SEARCH · Search PubMed

Results for “Microglia”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 919 records · Page 51Linked to original sources

PubMed1998

Expression of Kv1.5 K+ channels in activated microglia in vivo.

We examined the expression of outward rectifier K+ channels in activated microglia in vivo. For this purpose, lipopolysaccharide (LPS, 2 microg) was injected into the cortex near the hippocampal region of rat brains, and K+ channel expression was examined using antibodies against shaker-type K+ channels, Kv1.5 and Kv1.3. OX-42-positive microglia were found around the injection sites from 8 h after the LPS injection and remained there for 3 days. The OX-42-positive microglia expressed Kv1.5 immunoreactivity, and the time course of Kv1.5 expression was closely correlated with that of OX-42. In saline-injected brains, OX-42-positive cells also expressed Kv1.5 immunoreactivity even though far fewer OX-42-positive cells were found. Increase of Kv1.5 expression after LPS injection was also demonstrated by immunoblot analysis. On the other hand, Kv1.3 immunoreactivity was barely detected in OX-42-positive cells over the entire experimental period. The expression of Kv1.5 preceded that of inducible nitric oxide synthase (iNOS), which is a prominent indication of microglial activation. iNOS was not detectable until 12 h, and thereafter it was maintained for 3 days together with Kv1.5 and OX-42. These results suggest that in vivo as well as in vitro activated microglia expressed outward K+ channels and that some of the channels at least are Kv1.5.

Animals↗

PubMed1999

Regulation of K+ channel mRNA expression by stimulation of adenosine A2a-receptors in cultured rat microglia.

Previous investigations suggest that the expression of K+ channels in cultured rat microglia is related to the activation status of these cells. Both, lipopolysaccharide (LPS) and agents that raise intracellular cyclic AMP have been shown to inhibit microglial proliferation. LPS also regulates the mRNA expression levels of K+ channels in cultured microglia, which led us to investigate possible regulatory interactions between K+ channels and adenosine A2a-receptors, which are coupled to the cAMP-signal transduction pathway. The selective adenosine A2a-receptor agonist CGS 21680 induced enhanced mRNA expression of both Kv1.3 and ROMK1, as well as an elevation of Kv1.3 protein. The selective adenosine A2a-receptor antagonist aminophenol (ZM 241385) and the nonselective antagonist 8-phenyltheophylline (8-PT) inhibited these effects. Elevations of cyclic AMP by use of dibutyryl cyclic AMP (dbcAMP), phosphodiesterase-inhibitor (RO 20-1724), forskolin, or cholera toxin (CTX), strongly enhanced Kv1.3-mRNA expression, but decreased ROMK1-mRNA levels. Results from experiments with actinomycin D suggest that K+ channel mRNA levels in cultured microglia were regulated by altered mRNA synthesis. Evidently, the CGS 21680-induced effects upon Kv1.3 were mediated via an increase in intracellular cyclic AMP, whereas ROMK1-mRNA expression appeared to be regulated by coupling of adenosine A2a-receptors to an alternative pathway, which involves activation of protein kinase C (PKC). It is concluded that the cyclic AMP second messenger system in microglia is not only involved in regulation of K+ channel activity, but also in regulation of de novo K+ channel synthesis.

Adenosine↗

PubMed1984

Genesis of resting microglia in the gray matter of mouse hippocampus.

The genesis of resting microglia in the gray matter of mouse hippocampus was studied by 3H-thymidine autoradiography in combination with electron microscopy. Newborn mice were injected with 3H-thymidine singly or repeatedly at different postnatal stages, and killed shortly after the injection or after various intervals. Tissue specimens of the hippocampus at CA1 and CA2 were processed for light and electron microscopic autoradiography. The results showed that at least 91% of glial cells in the stratum radiatum of the hippocampus are produced after birth. About three-fourths of astroglia in this area are produced before the sixth postnatal day, and a larger part of resting microglia are formed after the ninth postnatal day. Morphological transition can be traced from either proliferating cells in the stratum radiatum at late postnatal days to resting microglia, or from those in early postnatal days to astroglia. A continuous morphological transition was observed between the proliferating cells at the late postnatal days (microglial production period) and those at the early postnatal days (astroglial production period). The latter retain some fine structural characteristics similar to small glioblasts in the subependymal layer. These findings strongly suggest that resting microglia, as well as astroglia, are derived from glioblasts, and are of neurectodermal origin.

