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PubMed2000

Structure of the principal olfactory tract.

Although the purpose and importance of the sense of smell in human beings has not been totally clarified, it is one of the principal information channels in macrosmatic animals. It was the first long-distance information system to have appeared in phylogenetic evolution. The objective of this article is to deepen the knowledge of the pathways that join the olfactory epithelium with the cortical olfaction areas, to better understand olfactory dysfunction in human beings. Differential staining and marking techniques were applied to histologic sections obtained from 155 animals of different species, to study the different connections existing among olfactory tract components. Our study of the connections between the olfactory mucosa and the principal olfactory bulb deserves special mention. The distribution of second neuron connections of the olfactory tract with the central nervous system is quite complex and diffuse. This indicates an interrelation between the sense of smell and a multitude of functions. These connections seem to be of different quantitative importance according to species, but qualitatively they exist in both human beings and other macrosmatic animals.

Animals↗
PubMed1999

TC-83 vaccine protects against airborne or subcutaneous challenge with heterologous mouse-virulent strains of Venezuelan equine encephalitis virus.

Vaccination with TC-83 virus produced solid protection against subcutaneous challenge with Venezuelan equine encephalitis (VEEV) viruses from homologous and heterologous serogroups, but breakthrough infection and disease occurred after airborne challenge. Breakthrough occurred more often with time after vaccination, and was more frequent with epizootic, homologous serogroup 1A/B viruses than with enzootic, heterologous serogroup viruses. A decrease in VEEV-specific IgA levels in the respiratory tract of vaccinated mice may explain the increased frequency of breakthrough with time after vaccination. However increased breakthrough with the highly virulent homologous serogroup 1A/B viruses (compared to less virulent viruses from heterologous serogroups) may be a consequence of their greater ability to invade the brain via the olfactory neuroepithelium and olfactory nerve.

Animals↗
PubMed1996

Spatio-temporally differential expression of genes for three members of fatty acid binding proteins in developing and mature rat brains.

The chronological changes in the gene expression for three species of cytosolic fatty acid-binding proteins (FABPs) in the rat brain were examined by Northern and in situ hybridization analyses. The expression for heart(H)-FABP became evident after birth, with a gradual increase and confined to the gray matter, suggesting that the expression of H-FABP mRNA is neuron-specific in postnatal brain. The expression for brain(B)-FABP was very intense in the ventricular germinal zone, without expression in the cerebellar external granule cell layer, suggesting the dominant expression in the cells of glial lineage. B-FABP mRNA was transiently expressed in perinatal gray as well as white matter and the expression in glial cells persists only in the olfactory nerve fiber layer at the adult stage. On the other hand, the expression for skin type(S)-FABP was evident in the both ventricular germinal zone and cerebellar external granule cell layer, suggesting the expression in cells of neuronal lineage. The expression for S-FABP was evident in the prenatal gray matter and S-FABP mRNA was expressed in glial cells at early postnatal stage, whereafter the expression decreased to, but remained at weak levels in the adult brain. Discrete functions of the three FABPs were suggested in neurons and glia differentially at various developmental stages.

Animals↗
PubMed2002

Imaging of the upper cranial nerves I, III-VIII, and the cavernous sinuses.

This article discusses the upper cranial nerves (I, III-VIII) and their anatomy as it pertains to intra-axial nuclei and tracts, cisternal portions, and extracranial portions. In addition, the most common pathologic processes affecting the upper cranial nerves are discussed and illustrated. Because the evaluation of small structures requires imaging techniques that provide high resolution and contrast, MR imaging is the examination of choice. CT still plays a limited but important role in the evaluation of intraosseous portions of some cranial nerves.

Abducens Nerve↗
PubMed1997

The invasive behaviour of Cryptococcus neoformans: a possibility of direct access to the central nervous system?

