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Evidence of connections between cerebrospinal fluid and nasal lymphatic vessels in humans, non-human primates and other mammalian species.

BACKGROUND: The parenchyma of the brain does not contain lymphatics. Consequently, it has been assumed that arachnoid projections into the cranial venous system are responsible for cerebrospinal fluid (CSF) absorption. However, recent quantitative and qualitative evidence in sheep suggest that nasal lymphatics have the major role in CSF transport. Nonetheless, the applicability of this concept to other species, especially to humans has never been clarified. The purpose of this study was to compare the CSF and nasal lymph associations in human and non-human primates with those observed in other mammalian species. METHODS: Studies were performed in sheep, pigs, rabbits, rats, mice, monkeys and humans. Immediately after sacrifice (or up to 7 hours after death in humans), yellow Microfil was injected into the CSF compartment. The heads were cut in a sagittal plane. RESULTS: In the seven species examined, Microfil was observed primarily in the subarachnoid space around the olfactory bulbs and cribriform plate. The contrast agent followed the olfactory nerves and entered extensive lymphatic networks in the submucosa associated with the olfactory and respiratory epithelium. This is the first direct evidence of the association between the CSF and nasal lymph compartments in humans. CONCLUSIONS: The fact that the pattern of Microfil distribution was similar in all species tested, suggested that CSF absorption into nasal lymphatics is a characteristic feature of all mammals including humans. It is tempting to speculate that some disorders of the CSF system (hydrocephalus and idiopathic intracranial hypertension for example) may relate either directly or indirectly to a lymphatic CSF absorption deficit.

Journal Article↗

A hamster model of equine herpesvirus 9 induced encephalitis.

An acute and lethal infection of equine herpesvirus 9 (EHV-9), a new type of equine herpesvirus, was established in Syrian hamsters by intranasal inoculation. Clinical symptoms included the loss of body weight, nasal and ocular discharges and apparent neurological symptoms. Both LD50 and ID50 were equal at 33 plaque forming units. Histological and immunohistochemical examination demonstrated that the virus replicated in the olfactory mucosal cells and in the neurons of the olfactory bulbs, cerebrum and mesencephalon. The induction of encephalitis by intranasal but not by other routes of inoculation (i.v., i.p., i.m.) indicated that EHV-9 entered the brain via the olfactory nerve and then spread trans-synaptically to connecting neurons along the olfactory tract. This animal model should be useful for studying the pathogenesis and neurovirulence of this newly discovered neurotropic virus as well as other neurotropic herpesviruses.

Animals↗

Electrophysiological differentiation of new neurons in the olfactory bulb.

The subventricular zone produces neuroblasts that migrate to the olfactory bulb (OB) and differentiate into interneurons throughout postnatal life (Altman and Das, 1966; Hinds, 1968; Altman, 1969; Kishi et al., 1990; Luskin, 1993; Lois and Alvarez-Buylla, 1994). Although such postnatally generated interneurons have been characterized morphologically, their physiological differentiation has not been thoroughly described. Combining retroviral-mediated labeling of newly generated neurons with patch-clamp electrophysiology, we demonstrated that soon after new cells enter the layers of the olfactory bulb, they display voltage-dependent currents typical of more mature neurons. We also show that these "newcomers" express functional GABA and glutamate receptor channels, respond synaptically to stimulation of the olfactory nerve, and may establish both axodendritic and dendrodendritic synaptic contacts within the olfactory bulb. These data provide a basic description of the physiology of newly generated cells in the OB and show that such new cells are functional neurons that synaptically integrate into olfactory bulb circuitry soon after their arrival.

Animals↗

Identification of a cell surface glycoprotein family of olfactory receptor neurons with a monoclonal antibody.

