB. Gains in the mean air conduction thresholds were 9.5 dB in cases of partial ossicular reconstruction and 14.9 dB in cases with total ossicular reconstruction (p < 0.05). The overall extrusion rate was 4.21%. Conclusion: The cartilage-connecting hydroxyapatite prosthesis with a spearhead was found to restore hearing to a satisfactory level. The extrusion rate was relatively low. The cartilage-connecting hydroxyapatite prosthesis with a spearhead is an effective ossicular implant and offers an attractive alternative for ossicular reconstruction, particularly for total ossicular reconstructions.

Auditory pathway and auditory brainstem response in mice lacking NMDA receptor ϵ1 and ϵ4 subunits

Abstract There is considerable evidence that the N -methyl- d -aspartate receptor ((NMDAR) is a component of excitatory amino acid synapses in the ascending auditory pathway. The availability of mice that are defective in NMDAR ϵ 1 or NMDAR ϵ 4 subunit paves the way for investigations on the role of this receptor in auditory function. Non-radioactive in situ hybridization was used in the parent C57/6J wild strain to determine if these subunits are normally expressed in cochlear nucleus (CN) and superior olivary complex (SOC) and to confirm their absence in the respective mutant mice. Evoked auditory brainstem response (ABR) to normal acoustic stimulation was investigated to assess function. In situ hybridization revealed the expression of NMDAR ϵ 1 and ϵ 4 subunits mRNAs in major neuronal types in the CN and SOC of the wild type mice while ϵ 1 and ϵ 4 expression were absent in their respective mutant mice. The ABR threshold for the ϵ 1 mutant mice was similar to that of wild type mice however the threshold for the ϵ 4 mutant mice was significantly elevated. These results suggest a role for the NMDAR ϵ 4 in normal auditory functions while the NMDAR ϵ 1 may have a less critical function under normal conditions.

THE HEARING RESULTS OF OUR OPERATIVE METHOD USING A CARTILAGE CONNECTING HYDROXYAPATITE PROSTHESIS WITH A SPEARHEAD

In 1992, we newly designed a cartilage connecting hydroxyapatite prosthesis with a spearhead. The concept of this new prosthesis is to avoid the extrusion and dislocation of hydroxyapatite prostheses. This new prosthesis has a spearhead on the top and the cartilage and prosthesis are connected to each other using this spearhead. In 1995, we established a database for the hearing results of all tympanoplasty cases. From this database we selected 302 cases who underwent tympanoplasty with the cartilage connecting hydroxyapatite prosthesis. When we cannot preserve the tendon of the tensor tympani muscle in a severely diseased middle ear, we use the cartilage connecting hydroxyapatite prosthesis. There are two types of prostheses. We select a partial type of prosthesis when stapes is present, and a total type when stapes is absent. We show the extrusion rate and hearing results. The postoperative hearing levels have remained stable throughout the 7 years observation period.