RESUMEN
OBJECTIVE: Celiac disease (CD) is a gluten-triggered immune enteropathy caused by a genetic predisposition. Recent papers suggest that CD is increasingly recognized by extraintestinal findings. The aim of this study was to investigate the effect of CD on hearing pathway including the olivocochlear efferent system in children. METHODS: Forty-one pediatric CD patients and 31 controls were included in the study. Both groups were evaluated with audiometry, tympanometry, transiently evoked otoacoustic emission (TEOAE), distortion product otoacoustic emission (DPOAE), and contralateral suppression of the TEOAE. RESULTS: The threshold at 250 Hz of the patients with CD was significantly higher (p < 0.05 in CD compared to control group, p < 0.0001). The signal to noise ratio (SNR) amplitudes in DPOAE testing and the SNR amplitudes with and without contralateral acoustic stimulus in TEOAE testing were significantly lower at 1,000 Hz in the CD compared to the control group. There was no significant difference between the CD and the control group regarding contralateral suppression amplitudes. CONCLUSION: CD seems to have an important impact on the auditory system, and results in an elevation of the thresholds at 250 Hz on audiometry and a decrease in the amplitudes of DPOAE and linear TEOAE at 1,000 Hz in children.
Asunto(s)
Vías Auditivas/inmunología , Vías Auditivas/fisiopatología , Enfermedad Celíaca/complicaciones , Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Sensorineural/etiología , Pruebas de Impedancia Acústica , Adolescente , Audiometría de Tonos Puros , Umbral Auditivo/fisiología , Autoinmunidad/fisiología , Enfermedad Celíaca/inmunología , Niño , Preescolar , Núcleo Coclear/inmunología , Núcleo Coclear/fisiopatología , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Femenino , Pérdida Auditiva Sensorineural/inmunología , Humanos , Masculino , Núcleo Olivar/inmunología , Núcleo Olivar/fisiopatología , Emisiones Otoacústicas Espontáneas/fisiologíaRESUMEN
CONCLUSIONS: These results show that laryngeal inflammatory reactions may induce the expression of proinflammatory cytokines along the afferent laryngeal circuit and in nuclei associated with the HPA axis. Local laryngeal inflammation may induce functional and physiologic alterations in the laryngeal neural system via neuroimmunologic reactions. OBJECTIVE: Idiopathic laryngeal disorders associated with various neurologic conditions such as spasmodic dysphonia, idiopathic vocal fold paralysis and sudden infant death syndrome are causally related to upper respiratory tract infections, and it can be speculated that these disorders result in neurophysiologic alterations. The goal of this study was to identify the neurophysiologic effect on the central nervous system of local inflammatory alterations in the larynx. MATERIAL AND METHODS: The expression of c-fos and IL-1beta was identified after injecting saline solution, 10 microg of lipopolysaccharide or 100 microg of lipopolysaccharide into the larynx of 12 rats. RESULTS: The inflammatory cytokine IL-1beta was mainly expressed in the inferior olivary nucleus and raphe nucleus, which are associated with the hypothalamic-pituitary-adrenal (HPA) axis. IL-1beta expression was also found in the nuclei of afferent nervous pathways of the superior laryngeal nerve, such as the nucleus tractus solitarius, nucleus ambiguus, lateral reticular nucleus, magnocellular reticular nucleus and paragigantocellular reticular nucleus.