A monoclonal antibody (Mab) has been developed which recognizes a family of cell surface glycoproteins found in high levels of rat olfactory receptor neurons. This Mab, designated 2B8, was produced by the fusion of X63-Ag8.653 myeloma cells and spleen cells of a mouse immunized with PC12 rat pheochromocytoma cells. Immunofluorescence analyses of cryostat sections of neonatal olfactory epithelium show prominent 2B8 binding to receptor neurons. Within the olfactory bulb only the glomerular and olfactory nerve layers show 2B8 binding. All other neural structures in the main olfactory bulb have background levels of reactivity. Analyses of 2B8 binding to particulate protein preparations from several central and peripheral nervous system components demonstrated highest 2B8 antigen specific activity in olfactory bulb and epithelium and detectable levels in dorsal root ganglia (DRG), whole cerebrum, cerebellum, and brainstem. However, 2B8 antigen could not be detected in non-olfactory structures by immunofluorescence. Some non-neural tissues also had the ability to bind 2B8 Mab in the particulate protein radioimmunoassay. In order to compare the 2B8-reactive molecules found in each tissue, Mab was applied to polyacrylamide gels of unlabeled membrane proteins. A family of molecules with diverse molecular weights was found. Some were unique to individual tissues whereas others were shared among tissues. Olfactory bulb and epithelium had a unique band with Mr = 215,000 and another band with Mr = 142,000. The 142,000-dalton band was also found with PC12 cells. PC12 cells also had several bands of lesser molecular weight, including 51,000 and 43,000. Testes membranes had immunoreactive bands only at Mr = 46,000 and 43,000. Bone marrow, perinatal liver, and DRG each expressed a single 2B8-reactive band with Mr = approximately 114,000. Salivary gland had four reactive bands, two common to it and only PC12 cells, the 114,000-dalton band which is similar to that found in adult rat bone marrow and DRG, and a unique band at Mr = 152,000. 2B8 immunoprecipitates of olfactory bulb and epithelium were analyzed for glycosyl groups by lectin reactivity. Wheat germ agglutinin and Ricinus communus agglutinin I bound the 2B8 antigens using two distinct assay methods. This suggests that the 2B8 antigens recognized in the olfactory system are glycoproteins having sialic acid and D-galactosyl components.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Olfactory marker protein is present in olfactory receptor cells of human fetuses.

Light microscopic observations indicated that cellular differentiation of the primary olfactory pathway in human fetuses was relatively advanced by the end of the first trimester. However, immunohistochemical staining showed that olfactory marker protein was present in the receptor cells only at about 28 weeks post-conception. At about 32 weeks, modest amounts of the protein could be found in the peripheral olfactory nerve layer and a few glomeruli, with increased staining observed in subsequent weeks. The results show conclusively that human fetal olfactory neurons synthesize olfactory marker protein during the later half of gestation.

Central Nervous System↗

Leukemia inhibitory factor, interleukin-6, and their receptors are expressed transiently in the olfactory mucosa after target ablation.

Removal of the synaptic targets of olfactory receptor neurons by olfactory bulb ablation results in apoptosis of olfactory receptor neurons and up-regulation of proliferation of their progenitors. This study focuses on the expression of the neuropoietic cytokines leukemia inhibitory factor (LIF) and its receptor (LIFR) and interleukin 6 (IL-6) and its receptor (IL-6R) in intercellular signaling pathways in the olfactory mucosa after target ablation. Olfactory bulbectomy (OBX) resulted in several transient, early-onset, temporally integrated events that were detected immunohistochemically. Macrophages infiltrated the olfactory epithelium (OE) by 16 hours post-OBX. LIF expression was up-regulated transiently at 2 days post-OBX, when up-regulated expression of LIFR also was detected on globose basal cells (GBCs), a subpopulation of which are immediate progenitors of olfactory receptor neurons. GBC proliferation peaked at 3--4 days post-OBX. In the olfactory nerve (ON), LIF-positive and IL-6-positive macrophage infiltration was followed by the transient up-regulation of expression of LIFR, IL-6, and IL-6R in ensheathing cells by 3 days post-OBX. The mRNAs for LIF/LIFR, IL-6/IL-6R, and their common signal-transduction molecule, gp130, in olfactory-nasal mucosa from control mice and from 3-day post-OBX mice were detected with reverse transcriptase-polymerase chain reaction (RT-PCR). Analysis of Northern blot and relative quantitative RT-PCR demonstrated similar temporal patterns of changes in relative mRNA levels for both LIF and IL-6, which were up-regulated by 16 hours post-OBX and peaked at 2--3 days post-OBX. These data indicate that LIF from infiltrating macrophages acts as a mitogen for GBCs and that LIF from infiltrating macrophages and IL-6 from infiltrating macrophages and ensheathing cells act as repair factors in the ON.

