Takatoshi Inaoka

Piezoelectric materials mimic the function of the cochlear sensory epithelium

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.

Local application of hepatocyte growth factor using gelatin hydrogels attenuates noise-induced hearing loss in guinea pigs

Conclusion: Local application of hepatocyte growth factor using biodegradable gelatin hydrogels attenuates noise-induced hearing loss in guinea pigs. Objectives: To develop an inner ear drug delivery system using gelatin hydrogels that is capable of a sustained delivery of growth factors to the cochlea. We examined the efficacy of the local application of gelatin hydrogels containing hepatocyte growth factor (HGF) in protecting cochlear hair cells from noise-induced damage. Materials and methods: A piece of gelatin hydrogel previously immersed in either HGF or saline was placed on the round window membrane of a guinea pig 1 h after noise exposure (4 kHz octave band noise at 120 dB sound pressure level for 3 h). Auditory function was monitored using auditory brainstem responses (ABRs), and the loss of hair cells was evaluated quantitatively. Results: Local HGF treatment significantly reduced the noise exposure-caused ABR threshold shifts and the loss of outer hair cells in the basal portion of the cochleae.

Surgical Invasiveness of Cell Transplantation into the Guinea Pig Cochlear Modiolus

Objective: Previous studies have demonstrated the potential of cell transplantation for regeneration of spiral ganglion neurons (SGNs). However, the effect of surgical invasion on host cochleae has yet to be evaluated. The present study investigated the efficiency and invasiveness of our surgical procedure using a fine glass pipette for injections into the cochlear modiolus. Methods: We examined the survival of transplanted embryonic stem cell-derived neurons in the cochlear modiolus of guinea pigs. Surgical invasiveness was assessed by measurements of electrically evoked auditory brainstem responses (eABRs) and SGN densities after an injection of 5 ml of saline into the cochlear modiolus. Results: All of the transplanted animals exhibited localization of transplanted cells in the cochlear modiolus. No significant alterations in the eABR thresholds or SGN densities were found following surgery. Conclusion: These findings indicate that our procedure is a viable method for testing the potential of transplants for SGN replacement.

Transplantation of Bone Marrow-Derived Neurospheres Into Guinea Pig Cochlea

To investigate the potential of neurally induced bone marrow stromal cells (BMSCs) as transplants for replacement of spiral ganglion neurons.

Adipose tissue-derived stromal cells protect hair cells from aminoglycoside†

Previous studies have demonstrated the therapeutic paracrine activity of adipose tissue‐derived stromal cells (ADSCs). This study aimed to examine the ADSC potential for protecting auditory hair cells from aminoglycoside toxicity via paracrine of multiple growth factors and cytokines.

Hepatocyte growth factor protects auditory hair cells from aminoglycosides

To examine the effect of hepatocyte growth factor (HGF) for protection of auditory hair cells against aminoglycosides and its molecular mechanisms.

Development of an electrode for the artificial cochlear sensory epithelium.

An artificial cochlear sensory epithelium has been developed on the basis of a new concept that the piezoelectric membrane, which converts mechanical distortion into electricity, can mimic the function of the inner hair cell and basilar membrane of the mammalian cochlea. Our previous research demonstrated that the piezoelectric membrane generated electrical outputs in response to the sound stimulation after implantation into the guinea pig cochlea, whereas electrodes for the stimulation of spiral ganglion neurons have not been fabricated, and a method to fix the device in the cochlea is also required to show proof-of-concept. In the present study, to achieve proof-of-concept of hearing recovery by implantation of the artificial cochlear sensory epithelium, we fabricated new electrodes that stick into the cochlear modiolus, which also play a role in the fixation of the device in the cochlea. The efficacy of new electrodes for fixation of the device in the cochlea and for the stimulation of spiral ganglion neurons was estimated in guinea pigs. Four weeks after implantation, we confirmed that the devices were in place. Histological analysis of the implanted cochleae revealed inconspicuous fibrosis and scar formation compared with the sham-operated specimens (n = 5 for each). The terminal deoxynucleotidyl transferase dUTP nick end labeling method was used to assess cell death due to surgical procedures in the cochleae that were harvested after 1 day (n = 6) and 7 days (n = 6) of implantation; there was no significant increase in apoptotic cell death in the implanted cochleae compared with sham-operated cochleae. In seven animals, serial measurements of electrically evoked auditory brainstem responses were obtained, with the electrode positioned in the scala tympani and with the electrode inserted into the cochlear modiolus. With the insertion of electrodes into the cochlear modiolus, significant reduction was achieved in the thresholds of electrically evoked auditory brainstem responses compared with those placed in the scala tympani (p = 0.028). These findings indicated that the new electrodes efficiently fixed the device in the cochlea and were able to stimulate spiral ganglion neurons.

Parathyroid Adenoma Manifested by Posterior Mediastinal Hemorrhage

Parathyroid adenomas sometimes cause nephrolithiases or bone disorders, but most cases pass subclinical courses and are found incidentally by routine blood tests. We report a case of parathyroid adenoma causing posterior mediastinal hemorrhage. The parathyroid adenoma was excised five months subsequent to the hemorrhage, after the hematoma had efficiently subsided, with no major bleeding. The postoperative course was uneventful with an expected decrease in serum calcium and intact PTH.

Rhinolith with Nasal Septum Perforation

Rhinoliths, or nasal calculi, are formed by an unknown process. Most of them are small and unilateral, but some of them grow large enough to cause chronic sinusitis, nasal septum perforation and abscess, and palatal perforation. An unusual case of rhinolith with nasal septum perforation is reported. The rhinolith was removed piece by piece under endoscopic maneuver. Surgical removal of the rhinolith provided a good prognosis.