Biomedical subjects

Arata Horii

Publications and source records attributed to Arata Horii.

At least 19 recordsLinked to original sources

PubMed2006

Fos-enkephalin signaling in the rat medial vestibular nucleus facilitates vestibular compensation.

In the present study, we first observed up-regulation in preproenkephalin (PPE)-like immunoreactivity (-LIR), a precursor of Met- and Leu-enkephalin, in the rat ipsilateral medial vestibular nucleus (ipsi-MVN) after unilateral labyrinthectomy (UL). By means of double-staining immunohistochemistry with PPE and Fos, a putative regulator of PPE gene expression, we revealed that some of these PPE-LIR neurons were also Fos immunopositive. The time course of decay of these double-stained neurons was quite parallel to that of UL-induced behavioral deficits. This suggests that these double-labeled neurons could have something to do with development of vestibular compensation. We next examined correlation between Fos and PPE expression in the ipsi-MVN by means of a 15-min pre-UL application of antisense oligonucleotide probes against c-fos mRNA into the ipsi-MVN. Gel shift assay and Western blotting revealed that elimination of Fos expression significantly reduced both AP-1 DNA binding activity and PPE expression in the ipsi-MVN after UL. C-fos antisense study also revealed that depression of Fos-PPE signaling in the ipsi-MVN caused significantly more severe behavioral deficits during vestibular compensation. Furthermore, studies with PPE antisense and naloxone, an opioid receptor antagonist, demonstrated that specific depression of enkephalinergic effects in the ipsi-MVN significantly delayed vestibular compensation. All these findings suggest that, immediately after UL, Fos induced in some of the ipsi-MVN neurons could regulate consequent PPE expression via the AP-1 activation and facilitate the restoration of balance between bilateral MVN activities via the opioid receptor activation, resulting in progress of vestibular compensation.

Adaptation, Physiological↗

PubMed2006

Intracranial vertebral artery dissection mimicking acute peripheral vertigo.

When diagnosing and treating patients with acute vertigo, the clinician must differentiate brain lesions from benign peripheral disorders. We here report a rare case of acute vertigo caused by intracranial vertebral artery dissection mimicking peripheral disease. A 67-year-old man presented with spontaneous nystagmus and moderate ataxia preceded by neck pain. No other neurological signs were observed, suggesting acute peripheral vertigo. However, magnetic resonance imaging (MRI) demonstrated a cerebellar infarction. Simultaneous magnetic resonance angiography (MRA) showed no flow void of the left vertebral artery and contrast-enhanced MRA demonstrated a double lumen sign, suggesting that vertebral artery dissection was a cause of infarction. The clinical course was favorable without anticoagulation drugs, which are sometimes contraindicated because of the potential risk of subarachnoid hemorrhage. Vertebral artery dissection can cause cerebellar infarction in patients without vascular risk factors mimicking acute peripheral vertigo. Careful history regarding the neck pain is important and MRA in combination with MRI can replace angiography in diagnosing this disorder.

Aged↗

PubMed2006

Endolymphatic hydrops as a cause of audio-vestibular manifestations in relapsing polychondritis.

Relapsing polychondritis (RP) is characterized by inflammation and subsequent degeneration of cartilage. We report a 61-year-old woman who had RP with audio-vestibular manifestations. She was also diagnosed as having a myelofibrosis with myeloid metaplasia (MMM). Bilateral endolymphatic hydrops (EH) was confirmed by dominant -SP/AP of the electrocochleogram (ECochG). When thalidomide and prednisolone were prescribed for the treatment of MMM, symptoms of RP -- including the inner ear dysfunction -- were ameliorated. Isosorbide, one of the osmotic diuretics commonly used for the treatment of Meniere's disease (MD) in Japan, was also effective in keeping her free from inner ear dysfunction. This is the first report to confirm the existence of EH in a patient with RP with audio-vestibular manifestations. We suppose that an immunological imbalance due to MMM, in conjunction with a specific immunogenetic background, may have played a role in the pathogenesis of RP and the formation of EH in this patient.

Acute Disease↗

PubMed2006

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↗

PubMed2006

Lesions of the vestibular system disrupt hippocampal theta rhythm in the rat.

