BACKGROUND AND OBJECTIVES: The purpose of this study was to investigate the effects of low level laser for the prevention and treatment of aminoglycoside-induced vestibular ototoxicity. MATERIALS AND METHOD: An organotypic culture of 2 to 4 days old rat utricular maculae was established. Rats were divided into 6 groups according to the treadtment of the utricles: G (gentamicintreated), L (laser-irradiated), LG (laser-irradiated and gentamicin-treated), GL (gentamicin-treated and laser-irradiated), LGL (gentamicin-treated during laser-irradiated) and C (control). After organotypic culture, the utricles of 6 groups were examined by confocal laser scanning electron microscope and scanning electron microscope. The results of each group were compared with each other by statistical methods. RESULTS: The number of vestibular hair cells of the group G was smaller compared to that of the group C. The group L had no difference compared with the group C. The groups LG and GL showed more vestibular hair cells compared with the group G. The group LG showed more vestibular hair cells than the group GL. The group LGL showed most vestibular hair cells compared to that of the groups G, LG, and GL. CONCLUSION: The most effective treatment of aminoglycosideinduced vestibular otoxicity is the irradiation of low level laser before and after the insult of the aminoglycoside. Further clinical studies using low level laser were needed to prevent aminoglycoside-induced ototoxicity and to promote the regeneration of vestibular hair cells.
Animals ; Electrons ; Gentamicins ; Hair Cells, Vestibular ; Rats ; Regeneration ; Saccule and Utricle

Hypotension is one of the potential causes of dizziness. In this review, we summarize the studies published in recent years about the electrophysiological and pharmacological mechanisms of hypotension-induced dizziness and the role of the vestibular system in the control of blood pressure in response to hypotension. It is postulated that ischemic excitation of the peripheral vestibular hair cells as a result of a reduction in blood flow to the inner ear following hypotension leads to excitation of the central vestibular nuclei, which in turn may produce dizziness after hypotension. In addition, excitation of the vestibular nuclei following hypotension elicits the vestibulosympathetic reflex, and the reflex then regulates blood pressure by a dual-control (neurogenic and humoral control) mechanism. In fact, recent studies have shown that peripheral vestibular receptors play a role in the control of blood pressure through neural reflex pathways. This review illustrates the dual-control mechanism of peripheral vestibular receptors in the regulation of blood pressure following hypotension.
Blood Pressure* ; Dizziness ; Ear, Inner ; Epinephrine ; Glutamic Acid ; Hair Cells, Vestibular ; Hypotension* ; Reflex ; Vestibular Nuclei

BACKGROUND AND OBJECTIVES: To culture and maintain mammalian hair cells is still a big challenge. In this study, long-term organotypic culture of rat utricular maculae was established to study vestibular hair cell. The effects of low level laser on hair cell viability in postnatal organotypic culture of rat utricles were investigated. MATERIALS AND METHOD: Uticular explants were prepared from postnatal 2 to 7 rats and cultured. To improve hair cell survival, the utricles were irradiated daily with low level laser. Whole-mount utricles were stained with FM1-43 which is known to be an efficient marker to identify live hair cells in cultured tissues. Such cells visualized directly through tissue culture dish with cover glass bottom by Confocal laser scanning microscope at specific time points. RESULTS: The explanted utricular hair cells were cultured for up to 31 days in in vitro culture system. In low level laser irradiation group, utricular hair cells were more survived at 24 DIV and 31 DIV. CONCLUSION: These results suggest that low level laser promotes hair cell viability in utricular explants.
Animals ; Cell Survival* ; Glass ; Hair Cells, Vestibular ; Hair* ; Rats* ; Saccule and Utricle*

BACKGROUND AND OBJECTIVES: To culture and maintain mammalian hair cells is still a big challenge. In this study, long-term organotypic culture of rat utricular maculae was established to study vestibular hair cell. The effects of low level laser on hair cell viability in postnatal organotypic culture of rat utricles were investigated. MATERIALS AND METHOD: Uticular explants were prepared from postnatal 2 to 7 rats and cultured. To improve hair cell survival, the utricles were irradiated daily with low level laser. Whole-mount utricles were stained with FM1-43 which is known to be an efficient marker to identify live hair cells in cultured tissues. Such cells visualized directly through tissue culture dish with cover glass bottom by Confocal laser scanning microscope at specific time points. RESULTS: The explanted utricular hair cells were cultured for up to 31 days in in vitro culture system. In low level laser irradiation group, utricular hair cells were more survived at 24 DIV and 31 DIV. CONCLUSION: These results suggest that low level laser promotes hair cell viability in utricular explants.
Animals ; Cell Survival* ; Glass ; Hair Cells, Vestibular ; Hair* ; Rats* ; Saccule and Utricle*