Cryptococcocal meningoencephalitis is always considered secondary to initial lung infection. Because of the unquestionable evidence of haematogenious spread from the lungs, few publications have reported about other possible primary sites of infection or other routes to the central nervous system. This study was designed to investigate the infiltrative pattern of C. neoformans in immunocompromised mice by treatment with dexamethasone. The infection was performed by nasal instillation (30 mice) or injection into the retro-orbital space (12 mice). From the group infected intranasally, 3 mice presented diffuse invasive fungal colonisation of the mucosa and submucosa. The histologic findings showed infiltrative growth along the periosteum, sometimes surrounded nervous endings of submucosa, invasion along the olfactory nerve and simultaneous meningeal involvement in 2 mice on the 6th and 8th day of infection. All mice infected into the retro-ocular space developed lesions containing numerous cryptococci in the local of the inoculum. Out of the main lesion we observed preferential growth along the perineural spaces with adherence to the perineurium, perivascular spaces and sometimes along aponeurosis. Simultaneous invasion of trigeminal ganglio and trigeminal branches was observed in 4 mice. These morphologic patterns suggest the hypothesis of direct infiltrative invasion of the central nervous system.

Administration, Intranasal↗
PubMed1993

Effects of parturition and maternal experience on noradrenaline and acetylcholine release in the olfactory bulb of sheep.

Acetylcholine (ACh) and noradrenaline (NA) release in the olfactory bulb (OB) of ewes was monitored using microdialysis. Both ACh and NA release increased at parturition in multiparous but not in primiparous ewes. However, vaginocervical stimulation performed 6 hr postpartum induced an increase of ACh and NA release in both primiparous and multiparous ewes, indicating that a maturation process had occurred. Finally, pharmacological challenges to the ACh and NA inputs revealed differential responsiveness between nulliparous and multiparous nongestant ewes. These results suggest that the first parturition induces changes in neural circuitry involving ACh and NA inputs to the OB.

Acetylcholine↗
PubMed1999

Transplanted embryonic stem cells survive, differentiate and promote recovery in injured rat spinal cord.

Transplantation approaches using cellular bridges, fetal central nervous system cells, fibroblasts expressing neurotrophin-3 (ref. 6), hybridoma cells expressing inhibitory protein-blocking antibodies, or olfactory nerves ensheathing glial cells transplanted into the acutely injured spinal cord have produced axonal regrowth or functional benefits. Transplants of rat or cat fetal spinal cord tissue into the chronically injured cord survive and integrate with the host cord, and may be associated with some functional improvements. In addition, rats transplanted with fetal spinal cord cells have shown improvements in some gait parameters, and the delayed transplantation of fetal raphe cells can enhance reflexes. We transplanted neural differentiated mouse embryonic stem cells into a rat spinal cord 9 days after traumatic injury. Histological analysis 2-5 weeks later showed that transplant-derived cells survived and differentiated into astrocytes, oligodendrocytes and neurons, and migrated as far as 8 mm away from the lesion edge. Furthermore, gait analysis demonstrated that transplanted rats showed hindlimb weight support and partial hindlimb coordination not found in 'sham-operated' controls or control rats transplanted with adult mouse neocortical cells.

Animals↗
PubMed1996

Identification of Sonic hedgehog as a candidate gene responsible for holoprosencephaly.

Holoprosencephaly (HPE) is a genetically and phenotypically heterogenous disorder involving the development of forebrain and midface, with an incidence of 1:16,000 live born and 1:250 induced abortions. This disorder is associated with several distinct facies and phenotypic variability: in the most extreme cases, anophthalmia or cyclopia is evident along with a congenital absence of the mature nose. The less severe form features facial dysmorphia characterized by ocular hypertelorism, defects of the upper lip and/or nose, and absence of the olfactory nerves or corpus callosum. Several intermediate phenotypes involving both the brain and face have been described. One of the gene loci, HPE3, maps to the terminal band of chromosome 7. We have performed extensive physical mapping studies and established a critical interval for HPE3, and subsequently identified the sonic hedgehog (SHH) gene as the prime candidate for the disorder. SHH lies within 15-250 kilobases (kb) of chromosomal rearrangements associated with HPE, suggesting that a 'position effect' has an important role in the aetiology of HPE. As detailed in the accompanying report, this role for SHH is confirmed by the detection of point mutations in hereditary HPE patients.

