[OLFACTO-ELECTROENCEPHALOGRAPHY. CONTRIBUTION TO THE KNOWLEDGE OF TRAUMATIC ANOSMIA].
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Brain Concussion↗
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Neurotrophic properties of olfactory ensheathing glia.
Olfactory ensheathing cells (OEC) constitute a specialized population of glia that accompany primary olfactory axons and have been reported to facilitate axonal regeneration after spinal cord injury in vivo. In the present report we describe OEC neurotrophic factor expression and neurotrophic properties of OECs in vitro. Investigation of the rat olfactory system during development and adulthood by radioactive in situ hybridization revealed positive labeling in the olfactory nerve layer for the neurotrophic molecules S-100beta, CNTF, BMP-7/OP-1, and artemin, as well as for the neurotrophic factor receptors RET and TrkC. Ribonuclease protection assay of cultured OEC revealed expression of NGF, BDNF, GDNF, and CNTF mRNA, while NT3 and NT4 mRNA were not detectable. In vitro bioassays of neurotrophic activity involved coculturing of adult OEC with embryonic chick ganglia and demonstrated increased neurite outgrowth from sympathetic, ciliary, and Remak's ganglia. However, when culturing the ganglia with OEC-conditioned medium, neurite outgrowth was not stimulated to any detectable extent. Our results suggest that the neurotrophic properties of OEC may involve secretion of neurotrophic molecules but that cellular interactions are crucial.
Animals↗
Esthesioneuroblastoma imaged with bone scintigraphy.
An esthesioneuroblastoma, a rare malignancy of the olfactory nerve, was identified with bone imaging in a four year old male who presented with a history of headaches and proptosis of the right eye. Correlation with CT is provided.
Bone and Bones↗
Phantom smelling.
A case of phantom smelling (phantosmia) is described in a 28-yr.-old man who developed permanent bilateral anosmia after a serious injury to olfaction-related brain structures at the age of 25 years. The findings indicate that, even years after loss of input from olfactory receptors, the neural representation of olfactory perception can still recreate olfactory sensations without any conscious recall of them. This indicates that the neural representation of olfactory sensations remains functional and implies that neuronal activity in the olfactory organ or in other brain structures gives rise to olfactory experiences perceived as originating from the perception of original odor substances. The report suggests the intriguing possibility that the olfactory perception is not a passive process that merely reflects its normal input from the olfactory system but is continuously generated by a neural representation in the olfactory organ or in other olfaction-related brain structures, based on both genetic and sensory determinants. To the author's knowledge this is the first reported case of its kind.
Adult↗
Rat olfactory neurons can utilize the endogenous lectin, L-14, in a novel adhesion mechanism.
L-14 is a divalent, lactosamine-binding lectin expressed in many vertebrate tissues. In the rat nervous system, L-14 expression has been observed previously in restricted neuronal subsets within the dorsal root ganglia and spinal cord. In this study we report that L-14 is expressed by nonneuronal cells in the rat olfactory nerve. We demonstrate that L-14 binds and co-localizes with two ligands in the rat olfactory system: a beta-lactosamine-containing glycolipid, and a putative member of the laminin family. The former is expressed on the surfaces of nascent olfactory axons originating from neuron cell bodies in the olfactory epithelium. The latter is present in the extracellular matrix of the axonal path leading to synaptic targets in the olfactory bulb. In vitro, we find that recombinant L-14 promotes primary olfactory neuron adhesion to two laminin family members, and promotes intercellular adhesion. Both activities are dose-dependent, and are independent of integrin-mediated mechanisms. We have thus found that L-14 can serve two distinct adhesive functions in vitro, and propose that L-14 in vivo can promote olfactory axon fasciculation by crosslinking adjacent axons and promote axonal adhesion to the extracellular matrix.
Animals↗
Identification of a group of novel membrane proteins unique to chemosensory cilia of olfactory receptor cells.