The hippocampus has a major role in memory for spatial location. Theta is a rhythmic hippocampal EEG oscillation that occurs at approximately 8 Hz during voluntary movement and that may have some role in encoding spatial information. We investigated whether, as part of this process, theta might be influenced by self-movement signals provided by the vestibular system. The effects of bilateral peripheral vestibular lesions, made > or = 60 days prior to recording, were assessed in freely moving rats. Power spectral analysis revealed that theta in the lesioned animals had a lower power and frequency compared with that recorded in the control animals. When the electroencephalography (EEG) was compared in epochs matched for speed of movement and acceleration, theta was less rhythmic in the lesioned group, indicating that the effect was not a result of between-group differences in this behavior. Blood measurements of corticosterone were also similar in the two groups indicating that the results could not be attributed to changes in stress levels. Despite the changes in theta EEG, individual neurons in the CA1 region of lesioned animals continued to fire with a periodicity of approximately 8 Hz. The positive correlation between cell firing rate and movement velocity that is observed in CA1 neurons of normal animals was also maintained in cells recorded from lesion group animals. These findings indicate that although vestibular signals may contribute to theta rhythm generation, velocity-related firing in hippocampal neurons is dependent on nonvestibular signals such as sensory flow, proprioception, or motor efference copy.

Animals↗

PubMed2006

[Delayed facial nerve palsy after otologic surgery].

Delayed facial nerve palsy (DFP) is rarely experienced after otologic surgeries that do not directly touch the facial nerves, such as tympano-mastoidectomy, cochlear implants, and stapes surgery, and is troublesome to both surgeons and patients if it happens. Here, we report 7 cases of DFP, including one case that developed DFP after endolymphatic sac surgery. The ratios of occurrence were as follows: 0.7% (2/305) for tympano-mastoidectomy, 0.8% (3/354) for cochlear implant, 0.4% (1/260) for stapes surgery and 1.0% (1/98) for endolymphatic sac surgery. All otologic surgeries, except for endolymphatic sac surgery, exposed the chorda tympani, and all surgeries, except for stapes surgery, underwent drilling for a mastoidectomy. Furthermore, DFP was always observed ipsilaterally to the operated ear after otologic surgeries and was never seen after benign parotid tumor surgery or total laryngectomy. Therefore, there may be a strong relationship between DFP and the procedures, used during otologic surgeries.

Adult↗

PubMed2005

Ménière's disease is associated with single nucleotide polymorphisms in the human potassium channel genes, KCNE1 and KCNE3.

Although the bases for both the sporadic and inherited forms of Ménière's disease (MD) remain undefined, it is likely to be multifactorial, one of the factors being a genetic predisposition. Recently, genetic association studies on complex diseases have become very popular and most of them are case-control studies using single nucleotide polymorphisms (SNPs) as markers. Mutations/polymorphisms in KCNE potassium channel genes might play a causative role in MD, because KCNE potassium channels have been suggested to be present and active in transmembrane ion and water transports in the inner ear. In the present study, to identify MD susceptibility genes, we have conducted a genetic association study with optimized sampling, optimized phenotyping/genotyping, and a selection of KCNE genes as the candidate genes. The SNPs analyses identified 112G/A SNP in the KCNE1 gene and 198T/C SNP in the KCNE3 gene in 63 definite MD cases as well as 205 and 237 non-MD control subjects. For both KCNE1 and KCNE3 genes, a significant difference in frequency of each SNP was confirmed between MD cases and non-MD control subjects. The result indicates that 112G/A SNP in the KCNE1 gene and 198T/C SNP in the KCNE3 gene could determine an increased susceptibility to develop MD.

Adult↗

PubMed2005

Magnetic resonance imaging of syringocystadenoma papilliferum of the external auditory canal.

Syringocystadenoma papilliferum (SCAP) usually occurs on the face or the scalp and is very rare in the external auditory canal (EAC). There has been no information on magnetic resonance (MR) imaging of this tumor irrespective of its site. We report here a case of 57-year-old man having this tumor, which was surgically removed and its histopathology was confirmed. MR imaging demonstrated a lobulated 4-cm mass with clearly defined margins in the EAC. Although the tumor was bulky, these MR findings were different from the malignancies. The mass lesion showed intermediate signal intensity both on T1- and T2-weighted MR images and showed slight enhancement on gadolinium-enhanced T1-weighted images. Signal intensities on T2-weighted images of this tumor were low compared to those of pleomorphic adenoma. All ceruminous gland tumors including SCAP are thought to be potentially malignant; therefore, pre-operative biopsy should not be performed. Even though incisional biopsy is sometimes needed as in our case, the current MR features would be helpful for differential diagnosis of this rare condition and assessing the extension of the tumor.

