Role of nitric oxide in the peripheral and central vestibular system was summarized in this review. In the peripheral vestibular system, the existence of nitric oxide (NO) was evidenced in various groups of cells by immunohistochemistry using antibodies against nitric oxide synthase (NOS), indicating that NO has a role in normal vestibular function such as maintenance of blood flow. NO, especially produced by inducible NOS (i-NOS), was also implicated in the mechanisms of drug-induced ototoxicity. In the central vestibular system, NO was found in the all subnuclei of the vestibular nucleus complex, however, NO is most densely distributed of the neuronal circuits responsible for the vestibulo-ocular reflex. Production of NO in the brain stem vestibular nucleus as well as the cerebellar flocculus after unilateral labyrinthectomy is suggested to be involved in the mechanisms for vestibular compensation.
There are few methods of studying otolith function clinically. Ocular torsion, deviation of the eye in the roll plane in an upright position, is considered to reflect otolith function, especially that of the utricle. We measured ocular torsion by laser fundus photograph in 53 normal subjects. In the case of the right eye, counterclockwise rotation of the eye from the perspective of the examiner was defined as positive excyclotropia, while clockwise rotation was defined as positive in the left eye. The mean value was 7.7° (range; -0.2°-15.5°) in the left eye and 7.5° (range; 0°-15.8°) in the right eye. The mean difference in the values for both eyes was 3.3° (range; 0°-10.0°). Test·retest variability was found to be within 4° in the left eye, in the right eye and in the difference in values for both eyes. As a result, we concluded that a value beyond this range can be considered pathological. Research on otolith function in various peripheral vestibular diseases will be facilitated by these date.
Spinocerebellar degeneration (SCD) is severe and progressive disease with various symptoms. There are many reports describing the results of postural sway test, opto-kinetic pattern (OKP) and eye tracking test (ETT). However, there are few reports about the relationship of these findings to the severity of SCD. Therefore we recorded stabilometry, optokinetic pattern (OKP) and eye tracking test (ETT) in 7 patients of SCD. Results showed that the sway area of postural sway test and the slowest phase velocity of OKP were associated with the severity of SCD. Therefore it is suggested that postural sway test and OKP are methods of determining the severity of SCD.
This study investigated gender differences in various parameters when evaluating the center of foot pressure (CFP) during static standing posture based on the relationships between physical parameters characteristics. The subjects were 100 healthy young males and females. The measurement of CFP was carried out 3 times with a 1 minute rest, and the mean of trials 2 and 3 was used for the analysis. The measurement device was an Animas's stabilometer G5500. Data sampling frequency was 20 Hz. Sixty parameters with higher trial-to-trial reliability were selected from the following 7 domains: distance, center average, distribution of amplitude, area, velocity, power spectrum, and body sway vector. The parameters evaluating the amount of body sway tended to be greater in males than in females. The parameters showing a significant gender difference also showed strong relationship with body linearity (BL). A significant relationship of parameters and physical characteristics was found in body linearity (BL) and body width (BW) in males, and body girth (BG) and body fat (BF) in females. However, it is inferred that the influence of physical characteristics on parameters depends on the size of physical characteristics rather than the factor of a gender difference, and that the influence of body size sway was found when the physique was beyond a fixed value. The influence of physical characteristics tends to show in sway in the X-axis direction, and it was considered that the size of the support base or the characteristics of the foot and the knee joints, which easily move in a front-back direction, related to the sway. Even in the evaluation of parameters with the same body-sway characteristics, a gender difference was found and the relationships with the physical characteristics were not always the same.