We have used a library of monoclonal antibodies (mAbs) against chemosensory cilia of the olfactory epithelium of Rana catesbeiana to identify proteins that are unique to the ciliary membrane. Five different antibodies (mAb 8, 26, 34, 42/45, and 43) identify novel proteins in olfactory cilia that are not detected in olfactory nerve membranes, nonchemosensory cilia from respiratory epithelium, or membranes from brain, heart, liver, kidney, and lung. Deglycosylation of olfactory cilia with endoglycosidase H shows that most of these antibodies (mAb 8, 42/45, 43, and possibly 26) react with antigenic determinants comprised partially or entirely of carbohydrate, while only one (mAb 34) recognizes an 87-kDa protein that is resistant to endoglycosidase H treatment. Furthermore, a 59-kDa glycoprotein visualized by mAb 8 exists as membrane-associated oligomers connected via intermolecular disulfide bonds. These proteins, tagged with distinct high-mannose-containing carbohydrate moieties and found only in chemosensory cilia of olfactory receptor cells, may be involved in odorant recognition and/or olfactory transduction.
Animals↗
Development of olfactory and related structures in staged human embryos.
The staged sequence of development of the olfactory and related structures has been established from the serially sectioned human embryos of the Carnegie collection, from stage 11 to stage 23. The nasal epiblastic thickening appears at stage 11 and the nasal field is well outlined at stage 12. At stage 15, a continuous cellulovascular strand is observed between the nasal groove and the olfactory field. The vomeronasal groove appears at stage 16 (O'Rahilly 1967). During stage 17, the olfactory nerve is organized into two plexuses, lateral and medial, the latter mingled with the terminal-vomeronasal complex. The olfactory bulb begins to appear at stage 18. Stage 19 is characterized by the individualization of the olfactory bulb and nuclei. In addition, the distinction between olfactory structures and terminal and vomeronasal ones begins to be clear. The structure of the olfactory bulb is evident at stage 21. At stage 23, the olfactory strands are well individualized, and olfactory and terminal-vomeronasal fibers are easily distinguishable. The terminal ganglion is rather terminal-vomeronasal with an autonomic terminal contingent and a sensory one attached to the vomeronasal system.
Brain↗
Neuroglial arrangements in the olfactory glomeruli of the hedgehog.
The olfactory glomeruli represent morphological and functional units in which olfactory information is processed in specialized synaptic arrangements established between the central processes of sensory neurons, whose cell bodies are located in the olfactory epithelium, and the terminal (intraglomerular) portions of the dendrites of periglomerular, tufted, and mitral cells. The olfactory glomeruli are surrounded by distinctive glial formations in which the peripheral glia interacts with the central glia. We have studied the morphology and organization of neuroglial cells in the layer of olfactory nerves and the glomerular layer of the olfactory bulb in the insectivorous hedgehog (Erinaceus europaeus) with the electron microscope, Golgi method, and immunohistochemistry by using antibodies to glial fibrillary acidic protein (GFAP) and "rip," a monoclonal antibody that stains oligodendrocytes and their processes in the rat (Friedman et al.: Glia 2:380-390, '89). The peripheral glia is represented by a special category of cells that are closely related to astrocytes and known as sheathing cells. They accompany olfactory axons to their entrance in the glomeruli where they interact with the central glia, represented by astrocytes and oligodendrocytes. The sheathing cells typically display indented nuclei and protoplasmic expansions forming laminar processes wrapping several axons together. Astrocytes surrounding the glomerular neuropil belong to the velate type. They display numerous sheet-like processes enveloping dendritic segments and periglomerular cell bodies. Oligodendrocytes were found surrounding the glomeruli and at the interstices separating different glomeruli. Myelinated dendritic segments and cell bodies were found surrounding the olfactory glomeruli. These myelin coverings probably derive from oligodendrocytes. Together with the astrocytic lamellar expansions, they provide a rigid structural support that contributes to the segregation of group of different cells while remaining relatively isolated from other influences at the periphery of the glomeruli.
Animals↗
Odorant exposure increases olfactory sensitivity: olfactory epithelium is implicated.
Exposure-induced shifts in sensitivity to odors may involve peripheral and/or central components of the olfactory system. The ability to disconnect the olfactory epithelium from the bulbs provides a unique opportunity to examine how odorant exposure affects each component. In one experiment, odor thresholds were established for either amyl acetate or androstenone. The mice were then exposed for 10 days to the same test odorant for which a threshold was obtained. After exposure, sensitivity to the odorant increased relative to preexposure levels. The mice then underwent bilateral olfactory nerve transection (BNX). When both groups of mice were tested 45-50 days after recovery from surgery and return of olfactory function, increased sensitivity to the exposed odorant persisted; however, 121-203 days after surgery, sensitivity returned to preexposure levels. Another experiment was similar to the first except that mice were exposed to an odorant, either amyl acetate or androstenone, for 10 days beginning 1 day after BNX or sham surgery. When the mice were tested 45-50 days after surgery, sensitivity to the exposed odorant was increased relative to preexposure levels, whereas sensitivity to the nonexposed odorant remained at preexposure levels. Although further work is needed to determine the precise mechanism(s) underlying shifts in sensitivity to odors, these studies provide additional evidence for peripheral involvement in exposure-induced sensitization to odorants and demonstrate the remarkable capacity of the olfactory system to maintain or even regain sensitivity after injury.
