Neurotransmissions between neurons and via nerves to effector organs and from the peripheral apparatus to afferent fibers are mediated by neurotransmitters. These chemicals are composed of small molecular neurotransmitters including acetylcholine, monoamines such as dopamine, norepinephrine, serotonin, histamine and amino acids (GABA, glycine, glutamate) and large molecular transmitters (peptides such as substance P and neurokinnin). These neurotransmitters are stored in vesicles incorporated within the nerve terminals and are released by exocytosis upon arrival of impulses to the terminals resulting in Ca2+ influx. The neurotransmitters bind to selective receptors and are taken up into the nerve terminals by transporters. Receptors are composed of channel types such as nicotinic, 5-HT3, GABAA, glycine and glutamate receptors and G protein-coupled types. The latter receptors (ex: muscarinic, dopaminergic receptors) with 7-fold transcrossed-amino acids are composed of two second messenger-mediated groups via cAMP and IP3/DG, which activate protein kinase A and C, respectively. Second messengers produce a variety of responses including the iron-channel mechanism in the cell. The structure-activity relationship and receptor specificity is currently an important issue in drug research. One neurotransmitter usually acts on several kinds of receptor subtypes, therefore specific subtype receptor antagonists could be developed as potential candidates of therapeutic drugs.
Space motion sickness is a condition which frequently occurs shortly after attainment of sustained exposure to microgravity and affects 73% of crew members on the first 2 or 3 days of their initial flight. The characteristic symptoms and signs include vomiting, retching, pallor, flash, cold sweating, yawning, belching, flatulence, and decreased gastric tonus. The severity of space motion sickness is variable, but over half of the cases are categorized as moderate to severe. In-flight and post landing immunity to the coriolis sickness susceptibility test (CSSI) observed during the Skylab M131 experiment suggests that the otolith organs play an important role in space motion sickness. This view is supported by a study that ocular counter rolling asymmetries are correlated with space motion sickness incidence and severity. It has also been reported that sensory-motor adaptation to microgravity includes a process whereby central interpretation of the otolith signal is biased from tilt toward translation. Perceptual studies provide some support for this "otolith tilt-translation reinterpretation" hypothesis and have also suggested orientation to the long axis of the body or to the surrounding spacecraft after adaptation to microgravity. In the Neurolab project, using space shuttle "Columbia", several experiments were performed to determine how microgravity affects the orientation vectors of the vestibulo-ocular reflex (VOR) and optokinetic nystagmus (OKN) and how they are altered by introducing a linear force due to centrifugal acceleration in an eccentric rotator. We discussed here, some current aspects regarding space motion sickness.
The atrial natriuretic peptide family (ANP family) is comprised of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP). These peptides regulate body fluid and blood pressure homeostasis as a neuropeptide in the central nervous system as well as a cardiac hormone in the periphery. To assess the possible physiological role of the ANP family, we investigated the immunohistochemical localization of these peptides in the rat inner ear. ANP-like and CNP-like immunoreactivities were observed in the spiral ligament just beneath the stria vascularis, spiral limbus, dark cell area, endolymphatic sac, spiral ganglion cells and vestibular ganglion cells. We could not detect specific BNP-like immunoreactivity in the inner ear. These observations were consistent with our previous study concerning the ANP family gene expression. The results suggest that the ANP family influences the metabolism of the inner ear fluid as well as afferent nerve activities in the inner ear.
Diagnostic imaging for vertigo and dizziness has remarkedly advanced and has been used to diagnose the central origin. We investigated here, the quality of diagnostic imaging for vertigo and dizziness to improve the diagnostic accuracy using 67 patients. The examinations included brain CT, MRI, MRA, target CT, SPECT, vestibular function test and audiological tests. Of a total of 67 cases, the following conditions were identified: Menier's disease; 15 cases, vertebral basilar insufficiency (VBI); 16, benign paroxysmal positional vertigo (BPPV); 3, vestibular neuritis; 10, acoustic tumor (AT); 6, lateral medullary syndrome; 1, cerebellar infarction; 1, cerebellar degeneration; 1, and pontile glioma; 1, and others; 13. We found different advantages of diagnostic imaging compared to the vestibular function tests. For example, in 20% of cases of Menier' s disease, the distance between the posterior semicircular canal and the posterior proteus surface (P-P distance) on CT was significantly shorter in the affected side than that in the normal side. In 43% of VBI cases, multiple lacuna infarctions were found using MRI. It is important to choose the appropriate imaging technique to directly diagnose or differentiate between various diseases. We discused here, the importance and the merits of imaging for the diagnosis of vertigo and dizziness.