Asunto(s)
Interleucina-1/inmunología , Laringe/inmunología , Red Nerviosa/inmunología , Neuronas Aferentes/inmunología , Proteínas Proto-Oncogénicas c-fos/inmunología , Animales , Sistema Hipotálamo-Hipofisario/inmunología , Sistema Hipotálamo-Hipofisario/metabolismo , Inflamación/inducido químicamente , Inflamación/inmunología , Inflamación/patología , Interleucina-1/metabolismo , Laringe/metabolismo , Laringe/patología , Lipopolisacáridos/administración & dosificación , Lipopolisacáridos/efectos adversos , Red Nerviosa/metabolismo , Neuronas Aferentes/metabolismo , Núcleo Olivar/inmunología , Núcleo Olivar/metabolismo , Sistema Hipófiso-Suprarrenal/inmunología , Sistema Hipófiso-Suprarrenal/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Núcleos del Rafe/inmunología , Núcleos del Rafe/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
We examined immunoreactivity for gamma-aminobutyric acid (GABA) in auditory and vestibular brainstem nuclei of the bullfrog, Rana catesbeiana, across metamorphosis, a developmental period featuring significant anatomical and functional remodeling of the nervous system. In the early larval period, GABA-immunoreactive cell somata were visible in the vestibular nucleus complex and the torus semicircularis, as well as in the spinal cord, cerebellum and optic tectum. Fiber bundles such as the medial longitudinal fasciculus and the lemnsical pathways also exhibited intense label at these early stages. In contrast, only diffuse neuropil label was visible in the dorsolateral nucleus and the superior olivary nucleus at the same stages. This diffuse immunoreactivity became progressively more reduced over larval development, and stained somata were visible in these medullary nuclei by metamorphic climax stages. In the torus semicircularis, the numbers of labeled somata in both the developing laminar and principal nuclei increased over metamorphic development, and became progressively more organized into distinct layers. The adult pattern of GABA-like immunoreactivity in the auditory brainstem was reached by metamorphic climax stages, coincident with the maturation of the opercularis system, and preceding the final development of the external tympanum and the tympanic conduction pathway. The relatively earlier maturation of vestibular, compared to auditory, areas in the medulla might reflect the behavioral importance of vestibular-mediated motor reactions during tadpole life. The distribution of GABA in auditory brainstem nuclei in both developing and adult frogs is comparable to that observed in mammals and birds.
Asunto(s)
Tronco Encefálico/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Animales , Anticuerpos , Especificidad de Anticuerpos , Tronco Encefálico/embriología , Tronco Encefálico/inmunología , Fluorescencia , Inmunohistoquímica , Larva , Mesencéfalo/metabolismo , Núcleo Olivar/inmunología , Núcleo Olivar/metabolismo , Rana catesbeiana , Ácido gamma-Aminobutírico/inmunologíaRESUMEN
OBJECTIVE: To analyze the T-cell receptor (TCR) repertoire in the inflammatory infiltrates of the nervous system and tumor of patients with anti-Hu associated paraneoplastic encephalomyelitis and sensory neuronopathy (PEM/SN). BACKGROUND: In PEM/SN, the pathogenic role of the infiltrating T cells is speculative. TCR analysis may establish whether these lymphocytes are attracted nonspecifically by a proinflammatory environment or are driven by a specific antigen or superantigen. METHODS: We examined frozen tissues of seven patients with PEM/SN using immunohistochemical and PCR analysis. Of 62 tissue blocks from seven patients, 19 blocks from five patients had >100 CD3+ cells per section infiltrating the nervous system or tumor. These infiltrates allowed screening of the TCR Vbeta family repertoire using a panel of 18 antibodies that recognize family-specific regions of most TCR Vbeta families against which antibodies have been generated. To distinguish between antigen-driven clonal and superantigen-driven family expansion, we extracted RNA from frozen tissue and performed reverse transcriptase (RT)-PCR analysis followed by subcloning and sequencing of the antigen-specific CDR3 region of the TCR Vbeta chain. RESULTS: All five patients showed a limited Vbeta repertoire. An overrepresentation (>10% of total CD3+) of certain Vbeta families was identified in three patients (as high as 45% of total CD3+), which consisted mainly of CD8 + cells. CDR3 sequences obtained from one patient revealed an in situ expansion of two clones in the amygdala (one at a frequency of 57%) and four clones in the tumor. CONCLUSION: These findings suggest that an antigen-driven oligoclonal cytotoxic T-cell response plays a role in the pathogenesis of anti-Hu associated PEM/SN.