Animals↗
The influence of olfaction on exploratory behaviour in the paradise fish (Macropodus opercularis L.).
We studied the role of olfaction on the exploratory behaviour of the paradise fish. Intact animals showed habituation of exploratory behaviour toward a heterospecific fish after five consecutive encounters. Fish with olfactory nerves destroyed spent significantly longer time with exploration compared to the control even at the fifth encounter. We suggest that olfactory inputs have a strong influence on exploratory behaviour.
Animals↗
Differential expression of two cell surface proteins, neuropilin and plexin, in Xenopus olfactory axon subclasses.
Immunohistochemistry by using monoclonal antibodies named A5 and B2, which specifically recognize cell surface proteins the neuropilin and the plexin, respectively, revealed that olfactory axons in Xenopus tadpoles were classified into several subgroups by virtue of the expression levels of these two cell surface molecules. The vomeronasal axons expressed the plexin but not the neuropilin. The plexin-positive and neuropilin-negative vomeronasal axons form a discrete fiber bundle, even after they joined with the principal olfactory axons. However, the principal olfactory axons were divided into at least two subclasses; the neuropilin-predominant axons which expressed high levels of the neuropilin and low levels of the plexin, and the plexin-predominant axons which expressed high levels of the plexin and low levels of the neuropilin. Within the olfactory nerve the pathways for these two principal olfactory axon subclasses were initially intermingled with each other, but were gradually segregated throughout their courses from the nose to the cerebrum. Eventually, the neuropilin-predominant and the plexin-predominant principal olfactory axon subclasses projected to specified glomeruli in topographically related regions within the main olfactory bulb. Neuroanatomical tracings of the olfactory projection also confirmed the gradual segregation of the pathways for the principal olfactory axons. These results allow us to speculate that both the neuropilin and the plexin are involved in axon interactions, and play roles in the organization of the precise patterns of the olfactory pathway and projection.
Animals↗
Microvasculature of the olfactory organ in the Japanese monkey (Macaca fuscata fuscata).
Olfaction is an important and primitive sense. As its importance has changed with evolution, anatomic adjustments have occurred in its structure and vasculature. Primates are a family of vertebrates that have had to develop their visual system to adapt to the arboreal environment and have evolved from a macrosmatic to a microsmatic species as the optic system has enlarged. This has resulted in anatomic changes of a small but critical area at the base of the brain. This paper describes the three-dimensional vascular anatomy of the olfactory organ of the Japanese monkey (Macaca fuscata fuscata). This is best understood by dividing the organ into three parts: the olfactory tract, olfactory bulb, and olfactory nerves in the nasal mucosa. The bulb can be partitioned into an outer or cortical part and inner or medullary part. The vasculature and tissue were examined grossly and with light microscopy and scanning electron microscopy of vascular corrosion casts. The olfactory tract and bulb were supplied by an arteriole from the anterior cerebral artery on each side. The tract was supplied by capillaries running spirally with a coarse network. At the olfactory bulb, the arteriole ramified into the intracortical and medullary branches that formed capillary networks. The bulbar intracortical capillaries were divided into two layers with different densities and vascular patterns. The capillaries of the superficial layer had a ladder-like pattern. The branches that ran into the medulla of the olfactory bulb were more widely spaced. Twigs from the posterior ethmoidal artery ran along the nerve fiber and formed intra- and extrafascicular networks. Each region of the olfactory organ had characteristic three-dimensional vascular patterns that were related to their cellular architecture.
Animals↗
Synchronized rhythmic discharges of the secondary olfactory neurons in carp.
