Tadashi Ishimaru

Retrograde transport of nerve growth factor from olfactory bulb to olfactory epithelium

NGF is produced in the olfactory bulb and transported from the bulb to cholinergic neurons in the horizontal limb of the diagonal band. Although the expression of NGF receptors has been reported in olfactory epithelial cells, no correlation between NGF and olfactory epithelial cells has been found. This study aimed to define whether or not retrograde transport of NGF occurs in the olfactory neural system using the method of radioluminography. 125I-labeled NGF injected into the olfactory bulb was taken up and transported to the olfactory epithelium 18 h after injection. This finding suggests that bulbar NGF may act as a neurotrophic factor in olfactory epithelial cells.

Electrically Stimulated Olfactory Evoked Potential in Olfactory Disturbance

Olfactory evoked potential is considered a useful method of electrophysiological olfactometry for the diagnosis of olfactory disturbance. However, electrophysiological olfactometry is not as widely used as electrophysiological audiometry, such as the auditory brain stem response, because odor stimulation is difficult to perform. In contrast, electrical pulse stimulation is easy to perform, and its evoked potential is also easily recorded by the averaging method. We recorded olfactory evoked potentials from the scalp produced by electrical stimulation on the olfactory mucosa and investigated the relationship between this electrical olfactory evoked potential (EOEP) and the results of Toyoda and Takagis perfumists strip method (T&T) olfactometry, which is a standard Japanese means of psychophysical olfactometry. In EOEP-detectable cases, the detection and cognitive thresholds of T&T olfactometry were 1.32 ± 1.99 (mean ± SD; n = 10) and 3.02 ± 1.64 (n = 10), respectively. But in the undetectable cases, the thresholds were 4.67 ± 2.03 (n = 8; 5.8 means off the scale) and 5.80 ± 0.00 (n = 8), respectively. The differences between the T&T thresholds of EOEP-detectable and -undetectable cases were significant. We concluded that EOEP is suitable for electrophysiological olfactometry.

Near-infrared spectroscopy of the adult human olfactory cortex

Objective Near-infrared spectroscopy (NIRS) is a non-invasive method for investigating activation of the human cortex. The applicability of NIRS to the olfactory cortex was investigated. Material and Methods The relative oxy- and deoxy-hemoglobin levels of the orbito-frontal cortex during olfactory stimulation in healthy subjects were measured using NIRS. Results When perfumed strips containing the odorants β-phenyl ethyl alcohol, iso-valeric acid and γ-undecalactone were presented, the oxy-hemoglobin level increased but the deoxy-hemoglobin level did not change. The increase in the oxy-hemoglobin level was observed bilaterally. A placebo perfumed strip did not elicit a change in the hemoglobin level. It was also observed that the odorant intensity affected the oxy-hemoglobin level. Although the orbito-frontal cortices seemed to be activated bilaterally during olfaction, the right cortex was activated to a greater extent than the left. Conclusion NIRS appears to be an adequate method for investigating the human olfactory cortex.

TrkA expression in mouse olfactory tract following axotomy of olfactory nerves

The olfactory bulb is one of the brain regions that synthesizes the nerve growth factor (NGF). Functional roles of the bulbar NGF remain to be determined. The aim of the present study was, using an antibody specific to the high-affinity NGF receptor (trkA), to examine immunohistochemically the distribution of the NGF receptor in the mouse olfactory tract, under normal conditions and during regenerative processes. In normal mouse olfactory epithelia, trkA immunoreactive cell bodies were only seen in basal cells. Cell bodies of olfactory receptor cells did not express trkA immunoreactivity, but their neuronal processes (olfactory nerve fibres and bundles in the olfactory mucosa and the olfactory bulb) displayed trkA immunoreactivity. After axotomy of olfactory nerves, regenerating olfactory cells (basal cells and olfactory receptor cells) expressed trkA immunoreactivity in intramucosal and intrabulbar neuronal processes of olfactory receptor cells. These results suggest involvement of the bulbar NGF in the process of synaptogenesis and/or regeneration of the olfactory nervous system.

Patient with primary tonsillar and gastric syphilis

A male patient with syphilitic lesions in the tonsil and stomach is presented. The patient was infected while practising oral sex with heterosexual friends. He complained of nausea and snoring; his left tonsil was enlarged. Spirochetes were detected in a smear preparation from the left tonsil. As a gastric lesion, initially believed to be cancer, appeared to result from spirochete ingestion, the case is considered to represent primary syphilis. After antibiotic therapy with ampicillin, the left tonsil returned to normal size and gastric changes were no longer evident endoscopically. Gastroscopy should be considered if syphilis of the tonsil is observed, particularly when gastrointestinal symptoms are present. Both the oral and the gastric lesion can be mistaken for malignant neoplasm.

TrkA expression in olfactory epithelium and bulb during development.

