Transsynaptic degeneration in the inferior olivary nucleus associated with pontine glioblastoma

A case of glioblastoma arising in the pons of a 14-year-old boy in whom transsynaptic degeneration was found in the inferior olivary nucleus is reported. The tumor occupied most of the pons including the tegmental tract and invaded into the midbrain, medulla oblongata, cerebellar peduncles, thalamus, basal ganglia, and meninges. The right inferior olivary nucleus was devoid of the tumorous lesion, but many neurons were severely vacuolated. An immunohistochemical study using glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), and S-100 protein was performed. GFAP and S-100 protein were positive in the reactive glia of the nucleus and NSE gave a faint reaction in some degenerated neurons. These degenerative changes found in neurons of the inferior olivary nucleus were considered to be transsynaptic degeneration due to the destruction of the tegmental tract at the pons and of cerebellar peduncles by invasive pontine glioblastoma.     

立体学在分析人延髓脑桥毛细血管网密度的初步应用

采用立体学方法对5例人延髓脑桥毛细血管密度作了观测。结果表明:核团的血管比纤维束的丰富;血管密度高的核团包括了脑桥核、下橄榄核簇等与小脑相连系的核团,及楔束核、上橄榄核和展神经核;纤维束中以被盖中央束的血管密度最高。     

Regional distribution of the 5-HT innervation in the brain of normal and lurcher mice as revealed by [H]citalopram quantitative autoradiography

The neurological cerebellar mutant lurcher is characterized by a primary degeneration of Purkinje cells as well as a retrograde secondary partial degeneration of cerebellar granule cells and inferior olivary neurons. Since serotonin (5-HT) has been implicated in the modulation of excitatory amino acid systems of the cerebellum, the 5-HT innervation of the normal and lurcher mice was examined by quantifying uptake sites using [³H]citalopram autoradiography, and by biochemical assays of the indoles 5-HT, 5-hydroxy- -tryptophan and 5-hydroxyindole-3-acetic acid using high-performance liquid chromatography. Comparable results were found between [³H]citalopram binding and 5-HT tissue concentrations in different brain regions. The highest [³H]citalopram labelling was observed in defined structures of the mesencephalic and upper pontine regions, in limbic structures, in hypothalamus and in discrete thalamic divisions, while the lowest labelling of uptake sites was documented in cerebellum and brainstem reticular formation. In lurcher mutants, the histology confirmed cell degeneration and the reduction in width, leading to 65%, 45% and 25% atrophies of total cerebellum, deep nuclei and inferior olivary nucleus, respectively. The [³H]citalopram labelling corrected for surface loss was 45% and 20% higher in cerebellar deep nuclei and red nucleus, respectively, but remained unchanged in the cerebellar cortex and inferior olivary nucleus. Moreover, higher labelling was found in nucleus raphe dorsalis, ventral tegmental area, inferior colliculus, locus coeruleus, pontine central grey and anterior thalamic nuclei, areas known to be part of cerebellar afferent and efferent systems. The present results indicate that in such pathological conditions as described for the lurcher mutant, the 5-HT system may modulate motor function not only at the level of the cerebellum, but also in other forebrain structures functionally related to the motor system.     

肥大性下橄榄变性的临床及影像学特征

目的　肥大性下橄榄核变性（HOD）是由原发于齿状核-红核-下橄榄核环路（DROP）区病变所继发的一种特殊的跨突触变性,具有较为独特的临床和影像学表现。本文拟对HOD的临床特点进行探讨,以提高对其的认识。 方法　回顾性分析11例HOD患者的临床资料。 结果　男性10例,女性1例,平均年龄53.5岁。原发病包括中脑出血1例,脑桥出血8例,脑桥梗塞1例,脑桥胶质瘤1例。HOD临床表现为头晕、视物不清、眼震、言语含混、软腭阵挛、肌张力增高、不自主运动、姿势异常、共济失调等症候组合,平均晚于原发病3.8个月出现。MRI上表现为下橄榄核体积增大和T2WI高信号。当原发病变累及单侧脑桥被盖或红核时,HOD发生在同侧,临床症状出现在对侧;当原发病变累及双侧红核或脑桥被盖时,HOD和临床症状出现在双侧。巴氯芬、氯硝安定和卡马西平可以减轻临床症状。 结论　DROP区病变后要警惕HOD的发生,延迟损害是诊断的重要线索,共济失调和不自主运动是最常见的临床表现,MRI检查可以帮助确诊。     

