Kohichi Yamamoto

Calcitonin gene-related peptide containing sympathetic preganglionic and sensory neurons projecting to the superior cervical ganglion of the rat.

The origin of calcitonin gene-related peptide (CGRP)-containing fibers observed in the superior cervical ganglia (SCG) of the rat was investigated by a combined technique of retrograde axonal tracing and indirect immunofluorescence. Following the injection of Fast blue (FB) into the SCG, labeled neurons were observed in the C8-T5 spinal cord segments, with the highest density in T1-T3 (5-8 neurons per section). More than 90% of them were located in the ipsilateral intermediolateral cell column (IML) and the rest were found in the central autonomic area (CA) and intercalated region (IC) between the IML and CA. CGRP-like immunoreactive (IR) neurons were detected in these areas in animals pretreated with colchicine. About one-fourth of FB-labeled cells were CGRP-IR, which corresponded to three-fourths of the CGRP-IR neurons in the above-mentioned autonomic areas of these spinal cord segments. Most of these double-labeled cells were found in the IML (95%). A few FB-labeled cells were also observed in dorsal root ganglia (C8-T5) and 30% of them were CGRP-IR. These findings suggested that the CGRP-IR fibers in the rats SCG are supplied from both sympathetic preganglionic neurons in the spinal cord and sensory ganglion cells, although the latter projection is quite rare.

Effects of asymmetric vertebral blood flow upon the vestibulo-ocular reflex of the rabbit

SummaryPer-rotational nystagmus was recorded in rabbits with unilaterally narrowed vertebral arteries or following unilateral cervical sympathectomies. Asymmetry of per-rotational nystagmus could not be observed when the animals systemic arterial blood pressure was within the normal range (about 90–120 mm Hg). However, directional preponderance of nystagmus occurred when blood pressure either increased or decreased beyond this level. The reason for the occurrence of directional preponderance can be interpreted as a failure of autoregulation of cerebral and/or inner ear blood flow.

Norepinephrine in cochlear microcirculation of guinea pigs

The blood flow in the radiating arteriole through a small cochlear fenestra was recorded with motion pictures in anesthetized guinea pigs, before and after norepinephrine injection into the ipsilateral carotid artery. The flow velocity was determined by measuring the displacement of plasma space running through the radiating arteriole per second. Norepinephrine injection of 0.01 and 0.15 mg/kg increased both flow velocity and arterial blood pressure. The flow velocity increase related directly to the increase in arterial blood pressure. However, a larger norepinephrine dose (1.2 and 2.5 mg/kg) led to transient cessation in flow, which was independent of the blood pressure increase. Dilatation of vessel diameter was always observed with the rise in blood pressure, irrespective of norepinephrine doses. When blood flow in the radiating arteriole stopped after a large norepinephrine injection, the arterioles vascular lumen was completely obstructed by the aggregated red blood cells. These results suggested that cochlear microcirculation is disturbed by microemboli formed by norepinephrine-induced platelet hyperaggregation.

Effect of Changes in Blood Pressure on Per-rotational Nystagmus in Guinea Pigs with Obliterated Endolymphatic Sac

The effect of blood pressure (BP) changes on per-rotational nystagmus (PRN) was compared between normal guinea pigs and guinea pigs with unilaterally obliterated endolymphatic sac. Eye movements were recorded 3 months postoperatively. When the animal was rotated sinusoidally, asymmetry of PRN was minimal in the control animals. In the operated guinea pigs, however, nystagmus oscillating toward the operated side was largely suppressed when BP was decreased (30-40 mmHg). Thus, directional preponderance of PRN toward the nonoperated side was established. Oxygen tension (pO2) was measured in the perilymphatic space of the lateral semicircular canal to investigate the mechanisms underlying the PRN asymmetry. When BP was reduced below normal, pO2 on the operated side decreased much more than that on the intact side. It is suggested that obliteration of the endolymphatic sac results in an autoregulatory dysfunction in the semicircular canal. Asymmetry of the vestibulo-oculomotor reflex at low BP may be the result of decreased blood flow to the semicircular canal.

