Surgical Invasiveness of Cell Transplantation into the Guinea Pig Cochlear Modiolus

Ogita, Hideaki; Nakagawa, Takayuki; Lee, Kyu Yup; Inaoka, Takatoshi; Okano, Takayuki; Kikkawa, Yuichiro; Sakamoto, Tatsunori; Ito, Juichi

doi:10.1159/000165915

Cited by 17 publications

(18 citation statements)

References 37 publications

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“…Measurements of eABRs were performed as previously described (30). Biphasic voltage pulses were generated under computer control using a real-time processor (Tucker-Davis Technologies).…”

Section: Methodsmentioning

confidence: 99%

Piezoelectric materials mimic the function of the cochlear sensory epithelium

Inaoka

Shintaku²,

Nakagawa³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Cochlear hair cells convert sound vibration into electrical potential, and loss of these cells diminishes auditory function. In response to mechanical stimuli, piezoelectric materials generate electricity, suggesting that they could be used in place of hair cells to create an artificial cochlear epithelium. Here, we report that a piezoelectric membrane generated electrical potentials in response to sound stimuli that were able to induce auditory brainstem responses in deafened guinea pigs, indicating its capacity to mimic basilar membrane function. In addition, sound stimuli were transmitted through the external auditory canal to a piezoelectric membrane implanted in the cochlea, inducing it to vibrate. The application of sound to the middle ear ossicle induced voltage output from the implanted piezoelectric membrane. These findings establish the fundamental principles for the development of hearing devices using piezoelectric materials, although there are many problems to be overcome before practical application.cochlear implant | hearing loss | mechanoelectrical transduction | traveling wave | regeneration T he cochlea is responsible for auditory signal transduction in the auditory system. It responds to sound-induced vibrations and converts these mechanical signals into electrical impulses, which stimulate the auditory primary neurons. The human cochlea operates over a three-decade frequency band from 20 Hz to 20 kHz, covers a 120-dB dynamic range, and can distinguish tones that differ by <0.5% in frequency (1). It is relatively small, occupying a volume of <1 cm 3 , and it requires ∼14 μW power to function (2). The mammalian ear is composed of three parts: the outer, middle, and inner ears (Fig. 1A) (3). The outer ear collects sound and funnels it through the external auditory canal to the tympanic membrane. The cochlea consists of three compartments: scala vestibuli and scala tympani, which are filled with perilymph fluid, and scala media, which is filled with endolymph fluid (Fig. 1C). The scala vestibuli and scala tympani form a continuous duct that opens onto the middle ear through the oval and round windows. The stapes, an ossicle in the middle ear, is directly coupled to the oval window. Sound vibration is transmitted from the ossicles to the cochlear fluids through the oval window as a pressure wave that travels from the base to the apex of the scala vestibuli through the scala tympani and finally to the round window (Fig. 1B). The scala media are membranous ducts that are separated from the scala vestibuli by Reissner's membrane and separated from the scala tympani by the basilar membrane. The pressure wave propagated by the vibration of the stapes footplate causes oscillatory motion of the basilar membrane, where the organ of Corti is located. The organ of Corti contains the sensory cells of the auditory system; they are known as hair cells, because tufts of stereocilia protrude from their apical surfaces (Fig. 1D). The oscillatory motion of the basilar membrane results in the shear motion of the st...

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“…Measurements of eABRs were performed as previously described (30). Biphasic voltage pulses were generated under computer control using a real-time processor (Tucker-Davis Technologies).…”

Section: Methodsmentioning

confidence: 99%

Piezoelectric materials mimic the function of the cochlear sensory epithelium

Inaoka

Shintaku²,

Nakagawa³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

123

127

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“…In addition, functional evaluation following cell transplantation is virtually impossible. On the other hand, guinea pig10, 13 or chinchilla6 model systems exhibited better settlement of transplants in the cochlear modiolus and enabled functional evaluation using eABRs 10, 13. Moreover, our refined technique for cell introduction into the cochlear modiolus of guinea pigs caused no significant elevation of eABR thresholds 10.…”

Section: Discussionmentioning

confidence: 92%

“…After labeling with DiI (Invitrogen, 5 μg/mL), the cell suspension of BMSC‐derived spheres (10 5 cells in 10 μL DMEM) was injected into the cochlear modiolus of guinea pigs weighing 300 to 330 g as described previously 10. Briefly, under general anesthesia with midazolam and xylazine, a small hole was made on the left otic bulla to expose the round window niche and the basal turn of the cochlea.…”

Section: Methodsmentioning

confidence: 99%

“…Ten guinea pigs received local application of ouabain (5 μL at a concentration of 5 mM in saline; Sigma), which causes SGN degeneration,9 through the round window membrane under general anesthesia with midazolam and xylazine. One week after application, the electrically evoked auditory brainstem response (eABR), which has been used for functional evaluation of SGNs, was measured before cell transplantation as previously described 10. Eight animals that showed no eABRs were used in the following experiments.…”

Section: Methodsmentioning

confidence: 99%

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Transplantation of bone marrow‐derived neurospheres into guinea pig cochlea

et al. 2010

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“…Measurements of electrically EABRs were performed as described in previous studies (Hall, 1990b; Ogita et al, 2009; Shintaku et al, 2013). Briefly, we used a conventional retroauricular approach with the animal in a lateral recumbent position.…”

Section: Methodsmentioning

confidence: 99%

A hardware model of the auditory periphery to transduce acoustic signals into neural activity

et al. 2013

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To improve the performance of cochlear implants, we have integrated a microdevice into a model of the auditory periphery with the goal of creating a microprocessor. We constructed an artificial peripheral auditory system using a hybrid model in which polyvinylidene difluoride was used as a piezoelectric sensor to convert mechanical stimuli into electric signals. To produce frequency selectivity, the slit on a stainless steel base plate was designed such that the local resonance frequency of the membrane over the slit reflected the transfer function. In the acoustic sensor, electric signals were generated based on the piezoelectric effect from local stress in the membrane. The electrodes on the resonating plate produced relatively large electric output signals. The signals were fed into a computer model that mimicked some functions of inner hair cells, inner hair cell–auditory nerve synapses, and auditory nerve fibers. In general, the responses of the model to pure-tone burst and complex stimuli accurately represented the discharge rates of high-spontaneous-rate auditory nerve fibers across a range of frequencies greater than 1 kHz and middle to high sound pressure levels. Thus, the model provides a tool to understand information processing in the peripheral auditory system and a basic design for connecting artificial acoustic sensors to the peripheral auditory nervous system. Finally, we discuss the need for stimulus control with an appropriate model of the auditory periphery based on auditory brainstem responses that were electrically evoked by different temporal pulse patterns with the same pulse number.

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Surgical Invasiveness of Cell Transplantation into the Guinea Pig Cochlear Modiolus

Cited by 17 publications

References 37 publications

Piezoelectric materials mimic the function of the cochlear sensory epithelium

Piezoelectric materials mimic the function of the cochlear sensory epithelium

Transplantation of bone marrow‐derived neurospheres into guinea pig cochlea

A hardware model of the auditory periphery to transduce acoustic signals into neural activity

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