Fang-Lu Chi

Development and evaluation of the Nurotron 26-electrode cochlear implant system.

Although the cochlear implant has been widely acknowledged as the most successful neural prosthesis, only a fraction of hearing-impaired people who can potentially benefit from a cochlear implant have actually received one due to its limited awareness, accessibility, and affordability. To help overcome these limitations, a 26-electrode cochlear implant has been developed to receive Chinas Food and Drug Administration (CFDA) approval in 2011 and Conformité Européenne (CE) Marking in 2012. The present article describes design philosophy, system specification, and technical verification of the Nurotron device, which includes advanced digital signal processing and 4 current sources with multiple amplitude resolutions that not only are compatible with perceptual capability but also allow interleaved or simultaneous stimulation. The article also presents 3-year longitudinal evaluation data from 60 human subjects who have received the Nurotron device. The objective measures show that electrode impedance decreased within the first month of device use, but was stable until a slight increase at the end of two years. The subjective loudness measures show that electric stimulation threshold was stable while the maximal comfort level increased over the 3 years. Mandarin sentence recognition increased from the pre-surgical 0%-correct score to a plateau of about 80% correct with 6-month use of the device. Both indirect and direct comparisons indicate indistinguishable performance differences between the Nurotron system and other commercially available devices. The present 26-electrode cochlear implant has already helped to lower the price of cochlear implantation in China and will likely contribute to increased cochlear implant access and success in the rest of the world. This article is part of a Special Issue entitled .

Sensitivity and fidelity of a novel piezoelectric middle ear transducer.

Objective: A novel implantable piezoelectric transducer has been developed in this laboratory. The transfer functions of the transducer were assessed in anesthetized acutely implanted cats, and were compared with the microphone of a cochlear implant’s speech processor. Methods: The piezoelectric transducer was fixed to the head of the malleus of the cat. Pure tone signals of 97 dB SPL ranging from 250 to 8,000 Hz delivered from a loudspeaker placed beside the auricle of the cat were used to vibrate the tympanic membrane. The frequency response of the transducer was measured by monitoring the output signal of the transducer with an oscilloscope. The transfer functions of the transducer were then compared with the standard external microphone receiving the same tonal stimulus. Results: The average sensitivity of the implantable piezoelectric transducer was –38.7 dB re 1 V/Pa at 1,000 Hz. The frequency-response curve of the transducer mirrored that of the external microphone, even with high-frequency stimuli. Conclusion: The implantable piezoelectric transducer developed in this laboratory transmits tonal stimuli with high fidelity.

Therapeutic efficacy of topical application of dexamethasone to the round window niche after acoustic trauma caused by intensive impulse noise in guinea pigs

OBJECTIVE To assess the therapeutic efficacy of dexamethasone administered topically to the round window niche, following acoustic trauma induced by intensive impulse noise, in guinea pigs. METHODS Adult, male, albino guinea pigs with a normal Preyers reflex were exposed to 80 impulse noises (peak value 167 dB, duration 0.5 ms, interval 2 s). Dexamethasone (40 mg/ml) or saline was then topically applied to the round window niche. Each animals auditory brainstem response was measured before and one day after exposure, and three weeks after topical treatment. Cochlear morphology was examined to assess hair cell loss and spiral ganglion cell damage. To assess oxidative activity, cochlear malondialdehyde and superoxide dismutase concentrations were determined three weeks post-treatment. Following topical application, the pharmacokinetic characteristics of dexamethasone in cochlear perilymph were analysed using high-performance liquid chromatography. RESULTS Animals receiving dexamethasone showed reduced noise-induced outer hair cell loss (three weeks post-treatment), and significant attenuation of noise-induced auditory brainstem response threshold shifts (one day post-exposure and three weeks post-treatment), compared with controls. There was no difference in spiral ganglion morphology. Animals receiving dexamethasone also showed a significantly lower malondialdehyde concentration and a higher superoxide dismutase concentration, post-exposure. Following topical application, the perilymph dexamethasone level peaked at 5330.522 µg/ml (15 minutes post-treatment), and was 299.797 µg/ml 360 minutes later. CONCLUSION Topical application of dexamethasone to the round window niche has protective effects against intensive impulse noise induced trauma in the guinea pig cochlea. This drug can diffuse into the inner ear through the round window membrane and persist in the perilymph for a relatively long period. The mechanism of protection may involve an anti-oxidant effect.