The oral glycerol test is useful to diagnose endolymphatic hydrops. The test is known to indicate positive results in almost 50% of the patients with Meniere's disease. However, it prohibits food intake before the test, requires a long examination time, and is associated with side effects such as headache, nausea and vomiting. The intravenous glycerol test is known to have no such disadvantages. We examined here, the usefulness of the intravenous test. The intravenous glycerol test was performed in 30 ears of 30 cases of Meniere's disease. Audiometry was carried out before the administration. A total amount of 100 ml Glyceol (10% glycerol) was intravenously injected over 30 min. Audiometry was also performed immediately after, and then 1 hour and 3 hours after the injection. Before the examination, food intake was not prohibited. A positive result was defined as a threshold improvement of the audiogram of 10 dB or more in at least 2 frequencies. Positive results were observed in 11 of 30 ears (36.7%) immediately after the injection, in 15 of 30 ears (50.0%) 1 hour later, and in 10 of 20 ears (50%) 3 hours later. The positive ratio 1 hour later was almost the same as that of the oral glycerol test, which was previously described. Thus, the injection test can evaluate the disease 1 hour after the administration without prohibition of food intake before the test. No side effects such as headache, nausea or vomiting were observed in any case. The intravenous glycerol test has the following advantages compared to the oral test: it does not prohibit food intake before the test, the examination time is shortened, and it is not associated with side effects.
A total of 204 patients with vertigo or dizziness were examined using N-isopropylp-(I-123) iodoamphetamine (IMP) and single photon emission computed tomography (SPECT) and the findings were compared to X-ray CT and magnetic resonance imaging (MRI) findings. SPECT was performed using a rotating gamma camera. Decreased IMP in the cerebellum and brain stem was observed in 123/204 (60.3%) studies of these patients. Of these 123 patients, 98 were diagnosed as having a vascular disorder. All 98 patients were examined by X-ray CT and only 12 patients (12/98, 12.2%) showed vascular lesions by X-ray CT. Of the 98 patients, 26 were assessed by MRI and 8 patients (8/26, 30.8%) showed vascular lesions. Our findings showed that most patients with vertigo or dizziness of so-called vertebro-basilar insufficiency (VBI) may have some vertebral blood flow disorder, which in some cases is not clearly diagnosed by conventional vestibular examinations, X-ray CT or MRI. SPECT with IMP would likely be useful to evaluate abnormal cerebellar and brain stem perfusion.
Forward body sway induced by a downward optokinetic stimulus (OKS) was observed in 38 healthy subjects. The downward OKS was generated by a moving random dot pattern projected onto a half-pipe screen 2 m in diameter and was provided by a rectangular-like step function with velocities of 10, 20, 30 and 40 deg/sec. A fixation target was set by a red laser spot projected onto the screen in front of the subjects. As an additional stimulatory condition, 20 deg/sec of OKS with no fixation target was employed. The induced forward body sway was measured by a force-detecting platform as displacement of the center of gravity (COG). The gradual forward shift of COG followed by the plateau state was closely akin to a graphical representation of an equation of the first order lag time. As OKS velocities increased, the plateau level increased. Curve fitting analysis using a computer was employed to establish an approximation equation of the first order lag time. This analysis showed that the time constant of the optokinetic spinal response system was approximately 15 sec and the value of the time constant was independent of OKS velocity. Based on this long time constant, we concluded that the postural readjustment induced by OKS mainly plays a role in the low frequency range of human postural control.
In our department, we utilized a superimposed technique with electronystag-mography and video images of eye movement to analyze three dimensional eye movements. The system consisted of a small infra-red video charge-coupled device camera, a video tape recorder, a computerized electronystagmograph and a microcomputer. Both horizontal and vertical components of eye movement in the electronystagmogram were superimposed on a video image. The composite image allowed quantitative analysis of eye movement.
The Intractable Disease (Vestibular Disorder) Committee of the Ministry of Health and Welfare, Japan (1997-1998), has proposed a new grading system to assess the severity of symptoms in patients with Ménière's disease. This grading system is based on the progress of the disease, subjective assessment of patient's symptoms and the extent to which the disease interferes with the patient's daily life. This system can also be applied as a guide for the treatment of Menière's disease. To improve this grading system, the accuracy must be evaluated by applying it to many patients with Ménière's disease.