Asunto(s)
Neoplasias Encefálicas/inmunología , Encefalomielitis/inmunología , Proteínas del Tejido Nervioso , Síndromes Paraneoplásicos/inmunología , Proteínas de Unión al ARN/análisis , Receptores de Antígenos de Linfocitos T alfa-beta/análisis , Anciano , Anciano de 80 o más Años , Amígdala del Cerebelo/inmunología , Neoplasias Encefálicas/complicaciones , Complejo CD3/análisis , Carcinoma de Células Pequeñas/complicaciones , Carcinoma de Células Pequeñas/inmunología , Núcleos Cerebelosos/inmunología , ADN de Neoplasias/análisis , Proteínas ELAV , Encefalomielitis/complicaciones , Femenino , Ganglios Espinales/inmunología , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/inmunología , Masculino , Persona de Mediana Edad , Núcleo Olivar/inmunología , Síndromes Paraneoplásicos/complicaciones , Proteínas de Unión al ARN/inmunología , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Receptores de Antígenos de Linfocitos T alfa-beta/inmunología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Linfocitos T Citotóxicos/química , Linfocitos T Citotóxicos/inmunologíaRESUMEN
The identities of neurotransmitters of the pretecto-olivary projection neurons and of the nerve terminals contacting them were investigated using a double-label method with retrograde labelling in combination with gamma-aminobutyric acid (GABA) and glutamate immunocytochemistry in the nucleus of the optic tract and the dorsal terminal nucleus of the accessory optic system in the rat both light and electron microscopically. At the light microscopic level, the somata of all projection neurons identified by a label of horseradish peroxidase reaction product were stained moderately but reliably for glutamate immunoreactivity. In no case, any retrogradely labelled neuron was found to be stained for GABA immunoreactivity. However, the somata and proximal dendrites of these cells were surrounded with many intensively stained puncta, indicating strong reactions with the anti-GABA antibodies. In contrast, no immunostaining with anti-glycine or anti-taurine antibodies was obtained. Electron microscopic investigations demonstrated that immunogold-positive axosomatic or axodendritic synapses on the retrogradely labelled neurons corresponded to some of the GABA-positive puncta in semithin sections. The results suggest that the projection neurons receive a strong inhibitory input mediated by GABA and send their directionally selective information to the inferior olive by glutamatergic projections.
Asunto(s)
Glutamatos/metabolismo , Núcleo Olivar/metabolismo , Colículos Superiores/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Animales , Glutamatos/inmunología , Ácido Glutámico , Peroxidasa de Rábano Silvestre , Inmunohistoquímica , Microscopía Electrónica , Vías Nerviosas/inmunología , Vías Nerviosas/metabolismo , Núcleo Olivar/inmunología , Ratas , Colículos Superiores/inmunología , Fijación del Tejido , Ácido gamma-Aminobutírico/inmunologíaRESUMEN
We examined the effects of constant dark or constant light on substance P (SP) and/or neuropeptide Y (NPY) immunoreactive fibres in the rat suprachiasmatic nucleus (SCN) and olivary pretectal nucleus (OPT) by immunohistochemistry. After constant dark, SP immunoreactive fibres and terminals decreased slightly in the SCN, while they increased markedly in the OPT. After constant light, they increased markedly in the SCN, but were little changed in the OPT. NPY immunoreactive fibres and terminals in the SCN decreased slightly after after constant light, but there were no effects on these fibres after constant dark. These findings suggest that SP immunoreactive fibres are involved in mediating illumination discrimination in the SCN and/or OPT.
Asunto(s)
Núcleo Olivar/metabolismo , Sustancia P/metabolismo , Núcleo Supraquiasmático/metabolismo , Animales , Especificidad de Anticuerpos , Oscuridad , Inmunohistoquímica , Luz , Terminaciones Nerviosas/inmunología , Terminaciones Nerviosas/metabolismo , Neuropéptido Y/inmunología , Neuropéptido Y/metabolismo , Núcleo Olivar/anatomía & histología , Núcleo Olivar/inmunología , Ratas , Ratas Wistar , Sustancia P/inmunología , Núcleo Supraquiasmático/anatomía & histología , Núcleo Supraquiasmático/inmunologíaRESUMEN
The aim of this study was to examine how the functional specialization of the barn owl's auditory brainstem might correlate with histochemical compartmentalization. The barn owl uses interaural intensity and time differences to encode, respectively, the vertical and azimuthal positions of sound sources in space. These two auditory cues are processed in parallel ascending pathways that separate from each other at the level of the cochlear nuclei. Sections through the auditory brainstem were stained for acetylcholinesterase (AChE) to examine whether nuclei that process different auditory cues stain differentially for this enzyme. Of the two cochlear nuclei, angularis showed more intense staining than nucleus magnocellularis. Nucleus angularis projects to all of the nuclei and subdivisions of nuclei that belong to the intensity processing pathway. Acetylcholinesterase stained all regions that contain terminal fields of nucleus angularis and thus provided discrimination between the time and intensity pathways. Moreover, staining patterns with acetylcholinesterase were complementary to those previously reported with an anti-calbindin antibody, which stains terminal fields of nucleus laminaris, and thus stains all the nuclei and subdivisions of nuclei that belong to the time pathway. Some of the gross staining patterns observed with AChE were similar to those reported with antibodies to glutamate decarboxylase. However, AChE is a more convenient and definitive marker in discriminating between these pathways than is calbindin or glutamate decarboxylase. Acetylcholinesterase staining of the intensity pathway in the owl may be related to encoding of sound intensity by spike rate over large dynamic ranges.