Animals↗

Characterization of olfactory receptor neurons and other cell types in dissociated rat olfactory cell cultures.

In dissociated cell cultures, control over the cellular environment facilitates study of the differentiation of mature cellular phenotypes. Central to this approach is a rigorous characterization of the cells that reside in culture. Therefore, we have used a battery of cell type-specific antibody markers to identify the cell types present in dissociated cultures of olfactory mucosal cells (containing cells from both the epithelium and lamina propria). To identify olfactory receptor neurons in the cultures, staining with antibodies against neuron-specific tubulin was compared to staining with antibodies to neuron-specific enolase, the neural cell adhesion molecule, N-CAM, and the adhesion molecule, LI. Staining of mature olfactory neurons in culture, with an antibody against the olfactory marker protein, was compared to staining with antibodies to carnosine. In contrast to tissue section staining, the overlap between carnosine and olfactory marker protein staining was not complete. Olfactory nerve glial cells were immunoreactive for the S100 beta protein and nestin, an intermediate filament found in early neuronal progenitor cells and Schwann cells. Antibodies to nestin did not label olfactory neurons or progenitor cells. An antibody to an oligodendrocyte-Schwann cell enzyme, 2',3'-cyclic nucleotide 3'-phosphodiesterase, did not label olfactory glia, but did label oligodendrocyte-like cells that appeared to be derived from the CNS glial feeder layer. An antibody against the heavy (200 kDa) neurofilament protein stained a minor subset of cells. The cultures also contained muscle cells, cartilage cells and macrophages (and/or microglia). These results demonstrate that multiple cell types either maintain or re-establish differentiated, cell type-specific phenotypes in dissociated olfactory cell cultures.

Animals↗

[A population of neurons expressing tyrosine hydroxylase and migrating from olfactory placode into forebrain during ontogenesis in rats].

Olfactory placodes, that give rise to the olfactory and respiratory epithelia during ontogenesis, are a source of many neurons migrating into forebrain in the direction of growth of the olfactory nerves. The neurons expressing gonadotropin releasing hormone (GnRH) are among the best studied in the population in question. This hormone is responsible for the central regulation of reproduction in adult animals. It was already shown that, in addition to the GnRH-immunoreactive neurons, a small amount of neurons expressing tyrosine hydroxylase (TH), the first enzyme of catecholamine synthesis, migrates into the forebrain. Such a transient population of TH-immunoreactive neurons was shown by means of single and double immmunohistochemical labeling. The TH neurons were first found on branches of the olfactory, terminal, and vomeronasal nerves, along the trajectory of migration of GnRH-immunoreactive neurons on day 15 of embryogenesis, which preceded the appearance of GnRH-immunoreactive neurons. On days 17-21 of embryogenesis, both populations of neurons were found in almost the same areas and on day 21 single neurons contained both GnRH and TH. There were no neurons expressing decarboxylase of aromatic acids (DAA), the second enzyme of catecholamine synthesis, among TH-immunoreactive neurons, thus suggesting noncatecholaminergic nature of these neurons. However, single nonenzymatic DAA-immunoreactive neurons were found in the area of anterior olfactory nuclei in the forebrain, which suggests their involvement in local cooperative synthesis of catecholamines in the area where GnRH-immunoreactive neurons penetrate in the forebrain. Thus, the neurons expressing TH, TH and GnRH, and DAA were found in rats during prenatal period in the nasal part of the head along the nerves projecting into the forebrain and in the rostral part of forebrain. The origin and functional significance of these neurons are discussed.