大鼠脑干神经元型一氧化氮合酶免疫阳性神经元的分布

目的　观察大鼠脑干神经元型一氧化氮合酶 (nNOS)免疫阳性神经元的分布 ,为探讨nNOS的作用提供形态学资料。方法　用ABC免疫细胞化学方法显示脑干nNOS免疫阳性神经元。结果　大鼠脑干nNOS免疫阳性神经元以中脑和脑桥分布丰富 ,延髓较稀少 ;在中脑 ,nNOS免疫阳性神经元主要分布于中脑水管周围灰质的背侧部、被盖背外侧核、中缝背核、上下丘灰质等部位 ;在脑桥 ,主要分布于被盖背外侧核、脑桥中缝核、被盖脚桥核、蓝斑、臂旁核、斜方体核 ,以及脑桥网状结构 ;与中脑和脑桥相比 ,延髓nNOS免疫阳性神经元较少 ,主要分布于延髓网状结构、三叉神经脊束核和孤束核等核团。结论　分布于脑干内丰富的nNOS免疫阳性神经元可能通过其生成的NO调节其他神经递质的分泌 ,共同参与内脏活动、感觉和运动的传导 ,以及睡眠和觉醒等脑的高级整合功能的调节。     

Retrograde and anterograde labeling of cerebellar afferent projection by the injection of recombinant adenoviral vectors into the mouse cerebellar cortex

 Adenoviral vectors have recently been recognized as highly efficient systems for gene delivery into various tissues. We show that a reporter gene introduced into nerve terminals via an adenovirus can be used to label cell bodies retrogradely and then label the axons and nerve terminals of the infected neurons anterogradely in vivo. We injected a replication-defective recombinant adenovirus carrying the E. coli β-galactosidase gene (lacZ) into the cerebellar cortex of the adult mouse. The first evidence of retrograde labeling was obtained at 2 days after the infection when neurons in the pontine nuclei and the reticulotegmental nucleus of the pons weakly expressed β-galactosidase, and at 3 days post-infection when neurons in all precerebellar nuclei, known to project to the cerebellar cortex, were strongly stained with X-gal in a Golgi-like manner. Anterograde transport of lacZ gene products was recognized at 3 days post-infection; β-galactosidase-positive axons arose from somata or dendrites of retrogradely labeled neurons, passed through the middle or inferior cerebellar peduncles, and entered the cerebellum. Anterogradely labeled mossy terminals were recognized on the injection side at 8 days post-infection, and on the contralateral side at 14 days post-infection. β-Galactosidase expression persisted for up to two months, with a decrease in the total number of labeled cells over time. We could not find any signs of anterograde or retrograde transsynaptic labeling in the nuclei synaptically linked to the cerebellar cortex at any time point after injection up to 58 days post-infection. Accepted: 2 June 1997     

The afferent connections of the inferior olivary complex in rats. An anterograde study using autoradiographic and axonal degeneration techniques

Autoradiographic and axonal degeneration techniques were employed to determine the distribution patterns of inferior olivary afferents whose origins were determined using the horseradish peroxidase method.⁷⁰ The Fink-Heimer stain for degenerating axons was used following lesions of the cerebral cortex and spinal cord, while brainstem and cerebellar afferents were mapped by tritiated leucine autoradiography.After unilateral lesions of the mid-thoracic spinal cord, degenerating axons were observed within the subnuclei a and b of the caudolateral medial accessory olive and in the caudolateral dorsal accessory olive. Degeneration after upper cervical cord lesions extended more rostrally and medially within the same olivary subdivisions.Several nuclei within the caudal brainstem projected to the inferior olivary complex. The dorsal column nuclei distributed fibers primarily contralaterally to the lateral part of the dorsal accessory olive and to the caudolateral part of the medial accessory olive; the spinal trigeminal nucleus projected contralaterally to the rostromedial dorsal accessory olive; the medial and inferior vestibular nuclei projected to the ipsilateral subnuclei b, c, and β of the medial accessory olive and to the contralateral dorsomedial cell column; the nucleus prepositus hypoglossi sent fibers to the subnuclei c and β, the dorsal cap and the ventrolateral outgrowth; the lateral reticular nucleus projected to the subnucleus a of the caudolateral medial accessory olive bilaterally; and the reticular formation distributed fibers to the dorsal accessory olive contralaterally and to the β subnucleus ipsilaterally.Study of inferior olivary complex afferents from the deep cerebellar nuclei showed a projection from the fastigial nucleus to the β subnucleus and the ventrolateral outgrowth. The dentate and interpositus nuclei demonstrated topographic connections from these nuclei to the principal olive and accessory olives, respectively. All cerebellar connections were predominantly contralateral.Analysis of mesencephalic and diencephalic areas also demonstrated several inferior olivary complex afferent systems: the caudal pretectum and the superior colliculus projected to the subnucleus c contralaterally and the dorsal lamella of the principal olive ipsilaterally; the nucleus of the optic tract sent fibers to the dorsal cap; the lateral deep mesencephalic nucleus distributed fibers to the ipsilateral dorsal accessory olive and β subnucleus; the medial terminal nucleus of the accessory optic tract projected ipsilaterally to the ventrolateral outgrowth; and several areas including the medial deep mesencephalic nucleus, periaqueductal gray, the nucleus of Darkschewitsch, the subparafascicular nucleus, the rostral red nucleus and the prerubral field all projected ipsilaterally to the principal olive, rostral medial accessory olive, ventrolateral outgrowth and, to a lesser extent, the caudal medial accessory olive, dorsal cap and β subnucleus.Lesions of the frontal cortex produced axonal degeneration primarily ipsilaterally within many olivary subdivisions, especially the medial dorsal accessory olive and the caudomedial medial accessory olive.Although some notable differences in the distribution and laterality of fibers are described, our findings generally corroborate several earlier reports which used different techniques on a variety of species. Inferior olivary afferents from functionally related areas typically demonstrated similar distribution patterns within the subdivisions of the inferior olivary complex. These patterns suggest a functional localization within the inferior olivary complex which may facilitate an understanding of afferents from areas whose functions are not clearly known.     