(1) Rhythmic and synchronized multiunit bursts of spike discharges, which were superimposed on the peaks of the oscillatory potentials of 4--10 Hz (olfactory tract waves), were induced in the olfactory tract fibers of the carp in response to olfactory stimulation. Suppression of the spike discharges was observed during the interburst periods of discharges. (2) Single-unit analysis revealed three types of discharge patterns in the olfactory tract fibers in response to olfactory stimulation: rhythmic excitation (Type 1), suppression (Type 2) and no response (Type 3). A synchronization of spike discharges was observed among the Type 1 units. (3) Mass potentials were evoked in the olfactory tract by electrical stimulations applied to the olfactory nerve. When the time interval between the conditioning stimulation and the test stimulation was about 200 msec, a transient recovery of the evoked mass response was observed. This interval approximately corresponded to the cycle length of the olfactory tract waves. (4) It was concluded from the results obtained that the olfactory tract waves are the summated action potentials from the axons of the secondary olfactory neurons discharging rhythmically and synchronously. (5) An inhibitory phasing mechanism in the olfactory bulb was suggested which may cause the synchronized rhythmic activity of the secondary olfactory neurons.
Action Potentials↗
Mode of entry of a neurotropic arbovirus into the central nervous system. Reinvestigation of an old controversy.
The mechanism by which neurotropic arboviruses gain access to the central nervous system remains uncertain, although it is generally assumed that viremic infection results in growth across or passive diffusion through brain capillaries. In contrast to the natural reservoir hosts of these arboviruses, clinical hosts (e.g., horses, humans) have viremias of very brief duration and low magnitude. We investigated the question of neuroinvasion in 5- to 6-week-old Syrian hamsters infected with St. Louis encephalitis virus (strain TBH-28). This model shares with the human disease low or undetectable viremia and many clinical and pathoanatomical features. The mortality rate after intraperitoneal inoculation of a moderate viral dose was 88%. No viremia was detectable by a sensitive assay in 31% of the animals. In the remaining hamsters, the mean peak viremia was 1.0 log10 plaque-forming units/0.05 ml and the mean duration 1 to 2 days. There was no correlation between viremia and outcome of infection, length of incubation period, or brain virus titer. Tissue infectivity studies showed a rise in titer in the olfactory neuroepithelium on day 4 postinoculation, then in the olfactory bulbs (day 5 postinoculation), and finally in the remainder of the brain (day 6 postinoculation). Specific immunofluorescence was demonstrated in the bipolar neurons of the olfactory epithelium, their dendrites, and in axon bundles of the olfactory nerves in the submucosa. By electron microscopy, virus particles and associated tubular structures were demonstrated within dendrites, perikarya, and axons of olfactory neurons, and to a lesser extent in macrophages and Bowman's gland cells in the lamina propria. In cells of Bowman's glands large numbers of virions were sequestered within secretory granules. Virus was recovered from nasal washings on day 4 postinoculation. Similar findings were obtained in weanling mice inoculated intraperitoneally with another (mouse-virulent) St. Louis encephalitis viral strain (77V-12908). These data taken together indicate that the olfactory pathway is the principal route of viral entry into the central nervous system. After peripheral inoculation a low-level viremia results in infection of highly susceptible cells in the olfactory neuroepithelium, allowing centripetal axonal transport of virus to the olfactory bulb, whence spread is unimpeded throughout the neuropil of the central nervous system. Infection of Bowman's gland cells in the olfactory mucosa and shedding of virus in nasal mucus may be an adaptation for nonarthropod-borne transmission, a feature of many flaviviruses.
Animals↗
Partial characterization of a tetrodotoxin-binding component from nerve membrane.
Tetrodotoxin from Japanese puffer fish has been labeled with tritium and purified from the crude mixture obtained. The interaction between the purified [(3)H]tetrodotoxin and membrane suspensions from the olfactory nerve of long-nosed garfish has been investigated by equilibrium dialysis. Tetrodotoxin binds to membrane suspensions with a dissociation constant K(D) = 8.3 nM. The nerve preparation binds 42 pmol of [(3)H]tetrodotoxin/g of wet tissue at saturating toxin concentrations. With various hydrolytic enzymes, the binding component is shown to be a protein embedded in a phospholipid environment. The binding is inhibited below pH 4.0 and is not stable towards heat. Tetrodotoxin binding is not inhibited by the local anesthetic, procaine.
Animals↗
Brain neuronal degeneration caused by episodic alcohol intoxication in rats: effects of nimodipine, 6,7-dinitro-quinoxaline-2,3-dione, and MK-801.