Animals↗

PubMed1991

Characterisation of two new monoclonal antibodies directed against rat microglia.

With the aid of cultured rat microglial cells as immunogen, we raised two monoclonal antibodies, designated murine clone (MUC) 101 and 102, which recognised subsets of resident microglial cells in the normal central nervous system and cells of the mononuclear phagocyte system in peripheral organs. These antibodies were characterised by immunoperoxidase immunocytochemistry, immunoelectron microscopy, and immunoblotting. The immunostained cells were identified as microglial cells by double-immunofluorescence labelling with the B4-isolectin from Griffonia simplicifolia, an established microglial cell marker. Under normal conditions, both antibodies labeled resident microglia but with different distribution patterns. Under pathological conditions, e.g., after facial nerve transection, they labeled activated, perineuronal microglia in the operated facial nucleus. Immunoelectron microscopy demonstrated a membrane localisation of the antigen recognised by MUC 102. In peripheral organs, MUC 101 and 102 reacted with different cell populations of the mononuclear phagocyte system, particularly in thymus, spleen, and peripheral lymph node. Western blot experiments showed that MUC 101 recognised two proteins of 116 and 95 kD in fractions obtained from operated facial nucleus while MUC 102 reacted with two proteins of 62 and 70 kD molecular weight. These immunocytochemical results 1) confirm the antigenic similarity between microglia and cells of the monocyte-macrophage cell lineage, and 2) indicate that considerable antigen heterogeneity might exist among resident microglia. MUC 101 and 102 could thus become useful for studying the function of microglial cells both under normal and pathological conditions.

Animals↗

PubMed1988

Functional plasticity of microglia: a review.

The present review summarizes recently acquired data in vivo, which support a role of CNS microglia as a source of defense cells in the CNS capable of carrying out certain immune functions autonomously. We have kept the following discussion restricted to microglial cells and have not included work on the immunological functions of astrocytes, which has been recently reviewed elsewhere (Fontana et al.: Immunological Reviews 137:3521-3527, 1987). Resting microglia are scattered uniformly throughout the CNS forming a network of potential immunoeffector cells, which can be activated by stimuli ranging from peripheral nerve injury over viral infections to direct mechanical brain trauma. The term "activated microglia" is used here to describe proliferating cells that demonstrate changes in their immunophenotype but have not undergone transformation into brain macrophages. Such a transformation can be stimulated by neuronal death but not by sublethal neuronal injury. Microglia may function as antigen-presenting cells and may thus represent the effector cell responsible for the recruitment of lymphocytes to the brain resulting in an inflammatory reaction. The recent developments in the understanding of microglial cell function may lead to a redefinition of the often cited "immune privilege" of the brain.

Animals↗

PubMed1991

Natural and induced cytotoxicity of oligodendrocytes by microglia is inhibitable by TGF beta.

Blood macrophages and brain macrophages (microglia) have been implicated in demyelination and destruction of the oligodendrocyte in multiple sclerosis (MS), a disease affecting primarily white matter of the central nervous system (CNS). In this study, we demonstrate that at high effector to target cell ratios, normal rat microglia exhibit a natural cytotoxicity against normal rat oligodendrocytes in vitro. The killing is not mediated by the release of soluble factors. The cytotoxic activity is upregulated by pretreatment of microglia with interferon gamma (IFN gamma) or phorbol myristate acetate (PMA). Both the natural and induced cytotoxicities are inhibitable by transforming growth factor beta (TGF beta). The increase in numbers and apposition of primed or activated microglia to oligodendrocytes in MS lesions may give rise to natural or induced killing from which oligodendrocytes may be protected by TGF beta.

Animals↗

PubMed1993

Bone marrow derived elements and resident microglia in brain inflammation.