The site of origin of calcitonin gene-related peptide-like immunoreactive afferents to the inferior olivary complex of the mouse.

The intent of the present study is to define the brainstem nuclei which give rise to CGRP-immunolabeled afferents to the inferior olivary complex of the mouse. A technique which combines retrograde transport of fluorescent microspheres with immunohistochemistry was used to address this question. In the present study, intensely labeled CGRP neurons were localized within several cranial nerve nuclei including the hypoglossal, facial, oculomotor, motor nucleus of the trigeminal nerve and nucleus ambiguus, as well as in the parabrachial nucleus, locus coeruleus and medullary and pontine reticular formation. In addition, lightly labeled CGRP neurons were identified within the deep cerebellar nuclei, the inferior olivary complex, lateral reticular nucleus, medial and lateral vestibular nuclei, nucleus Darkschewitsch, interstitial nucleus of Cajal, the central gray area adjacent to the third ventricle, and the zona incerta. The origin of the projection to the inferior olivary complex primarily arises from the deep cerebellar nuclei, the locus coeruleus, and the central gray matter of the mesodiencephalic area. In addition, a small CGRP input is derived from the superior and lateral vestibular nuclei as well as the zona incerta. In conclusion, we have identified several extrinsic sources of CGRP to the inferior olivary complex and have localized it within afferents that have been shown to have either excitatory (mesodiencephalic nuclei) or inhibitory (cerebellar nuclei) effects on olivary circuits. The presence of CGRP in these functionally diverse brainstem and cerebellar afferents suggests that the peptide may act as a co-transmitter to modulate the activity of olivary neurons.     