Dexamethasone suppresses cochlear Hes1 expression after noise exposure

Abstract Conclusion: Dexamethasone provides protection against noise-induced hearing loss (NIHL) possibly by suppressing cochlear Hes1 expression via a glucocorticoid receptor (GR)-dependent mechanism. Objectives: The purpose of the present study was to explore whether hairy and enhancer of split 1 (Hes1) was involved in the protective effect of dexamethasone against NIHL. Methods: Guinea pigs, which were administered intraperitoneal injections of either saline, 1.0 mg/kg dexamethasone, 20.0 mg/kg RU38,486, or a combination of both drugs (dexamethasone plus RU38,486) for 5 consecutive days, were exposed to white-band noise (115 dB sound pressure level). The expression level of Hes1 in cochleae was compared using real-time RT-PCR and Western blot analysis. Results: Noise exposure for 3 h induced auditory brainstem response (ABR) threshold elevations, outer hair cell losses, and increase of Hes1 expression. Dexamethasone pretreatment prevented the NIHL with decreased Hes1 expression, which could be blocked by GR antagonist RU38,486.

Topological and Developmental Expression Gradients of Kir2.1, an Inward Rectifier K + Channel, in Spiral Ganglion and Cochlear Hair Cells of Mouse Inner Ear

Objectives: Inwardly rectifying potassium current plays critical roles in setting resting membrane potential and thus modulating the excitability of many excitable cells including the hair cells in inner ears, which are excitable during early development. Up to 7 subfamilies have been identified as channels for this current. The present study investigated the developmental and spatial expression of one member, Kir2.1, in the sensorineural epithelia and spiral ganglion neurons of mouse cochleae starting from neonatal stage to the maturation of hearing function, in an attempt to verify its role in the postnatal cochlear development. Methods: The distribution of Kir2.1 protein and mRNA was observed using immunofluorescence staining and in situ hybridization on samples of surface preparation and cross sections of cochleae. The protein and mRNA were further measured with semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blotting to show the developmental change of this channel in the cochlea of mice. Results: The expression of Kir2.1 appears to have a clear temporal pattern: increasing from the first postnatal day (PD0) to PD12 and then quickly decreasing after that. The expression cannot be detected on PD20. Throughout this developmental pattern, the expression was stronger at the basal turn on PD0 and shifted upwards (longitudinal gradient), so that stronger signals were generally seen in the apical parts of the cochlea after PD0. A radial gradient of the Kir2.1 protein was also evident with a stronger and consistent signal usually occurring on row 3 outer hair cells. The spatial and developmental changes of Kir2.1 mRNA in in situ hybridization exhibited similar patterns as seen for the Kir2.1 protein on PD8 and PD12. Western blot data showed a slightly higher concentration of the protein in the apical half of the cochlea and a slight increase from PD4 to PD12. This result is consistent with the quantification of mRNA in RT-PCR. No significant expression of Kir2.1 was found in spiral ganglion neurons. Conclusions: Kir2.1 exhibits a clear and temporal expression in the hair cells of mouse cochleae which may be related to the functional maturation of the hair cells and the neurons.

The distribution of vestibular efferent neurons receiving innervation of secondary vestibular afferent nerves in rats.

To explore the innervation areas of the medial vestibular nucleus (MVN) afferent neurons onto vestibular efferent neurons in the brain stem of rats.

Feasible pickup from intact ossicular chain with floating piezoelectric microphone

ObjectivesMany microphones have been developed to meet with the implantable requirement of totally implantable cochlear implant (TICI). However, a biocompatible one without destroying the intactness of the ossicular chain still remains under investigation. Such an implantable floating piezoelectric microphone (FPM) has been manufactured and shows an efficient electroacoustic performance in vitro test at our lab. We examined whether it pick up sensitively from the intact ossicular chain and postulated whether it be an optimal implantable one.MethodsAnimal controlled experiment: five adult cats (eight ears) were sacrificed as the model to test the electroacoustic performance of the FPM. Three groups were studied: (1) the experiment group (on malleus): the FPM glued onto the handle of the malleus of the intact ossicular chains; (2) negative control group (in vivo): the FPM only hung into the tympanic cavity; (3) positive control group (Hy-M30): a HiFi commercial microphone placed close to the site of the experiment ear. The testing speaker played pure tones orderly ranged from 0.25 to 8.0 kHz. The FPM inside the ear and the HiFi microphone simultaneously picked up acoustic vibration which recorded as .wav files to analyze.ResultsThe FPM transformed acoustic vibration sensitively and flatly as did the in vitro test across the frequencies above 2.0 kHz, whereas inefficiently below 1.0 kHz for its overloading mass. Although the HiFi microphone presented more efficiently than the FPM did, there was no significant difference at 3.0 kHz and 8.0 kHz.ConclusionsIt is feasible to develop such an implantable FPM for future TICIs and TIHAs system on condition that the improvement of Micro Electromechanical System and piezoelectric ceramic material technology would be applied to reduce its weight and minimize its size.