Asunto(s)
Acetilcolinesterasa/metabolismo , Vías Auditivas/anatomía & histología , Aves/fisiología , Acetilcolinesterasa/inmunología , Estimulación Acústica , Animales , Vías Auditivas/fisiología , Tronco Encefálico/anatomía & histología , Tronco Encefálico/fisiología , Calbindinas , Cóclea/anatomía & histología , Cóclea/fisiología , Electrodos , Femenino , Inmunohistoquímica , Colículos Inferiores/anatomía & histología , Masculino , Núcleo Olivar/inmunología , Núcleo Olivar/metabolismo , Proteína G de Unión al Calcio S100/inmunología , Proteína G de Unión al Calcio S100/metabolismo , Coloración y EtiquetadoRESUMEN
An immunohistochemical analysis of the cat central nervous system revealed that a monoclonal antibody which recognizes a soluble cytosolic protein, R2D5, bound two regions in a prominent spatial gradient. In the medial and lateral superior olivary nuclei of the brainstem, R2D5 immunoreactivity appeared as a gradient across a population of topographically ordered principal neurons. The spatial gradient corresponded to the tonotopic organization in the superior olivary nuclei: i.e., R2D5 immunoreactivity tended to occur more frequently and intensely in low-frequency neurons than in high-frequency neurons. Granule cells in the hippocampal dentate gyrus also had a pronounced spatial gradient in R2D5 immunoreactivity expression, and this gradient corresponded to the septotemporal axis of the hippocampus. Granule cells of the temporal (ventral) portions of the hippocampus were labeled intensely with R2D5 antibody, while those located in progressively more septal (dorsal) portions had gradually less immunoreactivity. These results suggest that in both the superior olivary nuclei and the hippocampal dentate gyrus, neurons differ in intrinsic properties by their position along specific axes. They suggest also that the hippocampus has an intrinsic functional organization related to the spatial gradient along its septotemporal axis.
Asunto(s)
Anticuerpos Monoclonales/inmunología , Hipocampo/inmunología , Núcleo Olivar/inmunología , Animales , Gatos , Inmunohistoquímica/métodos , Coloración y Etiquetado , Distribución TisularRESUMEN
The postnatal maturation of the GABAergic innervation of the rat inferior olive was studied with an antiserum to glutamic acid decarboxylase (GAD), the GABA-synthesizing enzyme. GAD-positive axons were present at a very low density in the periolivary and interlamellar regions of newborn rats, as well as in certain precise areas of the lamellae, at the mediodorsal limit. The immature distribution indicates that the GABAergic projections reach the inferior olive shortly before birth and that the greater part of synaptogenesis and the establishment of the adult organization occurs postnatally. Light and electron microscopic analyses disclosed that the maturation of this system of olivary afferents passes through three well-defined stages: (1) During the first, or immature stage (from PO to P5), GAD immunoreactivity is not confined to axon terminals, as in adult rats. The labeled fibers penetrate progressively into the periphery of the lamellae and reach their centers in an irregular manner by the end of the immature stage. This staggered invasion of the lamellae accentuates intraregional olivary differences and begins to take the adult configuration. As fiber penetration advances, the density of labeled axons establishing synaptic contacts increases, while the number of completely immunostained fibers decreases. This distribution prevails until the end of the immature stage and suggests that the GABAergic afferent projections remain in a "waiting compartment" from their prenatal arrival until the moment they invade the olivary parenchyma. (2). The second stage is designated as an intermediate stage of maturation and lasts from P7 to P10. During this period, GAD axoplasmic compartmentation occurs, and henceforth only axon terminals exhibit GAD immunoreactivity. Concomitantly, intraregional differences in the pattern of innervation become more marked, because of the continuing irregular distribution of the growing labeled axons. This intermediate maturational stage is also characterized by a rapid increase in labeled axon terminals bearing synaptic complexes and by the formation of complex synaptic arrangements, the protoglomeruli. From the beginning of protoglomeruli formation, GAD-positive axon terminals are one of their constituents, and they are systematically localized at the periphery of the incipient dendritic protrusions. (3) The final stage of maturation takes place from P10 to P15. During this stage, the adultlike pattern of GABAergic innervation of the inferior olive is attained. Toward P15, intraregional differences in GAD immunoreactivity are similar to those of the adult rat.(ABSTRACT TRUNCATED AT 400 WORDS)
