Hideaki Ogita

Transplantation of mouse induced pluripotent stem cells into the cochlea

This study examined the potential of induced pluripotent stem (iPS) cells for use as a source of transplants for the restoration of auditory spiral ganglion neurons. We monitored neurite outgrowth from iPS cell-derived neural progenitors toward cochlear hair cells ex vivo, and followed their survival and fates after transplantation into mouse cochleae in vivo. Neurons derived from iPS cells projected neurites toward cochlear hair cells. The settlement of iPS cell-derived neurons was observed 1 week after transplantation into the cochlea. Some transplants expressed vesicular glutamate transporter 1, which is a marker for glutamatergic neurons. These findings indicate that iPS cells can be used as a source of transplants for the regeneration of spiral ganglion neurons.

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.

Benign paroxysmal positional vertigo and head position during sleep

To determine whether any particular head positions during sleep are associated with BPPV, head position during sleep was monitored for 3 days in 50 BPPV patients after the disappearance of positional nystagmus and in 25 normal control subjects. A gravity sensor was attached to the center of the subjects forehead at home. The positional angle of the head was measured at 5-second intervals during sleep. In BPPV, the posterior semicircular canal was involved in 40 patients and the lateral semicircular canal in 10 patients. Recurrence was found in 22 of 50 BPPV patients. BPPV patients with recurrence were significantly more likely to sleep in the affected-ear-down 45-degree head position than were patients with no history of recurrence (P< 0.02). When the head is in the affected-ear-down 45-degree head position, the non-ampullated half of the posterior semicircular canal and the non-ampullated half of the lateral semicircular canal are nearly in the earth-vertical position, making it easier for detached otoconia to fall into the posterior or lateral semicircular canal and to agglomerate and attain a certain size in the lowest portion of each semicircular canal. Our findings showed that the affected-ear-down 45-degree head position during sleep could be an etiological factor of BPPV, more particularly in patients with recurrent BPPV.

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.

Mechanical stress-induced reactive gliosis in the auditory nerve and cochlear nucleus.

OBJECT Hearing levels following microsurgical treatment gradually deteriorate in a number of patients treated for vestibular schwannoma (VS), especially in the subacute postoperative stage. The cause of this late-onset deterioration of hearing is not completely understood. The aim of this study was to investigate the possibility that reactive gliosis is a contributory factor. METHODS Mechanical damage to nerve tissue is a feature of complex surgical procedures. To explore this aspect of VS treatment, the authors compressed rat auditory nerves with 2 different degrees of injury while monitoring the compound action potentials of the auditory nerve and the auditory brainstem responses. In this experimental model, the axons of the auditory nerve were quantitatively and highly selectively damaged in the cerebellopontine angle without permanent compromise of the blood supply to the cochlea. The temporal bones were processed for immunohistochemical analysis at 1 week and at 8 weeks after compression. RESULTS Reactive gliosis was induced not only in the auditory nerve but also in the cochlear nucleus following mechanical trauma in which the general shape of the auditory brainstem response was maintained. There was a substantial outgrowth of astrocytic processes from the transitional zone into the peripheral portion of the auditory nerve, leading to an invasion of dense gliotic tissue in the auditory nerve. The elongated astrocytic processes ran in parallel with the residual auditory neurons and entered much further into the cochlea. Confocal images disclosed fragments of neurons scattered in the gliotic tissue. In the cochlear nucleus, hypertrophic astrocytic processes were abundant around the soma of the neurons. The transverse diameter of the auditory nerve at and proximal to the compression site was considerably reduced, indicating atrophy, especially in rats in which the auditory nerve was profoundly compressed. CONCLUSIONS The authors found for the first time that mechanical stress to the auditory nerve causes substantial reactive gliosis in both the peripheral and central auditory pathways within 1-8 weeks. Progressive reactive gliosis following surgical stress may cause dysfunction in the auditory pathways and may be a primary cause of progressive hearing loss following microsurgical treatment for VS.