The purpose of the present study was to examine immunohistochemically the expression of high-affinity nerve growth factor receptor (trkA) in the olfactory nervous system of developing mice and of colchicine-treated adult mice. Olfactory epithelia of embryos and neonates showed trkA immunoreactivity not only in basal cells but in receptor cells, with trkA-immunoreactive olfactory nerve fibers in the subepithelium and the bulb. In adults, trkA immunoreactivity was found only in basal cells of olfactory epithelia. Olfactory epithelia of colchicine-treated adult mice, however, exhibited appearance of trkA-immunoreactive receptor cells and increased trkA immunoreactivity in olfactory nerve fibers. These findings indicate that expression of trkA continually occurs in the olfactory nervous system during life and that trkA can be highly expressed during development.

Olfactory Evoked Potentials Produced by Electrical Stimulation of the Olfactory Mucosa

We stimulated the olfactory mucosa electrically and elicited evoked potentials in rabbits. A bipolar stimulating electrode was placed on the olfactory region of the nasal mucosa via an anterior naris non-invasively. Evoked potentials were detected from the surface of a head. In most instances they were composed of triphasic negative-positive-negative peaks, the latencies of these peaks were about 25, 40, and 65 ms, respectively. This peak complex seemed to originate in the olfactory bulb. This method is non-invasive and is applicable to studying the olfactory system in animals and also in humans.

Optical recording of the intrinsic signal from the human olfactory cleft.

Objectives: Endoscopy of the human olfactory cleft is important for both research in human olfaction and clinical examination with regard to olfactory disorders. However, endoscopy only provides information on the morphology and functional status of the epithelium, and it does not allow discrimination between respiratory and olfactory mucosa. To obtain information on the functional status of the olfactory mucosa, I used endoscopy to investigate the optical intrinsic signal recording from the human olfactory cleft. Methods: A light-emitting diode (617 nm) light source and a cooled charge-coupled device camera were prepared for endoscopy of the olfactory cleft. Subjects were exposed to various odors presented in front of their nostrils. In addition, blanks were used for control. Results: When normosmic subjects sniffed the odors, the intensity of the signal from the olfactory mucosa changed, which was not the case when blank stimuli were presented. Different odors activated different response patterns. A decrease of the oxyhemoglobin level in the activated olfactory epithelium is suspected to be responsible for this observation. Conclusions: The optical intrinsic signals were recorded from the human olfactory cleft with an endoscope. This technique may be applicable to basic research in olfaction and to a clinical test for the assessment of olfactory disorders.

Potential oscillation elicited by i.v. olfaction and its applicability as an objective clinical olfaction test.

OBJECTIVE Alinamin has long been applied in Japan for testing i.v. olfaction and to diagnose olfactory disorders. The test is subjective, each subject being asked about the presence or absence of olfaction. The credibility of the answers is highly questionable in some cases; as a result, the reliability of the test is poor. Recent studies demonstrated an induced electric potential in the scalp during i.v. olfactory testing. Some patients complain of the pain of the injection during i.v. olfactory testing; therefore, the effect of this pain must be considered with respect to measurement of the i.v. olfaction-elicited potential (IVOP). MATERIAL AND METHODS This investigation involved 179 subjects with various olfaction levels. Each subject received an Alinamin injection; the elicited potential amplitude was compared before and after the injection and the increasing ratio (IR) was computed. Gender, age, level of olfactory disorder, the presence or absence of olfaction and the presence or absence of the pain of injection were considered as factors affecting IR. RESULTS IR showed significant increases in groups characterized by the presence of olfaction as well as in groups reporting pain of injection. The test subjects were further divided into four groups based on their olfaction and pain of injection patterns as follows: Group A, no smell and no pain; Group B, smell and no pain; Group C, no smell and pain; and Group D, smell and pain. Subjects exhibiting no recognizable olfaction or pain of injection (Group A) revealed no increase in IVOP following injection. Subjects with either recognizable olfaction or pain of injection (Groups B and C) exhibited a slight increase in IVOP following injection. Subjects with both noticeable olfaction and pain of injection (Group D) demonstrated a significant increase in IVOP following the injection with a very high value of IR (>2). Furthermore, there were significant differences between the four groups in terms of IR level, with the exception of Groups B and C. CONCLUSIONS Olfaction is largely involved with the generation of IVOP. However, pain resulting from injection of Alinamin is considered to be a significant factor. IVOP showed significant effectiveness for diagnosing olfactory disorders in cases who did not experience pain of injection.

Reversible hyposmia caused by intracranial tumour

Two patients with hyposmia caused by an intracranial tumour recovered olfactory functions after craniotomy. The first case was a 68-year-old male with a tumour metastasized from the lung to the right frontal lobe. The second case was a 75-year-old male with meningioma of the right frontal lobe. Results of T & T olfactometry and venous olfaction tests also indicated suspected central hyposmia. Magnetic resonance imaging (MRI) indicated compression of the frontal lobe by intracranial tumour. Pressure on the olfactory centre located in the frontal lobe produced hyposmia. Decompression of the frontal lobe by craniotomy improved the sense of smell. Therefore, some cases of olfactory disturbance caused by intracranial tumour may be reversible if they are the result of simple compression of the olfactory centre.