Animals↗

Substance P and catecholaminergic expression in neurons of the hamster main olfactory bulb.

A coordinated series of immunohistochemical and biochemical analyses have been conducted in the hamster to examine the dependence of substance P and tyrosine hydroxylase (TH) expression by second-order olfactory neurons, and the level of dopamine in the main olfactory bulb (MOB), on the integrity of carnosine- and olfactory marker protein (OMP)-containing primary afferent neurons. Substance P-like immunoreactivity (SPLI) is localized in external tufted cells and centrifugal afferents of the MOB; TH immunoreactivity has a wider distribution, in external tufted, middle tufted, periglomerular, and deep short-axon cells as well as in centrifugal afferents. To characterize the SPLI, this material was isolated by guanidine-HCl extraction and passage over a C18 SEP-PAK. The SPLI coelutes on HPLC with authentic substance P and, following oxidation, coelutes with substance P sulfoxide. It is sensitive to alpha-chymotrypsin and is resistant to trypsin. Thus, the SPLI in the MOB behaves as authentic substance P. Intranasal irrigation with 0.17 M ZnSO4 results in peripheral deafferentiation of the MOB for up to 8 months as evidenced by a persistent loss of OMP immunoreactivity and shrinkage of the olfactory nerve layer and glomeruli. By these criteria, the vomeronasal inputs to the accessory olfactory bulb are not destroyed and the spared vomeronasal receptor neurons do not innervate the vacated peripheral projection field in the MOB. The loss of peripheral inputs to the MOB is accompanied by marked and parallel reductions in the incidences of SPLI- and TH-positive second-order neurons despite an increase in the density of neuronal somata in the glomerular layer. Biochemical quantifications following peripheral deafferentation also demonstrate significant decreases of both substance P and dopamine, together with the expected decrease of carnosine. In contrast, the SPLI and the TH and serotoninlike immunoreactivities in centrifugal afferents as well as the TH immunoreactivity in deep interneurons do not appear to be reduced, and the MOB content of norepinephrine in centrifugal afferents is unaffected. These results collectively indicate that the loss of inputs from the primary olfactory receptor neurons can reduce the levels of at least two different, putatively neuroactive compounds (substance P and dopamine) in at least three classes of second-order neurons (external tufted, middle tufted, and periglomerular cells). The control of central neuron phenotype by the peripheral olfactory neurons thus appears to be a phenomenon of broad influence. It may play a role in processing chemosensory information as well as offering a system in which to study neuronal plasticit

Animals↗

Synaptophysin-like immunoreactivity in the rat olfactory bulb during postnatal development and after restricted early olfactory experience.

Synaptophysin is a synaptic vesicle protein that provides a marker of synaptic distribution in the brain. We used synaptophysin immunohistochemistry to detect changes in synaptic distribution in the main olfactory bulb during normal early postnatal development and following early olfactory restriction. Synaptophysin-like immunoreactivity appears early in the postnatal development of most bulbar laminae. In the first postnatal week, the entire glomerular neuropil is stained intensely, but by PND 19, the glomerular perimeter becomes more intensely stained than its core. This immunoreactivity is especially dense along that aspect of the perimeter facing the olfactory nerve layer. To determine if this developmental pattern could be affected by early olfactory experience, unilateral naris closure was performed on PND 1. In deprived bulbs at PND 19, the difference in staining between the glomerular border and the glomerular core is significantly less than in either contralateral glomeruli or glomeruli from unoperated animals. The difference between the glomerular border and the glomerular core is greater in bulbs contralateral to a closed naris than in bulbs from unoperated animals. Staining intensity measured over entire glomeruli is not altered by naris closure, nor is staining of other laminae. The changes detected after naris closure indicate that the glomerular distribution of synaptophysin may be particularly sensitive to early olfactory experience.

Aging↗

Subcellular localization of m2 muscarinic receptors in GABAergic interneurons of the olfactory bulb.