Infection of the central nervous (CNS) system by the human immunodeficiency virus (HIV) depends on the migration of infected hematogenous cells into the brain. We thus used quantitative light and electron microscopic immunocytochemistry to study the homing and turnover of bone marrow derived cells in the CNS in radiation bone marrow chimeras under normal conditions and in experimental autoimmune encephalomyelitis (EAE) as an experimental model of brain inflammation. Our studies suggest the following conclusions. First, the central nervous system is continuously patrolled by a small number of T-lymphocytes and monocytes. Meningeal and perivascular monocytes are slowly replaced by hematogenous cells under normal conditions, and this turnover is accelerated in the course of inflammation. In contrast, resident microglia represent a very stable cell pool, which in adult animals is only exceptionally replaced by hematogenous cells, even after recovery from severe brain inflammation. Second, although in bone-marrow-chimeric animals resident microglia, astrocytes, and ependymal cells are not able to present antigen to Lewis T-lymphocytes, the inflammatory reaction in EAE is qualitatively and quantitatively similar in these animals compared to fully histocompatible Lewis rats. Finally, resident microglia express the macrophage activation antigen ED1. Thus, microglia cells appear to function as effector cells in EAE lesions.

Animals↗

PubMed1993

Microglia progenitor cells: a subpopulation in cultures of mouse neopallial astroglia.

We have shown that astroglia cultures initiated from newborn mouse neopallium contain microglia progenitor cells. Astroglia secrete growth factor(s) that transform the progenitor cells into microglia. One of the trophic factors is bone marrow macrophage growth factor CSF-1. Mouse embryonic fibroblast cells STO also secrete trophic factor(s) that acts synergistically or additively with CSF-1 on microglia progenitor cells. Using limiting dilution analysis we estimated that in the presence of CSF-1 and STO cells, 1 in every 8 cells in astroglia cultures is a potential microglia progenitor cell.

Animals↗

PubMed1993

Characterization of microglia and macrophages in the central nervous system of rats: definition of the differential expression of molecules using standard and novel monoclonal antibodies in normal CNS and in four models of parenchymal reaction.

This report describes the development of a new panel of monoclonal antibodies produced following immunization of mice with cultured rat microglial cells. Using these new reagents and previously defined antibodies that bind to microglia or macrophages, the responses of parenchymal microglia, perivascular "microglial" cells, and infiltrating macrophage/monocytes were examined in 4 divergent models of central nervous system reaction. These were brain abscess, experimental allergic encephalomyelitis, Wallerian degeneration, and stab wound. No single new antibody was specific only for microglia; all antibodies positively staining microglial cells also labeled various subsets of macrophage/monocytic cells in normal tissues of the immune system. Moreover, the results indicate that microglia are capable of different levels and a variety of types of response, as defined by the molecules they elaborate. These findings suggest that these CNS resident cells belong to the extended monocyte/macrophage/dendritic cell family and that they do not respond in a stereotypic manner to all forms of CNS insult.

Animals↗

PubMed1993

Cytotoxicity of microglia.

The most characteristic property of microglia is their swift activation in response to neuronal stress and their capacity for site-directed phagocytosis. The transformation of microglia into intrinsic brain macrophages appears to be under strict control and takes place if neuronal and/or terminal degeneration occurs in response to nerve lesion. The differentiation of microglia into brain macrophages is accompanied by the release of several secretory products, e.g., proteinases, cytokines, reactive oxygen intermediates, and reactive nitrogen intermediates. Interference with the microglial activation or the productions of cytotoxic metabolites by microglia may thus offer new therapeutic opportunities for the prevention of neuronal cell death in CNS disease.

Amino Acids↗

PubMed1993

Lymphokine induction of rat microglia multinucleated giant cell formation.

Multinucleated giant cell formation (MNGC) occurs in central nervous system AIDS. The mechanism of fusion of microglia in these cases is unknown. We investigated the ability of lymphokines to induce fusion and found that interleukin-3 (IL-3), interleukin-4 (IL-4), gamma interferon (gamma-IFN), and granulocyte-macrophage colony stimulating factor (GM-CSF) induced MNGC formation in cultures of rat microglia in vitro. The diacylglycerol analogue phorbol myristate acetate (PMA) also induced MNGC. Interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF alpha) failed to induce fusion. Preincubation of the IL-3 treated cultures with anti-IL-3, anti-leukocyte function associated antigen-1 (LFA-1) alpha-chain (CD11a), and anti-intercellular adhesion molecule-1 (ICAM-1) inhibited cell fusion. Antibody to polymorphic Class II major histocompatibility complex (MHC) determinants also inhibited MNGCs. Cell surface LFA-1 was predominantly observed on MNGC, suggesting that LFA-1 expression is involved in microglia fusion. We thus propose that MNGC formation of microglia result from the effects of T cell-derived cytokines probably through the induction of cell surface adhesion molecules.