The GABAergic cerebello-olivary projection in the rat

Summary Immunocytochemical detection of glutamate decarboxylase (GAD), the predominant biosynthetic enzyme of gamma-aminobutyric acid (GABA), reveals the presence of a dense GABAergic innervation in all parts of the inferior olive. One brain center that provides a substantial projection to the inferior olive is the cerebellar nuclei, which contain many small GABAergic neurons. These neurons were tested as a source of GABAergic olivary afferents by combining retrograde tract tracing with GAD immunocytochemistry. As expected from previous studies, injections of wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) into the inferior olive retrogradely label many small neurons in the interposed and lateral cerebellar nuclei and the dorsal part of the lateral vestibular nucleus, and fewer neurons in the ventro-lateral region of the medial cerebellar nucleus. These projections are predominantly crossed and are topographically arranged. The vast majority, if not all, of these projection neurons are also GAD-positive. The relative contribution of this projection to the GABAergic innervation of the inferior olive was tested by lesion of the cerebellar nuclei, or the superior cerebellar peduncle. Within 10 days the lesion eliminates most GAD-immunoreactive boutons in the principal olive, the rostral lamella of the medial accessory olive, the ventrolateral outgrowth, and the lateral part of the dorsal accessory olive ventral fold. Thus, the effectiveness of this depletion demonstrates that the cerebellar nuclei provide most of the GABAergic innervation to regions of the inferior olive known to receive a cerebellar projection. Moreover, when the lateral vestibular nucleus is damaged, the dorsal fold of the dorsal accessory olive is depleted of GABAergic boutons. The synaptic relations that boutons of the GABAergic cerebello-olivary projection share with olivary neurons were investigated at the electron microscopic level by GAD-immunocytochemistry, anterograde degeneration of the cerebellar axons or anterograde transport of WGA-HRP. All of these methods confirm that GABAergic, cerebello-olivary axon terminals contain pleomorphic vesicles, and synapse on various portions of olivary neurons, and especially on dendritic spines within glomeruli, often in very close proximity to the gap junctions that characteristically couple the dendritic profiles. These results demonstrate four major points: that virtually all of the GABAergic, and presumably inhibitory, neurons of the cerebellar and dorsal lateral vestibular nuclei are projection neurons; that a large portion of the inferior olive receives GABAergic afferents from the cerebellar nuclei; that a portion of the dorsal accessory olive receives GABAergic afferents from the dorsal lateral vestibular nucleus; and that cerebello-olivary fibers often synapse near gap junctions, and therefore could influence electrical coupling of olivary neurons.Abbreviations aMAO subnucleus a of MAO - beta beta nucleus - bMAO subnucleus b of MAO - cMAO subnucleus c of MAO - dc dorsal cap - DC dorsal cochlear nucleus - dfDAO dorsal fold of DAO - dlh dorsal lateral hump of cerebellar nuclei - dIPO dorsal lamella of PO - Gia gigantocellular reticular nucleus - dmcc dorsomedial cell column - GABA gamma-aminobutyric acid - GAD glutamate decarboxylase - HRP horseradish peroxidase - icp inferior cerebellar peduncle - IC inferior colliculus - Inf infracerebellar nucleus - IntA anterior interposed cerebellar nucleus - IntP posterior interposed cerebellar nucleus - Lat lateral cerebellar nucleus - LRt lateral reticular nucleus - LSO lateral superior olive - LVe lateral vestibular nucleus - MAO medial accessory olive - Med medial cerebellar nucleus - Me5 mesencephalic trigeminal nucleus - MVe medial vestibular nucleus - PFl paraflocculus of the cerebellar cortex - PO principle olive - RMg raphe magnus - rMAO rostral lamella of MAO - rs rubrospinal tract - scp superior cerebellar peduncle - SuVe spinal vestibular nucleus - SuVe superior vestibular nucleus - vfDAO ventral fold of DAO - vlo ventrolateral outgrowth - vlPO ventral lamella of PO - Y Y, y vestibular nucleus - WGA wheatgerm agglutinin This paper is dedicated to Professor Fred Walberg on the occasion of his 70th hirthdav     

Supramedullary projections to the dorsal and ventral divisions of the paramedian reticular nucleus in the cat

Summary Injections of combined lectin-conjugated and unconjugated horseradish peroxidase were made in the dorsal (d) and ventral (v) divisions of the paramedian reticular nucleus (PRN), a precerebellar relay nucleus, of the cat. The origins of supramedullary afferent projections to the PRN were identified in the pons, midbrain and cerebral cortex using the transverse plane of section. The data indicate a segregation of input from a number of sites to the dPRN and vPRN. The interstitial nucleus of Cajal projects bilaterally to the dPRN and predominantly to the ipsilateral side. The vPRN receives only a unilateral projection from the ipsilateral nucleus of Cajal. Major afferent projections to the vPRN arise from the ipsilateral nucleus of Darkschewitsch and the intermediate layer of the contralateral superior colliculus. Neither of these sites projected to the dPRN. The raphe nuclei and medial reticular formation of the pons and midbrain contribute a moderate input to both divisions of the PRN. A moderate bilateral cerebral cortical projection arises from the first somatomotor area (SMI). The ventral coronal and anterior sigmoid gyri project mainly to the dPRN and vPRN respectively. Smaller afferent projections arise from the posterior sigmoid gyri and area 6 of Hassler and Mühs-Clement (1964) in the medial wall of the anterior sigmoid gyrus. Inputs from the accessory oculomotor nuclei, tectal regions and the first somatomotor cortex suggest a role in postural control for the PRN which may underlie its involvement in mediating orthostatic reflexes.Abbreviations 3N oculomotor nerve - 5ME mesencephalic nucleus (trigeminal) - 5MN motor nucleus (trigeminal) - 5PN sensory nucleus, parvocellular division (trigeminal) - 5SM sensory nucleus, magnocellular division (trigeminal) - 12M hypoglossal nucleus - 12N hypoglossal nerve - AQ aqueduct - BC brachium conjunctivum - BP brachium pontis - CAE nucleus caeruleus - Cl inferior central nucleus (raphe) - CM centromedian nucleus - CNF cuneiform nucleus - CS superior central nucleus (raphe) - D nucleus of Darkschewitsch - DRM dorsal nucleus of the raphe (median division) - EW Edinger-Westphal nucleus - FTC central tegmental field - FTG gigantocellular tegmental field - FTP paralemniscal tegmental field - ICA interstitial nucleus of Cajal - ICC inferior colliculus (central nucleus) - INC nucleus incertus - INT nucleus intercalatus - ION inferior olivary nucleus - LLV ventral nucleus of lateral lemniscus - LP lateral posterior complex of thalamus - MGN medial geniculate nucleus - MLF medial longitudinal fasciculus - TN nucleus of optic tract - P pyramidal tract - PCN nucleus of posterior commissure - PF parafascicular nucleus - PH nucleus praepositus hypogloss - PRN paramedian reticular nucleus (a — accessory division; d — dorsal division; v — ventral division) - PUL pulvinar - SCD superior colliculus (deep layer) - SNC substantia nigra (compact division) - SON superior olivary nucleus - RM red nucleus (magnocellular) - RR retrorubral nucleus - TB trapezoid body - TDP dorsal tegmental nucleus (pericentral division) - TRC tegmental reticular nucleus (central division) - TV ventral tegmental nucleus - V3 third ventricle - V4 fourth ventricle - VB ventrobasal complex of thalamus - VIN inferior vestibular nucleus - VSN superior vestibular nucleus - ZI zona incerta Supported by the Medical Research Council of Canada     