Effects of Kir2.1 gene transfection in cochlear hair cells and application of neurotrophic factors on survival and neurite growth of co-cultured cochlear spiral ganglion neurons.

Immature inner hair cells (IHCs) produce spontaneous action potentials, which may be associated with the survival of spiral ganglion neurons (SGNs) during early development. Later, this activity ceases in part by the expression of Kir channels. In the present study, SGNs were co-cultured with organ of Corti in which a Kir2.1 channel was over-expressed in an attempt to block the spontaneous activity of IHCs. The over-expression led to a reduced survival and neurite growth accompanied by increased SGN apoptosis. The enhanced activation of apoptosis was consistent with the inhibition of the survival-promoting pathway and the disruption of [Ca(2+)](i) homeostasis. Furthermore, the effect of Kir2.1 over-expression can be reversed by exogenous neurotrophic factors (NTFs). These results are consistent with the hypothesis that the earlier-than-normal expression of Kir2.1 in HCs inhibits their spontaneous activity required for SGN survival and neurite growth.

The effects of different auditory activity on the expression of phosphorylated c-Jun in the auditory system

Conclusion: The data revealed that calcium influx via the NMDA receptor up-regulated the expression of phosphorylated c-Jun in the primary auditory cortices following sensory stimulation and after different neural injury stimulations which guide activity-dependent changes in gene expression and neural plasticity. Objectives: Activator protein-1 (AP-1) transcription factor, which is mainly composed of c-Fos and c-Jun proteins, is believed to be a key participant in molecular processes that guide activity-dependent changes in gene expression. Our previous study had shown that the expression of NMDAR2A gene on synaptosomes membrane of auditory cortical neurons varied by electrical intracochlear stimulation (EIS) and neural injury induced by acoustic trauma. In this study, we investigated the role of the NMDA receptor (NMDAR) in regulating the expression of phosphorylated c-Jun in the primary auditory cortex (AI). The modulation factors observed for gene expression included EIS and noise traumas. Materials and methods: EIS was applied in rats with early postnatal auditory deprivation. The impact of the noise traumas on the ultrastructures of spiral ganglion neurons (SGNs) and their innervations to inner hair cells (IHCs) were verified by transmission electron microscopy (EM). These changes include a decrease in subcellular organelles, the swelling of mitochondria and endoplasmic reticulum, the morphological changes in cell nuclei, and damage in the afferent synapse. Results: Immunohistochemistry observations showed that the expression of phosphorylated c-jun and active caspase-3 in hair cells and SGNs varied with amount of noise. Immunocytochemistry and Western blotting showed that the auditory cortex began to express phosphorylated c-jun 24 h after 2 h of EIS. However, this expression was not changed by EIS if NMDAR antagonist was applied. The level of phosphorylated c-Jun was remarkably increased in AI after noise overstimulation at 115 dB SPL for 3 h. Again, such an increase was not seen if NMDAR antagonist 3-(2 carboxypiperazin-4yl) propyl-1-phosphonic acid (CPP, 10 mg/kg, i.p.) was applied 30 min before the noise exposure.

Analysis of the Damage Mechanism Related to CO2 Laser Cochleostomy on Guinea Pig Cochlea

Different types of lasers have been used in inner ear surgery. Therefore, it is of the utmost importance to avoid damage to the inner ear (e.g., hyperthermia and acoustic effects) caused by the use of such lasers. The aim of this study was to use a high powered fibre-enabled CO2 laser (10 W, 606 J/cm2) to perform cochleostomies on guinea pig cochlea and to investigate the possible laser-induced damage mechanisms. The temperature changes in the round window membrane, auditory evoked brainstem response, and morphological of the hair cells were measured and recorded before and after laser application. All of the outcomes differed in comparison with the control group. A rise in temperature and subsequent increased hearing loss were observed in animals that underwent surgery with a 10 W CO2 laser. These findings correlated with increased injury to the cochlear ultrastructure and a higher positive expression of E-cadherin and β-catenin in the damaged organ of Corti. We assume that enhanced cell-cell adhesion and the activated β-catenin-related canonical Wnt-signalling pathway may play a role in the protection of the cochlea to prevent further damage.