Contrast Media↗

PubMed2005

Immunocytochemical and stereological analysis of GABA(B) receptor subunit expression in the rat vestibular nucleus following unilateral vestibular deafferentation.

The process of behavioral recovery that occurs following damage to one vestibular labyrinth, vestibular compensation, has been attributed in part to a down-regulation of GABA(B) receptors in the vestibular nucleus complex (VNC) ipsilateral to the lesion, which could potentially reduce commissural inhibition from the contralateral VNC. In this study, we tested the possibility that this occurs through a decrease in the expression of either the GABA(B1) or GABA(B2) subunits of the GABA(B) receptor. We used Western blotting to quantify the expression of these subunits in the VNC at 10 h and 50 h following unilateral vestibular deafferentation (UVD) or sham surgery in rats. We then used immunocytochemistry and stereological counting methods to estimate the number of neurons expressing these subunits in the MVN at 10 h and 2 weeks following UVD or sham surgery. Compared to sham controls, we found no significant changes in either the expression of the two GABA(B) receptor subunits in the VNC or in the number of MVN neurons expressing these GABA(B) receptor subunits post-UVD. These results suggest that GABA(B) receptor expression does not change substantially in the VNC during the process of vestibular compensation.

Afferent Pathways↗

PubMed2005

The effects of vestibular lesions on hippocampal function in rats.

Interest in interaction between the vestibular system and the hippocampus was stimulated by evidence that peripheral vestibular lesions could impair performance in learning and memory tasks requiring spatial information processing. By the 1990s, electrophysiological data were emerging that the brainstem vestibular nucleus complex (VNC) and the hippocampus were connected polysynaptically and that hippocampal place cells could respond to vestibular stimulation. The aim of this review is to summarise and critically evaluate research published in the last 5 years that has seen major progress in understanding the effects of vestibular damage on the hippocampus. In addition to new behavioural studies demonstrating that animals with vestibular lesions exhibit impairments in spatial memory tasks, electrophysiological studies have confirmed long-latency, polysynaptic pathways between the VNC and the hippocampus. Peripheral vestibular lesions have been shown to cause long-term changes in place cell function, hippocampal EEG activity and even CA1 field potentials in brain slices maintained in vitro. During the same period, neurochemical investigations have shown that some hippocampal subregions exhibit long-term changes in the expression of neuronal nitric oxide synthase, arginase I and II, and the NR1 and NR2A N-methyl-D-aspartate (NMDA) receptor subunits following peripheral vestibular damage. Despite the progress, a number of important issues remain to be resolved, such as the possible contribution of auditory damage associated with vestibular lesions, to the hippocampal effects observed. Furthermore, although these studies demonstrate that damage to the vestibular system does have a long-term impact on the electrophysiological and neurochemical function of the hippocampus, they do not indicate precisely how vestibular information might be used in hippocampal functions such as developing spatial representations of the environment. Understanding this will require detailed electrical stimulation and lesion studies to elucidate the way in which different kinds of vestibular information are transmitted to various hippocampal subregions.

Animals↗

PubMed2005

Does vestibular damage cause cognitive dysfunction in humans?

For more than a decade, evidence from animal studies has suggested that damage to the vestibular system leads to deficits in spatial navigation which are indicative of impaired spatial learning and memory. More recently, direct evidence has emerged to demonstrate that humans with vestibular disorders exhibit a range of cognitive deficits that are not just spatial in nature, but also include non-spatial functions such as object recognition memory. Vestibular dysfunction has been shown to adversely affect attentional processes and increased attentional demands can worsen the postural sway associated with vestibular disorders. Recent MRI studies also show that humans with bilateral vestibular damage undergo atrophy of the hippocampus which correlates with their degree of impairment on spatial memory tasks. These results are consistent with those from animal studies and, together, suggest that humans with vestibular disorders are likely to experience cognitive dysfunction which is not necessarily related to any particular episode of vertigo or dizziness, and therefore may occur even in patients who are otherwise well compensated. These findings may be related to the observation that patients with vestibular deficits experience a high incidence of depression and anxiety disorders.

Animals↗

PubMed2004

Expression of Musashi1, a neural RNA-binding protein, in the cochlea of young adult mice.