Amino Acid Sequence↗
PubMed1995

The molecular logic of smell.

Mammals can recognize thousands of odors, some of which prompt powerful responses. Recent experiments illuminate how the nose and brain may perceive scents.

Animals↗
PubMed2001

Brain targeting and glomerulus formation of two olfactory neuron populations expressing related receptor types.

Olfactory sensory neurons expressing different members of the mOR37 odourant receptor subfamily send their axons to distinct glomeruli located in the immediate vicinity in the olfactory bulb [Strotmann, J., Conzelmann, S., Beck, A., Feinstein, P., Breer, H. & Mombaerts, P. (2000) J. Neurosci., 20, 6927-6938]. In this study, the potential of transgenic mouse lines was used to explore the onset of receptor expression, the outgrowth of axons as well as the glomerulus formation for two neuron populations expressing different mOR37 subtypes. The data indicate a synchronous time course of these features for both neuron populations. From E15 until the day of birth, the axons of the two mOR37 populations terminate in a common, small area of the presumptive olfactory bulb. During a short postnatal phase, the two axon populations segregate into distinct, protoglomerular structures; some aberrant fibers can still be observed during this period.

Animals↗
PubMed2000

Hypothetical pathophysiology of acute encephalopathy and encephalitis related to influenza virus infection and hypothermia therapy.

BACKGROUND: To establish a treatment strategy for acute encephalopathy and encephalitis associated with influenza virus infection, the pathophysiology of the disease was investigated through manifestations and laboratory findings of patients. PATIENTS AND METHODS: A child with central nervous system (CNS) complications during the course of influenza virus infection was analyzed in view of immunologic abnormalities. In addition, four children with acute encephalopathy and encephalitis were enrolled in the hypothermia treatment for the purpose of stabilizing the cytokine storm in the CNS. RESULTS: The CNS symptoms preceded the systemic progression to the failure of multiple organs (MOF) and disseminated intravascular coagulopathy (DIC). The mild hypothermia suppressed the brain edema on computed tomography (CT) scanning and protected the brain from the subsequent irreversible neural cell damage. CONCLUSION: The replicated viruses at the nasopharyngeal epithelium may disrupt the olfactory mucosa and gain access to the brain via the olfactory nerve system. The direct virus-glial cell interaction or viral stimulation of the glial cells induces the production and accumulation of the pro-inflammatory cytokines, especially tumor necrosis factor (TNF)-alpha, in the CNS. The cytokine storm results in neural cell damage as well as the apoptosis of astrocytes, due to the TNF-alpha-induced mitochondrial respiratory failure. The disruption of the blood-brain barrier progresses to the systemic cytokine storm, resulting in DIC and MOF. Mild hypothermia appears promising in stabilizing the immune activation and the brain edema to protect the brain from ongoing functional, apoptotic neural and glial damage and the systemic expansion of the cytokine storm.

Acute Disease↗
PubMed1998

Cellular prion protein localization in rodent and primate brain.

The presence of an abnormal, protease-resistant form of the prion protein (PrP) is the hallmark of various forms of transmissible spongiform encephalopathies (TSE) which can affect a number of mammalian species, including humans. The normal, cellular form of this protein, PrPc, while abundant in brain is also present in many tissues and a number of species. In order to address the unresolved question of the precise localization of normal cerebral PrPc, we used a free-floating immunohistochemistry procedure to localize the protein at both the light and the electron microscopic levels in the brain of three TSE-sensitive species: hamster, macaque and humans. This method shows that PrPc is abundant in synaptic terminal fields in olfactory bulb, limbic-associated structures and in the striato-nigral complex, whereas many other regions of the hamster brain are essentially devoid of immunoreactivity. With the striking exception of the olfactory nerve, in which axons are continually growing throughout life, PrPc is not abundant in fibre pathways. PrPc distribution in the primate hippocampus and cortex is very similar to the distribution observed in hamster. PrPc was present at synaptic profiles as shown by immunoelectron microscopy, but was not detectable in neuronal perikaryon either by light or electron microscopy. Our results show that PrPc is abundant in a number of brain structures known for ongoing plasticity, and are consistent with the hypothesis that the protein also plays a role in synaptic function.

