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Zha, Dingjun

Publications and source records attributed to Zha, Dingjun.

Regional up-regulation of NOX2 contributes to the differential vulnerability of outer hair cells to neomycin

Highlights: • Even and low NOX2 expression in the outer hair cells (OHCs) in healthy conditions. • Regional and specific induction of NOX2 in the basal turn after neomycin treatment. • Inhibition of NOX2 significantly alleviates OHCs damage and hearing loss caused by neomycin. • ROS generation due to increased NOX2 promotes OHCs apoptosis. In hearing loss induced by aminoglycoside antibiotics, the outer hair cells (OHCs) in the basal turn are always more susceptible than OHCs in the apical turn, while the underlying mechanisms remain unknown. In this study, we reported that NAPDH oxidase 2 (NOX2) played an important role in the OHCs damage preferentially in the basal turn. Normally, NOX2 was evenly expressed in OHCs among different turns, at a relatively low level. However, after neomycin treatment, NOX2 was dominantly induced in OHCs in the basal turn. In vivo and in vitro studies demonstrated that inhibition of NOX2 significantly alleviated neomycin-induced OHCs damages, as seen from both the cleaved caspase-3 and TUNEL staining. Moreover, gp91 ds-tat delivery and DHE staining results showed that NOX2-derived ROS was responsible for neomycin ototoxicity. Taken together, our study shows that regional up-expression of NOX2 and subsequent increase of ROS in OHCs of the basal turn is an important factor contributing to the vulnerability of OHCs there, which should shed light on the prevention of hearing loss induced by aminoglycoside antibiotics.

60 APPLIED LIFE SCIENCES↗

The second filter’s second coming

We measured sound-evoked vibrations at the stereociliary side of inner and outer hair cells and their surrounding supporting cells, using optical coherence tomography interferometry in living anesthetized guinea pigs. Our measurements demonstrate a gradient in frequency tuning among different cell types, going from a high best frequency at the inner hair cells to a lower one at the Hensen cells. This causes the locus of maximum inner hair cell activation to be shifted toward the apex of the cochlea as compared to the outer hair cells. These observations show that additional processing and filtering of acoustic signals occurs within the organ of Corti prior to inner hair cell excitation, thus reinstating a transformed second filter as a mechanism contributing to cochlear frequency tuning.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Optical coherence tomography (OCT) leading to more insight into cochlear mechanics

Optical Coherence Tomography (OCT) was used to measure vibrations of the basilar membrane (BM) and the Reticular Lamina (RL) in the cochlea of the guinea pig, at frequencies up to 25 kHz. Because of the difficulty of the experiments the data have limited sets of parameters and are subject to high noise levels. In a viable guinea-pig cochlea, the RL moves in the region of maximum response with a larger amplitude than the BM. We cannot rule out that some of that difference is due to a geometrical factor. We also found a consistent increase of this amplitude difference with frequency, which points to a low-pass filtering process. That process might be linked to the mass of the fluid contained in the Organ of Corti channel (OoC channel)

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