Animals↗

PubMed1992

Growth control of cultured microglia.

Microglia, the resident macrophages of the brain, typically react to injuries or chronic diseases with proliferation and expression of differentiated features, such as production of cytokines associated with inflammatory events. Regulation and control of microglial cytokine expression, therefore, is a major focus of scientific interest. It has been shown that GMCSF and Il-3 are potent mitogens for microglia. Moreover, Il-3 and other cytokines are products of microglia. It is shown here that interleukin-1 (Il-1) as well as tumor necrosis factor (TNF alpha) increased microglial proliferation in mixed astrocyte-microglial cultures but had no mitogenic effects on isolated microglia. Lipopolysaccharide (LPS), the bacterial endotoxin, irreversibly inhibited microglial cell division in both mixed astrocyte-microglial cultures and in isolated microglial cultures. By contrast, the corticosteroids hydrocortisone and aldosterone and the synthetic glucocorticoid dexamethasone reversibly inhibited microglial proliferation. They also antagonized the stimulatory effects of Il-3 and granulocyte macrophage colony-stimulating factor (GMCSF). Estradiol and progesterone had no significant effects on mixed cultures but inhibited microglial proliferation in isolated cultures. Conditioned media from mixed cultures, isolated cultures, from the WEHI-2B cell line, or from fresh (serum-supplemented) media stimulated microglial proliferation to various extents. In summary, cytokine-mediated microglial proliferation can be down-regulated by a variety of steroid hormones. Along with their unimpaired access to brain cells in general, corticosteroids likely maintain an inhibitory tonus on microglial proliferation. It is hypothesized that this inhibition is overcome locally and temporally in brain injury and repair.

Acid Anhydride Hydrolases↗

PubMed1993

Activated microglia inhibit multiplication of Toxoplasma gondii via a nitric oxide mechanism.

The role of microglia in host defense against Toxoplasma gondii is unknown. In the present study, we investigated the multiplication of T. gondii tachyzoites in murine microglial cell cultures. T. gondii multiplied readily in these cells; multiplication was prevented when microglia were activated with interferon-gamma plus lipopolysaccharide, a treatment that also upregulates nitric oxide (NO) synthase activity. Simultaneous treatment of microglial cell cultures with activation signals and the NO synthase inhibitor NG-monomethyl-L-arginine (NGMA) prevented the antitoxoplasmic activity. Transmission electron microscopic analysis demonstrated degenerative tachyzoites in activated microglia but not in control or NGMA groups. These findings support the view that the host defense function of activated microglia against T. gondii involves generation of the free radical NO.

Animals↗

PubMed1992

Immunophenotypic analysis of infiltrating leukocytes and microglia in an experimental rat glioma.

The appearance and cellular distribution of major histocompatibility complex (MHC), as well as lymphocytic and macrophage antigens has been studied in a fully developed experimental rat forebrain glioma. Activated microglial cells and microglia-derived macrophages expressing CR3 complement receptor molecules and MHC class II (Ia) antigen were found throughout the tumor, and with increased density along the tumor's periphery. MHC class I antigen expression was entirely absent from tumor cells, and found only occasionally on microglia. The expression of leukocyte common antigen, and CD4 and CD8 antigens was conspicuous throughout the tumor, and associated with lymphocytes, perivascular cells, and microglia. Cells expressing the ED2 macrophage epitope were almost exclusively of the perivascular type and revealed a distribution dissimilar to that of cells positive for Ia antigen. The ED2 epitope was found sporadically on ramified microglial cells. The results show that despite heavy infiltration with blood mononuclear and CNS microglial cells, the tumor showed no evidence of destruction caused by inflammatory cells. Possible mechanisms of tumor immunosuppressive activity preventing the full immunological activation of microglia and blood mononuclear cells are discussed.