We analysed the ultrastructural distribution of the m2 muscarinic receptor (m2R) in the rat olfactory bulb (OB) using immunohistochemical techniques and light and electron microscopy. m2R was differentially distributed within the cellular compartments of gamma-aminobutyric acid (GABA)ergic bulbar interneurons. It is located in the gemmules of granule cells and in the synaptic loci of the interneurons of the external plexiform layer, suggesting that m2R activation could modulate the release of GABA from these interneurons onto principal cells by a presynaptic mechanism. By contrast, the receptor appears in the somata and dendritic trunks of second-order short-axon interneurons located in the inframitral layers, suggesting that postsynaptic muscarinic activation in these cells could elicit the inhibition of granule cells, leading to a disinhibition of principal cells. We also detail the anatomical substrate for a new putative muscarinic modulation that has not been previously described, and that could influence the reception of sensory information within the olfactory glomeruli. m2R appears in a subset of GABAergic/dopaminergic juxtaglomerular cells innervated by olfactory axons but is absent in juxtaglomerular cells that do not receive sensory inputs. This finding suggests that m2R activation could modify, through dopaminergic local circuits, the strength of olfactory nerve inputs onto principal cells. Activation of the muscarinic receptor may modulate the olfactory information encoding within olfactory glomeruli and may facilitate the bulbar transmission to superior centres influencing the GABA release by presynaptic and postsynaptic mechanisms. Taken together, our data provide the neuroanatomical basis for a complex action of m2R at different levels in the mammalian OB.

Acetylcholine↗

Quantification of cerebrospinal fluid transport across the cribriform plate into lymphatics in rats.

A major pathway by which cerebrospinal fluid (CSF) is removed from the cranium is transport through the cribriform plate in association with the olfactory nerves. CSF is then absorbed into lymphatics located in the submucosa of the olfactory epithelium (olfactory turbinates). In an attempt to provide a quantitative measure of this transport, 125I-human serum albumin (HSA) was injected into the lateral ventricles of adult Fisher 344 rats. The animals were killed at 10, 20, 30, 40, and 60 min after injection, and tissue samples, including blood (from heart puncture), skeletal muscle, spleen, liver, kidney, and tail were excised for radioactive assessment. The remains were frozen. To sample the olfactory turbinates, angled coronal tissue sections anterior to the cribriform plate were prepared from the frozen heads. The average concentration of 125I-HSA was higher in the middle olfactory turbinates than in any other tissue with peak concentrations achieved 30 min after injection. At this point, the recoveries of injected tracer (percent injected dose/g tissue) were 9.4% middle turbinates, 1.6% blood, 0.04% skeletal muscle, 0.2% spleen, 0.3% liver, 0.3% kidney, and 0.09% tail. The current belief that arachnoid projections are responsible for CSF drainage fails to explain some important issues related to the pathogenesis of CSF disorders. The rapid movement of the CSF tracer into the olfactory turbinates further supports a role for lymphatics in CSF absorption and provides the basis of a method to investigate the novel concept that diseases associated with the CSF system may involve impaired lymphatic CSF transport.

Animals↗

3-Phosphoglycerate dehydrogenase, a key enzyme for l-serine biosynthesis, is preferentially expressed in the radial glia/astrocyte lineage and olfactory ensheathing glia in the mouse brain.