Adult↗
PubMed2003

Developmental elimination of ectopic projection sites for the transgenic OR gene that has lost zone specificity in the olfactory epithelium.

In rodents, olfactory receptor (OR) genes are expressed in one of four zones in the olfactory epithelium (OE), and olfactory sensory neurons (OSNs) expressing the same OR project their axons to a specific set of glomeruli on the olfactory bulb (OB). Using the yeast artificial chromosome (YAC) transgenic system, we have analysed the expression of the murine OR gene MOR29A of the MOR28 cluster located on chromosome 14. Although expression of the endogenous MOR29A was restricted to the most dorsomedial zone, the transgenic MOR29A (Tg MOR29A) was expressed in all four zones of the OE. When the OB of the transgenic mouse was analysed, the axons of the OSNs expressing Tg MOR29A were found to project not only to the dorsal side but also to the ventral side of the OB as well. The ectopic projection sites on the ventral side gradually disappear during postnatal development. Naris occlusion prevents this elimination, suggesting that odorant stimulation is involved in eliminating the ectopic projection sites.

Animals↗
PubMed2004

From toxin to adjuvant: the rational design of a vaccine adjuvant vector, CTA1-DD/ISCOM.

Mucosally active vaccine adjuvants which will prime a full range of local and systemic immune responses against defined antigenic epitopes are much needed. Cholera toxin (CT) and lipophilic immune stimulating complexes (ISCOMs) containing Quil A can both act as adjuvants for orally administered antigens, but through separate pathways, as evidenced by the dependence on IL-12 for the effect of ISCOMs, whereas CT is independent of this cytokine. Unfortunately the toxicity of CT and recent findings of accumulation of CT in the olfactory nerve and bulb after intranasal administration precludes the clinical use of CT. However, we have been successful in separating the adjuvant and toxic effects of CT, by constructing a gene fusion protein, CTA1-DD, that combines the enzymatically active CTA1-subunit with a B cell targeting moiety, D, derived from Staphylococcus aureus protein A. The present review gives a background to mucosal immunization and the use of -adjuvants in general, followed by a description of a strategy to rationally design a vaccine adjuvant vector that fulfils the criteria of targeting and immunomodulating innate immunity in order to boost a strong adaptive immune response. We have combined CTA1-DD and ISCOMs into a new highly promising vaccine adjuvant vector, CTA1-DD/ISCOMs. The combined vector is immunogenic when given by the subcutaneous, oral or nasal routes, inducing strong cell--mediated and humoral immune responses, including local mucosal IgA. It requires the ADP ribosylating property of the CTA1-enzyme and the effect of the combined vector greatly exceeded the effect of either ISCOMs or CT used alone. Antigens could be incorporated into or just admixed with the new vector. Thus, we have demonstrated that rationally designed vectors consisting of CTA1-DD and ISCOMS may provide a novel strategy for the generation of potent and safe mucosal vaccines.

Adjuvants, Immunologic↗
PubMed1989

[Immunoreactive somatostatin in the peripheral olfactory system and nasal mucosa of the human].

Immunohistochemically, the cyclic retradecapeptide somatostatin was demonstrated in periglomerular cells and fibres of the glomerular layer (Fig. 3) of the human olfactory bulb as well as in the superficial granule layer and fibres (Fig. 2) of the olfactory tract. Additionally, somatostatin was found in endothelial cells of subepithelial arterioles and capillaries of the regio olfactoria (Fig. 4a, b) and superior turbinate. We assume that somatostatin has a paracrine transmitter function in the peripheral olfactory system and a regulative function on the blood flow of the superior nasal mucosa.

Adolescent↗