Search PubMed⌕ Search

Biomedical subjects

W J Streit

Publications and source records attributed to W J Streit.

84 records · Page 5Linked to original sources
PubMed1988

The microglial cytoskeleton: vimentin is localized within activated cells in situ.

Unlike astrocytes and oligodendrocytes, microglia are extremely plastic making them the chameleon among the glial cells in the CNS. This great mutability of the microglial cell shape suggests the presence of an elaborate cytoskeleton which is demonstrated here by applying a new ultrastructural method. Electron microscopic immunocytochemistry shows the presence of vimentin at intermediate filament sites in reactive microglia stimulated by rat facial nerve axotomy. It is suggested that vimentin-expression may serve as a marker for activated states of microglia, including brain macrophages.

Animals↗
PubMed1987

Lectin binding by resting and reactive microglia.

Conjugates of the B4 isolectin from Griffonia simplicifolia seeds and horseradish peroxidase were used as a histochemical reagent for the specific visualization of microglial cells in the rat CNS. Resident microglia bearing galactose-containing glycoconjugates were stained throughout the brainstem and cerebellum. In the first week following axotomy of the facial nerve, a profound and rapid accumulation of reactive microglia, as evidenced by increasing lectin reactivity, was seen to take place in the facial nucleus. Light microscopy of paraffin sections demonstrated binding of lectin-horseradish peroxidase conjugates to microglial cytoplasmic processes. When ultrastructural cytochemistry was performed, reaction product was found localized on microglial plasma membranes, as well as on intracytoplasmic membranes. The glial reaction to axotomy was studied further with double labelling of microglia and astrocytes by lectin histochemistry and immunostaining for glial fibrillary acidic protein, respectively. Our results demonstrated the presence of membrane-associated glycoconjugates containing terminal alpha-D-galactose residues on microglia, but not on other glial cell types. The possible nature and function of these glycoconjugates are discussed.

Animals↗
PubMed1986

Evidence for glycoconjugate in nociceptive primary sensory neurons and its origin from the Golgi complex.

Glycoconjugates with terminal galactose residues were localized in rat spinal cord and spinal ganglia using lectin-HRP conjugates of Griffonia simplicifolia and Glycine max agglutinins. Alternate staining of serial sections with HRP-labelled lectins and an antibody for substance P (SP) showed staining in identical primary sensory neurons with both methods. Similarly, lectin-reactive as well as SP-positive fibers were found in Rexed laminae I and II, Lissauer's tract, the spinal nucleus and tract of the trigeminal nerve, the nucleus commissuralis and a small bundle of fibers just ventral to the central canal. Administration of capsaicin to neonatal rats produced a significant decrease in lectin-reactive fibers of the substantia gelatinosa, and in the number of lectin-reactive sensory neurons. The coexistence of SP with galactose-containing glycoconjugates in spinal ganglion neurons, as well as sensitivity of these cells to capsaicin, provided a basis for classifying the reactive neurons as nociceptive in type. Ligation of dorsal roots resulted in disappearance of lectin reactivity in the spinal cord and caused accumulation of lectin-positive material proximal to the ligature, indicating somatofugal transport of galactose-containing glycoconjugates. Colchicine injection caused an increase in SP reactivity in dorsal ganglion neurons but no change in lectin staining of galactoconjugate. At the ultrastructural level affinity for the lectin conjugates was confined to the Golgi cisternae and the plasmalemma of B-type sensory neurons in the dorsal ganglion. The axolemma of unmyelinated processes stained selectively in dorsal roots and the substantia gelatinosa of the spinal cord. These findings provide evidence for the presence in certain sensory cells of a characteristic galactosylconjugate which may prove to be of significance in nerve function.

Animals↗
PubMed1985

Histochemical localization of galactose-containing glycoconjugate at peripheral nodes of Ranvier in the rat.