Musashi1 (Msi1) is an RNA-binding protein expressed in neural stem/progenitor cells, astroglial progenitor cells and astrocytes in the vertebrate central nervous system. We hypothesized that Msi1 is expressed in only some of the supporting cells in the cochlea, which could become hair cell progenitors under special circumstances after an injury. To observe this, we investigated Msi1 expression in young adult mouse cochlea by immunohistochemistry using monoclonal antibody against Msi1. Msi1 immunostaining was found in a variety of supporting cells but not in outer hair cells in the organ of Corti. Although an immunoreactive ring was found around the inner hair cells, it also seemed to originate from the supporting cells. We suppose that this wide expression of Msi1 in supporting cells indicates that those cells might have the potential to become hair cell progenitors if injured, but that some other mechanisms strictly inhibit this ability.

Animals↗

PubMed2004

Impaired spatial learning after hypergravity exposure in rats.

Most astronauts experience spatial disorientation after exposure to weightlessness, indicating that constant gravity is utilized as a stable external reference during spatial cognition. We attempted to elucidate the role of constant gravity in spatial learning using a radial arm maze test on rats housed in a hypergravity environment (HG) produced by a centrifuge device. Male Wistar rats were kept in 2G linear acceleration for 2 weeks before the spatial learning task, which lasted for 10 days. The control rats were placed close to the centrifuge device but not exposed to hypergravity. Spatial learning was evaluated by the accuracy and the re-entry rate, which were the rate of correct arm entries and the rate of entries into the arms that they had already visited, respectively. Locomotor activity was measured by number of entries per minute. The number of baits the animal took per minute was also measured. The results showed that accuracy was significantly inferior and the re-entry rate was significantly higher in the HG rats than in the controls, suggesting that animals use a constant gravity as a stable external reference in spatial learning. However, these differences disappeared at 5 days later, indicating that the HG rats learned the spatial task more rapidly than the controls. Locomotor activity was higher in the HG rats and there was no difference in number of baits per minute between the HG and control animals. In conclusion, if one sensory cue necessary for spatial cognition is disturbed by gravity change, animals can subsidize with other sensory cues such as proprioceptive and motor efference copy signals through increased locomotor activities.

Analysis of Variance↗

PubMed2004

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↗

PubMed2004

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↗

PubMed2003

Effects of unilateral labyrinthectomy on GAD, GAT1 and GABA receptor gene expression in the rat vestibular nucleus.

To elucidate the role of the GABAergic neuronal system in the recovery from peripheral vestibular damage (unilateral labyrinthectomy), we used a real-time quantitative reverse transcription-polymerase chain reaction method to investigate the mRNA expression of GAD65, GAD67, the GABAA receptor alpha1 subunit, the GABAB R1 subunit, and the GABA transporter GAT1, in the vestibular nucleus complex of the rat 6 and 50 h following the lesion GAD65 and GAD67 gene expression were also measured in the flocculus. The GABAA alpha 1 subunit mRNA was up-regulated in the ipsilateral vestibular nucleus 6 h post-lesion but decreased in expression thereafter. GAD65 mRNA was up-regulated in the vestibular nuclei bilaterally 50 h after the lesion. In the flocculus, GAD65 mRNA expression was bilaterally up-regulated 50 h post-operatively. GAT1 mRNA expression was initially up-regulated in the ipsilateral vestibular nucleus and then underwent a bilateral increase 50 h post-operatively. These results demonstrate that following unilateral labyrinthectomy, major changes in the expression of GAD, GAT and GABA receptor subunit genes occur in the vestibular nucleus, which are likely to affect the process of behavioural recovery.

Animals↗

PubMed2003

Vestibular influences on CA1 neurons in the rat hippocampus: an electrophysiological study in vivo.

Vestibular information is known to be important for accurate spatial orientation and navigation. Hippocampal place cells, which appear to encode an animal's location within the environment, are also thought to play an essential role in spatial orientation. Therefore, it can be hypothesized that vestibular information may influence cornu ammonis region 1 (CA1) hippocampal neuronal activity. To explore this possibility, the effects of electrical stimulation of the medial vestibular nucleus (MVN) on the firing rates of hippocampal CA1 neurons in the urethane-anesthetized rat were investigated using extracellular single unit recordings. The firing rates of CA1 complex spike cells (n=29), which most likely correspond to place cells, consistently increased during electrical stimulation of the MVN in a current intensity dependent manner. Stimulation applied adjacent to the MVN failed to elicit a response. Overall, the firing rates of non-complex spike cells (n=22) did not show a consistent response to vestibular stimulation, although in some cells clear responses to the stimulation were observed. These findings suggest that vestibular inputs may contribute to spatial information processing in the hippocampus.

Animals↗

PubMed2003

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↗