Some Factors Inducing Impairment of Blood Circulation in the Inner Ear and Brain

The impairment of inner ear circulation may result from abnormalities in either local or systemic parameters including blood pressure (BP), hemodynamics, the autonomic nervous system (ANS), and endolymphatic pressure. In testing this hypothesis, the blood circulation of guinea pigs and rabbits was measured by three different techniques (i.e., laser Doppler, hydrogen clearance, and oxygen tension methods). We found, first, in the normal guinea pig, blood flow (BF) in the brainstem was maintained constantly within BP range of 35-80 mmHg, though the inner ear showed weak autoregulatory functions for BF within the same BP range. The p02 decrease following lowered BP was significantly less in the cochlea than in canal. Second, ANS dysfunction induced by denervation of the carotid sinus nerve or administration of amphetamine led to instability of BP, inhibition of baroreflex sensitivity for BP modulation, and poor autoregulatory functions for brainstem BF. Head up tilt stimulation (at 40°) also induced similar results. Third, transient interruption of blood supply to the brain and inner ear regions by microembolism was produced by plasma hyperaggregability after intravertebral arterial injection of adenosine diphosphate. Finally, in guinea pigs, unilaterally obliterated endolymphatic sac and ducts caused no significant difference in cochlear BF between non-operated and operated ears when BP was within normal range. However, cochlear BF autoregulartory functions for lowering BP declined significantly, in the hydropic ear 3 to 7 months after surgery. We discussed the control mechanisms of inner ear circulation and some local and systemic parameters causing abnormality of autoregulatory functions for the inner ear and brain BF.

Effects of Blood Pressure Change upon Brain-stem pO2 in Rabbits with Surgically Removed Baroreceptor Nerve: Possible Mechanisms for Vertigo Due to Autonomic Nerve Dysfunction

The effect of denervation of carotid sinus nerve (CSD) on the brain-stem tissue pO2 tension was studied in the awake rabbit. Tissue pO2 around the vestibular nuclei was measured in two groups of rabbits, normal and CSD, under two experimental conditions, viz. blood pressure (BP) modulation and tilt stimulation. BP was either depressed by hemorrhage (up to 50 mmHg) or elevated by intravenous injection of phenylephrine (up to 160 mmHg). In the normal rabbit, tissue pO2 showed minimum change during BP modulation (ranging between 70 and 160 mmHg. In contrast, CSD surgery resulted in the failure to maintain pO2 at a constant level when BP was elevated. However, tissue pO2 did not change when BP decreased. Head-up tilt stimulation (up to 40 degrees) also induced a transient decrease in BP and pO2 in the CSD rabbit; however, these were maintained at a constant level in the normal rabbit. These conditions were assumed to be due to the decrease in autoregulation of cerebral blood flow (CBF), which resulted in CSD. In these experiments, tissue pO2 recovered first, even when BP still remained low. Therefore, it can be proposed that the carotid baroreceptor reflex works for CBF autoregulation of brain stem primarily during an early phase of BP change. Therefore a disturbed carotid sinus reflex, as shown in the present experiment, may be a possible explanation for the mechanism of stress-related vertigo and/or orthostatic vertigo.

Experimental Study on the Pathogenesis of Psychogenic Vertigo

This study was performed to determine whether electrical stimulation of the autonomic centers, that is, the medial nuclei of the hypothalamus in the diencephalon causes asymmetric per-rotational nystagmus (PRN) in healthy or sympathectomized rabbits. The superior cervical ganglion was removed on one or both sides. Asymmetric PRN occurred very rarely in normal or bilaterally sympathoectomized animals, while directional preponderance (DP) appeared in more than half of the recordings in unilaterally sympathectomized animals. Although the rise in blood pressure (BP) during the intravenous influsion of norepinephrine in unilaterally sympathectomized animals also caused significant DP (previous paper), it was less than the degree of DP appearing with the same increment of BP caused by hypothalamic stimulation. Three of 5 animals with asymmetric PRN caused by stimulation showed side differences of cerebellar oxygen tension.These findings show that asymmetric PRN following hypothalamic stimulation can be explained by a neural action on the vestibular neurons from the hypothalamus via the brainstem reticular formation or the cerebellum in addition to the asymmetric vertebral blood flow induced by symathetic vasoconstriction. We propose that this experimental model shows how psychogenic vertigo and/or dizziness can originate from distrubances of the central autonomic nervous system.