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Biomedical subjects

Atsuhiko Uno

Publications and source records attributed to Atsuhiko Uno.

12 recordsLinked to original sources

Factors relating to the vertigo control and hearing changes following intratympanic gentamicin for intractable Ménière's disease.

OBJECTIVE: To look for factors relating to the vertigo control and hearing changes after intratympanic injections of gentamicin (GM). STUDY DESIGN: Prospective. SETTING: Tertiary referral medical center. PATIENTS: Twenty-eight patients with intractable Ménière's disease. INTERVENTIONS: Three intratympanic injections of GM (once per day for three consecutive days). MAIN OUTCOME MEASURES: Although five patients needed further GM injections or vestibular neurectomy because of poor control (Group I), 23 patients had their vertigo controlled for more than two years without further treatment (Group II). The number of vertigo spells per month, pure-tone audiometry, electrocochleography, caloric response, post-head shake nystagmus, and plasma vasopressin as a stress marker were examined. RESULTS: Before GM injections, there was no difference in the number of vertigo spells per month between Groups I and II. However, the hearing thresholds were higher in Group I. Hearing improvement, increase in percentage of canal paresis and induction of post-head shake nystagmus were observed after GM injections only in Group II. Even in the 11 patients who showed an improvement in hearing of more than 10 dB (hearing improvement group), percentage of canal paresis was increased after GM. More, premedication plasma vasopressin levels were lower in the hearing improvement group as compared with the hearing loss/no changes group. Four of eight patients became negative for dominant negative summating potential in electrocochleography after GM injections in the hearing improvement group. CONCLUSION: Our data indicate that the frequency of vertigo is not a key factor in the vertigo control after GM injections, that induction of vestibular damage in the injected ear is essential for the control of vertigo and this effect is mostly pronounced in patients with milder hearing loss, and that hearing improvement is not only a consequence of good vertigo control but also affected by the stress level before treatment.

Adult↗

Effects of immersion in virtual reality on postural control.

In the present study, we examined the effects of the time lag between visual scene and the head movement in the virtual reality (VR) world on motion sickness and postural control in healthy volunteers. After immersion in VR with additional time lags (from 0 to 0.8 s) to the inherent delay (about 250 ms), the visual-vestibular conflict induced a slight motion sickness in experimental subjects, but no change was noticed in the body sway path with eyes open and closed. However, Romberg ratio of body sway path with eyes closed divided by that with eyes open after immersion in VR was significantly decreased in comparison with that before immersion in VR. Since Romberg ratio is an index of visual dependency on postural control, this finding indicates that the immersion in VR decreases the visual dependency on postural control. It is suggested that adaptation to visual-vestibular conflict in VR immersion increases the contribution of vestibular and somatosensory inputs to postural control by ignoring the conflicting delayed visual input in the VR world. VR may be a promising treatment for visual vertigo in vestibular patients with unsuccessful compensation by its ability to induce vestibular and somatosensory reweighing for postural control.

Adult↗

Unilateral labyrinthectomy modifies the membrane properties of contralesional vestibular neurons.

Vestibular compensation after a unilateral labyrinthectomy leads to nearly complete disappearance of the static symptoms triggered by the lesion. However, the dynamic vestibular reflexes associated with head movements remain impaired. Because the contralesional labyrinth plays a prominent role in the generation of these dynamic responses, intracellular recordings of contralesional medial vestibular nucleus neurons (MVNn) were done after 1 mo of compensation. Their firing properties and cell type were characterized at rest, and their response dynamics investigated using step, ramp, and sinusoidal current stimulations. The sensitivity of the contralesional MVNn firing rates to applied current was increased, which, along with increased phase leads, suggests that significant changes in active conductances occurred. We found an increased proportion of the phasic type B neurons relative to the tonic type A neurons in the contralesional MVN. In addition, the remaining contralesional type A MVNn response dynamics tended to approach those of type B MVNn. Thus the contralesional MVNn in general showed more phasic response dynamics than those of control MVNn. Altogether, the firing properties of MVNn are differentially modified on the ipsilesional and contralesional sides of the brain stem 1 mo after unilateral labyrinthectomy. Ipsilesional MVNn acquire more "type A-like" tonic membrane properties, which would contribute to the stabilization of the spontaneous activity that recovers in the deafferented neurons during vestibular compensation. The bilateral increase in the sensitivity of MVNn and the acquisition of more "B-like" phasic membrane properties by contralesional MVNn should promote the restoration of the vestibular reflexes generated by the remaining, contralesional labyrinth.