l-Serine is synthesized from glycolytic intermediate 3-phosphoglycerate and is an indispensable precursor for the synthesis of proteins, membrane lipids, nucleotides, and neuroactive amino acids d-serine and glycine. We have recently shown that l-serine and its interconvertible glycine act as Bergmann glia-derived trophic factors for cerebellar Purkinje cells. To investigate whether such a metabolic neuron-glial relationship is fundamental to the developing and adult brain, we examined by in situ hybridization and immunohistochemistry the cellular expression of 3-phosphoglycerate dehydrogenase (3PGDH), the initial step enzyme for de novo l-serine biosynthesis in animal cells. At early stages when the neural wall consists exclusively of the ventricular zone, neuroepithelial stem cells expressed 3PGDH strongly and homogeneously. Thereafter, 3PGDH expression was downregulated and eventually disappeared in neuronal populations, whereas its high expression was transmitted to the radial glia and later to astrocytes in the gray and white matters. In addition, 3PGDH was highly expressed throughout development in the olfactory ensheathing glia, a specialized supporting cell that thoroughly ensheathes olfactory nerves. These results establish a fundamental link of the radial glia/astrocyte lineage and olfactory ensheathing glia to l-serine biosynthesis in the brain. We discuss this finding in the context of the hypothesis that 3PGDH expression in these glia cells contributes to energy metabolism in differentiating and differentiated neurons and other glia cells, which are known to be vulnerable to energy loss.

Aging↗

Thyroxine-dependent modulations of the expression of the neural cell adhesion molecule N-CAM during Xenopus laevis metamorphosis.

During amphibian metamorphosis, a complete remodeling of the phenotype takes place under complex hormonal control whose final effectors are thyroid hormones. This process implies the activation of coordinated programs of cell death, proliferation, migration, adhesion and differentiation. Inasmuch as the neural cell adhesion molecule N-CAM is thought to play a central role in the control of morphogenetic processes, we have studied by immunohistofluorescence and immunoblots the patterns of expression of N-CAM at different stages of Xenopus laevis metamorphosis. A scan was made of all major organs and appendages. Before the metamorphic climax, all neuronal cell bodies and processes express high levels of N-CAM. During the metamorphic climax, N-CAM expression decreases sharply on the cell bodies and processes of the peripheral nervous system (PNS) but remains high in the central nervous system (CNS). Towards the end of metamorphosis, the PNS and spinal nerves are virtually negative for N-CAM while the CNS is still positive. The optic and olfactory nerves, although myelinated, are still strongly positive for N-CAM. The lens and olfactory epithelia express N-CAM throughout metamorphosis. In the brain. N-CAM is present at all times as three polypeptides of 180, 140, and 120 X 10(3) Mr; before metamorphosis some of the N-CAM is in its polysialylated form. During metamorphosis and the subsequent growth of the animal, the amount of N-CAM decreases gradually. In all polypeptides, the polysialylated form is the first to disappear. Cardiac muscle expresses high level of N-CAM from its first formation throughout metamorphosis; in contrast, the level of N-CAM in skeletal muscle is high in newly formed muscles, but decreases rapidly after myoblast fusion. The liver of adult Xenopus contains large amounts of a 160 X 10(3) polypeptide that is recognized by polyclonal and monoclonal antibodies against N-CAM. cDNA probes of Xenopus brain N-CAM recognize major transcripts of 9.2, 3.8 and 3.3 kb in Xenopus liver mRNA; these bands are different in size from those recognized in brain mRNA (9.5, 4.2 and 2.2 kb). Premetamorphic liver does not express the 160 X 10(3) form of N-CAM, which can be first detected at stage 59 and persists then through all the life of the animal. Expression of N-CAM in the liver can be induced in premetamorphic animals (stage 51-52) by a 48 h treatment with thyroxine. All hepatocytes are responsive.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Prion infection of oral and nasal mucosa.

Centrifugal spread of the prion agent to peripheral tissues is postulated to occur by axonal transport along nerve fibers. This study investigated the distribution of the pathological isoform of the protein (PrP(Sc)) in the tongues and nasal cavities of hamsters following intracerebral inoculation of the HY strain of the transmissible mink encephalopathy (TME) agent. We report that PrP(Sc) deposition was found in the lamina propria, taste buds, and stratified squamous epithelium of fungiform papillae in the tongue, as well as in skeletal muscle cells. Using laser scanning confocal microscopy, PrP(Sc) was localized to nerve fibers in each of these structures in the tongue, neuroepithelial taste cells of the taste bud, and, possibly, epithelial cells. This PrP(Sc) distribution was consistent with a spread of HY TME agent along both somatosensory and gustatory cranial nerves to the tongue and suggests subsequent synaptic spread to taste cells and epithelial cells via peripheral synapses. In the nasal cavity, PrP(Sc) accumulation was found in the olfactory and vomeronasal epithelium, where its location was consistent with a distribution in cell bodies and apical dendrites of the sensory neurons. Prion spread to these sites is consistent with transport via the olfactory nerve fibers that descend from the olfactory bulb. Our data suggest that epithelial cells, neuroepithelial taste cells, or olfactory sensory neurons at chemosensory mucosal surfaces, which undergo normal turnover, infected with the prion agent could be shed and play a role in the horizontal transmission of animal prion diseases.