Lectin-horseradish peroxidase conjugates were used to study glycoconjugates in paraffin sections of dorsal roots of the rat spinal cord. Griffonia simplicifolia-B4 isolectin (GSA I-B4) and peanut agglutinin (PNA) stained strongly the nodes of Ranvier, localizing, respectively, terminal alpha- and beta-D-galactose. Sialidase digestion did not increase staining with PNA at the node of Ranvier, suggesting the presence of a neutral glycoconjugate. Staining of the nodal but not the internodal axolemma was observed with PNA. The outer surface of the myelin sheath in axons of the dorsal root stained strongly with GSA I-B4 but only weakly with PNA, demonstrating an abundance of terminal alpha-galactose. PNA staining was enhanced in this site by sialidase digestion, showing terminal sialic acid-beta-galactose dimers. The presence of sialic acid here was further evidenced by labeling of these membranes with the lectin derived from the slug, Limax flavus (LFA). Affinity for a high iron diamine-Alcian blue (pH 2.5) sequence demonstrated, in addition, the presence of sulfate esters in glycoconjugates on the outer myelin membrane. GSA I-B4 imparted strong reactivity to nonmyelinated fibers in the dorsal root and the spinal nerve. The present findings appear to reflect several localizations of biochemically described nervous system glycoproteins containing O-glycosidically linked side chains terminated by alpha- and beta-D-galactose.

Animals↗
PubMed1985

Histochemical localization of galactose-containing glycoconjugates in sensory neurons and their processes in the central and peripheral nervous system of the rat.

We studied the distribution of sugar residues in the oligosaccharide chains of complex carbohydrates in tissue sections of rat spinal cord, brainstem, and sensory ganglia using twelve lectin-horseradish peroxidase conjugates. Glycoconjugates containing terminal galactose residues were localized apparently in the Golgi apparatus in a population of predominantly small B-type neurons in spinal and trigeminal ganglia. Large A-type neurons rarely showed reactivity with galactose-binding lectins. A cells stained for glycoconjugates with N-glycosidically linked oligosaccharides and glycogen. The central and peripheral processes of the small neurons, mostly unmyelinated C fibers in sensory roots and spinal nerves, contained an abundance of glycoconjugates with terminal alpha-galactose residues. The central projections and terminals of small to medium-sized primary sensory neurons in the spinal and trigeminal ganglia were visualized in Lissauer's tract and the substantia gelatinosa in the spinal cord, and in the spinal trigeminal tract and the nucleus trigeminus in the lower medulla with lectins specific for terminal alpha-galactose residues. In addition, fibers of the solitary system and the area postrema were reactive with these lectins. The peripheral and central nervous system elements with affinity for galactopyranosyl-specific lectins correspond in distribution with neuroanatomical regions thought to be involved in the transmission and relay of somatic and visceral afferent inputs such as pain and temperature. Such specific localization of a glycosubstance to a distinct subpopulation of neurons and their peripheral and central processes suggests that the particular glycoconjugate may be of physiological significance.

Animals↗
PubMedDate not supplied

Transforming growth factor-beta 1: a lesion-associated cytokine of the nervous system.

Lesions to the nervous system are nearly universally accompanied by a glial response involving both microglia and astrocytes. The growth and immunoregulatory cytokine transforming growth factor-beta 1 (TGF-beta 1) has potent effects on glial cells in vitro and may play a role in regulating glial activation in vivo. Though present only at very low levels in the normal brain, TGF-beta 1 mRNA is strongly upregulated in a number of different experimental models suitable to study glial responses. Following axotomy of the facial nerve of the rat, about a three-fold increase of TGF-beta 1 mRNA in the regenerating nucleus was observed with a time-course closely matching that of glial activation. Putative activated microglial cells are the major cellular source as revealed by in-situ hybridization. TGF-beta 1 was also found to be upregulated around brain tumors, in the spinal cord in response to peripheral nerve inflammation and in the postischemic hippocampus. In all systems investigated, TGF-beta 1 mRNA could be localized predominantly to cells with the typical nuclear morphology of microglia. In the peripheral nervous system, nerve transection leads to a massive increase in TGF-beta mRNA expression both proximal and distal to the cut site. However, whereas TGF-beta 1 mRNA is restricted to the nerve stump in the proximal segment, expression is diffuse and widespread throughout the denervated distal segment where it was localized mainly to cells with macrophage morphology.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Microglial-neuronal interactions.