Clinical and epidemiological study on inpatients with vertigo at the ENT Department of Kyoto University Hospital

Abstract Conclusion: The number of studies on inpatients with vertigo is limited. This study provides useful information for clarifying the underlying causes of vertigo. Objective: To investigate the epidemiological features of patients with vertigo. Methods: This retrospective study investigated 78 patients who had been emergently hospitalized in the Otolaryngology Department of Kyoto University Hospital with vertigo. Results: The number of female patients was significantly higher than the number of male patients. Menieres disease was the most common underlying pathology among hospitalized patients. Mean patient age was 56.1 years, with no significant difference between male and female patients.

Hearing preservation at low frequencies by insulin-like growth factor 1 in a guinea pig model of cochlear implantation

Abstract The hybrid or electric‐acoustic stimulation cochlear implant is indicated in patients with a residual hearing at low frequencies. It provides electric and acoustic stimulation for compensating for high‐ and low‐frequency sounds, respectively. However, the implantation procedure damages the cochlea, resulting in loss of the residual‐hearing and diminished effects of the acoustic‐hearing in several patients. To prevent hearing loss after implantation, corticosteroids have been used clinically although their effects are limited. As an alternative to corticosteroids, insulin‐like growth factor 1 (IGF1) has shown potent effects in various types of cochlear injury. In this study, the effects of IGF1 on hearing preservation were examined after cochlear implantation to a normal‐hearing guinea pig model. The electrode was inserted in an atraumatic way through the round window membrane of guinea pigs with the application of a gelatin‐sponge soaked with IGF1 or saline. The auditory brainstem response (ABR) was recorded pre‐operatively, immediately after cochlear implantation, and 7, 14, 28, and 56 days after electrode insertion. In comparison to the control group, the IGF1‐treated group showed better hearing preservation at low frequencies, 7 days after surgery. IGF1 application was effective at low frequencies (2 and 4 kHz) throughout the period of examination. Histological studies revealed that outer hair cell numbers, in the IGF1‐treated group, were maintained in the cochlear region responsible for low‐frequency hearing (upper midbasal turn) and that there was less fibrous tissue formation around the electrode. Both the outer hair cell counts and the extent of fibrosis significantly correlated with the ABR threshold shifts at low frequencies. These results indicate that IGF1 might attenuate loss of low‐frequency hearing after cochlear implantation, suggesting its possible clinical use in soft surgeries involving cochlear implants with electric‐acoustic stimulation for hearing preservation. HighlightsIGF1 preserved low‐frequency hearing 56 days after cochlear implantation.IGF1 maintained outer hair cell numbers in low frequency regions of the cochlea.IGF1 inhibited fibrosis around the electrode.Fibrosis in the basal turn correlates with low‐frequency hearing.

An attempt to measure the diametric relationship between slow and quick phases of nystagmus

Abstract Objective: To investigate whether our original method can precisely evaluate the angle between slow and quick phases of nystagmus (vector angle) and to determine whether vector angle analysis is helpful in differentiating between horizontal nystagmus and mixed nystagmus with horizontal and vertical components. Methods: We included 20 healthy volunteers, 17 patients with horizontal nystagmus, and 15 patients with mixed nystagmus. Caloric nystagmus was recorded in healthy volunteers; positional nystagmus was recorded in each patient. We extracted the velocity of nystagmus from eye movement of each subject and analysed the vector angle. Results: In caloric nystagmus, the vector angle approached 180 degrees as slow-phase velocity increased, suggesting that our vector angle measurement is more reliable with faster nystagmus. Importantly, in horizontal nystagmus from peripheral vestibular disease, the vector angle similarly approached 180 degrees as slow-phase velocity increased; in contrast, the vector angle in cases of mixed nystagmus from vertebrobasilar insufficiency or spinocerebellar degeneration significantly differed from the angle of caloric nystagmus. Conclusions: Vector angle analysis using our original algorithm can precisely evaluate the diametric relationship in vestibular nystagmus; it may be helpful in diagnosis of non-peripheral vestibular disorders.