Animals↗

PubMed1993

Perivascular cells act as scavengers in the cerebral perivascular spaces and remain distinct from pericytes, microglia and macrophages.

Perivascular cells in the rat brain are an immunophenotypically defined group of cells which can be identified by their expression of the ED2 antigen. The present study investigates the role of perivascular cells as scavengers in the perivascular spaces of the rat brain and the relationship of these cells to microglia, macrophages, pericytes and smooth muscle cells. Particulate matter (Indian ink) was injected selectively into the perivascular spaces of the left caudoputamen of 59 rats. Animals were killed by cardiac perfusion of formalin or glutaraldehyde 2 h-2 years after ink injection. Cerebral hemispheres were examined histologically and immunocytochemically using the ED2 antibody for perivascular cells, ED1 for microglia and macrophages and OX-6 directed against Ia antigen [major histocompatibility complex (MHC) class II]. ED2+ perivascular cells ingested Indian ink in the perivascular spaces and expressed MHC class II antigen. Reactive microglia and macrophages in the perivascular parenchyma expressed ED1, but no ED2+ cells were seen outside the perivascular spaces. Transmission electron microscopy distinguished perivascular cells, which ingested carbon particles, from pericytes, which did not. The results of this study suggest that perivascular cells remain distinct from pericytes, microglia and macrophages and that they play a major role as scavengers in the perivascular spaces of the rat brain. This role reflects the importance of perivascular spaces as drainage pathways for soluble and insoluble material from the brain.

Animals↗

PubMed1988

Microglia in the giant cell encephalitis of acquired immune deficiency syndrome: proliferation, infection and fusion.

The autopsied brains of three homosexual men with acquired immune deficiency syndrome (AIDS), progressive encephalopathy and widespread multinucleated giant cell encephalitis were investigated by lectin and immunohistochemical methods to ascertain the cellular distribution of a human immunodeficiency virus (HIV) core protein, p25. Abundant viral antigen was present in all brains, limited to perivascular macrophages, microglial and multinucleated cells, some bearing elongated cytoplasmic processes. The multinucleated cells were consistently labelled by the lectin Ricinus communis agglutinin-1, a marker for microglia, which demonstrated process-bearing variants of these cells. The prominent staining of microglia for viral antigen and the morphological suggestion that they fuse with other microglia and/or macrophages to form the multinucleated cells characteristic of HIV encephalitis indicate that microglia are probably direct targets of HIV infection and serve to propagate and amplify this retroviral encephalitis.

Acquired Immunodeficiency Syndrome↗

PubMed1986

A specific histochemical marker (lectin Ricinus communis agglutinin-1) for normal human microglia, and application to routine histopathology.

Microglia were demonstrated in paraffin-embedded human nervous tissues with an avidin-biotin peroxidase method and Ricinus communis agglutinin-1 (RCA-1). Specific staining was observed in cell bodies and processes of microglia. Although endothelial cells and blood cells reacted with RCA-1, they were easily distinguished morphologically from microglia. Astrocytes, oligodendrocytes, and neurons did not react with RCA-1. These results suggest that RCA-1 can be used as a new histochemical marker for microglia in normal human brain.

Adolescent↗

PubMed1978

Initial response of silver-impregnated "resting microglia" to stab wounding in rabbit hippocampus.

Adult rabbits received stab wound in the cerebrum and were sacrificed at intervals of 20, 30, and 39 h thereafter. Each animal was injected intracerebrally with 3H-thymidine 2h before fixation. Altered brain tissues of the stratum radiatum of hippocampus were taken for examination. Response of "resting microglia" to stab wounding was investigated by electron microscopic autoradiography and by autoradiography applied on silver-impregnated materials. Following results were obtained: (1) Resting microglia undergo marked swelling shortly after the brain damage. We designate these cells as "swollen microglia". (2) Swollen microglia form the only cell population that proliferate actively in the initial stage of glial response to the brain injury, and (3) astroglia do not proliferate during the same experimental periods, in the rabbit hippocampus.

Animals↗