Animals↗

Alignment of glial cells stimulates directional neurite growth of CNS neurons in vitro.

Olfactory ensheathing cells (OECs) together with olfactory nerve fibroblasts (ONFs) and neonatal astrocytes are potent stimulators of neurite growth in adulthood and during development, respectively. Since it is known that alignment of glial cells is important for the correct outgrowth of axon tracts, it was hypothesized that the alignment of glial cells stimulates directional and enhanced neurite outgrowth. Adult OEC/ONF and neonatal astrocytes were cultured either on biodegradable poly(d,l)-lactide matrices or in Petri dishes for 4 days. Thereafter neonatal cerebral cortical neurons were added. After a 2-days coculture period the cultures were fixed and processed for a combined MAP-2 and phosphorylated neurofilament (RT97) staining. The neurite growth (neurite elongation and neurite formation) and the neurite direction were assessed. We show that (1). OEC/ONF cultures are more potent in stimulating the length of the longest neurite of cocultured neurons, (2). alignment of glial is achieved in vitro on our biomatrices, (3). aligned glial/biomatrix complexes do not enhance neurite growth, and (4). aligned glial/biomatrix complexes direct neurite outgrowth. These data have significant implications for in vivo experiments focusing on glial transplantation. Transplanting glial/biomatrix complexes may stimulate the directional regrowth of severed axons across a lesion site.

Animals↗

An apparently new acrocraniofacial syndrome with cranial nerve and visceral anomalies.

We report details of a neonate with cranial bone dysplasia, broad nasal bridge, microphthalmia, optic and olfactory nerve anomalies, pulmonary segmentation defects, polydactyly, abnormally positioned and shaped thumbs, absent mesentery to the gut and streak gonads. Review of the literature and relevant databases does not identify a likely diagnosis.

Abnormalities, Multiple↗

[Laryngeal schwannoma treated with CO2 laser].

Neurinoma is a benign capsulate tumor originating from the Schwann cells of all nerve fibers outside the central nervous system, the sole exception being the optic and olfactory nerves. These tumors favor the head and neck district but rarely affect the larynx. This work presents the case of a 73-year-old woman treated in the emergency room for an episode of acute dispnea. The patient's case history indicated that for more than 10 years she had the sensation of a foreign body in the hypopharynx and stomatolalia. Direct hypopharyngo-laryngoscopy with a flexible fiberoptic showed a rounded submucosa neoformation 3.5 cm in diameter at the level of the left aryepiglottic fold, blocking the opening of the laryngeal vestibule. Laryngeal motility was perfectly preserved. The decision was made for prompt exeresis of the neoformation under direct microlaryngoscopy with a CO2 laser. Post-operative follow-up showed that all laryngeal functions were preserved. Three months later, the patient was still symptom-free and direct examination of the larynx showed no signs of recurrence. Histological diagnosis indicated a laryngeal schwannoma. Surgical removal is the treatment of choice and can be performed by endoscopy or through an external approach depending on the site and size of the tumor. Different external approaches have been described such as the median thyrofissure, lateral pharyngotomy and lateral thyrofissure. In the present case, although the neoformation was quite large, the decision was made to perform an endoscopy resection with CO2 laser, without resorting to a tracheotomy, reducing post-operative recovery to a minimum and preserving all laryngeal functions.

Aged↗