Retrograde labeling of neurons in the brain stem following injections of [3H]choline into the forebrain of the rat

Summary In an attempt to identify cholinergic neurons of the brain stem which project to the forebrain, retrograde labeling of neurons in the brain stem was examined by autoradiography following injections of 20 Ci [³H]choline into the thalamus, hypothalamus, basal forebrain and frontal cortex. After injections into the thalamus, retrogradely labeled neurons were evident within the lateral caudal mesencephalic and dorsolateral oral pontine tegmentum (particularly in the laterodorsal and pedunculopontine tegmental nuclei) and in smaller number within the latero-medial caudal pontine (Reticularis pontis caudalis, Rpc) and medullary (Reticularis gigantocellularis, Rgc) reticular formation. Following [³H]choline injections into the lateral hypothalamus and into the basal forebrain, retrogradely labeled neurons were localized in the dorsolateral caudal midbrain and oral pontine tegmentum and in smaller number in the medial medullary reticular formation (Rgc), as well as in the midbrain, pontine and medullary raphe nuclei. After injections into the anterior medial frontal cortex, a small number of retrogradely labeled cells were found in the brain stem within the laterodorsal tegmental nucleus and the dorsal raphe nucleus. In a parallel immunohistochemical study, choline acetyltransferase (ChAT)-positive neurons were found to be located in most of the regions of the reticular formation where cells were retrogradely labeled from the forebrain following [³H]choline injections. These results suggest that multiple cholinergic neurons within the lateral caudal midbrain and dorsolateral oral pontine tegmentum and a few within the caudal pontine and medullary reticular formation project to the thalamus, hypothalamus and basal forebrain and that a limited number of pontine cholinergic neurons project to the frontal cortex.Abbreviations of Neuroanatomical Terms 3 oculomotor nuc - 4 trochlear nuc - 4V fourth ventricle - 6 abducens nuc - 7 facial nuc - 7n facial nerve - 8n vestibulocochlear nerve - 10 dorsal motor nuc vagus - 12 hypoglossal nuc - 12n hypoglossal nerve - Amb ambiguus nuc - Aq cerebral aqueduct - bic brachium inf colliculus - CB cerebellum - CG central gray - CLi caudal linear nuc raphe - Cnf cuneiform nuc - cp cerebral peduncle - Cu cuneate nuc - D nuc Darkschewitsch - DCo dorsal cochlear nuc - DLL dorsal nuc lateral lemniscus - DPB dorsal parabrachial nuc - DR dorsal raphe nuc - dsc dorsal spinocerebellar tract - DTg dorsal tegmental nuc - dtgx dorsal tegmental decussation - ECu external cuneate nuc - Fl flocculus - IC inferior colliculus - icp inferior cerebellar peduncle - IF interfascicular nuc - InC interstitial nuc Cajal - IO inferior olive - IP interpeduncular nuc - KF Kolliker-Fuse nuc - LC locus coeruleus - Ldt laterodorsal tegmental nuc - Ifp longitudinal fasciculus pons - ll lateral lemniscus - LRt lateral reticular nuc - LRtS5 lateral reticular nucsubtrigeminal - LSO lateral superior olive - LTz lateral nuctrapezoid body - LVe lateral vestibular nuc - mcp middle cerebellar peduncle - Me5 mesencephalic trigeminal nuc - MGD medial geniculate nuc, dorsal - ml medial lemniscus - mlf medial longitudinal fasciculus - MnR median raphe nuc - Mo5 motor trigeminal nuc - MSO medial superior olive - MTz medial nuc trapezoid bbody - MVe medial vestibular nuc - PBg parabigeminal nuc - Pgl nuc paragigantocellularis lateralis - Pn pontine nuc - PPTg pedunculopontine tegmental nuc - Pr5 principal sensory trigeminal - PrH prepositive hypoglossal nuc - py pyramidal tract - Rgc reticularis gigantocellularis - Rgca reticularis gigantocellularis pars alpha - Rmes reticularis mesencephali - RMg raphe magnus nuc - RN red nuc - Ro nuc Roller - ROb raphe obscurus nuc - Rp reticularis parvicellularis - RPa raphe pallidus nuc - Rpc reticularis ponds caudalis - RPn raphe pontis nuc - Rpo reticularis pontis oralis - RR retrorubral nuc - rs rubrospinal tract - RtTg reticulotegmental nuc pons - s5 sensory root trigeminal nerve - SC superior colliculus - SCD superior colliculus,deep layer - SCI superior colliculus, intermediate layer - scp superior cerebellar peduncle - SCS superior colliculus, superficial layer - SGe suprageniculate nuc pons - SNC substantia nigra compact - SNL substantia nigra,lateral - SNR substantia nigra, reticular - SolL solitary tract nuc,lateral - SolM solitary tract nuc, medial - sp5 spinal tract trigeminal nerve - sp5I spinal trigeminal nuc, interpositus - Sp5O spinal trigeminal nuc, oral - spth spinothalamic tract - SpVe spinal vestibular nuc - SuVe superior vestibular nuc - tp tectopontine - ts tectospinal tract - tz trapezoid body - VCo ventral cochlear nuc - VLL ventral nuc lateral lemniscus - VPB ventral parabrachial nuc - vsc ventral spinocerebellar tract - VTA ventral tegmental area - VTg ventral tegmental nuc - vtgx ventral tegmental decussation - xscp decussation superior cerebellar peduncle This investigation was supported by grants from the Medical Research Council (MRC) of Canada (MT-6464: BEJ and MT 7376: AB). B.E. Jones holds a Chercheur Boursier Senior Award from the Fonds de la Recherche en Santé du Quebec (FRSQ), and A. Beaudet a Scientist Award from MRC     