Asunto(s)
Animales Recién Nacidos/fisiología , Neuronas Aferentes/fisiología , Núcleo Olivar/crecimiento & desarrollo , Ratas/crecimiento & desarrollo , Ratas/fisiología , Sinapsis/fisiología , Ácido gamma-Aminobutírico/fisiología , Animales , Glutamato Descarboxilasa/inmunología , Inmunohistoquímica , Microscopía Electrónica , Neuronas Aferentes/ultraestructura , Núcleo Olivar/inmunología , Núcleo Olivar/ultraestructura , Ratas EndogámicasRESUMEN
The distribution of GABA-producing neurons in the brainstem auditory nuclei of the rat was investigated immunohistochemically by using an antibody to glutamic acid decarboxylase (GAD). In the cochlear nuclei, GAD immunoreactive neurons are present only in the superficial granular and molecular layers, whereas terminals are found in all subdivisions of the nuclei and are particularly dense surrounding large spherical cells and one type of stellate cell. In the superior olivary complex, GAD immunoreactive neurons are located in the lateral olivary nucleus and throughout the periolivary region. Immunoreactive terminals are distributed along dendrites of principal cells of the medial and lateral olivary nuclei and are clustered around somata of globular neurons of the nucleus of the trapezoid body. An extremely dense band of immunoreactive somata and terminals is present along the ventral edge of the olivary complex. The ventral, intermediate, and dorsal nuclei of the lateral lemniscus contain small fusiform GAD-immunoreactive neurons and a moderately dense plexus of immunoreactive terminals. The inferior colliculus contains a large population of GAD-immunoreactive perikarya and an extremely dense accumulation of immunoreactive terminals in the central, dorsomedial, and external nuclei. These observations indicate that GABA systems are involved in function at all levels of the brainstem auditory pathway.
Asunto(s)
Vías Auditivas/inmunología , Tronco Encefálico/inmunología , Glutamato Descarboxilasa/inmunología , Animales , Nervio Coclear/inmunología , Histocitoquímica , Inmunoquímica , Colículos Inferiores/inmunología , Núcleo Olivar/inmunología , Ratas , Ratas EndogámicasRESUMEN
Met-enkephalin immunoreactivity was investigated with an indirect immunoperoxidase technique in the cervical spinal cord, brainstem and midbrain of the cat, paying special attention to pain-related nuclei. Different technical conditions were used to reveal preferentially met-enkephalin-containing fibres and terminals or perikarya. Immunoreactive fibres and terminals were revealed optimally in sections from control animals incubated with detergent (Triton X-100). Immunoreactive perikarya were revealed in colchicine treated animals. Comparison between different routes of administration showed that local injections of colchicine are needed to reveal optimally immunoreactive perikarya in nuclei located far from the ventricles. Met-enkephalin-containing fibres and terminals are widely distributed in the posterior brain and spinal cord. The densest network of immunoreactive fibers are observed in the superficial layers of the cervical spinal cord and the caudal trigeminal nucleus, in the nucleus of the solitary tract, the nucleus of the facial nerve, the nucleus of the prepositus hypoglossi, the nucleus raphe pallidus, the medial vestibular nucleus, the interpedoncular nucleus and the substantia nigra. A moderate staining of fibres is observed in various nuclei including the ventral horn of the spinal cord and caudal trigeminal nucleus, the brainstem and midbrain reticular formation, the inferior olivary complex, the nucleus of the descending trigeminal tract and the periaqueductal grey. Met-enkephalin-containing perikarya are present in all the nuclei cited before, except in the inferior olivary complex. The densest aggregation of enkephalin-like perikarya is observed in the nucleus raphe magnus, nucleus raphe obscurus, nucleus raphe pallidus, nucleus reticularis gigantocellularis pars alpha and nucleus reticularis lateralis. The general distribution of enkephalin-containing structures in the cervical spinal cord, brainstem and midbrain of the cat appears very similar to that of the rat except in the substantia nigra where met-enkephalin cell bodies are found in the cat but not in the rat. In particular the pain-related nuclei present a similar distribution of the peptide in the two species; however, met-enkephalin-containing cell bodies are much more numerous in the cat than in the rat (notably in the reticular formation). Similar types of met-enkephalin innervation occur in the dorsal and intermediate grey of the spinal cord and of the caudal trigeminal nucleus supporting further that the functional organizations of these regions are closely related.