Action Potentials↗

Paroxetine, a selective serotonin reuptake inhibitor, reduces depressive symptoms and subjective handicaps in patients with dizziness.

OBJECTIVE AND STUDY DESIGN: When treating dizzy patients, the psychiatric aspect should be carefully addressed regardless of whether a well-defined organic disease is present. In this prospective study, we aimed to elucidate the role of paroxetine, a selective serotonin reuptake inhibitor, in the treatment of dizziness. SETTING AND PATIENTS: Forty-seven patients who complained of dizziness were treated with 20 mg of paroxetine per day. The depressive state of the patient was evaluated by the Zung Self-Rating Depression Scale (SDS). Treatment outcomes were measured with self-assessment of subjective handicaps in daily life using a dizziness and unsteadiness questionnaire. The questionnaire consisted of five factors related to emotional or bodily dysfunction that could be affected by dizziness. Changes in Self-Rating Depression Scale scores and subjective handicaps were assessed at 4 and 8 weeks after the start of paroxetine. RESULTS: In patients having well-defined organic diseases with high Self-Rating Depression Scale scores, paroxetine improved all five subjective handicap factors as well as Self-Rating Depression Scale scores. The decline in Self-Rating Depression Scale scores showed a significant correlation with improvement of subjective handicaps, which was related to emotional problems but not factors related to bodily dysfunction. Paroxetine was also effective for an improvement of factors related to emotional problems and Self-Rating Depression Scale scores in patients not having organic diseases but with high Self-Rating Depression Scale scores. In patients either with or without organic diseases with low Self-Rating Depression Scale scores, paroxetine had no effect on any subjective handicap factors and Self-Rating Depression Scale scores. CONCLUSION: In the treatment of dizzy patients, paroxetine was effective at relieving subjective handicaps caused by dizziness, specifically, in patients with high Self-Rating Depression Scale scores.

Activities of Daily Living↗

Microarray analysis of gene expression in the rat vestibular nucleus complex following unilateral vestibular deafferentation.

To investigate the molecular background of vestibular compensation, a model of lesion-induced plasticity, we used a microarray analysis to examine genes that show asymmetrical expression between the bilateral vestibular nucleus complexes (VNCs) 6 h following unilateral vestibular deafferentation (UVD). Asymmetrical gene expression was then validated by a real-time quantitative PCR. Among the 88 genes for which the ipsilateral (ipsi) : contralateral (contra) was > 1.35, the number of known genes was 33 (38%), and the number of expressed sequence tag (EST) sequences was 55 (62%). Among the 130 genes for which the contra : ipsi was > 1.35, the number of known genes was 55 (42%), and the number of EST sequences was 75 (58%). Changes in some of the genes were consistent with previous studies; however, we found several new genes which could be functionally related to the molecular basis of the electrophysiological asymmetry between the VNCs following UVD. Ipsi > contra genes included the GABA(A) receptor rho subunit, regulatory proteins of G protein signaling, calcium signaling related molecules such as the voltage-dependent calcium channel alpha2/delta subunit 1, calcineurin subunit Abeta and Ca(2+) pump. Contra > ipsi genes included the neuronal high affinity glutamate transporter, 5-hydroxytryptamine receptor 1D, mitogen-activated protein kinase 12 and ubiquitin carboxy-terminal hydrolase L1.

Animals↗

Fos induction in the amygdala by vestibular information during hypergravity stimulation.