Interest in combining the studies of molecular biology and behavior is motivating research into the eye movements of guinea pigs. Unfortunately, recording eye movements in this small animal is technically difficult. We therefore investigated the measurement of spontaneous eye movements, (vestibulo-ocular reflexes, VOR) in alert guinea pigs using a method for obtaining calibrated eye movement images. During sinusoidal rotation (0.1-0.3 Hz, peak angular velocity: 60 deg/sec), VOR was recorded on videotapes under dark conditions using an infrared charge-coupled device (CCD) camera. The analysis was performed using public domain NIH Image program (developed by the U.S. National Institute of Health), and the horizontal and vertical components were calculated automatically. The VOR gain ranged from 0.343±0.052 (mean±SD) at 0.1 Hz to 0.321±0.056 at 0.3 Hz (n=20). This technique allows VOR gains to be measured in conscious guinea pigs.
To investigate whether an analysis of heart rate variability is efficient for diagnosing and treating idiopathic vertigo, we sought to elucidate the circulatory autonomic function in 44 dizzy patients with power spectrum analysis of heart rate variability (HRV) for each 10 min while supine and standing. Data were analyzed by Kaplan-Meier estimation to investigate the correlation between cure rate and each parameter of HRV (i.e., LF, HF, and LF/HF). The cure rate of patients with a value of less than 1.1 (median of 44 patients) on LF/HF of power spectrum analysis in a supine position was significantly higher than that of the other group (LF/HF>1.1). It is highly possible that the circulatory autonomic function of dizzy patients may have an effect upon the time course of resolution of dizziness. We therefore suggest that the results of HRV analysis in patients should be carefully considered in treating and diagnosing vertigo.
Vestibular compensation after unilateral labyrinthectomy (UL) in mice was investigated by measuring the gain of horizontal vestibulo-ocular reflex (HVOR) with an infrared system. Six C57BL/6 mice underwent unilateral labyrinthectomy by injection of ethanol into the semicircular canal. Before UL, HVOR gain under sinusoidal rotation with a maximal head velocity (HV max) of 40 deg/sec and a frequency range between 0.1 and 3.2 Hz was analyzed. Before and after UL, gain of HVOR under sinusoidal rotation with an HV max of 150 deg/sec and a frequency of 1.6 Hz was analyzed. After UL, HVOR gain decreased showing a minimal value of 21% of preoperative value on the second postoperative day, then recovered to 65% of the preoperative value by the 28th postoperative day. These results provide fundamental data as a reference for future studies on vestibular compensation in genetically-manipulated mice.
In recent years, due to the technological advances of molecular biology, many important findings are reported in the field of hereditary hearing impairment (HHI). Some of the HHI genes have been cloned and the mutations of those genes were identified. Much knowledge has accumulated about the HHI genes, however, little research has been done regarding the protein products of those genes. Two-dimensional gel electrophoresis and direct protein sequencing, together with searches in protein and DNA, EST databases, have accelerated the protein-identification process. The proteome is the expressed protein complement of a genome and proteomics is functional genomics at the protein level. To characterize deafness genes at the protein level as well as other inner ear proteins, we have performed a proteomic analysis of the inner ear proteins. In the process of analysis, we have found very unique properties of the protein product of a deafness gene, LOCH. The LOCH gene is responsible for one of the HHI, DFNA9. DFNA9 is the locus in humans reported to involve vestibular problems as part of the non-syndromic deafness phenotype. The primary pathologic change of the DFNA9 is a deposit of acid polymucosaccharide ground substance is the cribrose areas; in the spiral ligament, limbus, and spiral lamina of the cochlea; and in the stroma of the maculae and cristae. The end result is neuronal degeneration in association with varying degrees of atrophic change in the sense organs. Recently, it is suggested that missense mutation in the LOCH gene might be related to the pathogenesis of Meniere's disease. Our results show that the protein product of the Coch gene constitutes 70% of inner ear proteins and is composed of 16 different protein spots with charge and size heterogeneity. Amino acid analysis of these spots identified 3 groups of isoforms of Coch protein (Cochlin), p63s, p44s and p40s. All 6 mutations found in DFNA9 patients are found in p63s, not in p44s and p40s. Heterogeneity of this protein suggests that the Coch gene is processed in several ways and may suggest that the Coch protein is very important in the inner ear function. Study of the Coch protein might provide more information on the mechanism of hearing and vestibular disorders.