The question of whether activated microglial cells are potentially harmful or beneficial to injured central nervous system neurons is being addressed by examining in vivo and in vitro findings. While observations made in vivo suggest that microglial activation is triggered by injured neurons and may aid in regeneration, in vitro data show production of neurotoxic agents by cultured microglia. An effort is made to find a common denominator in these apparently conflicting findings by discussing microglial activation during motor neuron regeneration and during delayed neuronal death occurring as a consequence of global forebrain ischemia.

Animals↗
PubMedDate not supplied

Chemokines and Alzheimer's disease.

In recent years, increasing attention has been focused on chemokines as inflammatory mediators in the CNS. The limited number of studies that have investigated chemokine and chemokine receptor expression in Alzheimer's disease (AD) brain and in cell culture models seem to support a role for inflammation in AD pathogenesis. Here we provide a review of these studies, but in addition, point out the possible role of chemokines as communication molecules between neurons and microglia. Understanding neuron-microglia interactions is essential for understanding AD pathogenesis, and disturbances in chemokine-mediated intercellular communication may contribute toward a generalized impairment of microglial cell function.

Alzheimer Disease↗
PubMedDate not supplied

Microglial response to brain injury: a brief synopsis.

In addition to astrocytes and oligodendrocytes, microglia represent the third major population of glial cells within the central nervous system (CNS). Microglia are distributed ubiquitously throughout the brain and spinal cord, and one of their main functions is to monitor and sustain neuronal health. Microglial cells are quite sensitive to even minor disturbances in CNS homeostasis, and they become readily activated during most neuropathologic conditions, including peripheral nerve injury, trauma and stroke, inflammatory disease, and neurotoxicant-induced neuronal injury. During activation, microglia display conspicuous functional plasticity, which involves changes in cell morphology, cell number, cell surface receptor expression, and production of growth factors and cytokines. The many changes occurring in activated cells reflect the altered functional states of microglia that are induced by signals arising from injured neurons. Thus, neuronal-microglial signaling plays a fundamental role in understanding how the CNS responds to injury. Reactive microgliosis should be viewed as a cellular effort to initiate ameliorative and reparative measures in the injured brain.

Animals↗
PubMedDate not supplied

Colonization of neural allografts by host microglial cells: relationship to graft neovascularization.

In order to illuminate functional roles of microglial cells within neural allografts, we have transplanted both whole and microglial and endothelial cell-depleted E14 neural cell suspensions into the intact striatum of Sprague-Dawley rats. Following posttransplantation times of up to 30 days, the intrastrial allografts were analyzed histochemically using the Griffonia simplicifolia B4 isolectin, a marker for both microglia and blood vessels. Our results indicate that both whole and depleted suspension grafts develop identically in terms of neovascularization and microglial colonization. In both types of transplants microglial cells appeared before any blood vessels were apparent. The main phase of graft vascularization occurred between days 7 and 10 posttransplantation and neovascularization was complete by day 21, as revealed by quantitative image analysis. Microglial cells, which were present as ameboid cells during early posttransplantation times, underwent continuing cell differentiation with time that paralleled graft vascular development. By 30 days posttransplantation microglia within the grafts had assumed the fully ramified phenotype characteristic of resting adult microglia. During graft development and vascularization, microglia were often seen in close proximity to ingrowing blood vessels and vascular sprouts. In conclusion, our study has shown that microglial colonization of grafts and graft vascularization occurs independent of donor-derived microglial and endothelial cells, and suggests that the great majority of microglia and vessels within the graft are host derived. We hypothesize that the host microglia invading the allografts play an active role in promoting graft neovascularization.

Animals↗
PubMedDate not supplied

The role of microglia in brain injury.

Microglial cells are exquisitely sensitive to neuronal damage. Neurons which have been damaged by an injury or a neurotoxicant will stimulate microglia in their immediate vicinity to become activated and undergo a series of morphologic and phenotypic changes. The changes occurring on microglial cells can be documented quite readily using histochemical methods, and it is suggested that the histological demonstration of microglial activation can serve as a very sensitive biological marker for neuron damage. While the functional significance of microglial activation is unknown, there is evidence to suggest that microglia may exert both neurotrophic and neurotoxic effects. However, proving that these functions are indeed carried out by microglia in vivo remains a formidable challenge for future investigations.

Animals↗