Altered gravity environments including both hypo- and hypergravity can elicit motion sickness. Vestibular information is known to be essential for motion sickness, but its other neural substrates are poorly understood. We previously showed that bilateral lesions of the amygdala suppressed hypergravity-induced motion sickness in rats, using pica behavior as an emetic index. We show in the present study that during hypergravity stimulation, vestibular information activated the central nucleus of the amygdala (CeA), as determined by the induction of Fos expression, in comparison between normal and bilaterally labyrinthectomized rats. The finding that Fos expression was confined to the CeA and almost completely absent in other subnuclei of the amygdala contrasted with many previous studies that used other stressful stimuli such as foot shock, restraint and forced swimming, suggesting a specific vestibular effects on the amygdala. Prolongation of hypergravity resulted in reduction of Fos expression in the CeA, suggesting a process of habituation. Such decreases appeared earlier than in the vestibular nucleus, suggesting that adaptive changes in the CeA to hypergravity were independent of changes in the vestibular input. Our results suggest the amygdala is a neural substrate involved in the development of and habituation to motion sickness.

Afferent Pathways↗

Static and dynamic membrane properties of lateral vestibular nucleus neurons in guinea pig brain stem slices.

In vitro intracellular recordings of central vestibular neurons have been restricted so far to the medial vestibular nucleus (MVN). We performed intracellular recordings of large Deiters' neurons in the lateral vestibular nucleus (LVN) to determine their static and dynamic membrane properties, and compare them with those of type A and type B neurons identified in the MVN. Unlike MVN neurons (MVNn), the giant-size LVN neurons (LVNn) form a homogeneous population of cells characterized by sharp spikes, a low-amplitude, biphasic after-hyperpolarization like type B MVNn, but also an A-like rectification like type A MVNn. In accordance with their lower membrane resistance, the sensitivity of LVNn to current injection was lower than that of MVNn over a large range of frequencies. The main difference between LVNn and MVNn was that the Bode plots showing the sensitivity of LVNn as a function of stimulation frequency were flatter than those of MVNn, and displayed a weaker resonance. Furthermore, most LVNn did not show a gradual decrease of their firing rate modulation in the frequency range where it was observed in MVNn. LVNn synchronized their firing with the depolarizing phase of high-frequency sinusoidal current injections. In vivo studies have shown that the MVN would be mainly involved in gaze control, whereas the giant LVNn that project to the spinal cord are involved in the control of posture. We suggest that the difference in the membrane properties of LVNn and MVNn may reflect their specific physiological roles.

Action Potentials↗

Long-term plasticity of ipsilesional medial vestibular nucleus neurons after unilateral labyrinthectomy.

Unilateral labyrinthectomy results in oculomotor and postural disturbances that regress in a few days during vestibular compensation. The long-term (after 1 mo) consequences of unilateral labyrinthectomy were investigated by characterizing the static and dynamic membrane properties of the ipsilesional vestibular neurons recorded intracellularly in guinea pig brain stem slices. We compared the responses of type A and type B medial vestibular nucleus neurons identified in vitro to current steps and ramps and to sinusoidal currents of various frequencies. All ipsilesional vestibular neurons were depolarized by 6-10 mV at rest compared with the cells recorded from control slices. Both their average membrane potential and firing threshold were more depolarized, which suggests that changes in active conductances compensated for the loss of excitatory afferents. The afterhyperpolarization and discharge regularity of type B but not type A neurons were increased. All ipsilesional vestibular cells became more sensitive to current injections over a large range of frequencies (0.2-30 Hz), but this increase in sensitivity was greater for type B than for type A neurons. This was associated with an increase of the peak frequency of linear response restricted to type B neurons, from 4-6 to 12-14 Hz. Altogether, we show that long-term vestibular compensation involves major changes in the membrane properties of vestibular neurons on the deafferented side. Many of the static and dynamic membrane properties of type B neurons became more similar to those of type A neurons than in control slices, leading to an increase in the overall homogeneity of medial vestibular nucleus neurons.

Action Potentials↗

A new rotational test for vertical semicircular canal function.