BACKGROUND AND OBJECTIVES: In normal postnatal mammalian inner ear sensory epithelium, regeneration of hair cells is a very rare event, but there is hair cell regeneration with partial restoration of the vestibular sensory epithelium following ototoxic damage. In this study, the effects of low-level laser on hair cell regeneration following gentamicin exposure in postnatal organotypic culture of rat utricles were investigated. MATERIALS AND METHOD: A long term organotypic culture of 2 to 7 day old rat utricular maculae was established to study aminoglycoside-induced vestibular hair cell renewal. The utricles were exposed to 1 mM of gentamicin for 48 hr and allowed to recover in a culture medium only or in a medium with daily irradiation of low-level laser, whereas the control group was not exposed to gentamicin. Whole-mount utricles were stained with FM1-43, which are known to be an efficient marker, to identify live hair cells in cultured tissues. RESULTS: Loss of hair cells was nearly stopped from 2 days after exposure to gentamicin ; a peak of regeneration was reached after 18 days and sustained for two weeks in the medium with the irradiation of low-level laser. CONCLUSION: These results suggest that low-level laser promotes spontaneous hair cell regeneration following gentamicin damage in utricular explants.
Animals ; Ear, Inner ; Epithelium ; Gentamicins* ; Hair Cells, Vestibular ; Hair* ; Rats* ; Regeneration* ; Saccule and Utricle*

The basic mechanism for the excitation of the peripheral vestibular receptors following acute hypotension induced by sodium nitroprusside (SNP) or hemorrhage was investigated in anesthetized rats. Electrical activity of the afferent vestibular nerve was measured after pretreatment with kynurenic acid, an NMDA receptor antagonist. The activity of the vestibular nerve at rest following acute hypotension induced by SNP or simulating hemorrhage was a greater increase than in control animals. The gain of the vestibular nerve with sinusoidal rotation following acute hypotension increased significantly compared to control animals. The acute hypotension induced by SNP or hemorrhage did not change the activity of the afferent vestibular nerve after kynurenic acid injection. These results suggest that acute hypotension produced excitation of the vestibular hair cells via glutamate excitotoxicity in response to ischemia.
Animals ; Glutamic Acid ; Hair Cells, Vestibular ; Hemorrhage ; Hypotension* ; Ischemia ; Kynurenic Acid ; N-Methylaspartate ; Nitroprusside ; Rats* ; Vestibular Nerve*

Bilateral loss of vestibular sensation from injuries of vestibular hair cells causes individuals suffering poor vision during head movement, postural instability, chronic disequilibrium, and cognitive distraction. A vestibular prosthesis analogous to cochlear implants but designed to modulate vestibular nerve activity during head movement should improve quality of life for these chronically dizzy individuals. An implantable prosthesis that partly restores normal activity on branches of the vestibular nerve should improve quality of life for individuals disabled by this disorder. There have been many efforts to develop and restore 3-dimensional angular vestibule-ocular reflex and the Johns Hopkins vestibular neuro-engineering laboratory has been developing a head-mounted multichannel vestibular prosthesis that restores sufficient semicircular canal function to partially recreate a normal 3-dimensional angular vestibulo-ocular reflex. In this review, their results are described.
Cochlear Implants ; Dizziness ; Ear, Inner ; Hair Cells, Vestibular ; Head Movements ; Prostheses and Implants ; Quality of Life ; Reflex ; Reflex, Vestibulo-Ocular ; Semicircular Canals ; Sensation ; Stress, Psychological ; Vestibular Nerve ; Vision, Ocular

BACKGROUND AND OBJECTIVES: The caveolin is known as a mediator of cell death or survival of injured cell and inhibitor of various signaling pathways. We examined expression of caveolin-1 involved by protein kinase A(PKA) signaling pathway in the differentiated mouse vestibular cell line(UB/UE-1) after gentamicin toxicity. MATERIALS AND METHOD: We observed caveolae in the vestibular hair cell of healthy guinea pig through electron microscope. UB/UE-1 cells were cultured at 95% CO2, 5% O2, 33DegreeC for 2days and at 95% CO2, 5% O2, 39DegreeC for 24 hours for differentiation. Cells were treated with 1 mM of gentamicin, 0.02 mM H89 (PKA inhibitor), and then incubated for 24 hours. Caveolin-1 expression was examined by western blot and PKA activity by PepTag? assay. RESULTS: Caveolae were observed in the vestibular hair cell of healthy guinea pig by electron microscope. Caveolin-1 was expressed spontaneously in differentiated UB/UE-1 cells and increased after gentamicin treatment. PKA is overactivated by gentamicin treatment. The gentamicin induced caveolin-1 expression and PKA overactivation was inhibited by H89. CONCLUSION: Our results indicate that gentamicin induced caveolin-1 expression is mediated by PKA signaling pathway. We conclude that the caveolae/caveolin through a PKA signaling pathway is the important mechanism of gentamicin induced ototoxicity.
Animals ; Blotting, Western ; Caveolae ; Caveolin 1* ; Cell Death ; Cell Line* ; Gentamicins* ; Guinea Pigs ; Hair Cells, Vestibular ; Mice ; Protein Kinases