Myoepitheliomas and myoepithelial adenomas of salivary gland origin. Immunohistochemical evaluation of filament proteins, S-100 alpha and beta, glial fibrillary acidic proteins, neuron-specific enolase, and lactoferrin

Immunohistochemical identification of keratin proteins (TK, KL1 and PKK1), vimentin, myosin, S-100 protein (using polyclonal antiserum) and S-100 alpha and beta subunits, glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), lactoferrin, and lysozyme was made in myoepitheliomas, myoepithelial adenomas, and clear cell adenomas of salivary gland origin. Myoepithelioma cells were divided into two types: plasmacytoid cells, which showed great heterogeneity in terms of keratins and S-100 alpha and beta proteins and a lack of GFAP, NSE, lactoferrin, and lysozyme in most the cells, and fibrous and dendritic tumor cells, which displayed variable staining for keratin and S-100 alpha and beta proteins. Myoepithelial adenomas were composed of small-, intermediate-, and large-sized spindle cells that showed irregular positive reactions for keratins and S-100 alpha and beta. Immunohistochemical deposition of S-100 protein was restricted strongly to the dendritic cells present in hyalinous and myxomatous areas. Clear cell adenomas revealed uniformly slight staining of keratins and S-100 proteins, and negative staining or rarely positivity for GFAP, NSE, lactoferrin, and lysozyme. When the immunohistochemical deposition of these proteins was compared between normal glands and myoepithelial tumors, heterogeneity of expression of keratins, S-100 proteins, GFAP, and NSE was notable in the tumors. Progenitor cells of several kinds of myoepithelioma were suggested to be intercalated reserve cells, which are thought to be the same cell that gives rise to pleomorphic adenoma of salivary glands.     

Neurospecific proteins: potentials and prospects for their use in morphological research on tumors

Data on the application of neurospecific proteins S-100, GFAP, D2 glycoprotein and neuron-specific enolase (NSE) in the differential tumor diagnosis are reviewed. S-100 protein and GFAP are found in well differentiated astroglial tumors. S-100 protein can be used as melanoma and Schwannoma specific marker. In malignant CNS tumors there is a decrease of S-100 protein content up to its complete disappearance, while the content of GFAP is variable. D2 glycoprotein is detected in gliomas and medulloblastomas, being absent in other brain tumors. NSE is invariably present in apudomas and was also found in the majority of investigated astrocytomas, ependymomas, glioblastomas and in some medulloblastomas.     