OBJECTIVE: We developed a new rotating chair in order to assess the function of the vertical semicircular canal (VSCC) by analyzing VSCC-induced post-rotatory nystagmus (PRN). METHODS: We examined 14 healthy subjects, wearing goggles equipped with an infrared CCD camera, and sitting on a chair which was designed to stimulate a pair of the VSCCs by tilting the head 60 degrees backward with a 45 degrees rotation to the left or right side from the sagital plane. The time constant (TC) or maximal slow phase eye velocity (MSPEV) of the vertical component of four kinds of PRN were analyzed in four corresponding rotatory conditions, and used as functional index of the corresponding VSCC. RESULTS: The mean values of MSPEV in both anterior semicircular canal (ASCC) and posterior semicircular canal (PSCC)-induced PRN tended to be lower (P<0.10) than those induced by the lateral semicircular canal (LSCC). The result suggests that the threshold to the angular velocity in the VSCC is lower than that in the LSCC. The mean values of TC in both ASCC and PSCC-induced PRN were significantly lower (P<0.05) than those induced by the LSCC. CONCLUSION: The significant reduction of TC in VSCC-induced PRN compared with LSCC-induced PRN indicates that VSCC function is less affected by velocity storage mechanisms than LSCC function. The rotational test with respect to the VSCC can be used as a tool for assessing vertical canal function.

Adult↗

Magnetic cortical responses evoked by visual linear forward acceleration.

Cortical site processing the information of whole body linear acceleration has not yet been identified. In this study, neuromagnetic responses to visually induced linear forward acceleration were recorded in six healthy-right-handed adult subjects using a 122-channel whole cortex neuromagnetometer. Significant activation was estimated in the cortex around the posterior insula, which belongs to the vestibular cortex. Hence, it is suggested that the vestibular cortex not only receives vestibular input from the peripheral vestibular apparatus, but also processes the vestibular sensation from multi-modal information.

Acceleration↗

Quantitative changes in mRNA expression of glutamate receptors in the rat peripheral and central vestibular systems following hypergravity.

In order to investigate the mechanisms responsible for adaptation to altered gravity, we assessed the changes in mRNA expression of glutamate receptors in vestibular ganglion cells, medial vestibular nucleus, spinal vestibular nucleus/lateral vestibular nucleus, cerebellar flocculus, and uvula/nodulus from rats exposed to hypergravity for 2 h to 1 week using real-time quantitative RT-PCR methods. The mRNA expression of GluR2 and NR1 receptors in the uvula/nodulus and NR1 receptors in the medial vestibular nucleus increased in animals exposed to 2 h of hypergravity, and it decreased gradually to the control level. The mRNA expression of GluR2 receptors in vestibular ganglion cells decreased in animals exposed to 1 week of hypergravity. Neither the metabotropic glutamate receptor 1 nor delta2 glutamate receptor in flocculus and uvula/nodulus was affected by a hypergravity load for 2 h to 1 week. It is suggested that the animals adapted to the hypergravity by enhancing the cerebellar inhibition of the vestibular nucleus neurons through activation of the NR1 and GluR2 receptors on the Purkinje cells in uvula/nodulus especially at the early phase following hypergravity. In the later phase following hypergravity, the animals adapted to the hypergravity by reducing the neurotransmission between the vestibular hair cells and the primary vestibular neurons via down-regulation of the postsynaptic GluR2 receptors in the vestibular periphery.

Animals↗

Three-dimensional eye rotation axis analysis of benign paroxysmal positioning nystagmus.

We have developed a new technique for analyzing the rotation vector of eye movement with an infrared CCD camera [Imai et al.: Acta Otolaryngol 1999;119:24-28]. We used this technique to analyze the eye rotation axis of benign paroxysmal positioning nystagmus (BPPN) that was induced by the Dix-Hallpike maneuver in 14 patients with benign paroxysmal positioning vertigo (BPPV). Eye rotation axes of BPPN in 8 patients were closely perpendicular to the posterior canal of the undermost ear in the provocative head position. Under the hypothesis that BPPN is due to a mechanical stimulation of the posterior canal by canalolithiasis, this finding suggested that the posterior canal of the undermost ear is the lesion. On the other hand, eye rotation axes of BPPN in the other 6 patients were closely aligned with the naso-occipital axis. It is suggested that canalolithiasis induces endolymphatic flow in both posterior and anterior canals via the common crus and the summation of the eye movements induced by stimulation of both the posterior and anterior canals rotates the eye along the naso-occipital axis.

Adult↗