OBJECTIVETo investigate the mechanism of intense noise-induced apoptosis of vestibular hair cells in guinea pigs and the effect of phosphorylated c-Jun N-terminal kinase (JNK) signal transduction pathway in intense noise-induced apoptosis of vestibular hair cells.

METHODSThirty-two guinea pigs were randomly and equally divided into 1, 5, and 15 d experimental groups and control group. The guinea pigs in the experimental groups were exposed to 4 kHz narrow-band noise at 120 dB SPL for 4 h and then subjected to measurement of auditory brainstem response at 1, 5, or 15 d after noise exposure. In each group, four guinea pigs were used to prepare paraffin sections of vestibular hair cells, and the rest for extraction of total protein from vestibular hair cells. The apoptosis of vestibular hair cells was detected by terminal deoxynucleotidyl transferase (TdT)-mediated d-UTP nick-end labeling (TUNEL). The expression levels of p-JNK and pc-Jun were measured by immunohistochemistry and Western blot.

RESULTSTUNEL-positive cells were found in the vestibular hair cells in the experimental groups, most in the 1 d experimental group and least in the 15 d experimental group, but no positive cells were found in the control group. The immunohistochemical results showed that p-JNK and pc-Jun were detected in the cell nuclei in the experimental groups, but no p-JNK- and pc-Jun-positive cells were found in the control group. The Western blot showed that p-JNK and pc-Jun were increased and activated quickly at 1d after noise exposure, reached the peak levels at 5 d after noise exposure, and were then decreased gradually, but they were still at relatively high levels at 15 d after noise exposure.

CONCLUSIONIntense noise can cause injury to vestibular hair cells by inducing cell apoptosis, and p-JNK marks the activation of JNK signal transduction pathway, suggesting that JNK signal transduction pathway plays an important role in intense noise-induced apoptosis of vestibular hair cells in guinea pigs.

Animals ; Apoptosis ; Guinea Pigs ; Hair Cells, Vestibular ; cytology ; MAP Kinase Kinase 4 ; metabolism ; Noise ; adverse effects ; Phosphorylation ; Signal Transduction

BACKGROUND AND OBJECTIVES: Gentamicin (GM) is well known for its vestibulotoxicity. There have been many reports about vestibulotoxicity, however, its mechanism is still unclear. So far, it is known that GM affects the voltage-dependent K+ current and nitric oxide (NO) production. Epigallocatechin-3-gallate (EGCG) is the major component of green tea and is known to have anti-oxidative and anti-toxic effect. This study was undertaken to investigate the protective effect of EGCG against gentamicin on vestibular hair cell (VHC). MATERIALS AND METHOD: White guinea pigs (200-250 g) were rapidly decapitated and the temporal bones were immediately removed. Under a dissecting microscope, the crista ampullaris was obtained. The dissociated VHCs were transferred into a recording chamber mounted onto an inverted microscope. Whole-cell membrane currents and potentials were recorded using standard patch-clamp techniques. In addition, measurements of NO production were obtained using the NO-sensitive dye, 4,5-diamino-fluorescein diacetate (DAF-2DA). RESULTS: Type I VHCs Voltage-dependent K+ current was activated from low depolarizing stimulation. As the stimulation increased, higher current was detected. Voltage-dependent K+ current in type I VHCs was decreased when GM (200 microM) was administrated and GM effects of K+ current inhibition was significantly blocked by EGCG. Extracellular GM-induced an increase in DAF-2DA fluorescence, which thus indicates NO production in VHCs. Also, the GMinduced NO production was inhibited by EGCG. CONCLUSION: GM inhibits voltage-dependent K+ current by releasing NO in isolated type I VHCs. EGCG blocks this inhibitory effects, suggesting a protective role on GM vestibulotoxicity.
Animals ; Fluorescence ; Gentamicins* ; Guinea Pigs* ; Hair Cells, Vestibular* ; Membranes ; Nitric Oxide ; Patch-Clamp Techniques ; Semicircular Ducts ; Tea ; Temporal Bone