AN IMMUNOHISTOCHEMICAL STUDY ON THE DISTRIBUTION OF GLIAL FIBRILLARY ACIDIC PROTEIN, S-100 PROTEIN, NEURON-SPECIFIC ENOLASE, AND NEUROFILAMENT IN MEDULLOBLASTOMAS

In order to clarify the differentiation of medulloblastomas, the authors studied on the morphological features and immunohistochemical expression of glial flbrillary acidic protein (GFAP), S-100 protein, neuron-specific enolase (NSE), and neuroftlament (NF) in 31 medulloblastomas. GFAP was detected only in a small number of tumor cells of 5 medulloblastomas; S-100 protein in both small tumor cells and some so-called spongloblastic cells in 16 medulloblastomas; NSE in the more abundant tumor cells and the matrix in 28 medulloblastomas; NF in a few tumor cells of 12 medulloblastomas; GFAP and NF in 2 medulloblastomas, but each of them in different tumor cells. These results suggest that medulloblastomas have a capacity of differentiation along neuronal and/or glial lines. The conventional morphological markers of differentiation in medulloblastomas such as spongioblastic cells and Homer Wright rosettes were not necessarily compatible with expression of immunohistochemical markers such as GFAP or NF. NSE and S-100 protein seem less valuable markers of differentiation because they were detected in both neuronal and glial elements. But NSE, which was observed in most medulloblastomas, might have a value as a marker for medulloblastomas.     

An immunocytochemical mapping of methionine-enkephalin-Arg6-Gly7-Leu8 in the cat brainstem

The distribution of methionine-enkephalin-Arg6-Gly7-Leu8-immunoreactive cell bodies and fibres was studied in the brainstem of the cat using an indirect immunoperoxidase technique. In the mesencephalon, immunoreactive cell bodies were observed in the periaqueductal grey, the dorsal raphe nucleus, the central and pericentral nuclei of the inferior colliculus and the pericentral division of the dorsal tegmental nucleus. In the pons, immunoreactive cell bodies were observed in the dorsolateral division of the pontine nucleus; below the central division of the dorsal tegmental nucleus; above the dorsolateral division of the pontine nucleus, and close to the superior cerebellar peduncle. In the medulla oblongata, immunoreactive cell bodies were observed in the laminar spinal trigeminal nucleus and in the lateral tegmental field; the dorsal motor nucleus of the vagus; the prepositus hypoglossal nucleus; the medial nucleus of the solitary tract; the rostral division of the cuneate nucleus, and close to the parvocellular division of the alaminar spinal trigeminal nucleus. The highest (moderate) density of immunoreactive fibres was observed in the periaqueductal grey; the parvocellular and magnocellular divisions of the alaminar spinal trigeminal nucleus; the laminar spinal trigeminal nucleus; the rostral division of the cuneate nucleus; the dorsal motor nucleus of the vagus; the lateral nucleus of the solitary tract, and in the midline between the central divisions of the reticulotegmental pontine nucleus. The widespread distribution of methionine-enkephalin-Arg6-Gly7-Leu8 in the cat brainstem indicates that the peptide might be involved in several physiological functions.     

An immunohistochemical study on the distribution of glial fibrillary acidic protein, S-100 protein, neuron-specific enolase, and neurofilament in medulloblastomas

In order to clarify the differentiation of medulloblastomas, the authors studied on the morphological features and immunohistochemical expression of glial fibrillary acidic protein (GFAP), S-100 protein, neuron-specific enolase (NSE), and neurofilament (NF) in 31 medulloblastomas. GFAP was detected only in a small number of tumor cells of 5 medulloblastomas; S-100 protein in both small tumor cells and some so-called spongioblastic cells in 16 medulloblastomas; NSE in the more abundant tumor cells and the matrix in 28 medulloblastomas; NF in a few tumor cells of 12 medulloblastomas; GFAP and NF in 2 medulloblastomas, but each of them in different tumor cells. These results suggest that medulloblastomas have a capacity of differentiation along neuronal and/or glial lines. The conventional morphological markers of differentiation in medulloblastomas such as spongioblastic cells and Homer Wright rosettes were not necessarily compatible with expression of immunohistochemical markers such as GFAP or NF. NSE and S-100 protein seem less valuable markers of differentiation because they were detected in both neuronal and glial elements. But NSE, which was observed in most medulloblastomas, might have a value as a marker for medulloblastomas.     