Rats repeatedly intoxicated with alcohol (ethanol, three times daily) over a 4-day period display neuronal degeneration in the dentate gyrus; entorhinal, piriform, insular, orbital, and perirhinal cortices; and in the olfactory nerve fibers and terminals in the olfactory bulb. Postulating a role for excitotoxicity, we have attempted to prevent the degeneration using antagonists that are neuroprotective in this type of brain damage. In an initial study, continuous subcutaneous infusion of a high dose of the glutamate/NMDA receptor antagonist MK-801 (2 mg/kg/day) by itself caused extensive neuronal degeneration in several brain regions and severe behavioral intoxication that precluded survival if combined with high blood alcohol levels (approximately 300 mg/dl). Moreover, the lower, nonneurotoxic blood alcohol levels (approximately 150 mg/dl) that were compatible with survival worsened the MK-801-induced brain damage. In a subsequent experiment, daily intraperitoneal injections of a lower dose of MK-801 (1 mg/kg/day) resulted in no MK-801 toxicity and, when combined with neurotoxic levels of alcohol, no reduction in alcohol-induced neurotoxicity. Nimodipine, a voltage-gated Ca2+ channel blocker, reduced the neuronal damage in the dentate gyrus, but greatly increased it in the piriform cortex when administered intragastrically at 600 mg/kg/day; it provided no protection from alcohol-dependent degeneration when given intragastrically at 100 mg/kg/day. Continuous intracerebroventricular delivery of 0.24 to 0.29 mg/day of 6,7-dinitro-quinoxaline-2,3-dione, a glutamate/alpha-amino-3-hydroxy-5-methyl-4-isoxazole receptor antagonist, failed to diminish alcohol-dependent neuronal damage in any brain region. We conclude that brain damage from episodic "binge" alcohol intoxication is not primarily mediated by excitotoxic mechanisms, implying that other, nonexcitotoxic pathophysiological mechanisms, are involved. Furthermore, MK-801, far from protecting from the alcohol-induced damage, at high doses causes widespread neuropathology that is significantly potentiated by alcohol.
Alcoholic Intoxication↗
Functional anatomy of the peripheral olfactory system of the African lungfish Protopterus annectens Owen: macroscopic, microscopic, and morphometric aspects.
An anatomical functional study of the olfactory system of Protopterus annectens along the course of the primary olfactory neuron was made by means of macroscopic and microscopic methods on samples of specimens weighing from 3 to 1.250 gm. The olfactory organ, opening by anterior and posterior nostrils into the oral cavity, may be considered a macrosmatic fish type according to the repartition of receptor areas along parallel grooves and on the basis of its active irrigation mechanism. A morphometric study of Protopterus, using a set of seven specimens weighing from 4 to 350 gm, is compared with two morphometric studies on Silurid fishes and reveals some original features concerning the increase of the surface area of the receptor epithelium. The olfactory organ is meant to function in water; its isolation from the aerial environment is carried out by closing the apertures with edema linked to the hypothyroid and cholinergic crisis during the starvation stage; it represents an adaptation to the life in a special environment. This study does not support the assimilation of the posterior intrabuccal opening to a choana, nor the presence of a functional vomeronasal organ. The olfactory nerve shows a definite degree of organization, but it was not possible to recognize any vomeronasal nerve linked with the former. The histological organization of the bulbar relay is of a primitive type; it was impossible to locate an accessory olfactory bulb corresponding to a functional vomeronasal organ, the presence and the innervation of which by the nervus terminalis is discussed.
Animals↗
Differentiation of olfactory receptor cells in organ culture.
Presumptive olfactory mucosa was excised from the heads of rat fetuses in the eleventh and twelfth days of gestation and explanted in organ cultures. At the time of explanation, the presumptive olfactory cells were recognizable by their long narrow apical processes and basally located nuclei. However at this stage they were in an early phase of differentiation as indicated by the large numbers of free ribosomes and virtual absence of microtubules and cilia in the apical cytoplasm. After three to eight days in culture, there was a progressive increase in the total number of cells in the epithelium. Differentiation in olfactory receptor cells was detectable by the appearance in the apical processes of axially oriented microtubules and centrioles or basal bodies, some of which generated cilia. At their basal ends, the cytoplasm narrowed into axons and bundles of these axons, arranged in the unique manner of olfactory nerve axons, entered the connective tissue. Olfactory receptor cells, as defined by morphological criteria, differentiated under suitable organ culture conditions in the absence of any tissue from the central nervous system.
Animals↗