含Calbindin-D28K mRNA的神经元在大鼠脑干中的分布—原位杂交组织化学法观察

用原位杂交组织化学技术,对含Calbindin-D28K mRNA的神经元在大鼠脑干中的分布进行全了面观察。发现不同脑区或核团中所含阳性神经元的数量及其标记强度各不相同。其中含强阳性杂交信号的区域有:小脑皮质、外侧丘系核、斜方体核、下橄榄核及臂旁核;含中等强度杂交信号的区域包括:脚间核、黑质致密部、耳蜗核和最后区。而在其它大部分脑区中杂交信号呈弱阳性,如:上丘、顶盖前区、红核、三叉神经感觉核簇、后索核、下丘、前庭核群、孤束核、中央灰质和网状结构中的部分核团。含Calbindin-D28KmRNA的神经元在脑干中的这种区域特异性分布特点提示在神经系统的某些生理功能中,Calbindin-D28K可能起重要的作用。     

Olivo-vestibular and cerebello-vestibular connections in albino rabbits

This study analyzes the organization of olivo-vestibular and cerebello-vestibular projections in rabbits. Iontophoretic injections of horseradish peroxidase, placed under physiological guidance into the superior, medial and lateral vestibular nuclei, produced retrogradely labeled neurons in the dorsal cap, ventrolateral outgrowth and lateral flexure of the principal olivary nucleus, the caudal half of the medial accessory olive and the caudal three-fourths of the dorsal accessory olive. This inferior olivary labeling was strictly contralateral. The same injections labeled groups of Purkinje cells in the ipsilateral cerebellar cortex, oriented perpendicular to the long axes of the folia of lobules I-V, VId-e and VIII-X of the vermis and the flocculus. The patterns of olivo-vestibular and cerebello-vestibular connections were consistent with the general hypothesis that inferior olivary axon collaterals project to both Purkinje cells and subcortical neurons inhibited by those Purkinje cells. In addition, the analysis of flocculo-nodular and dorsal cap-ventrolateral outgrowth projections to the medial and superior vestibular nuclei suggests that these connections are discrete at the level of a pool of olivary neurons which projects to functional pools of neurons in both cerebellar cortex, and in the vestibular nuclei. Thus, it is likely that inferior olivary projections define functional networks spanning cerebellar cortex and the vestibular nuclei.     

Immunohistochemical detection of NSE and S-100 protein in the thalamic VB nucleus after ablation of somatosensory cortex in the rat

The ventrobasal (VB) nucleus has been studied after ablation of somatosensory cortex in 39 adult rats by the application of both NSE- and S-100 protein-immunoreactivity. Both NSE- and S-100 protein-immunoreactivity are confirmed in neurons and reactive astrocytes in the affected VB area and its surroundings, respectively. The NSE-immunoreactivity first starts in the affected VB at seven days postlesion and appears more active in its surrounding area at fourteen days postlesion. At the twenty-eight days, NSE-positive neurons are reduced in number and their stainability becomes weak. The time course of NSE-immunoreactivity is based on the progression of neuronal damage. And it is conceivable that the accumulation of NSE in neurons correlates with the regeneration. The S-100 protein-immunoreactivity is also first detected in the affected area at seven days postlesion and spread in its surrounding area at fourteen days postlesion. At twenty-eight days, S-100 protein-positive astrocytes are reduced in cell volume and their processes become thin. The time course of S-100 protein-immunoreactivity correlates with the degree of astrocytic hypertrophy. And the potent accumulation of S-100 protein appears after the onset of gliosis. The onset of neuronal damage and the repair process can be followed with immunohistochemical technique for both NSE and S-100 protein morphologically. Namely, NSE and S-100 protein can be of potential use as markers for destructive processes in the CNS.     

Brainstem origin of corticotropin-releasing factor afferents to the nucleus interpositus anterior of the cat

Corticotropin-releasing factor (CRF) has been described within varicosities that have a uniform distribution throughout the cerebellar nuclei of the cat. To date, however, no data are available as to the source of these nuclear afferents. Thus, a double-label technique was used to identify brainstem neurons which give rise to the CRF-containing afferents in the nucleus interpositus anterior (NIA) of the cat's cerebellum. Injections of fluorescent-tagged microspheres, which are retrogradely transported by cells with axons in the injection site, were made into lateral and medial aspects of the nucleus. The same sections were also processed for CRF immunohistochemistry. The primary source of CRF afferents to the NIA are the medial and dorsal accessory olivary nuclei. In addition to the inferior olive, several other brainstem nuclei also provide CRF afferents to the cerebellar nuclei. The medial aspect of the NIA receives afferents from the lateral reticular nucleus, external cuneate nucleus, perihypoglossal nucleus, medial vestibular nucleus and inferior central raphe nucleus. Additional afferents to more lateral aspects of the NIA are derived from the lateral reticular nucleus, external cuneate nucleus, and the magnocellular, lateral and gigantocellular tegmental areas. The brainstem nuclei that give rise to the CRF projection to the NIA receive input primarily from the spinal cord and likely relay information related to the status of an ongoing movement. A previous physiological study by Bishop has shown that CRF enhances the excitatory activity of nuclear neurons. CRF released from these afferents likely would enhance nuclear cell activity and thus provide a stronger or more prolonged effect on their respective target neurons in the brainstem.