Abstract:
:The biologically active lipid metabolite, platelet-activating factor (PAF), is thought to contribute to inflammatory processes and tissue damage in a variety of central nervous system (CNS) injuries. In previous studies, we found that after contusion spinal cord injury, treatment with a PAF antagonist led to significantly increased white matter tissue sparing as well as decreased mRNA levels for pro-inflammatory cytokines. Some studies suggest that PAF can also have toxic effects on neurons in vitro. Few studies, however, have examined the effects of PAF on glial cells of the CNS. In the present study, the potential for PAF to act as a toxin to cultured astrocytes was examined. Also investigated were the effects of PAF on oligodendrocytes at two different stages of development. Treatment with 0.02-2 microM PAF for 72 h resulted in significant levels of cell death in both cell types (P < 0.05), an effect that was blocked by the PAF receptor antagonists, WEB 2170 and BN 52021. To investigate PAF-induced glial cell death further, we looked for activation of the enzyme, caspase-3, which can be indicative of apoptosis. Immunocytochemistry demonstrated that PAF at all concentrations caused activation of caspase-3 at 24, 48, and 72 h after treatment in both cell types. Caspase-3-dependent cell death was further confirmed using knockout mice (-/-) deficient in the caspase-3 gene. Toxicity was lost when astrocytes (-/-) were exposed to 0.02-2 microM PAF (P < 0.01). Oligodendrocytes (-/-) were not susceptible to toxicity at 2 microM PAF (P < 0.001). The results demonstrate that the pro-inflammatory molecule, PAF, induces cell death in cultured CNS glial cells and that this effect is, in part, dependent on caspase-3 activation.
journal_name
Gliajournal_title
Gliaauthors
Hostettler ME,Knapp PE,Carlson SLdoi
10.1002/glia.10065subject
Has Abstractpub_date
2002-05-01 00:00:00pages
228-39issue
3eissn
0894-1491issn
1098-1136journal_volume
38pub_type
杂志文章相关文献
GLIA文献大全abstract::Microglial cells are the resident macrophages that are involved in brain injuries and infections. Recent studies using transcranial two-photon microscopy have shown that ATP and P2Y receptors mediated rapid chemotactic responses of miroglia to local injury. However, the molecular mechanism for microglial chemotaxis to...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.20500
更新日期:2007-06-01 00:00:00
abstract::Oligodendrocytes (OL), cells that myelinate axons in the CNS, differentiate from early to late oligodendrocyte progenitor cells (OPC) to become mature OL. Unlike the case in the rodent brain, myelin formation starts prenatally in the human brain, but the sequence of OL development and the onset of myelination are not ...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.20134
更新日期:2005-03-01 00:00:00
abstract::The myelin basic protein gene (Mbp) encodes for the major myelin structural proteins and it is included in the Golli-Mbp gene complex. Previously, we observed MBP-like proteins in the human central nervous system (CNS) at developmental stages preceding myelination. In an effort to distinguish between Golli (HOG5 and H...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.10028
更新日期:2002-03-01 00:00:00
abstract::Despite the increasing evidence for a prominent role played by the perivascular endfeet of astrocytes in the functional metabolic coupling between astrocytes and neurons, a clear picture of their spatial organization is still lacking. To examine the three-dimensional structure of the astrocyte endfeet and their relati...
journal_title:Glia
pub_type: 杂志文章
doi:
更新日期:1998-05-01 00:00:00
abstract::Individuals with neurofibromatosis 1 (NF1) develop low-grade astrocytomas at an increased frequency. To gain insight into the function of the Nf1 gene product as a growth regulator for astrocytes, we examined mice heterozygous for a targeted Nf1 mutation. In our previous studies, we demonstrated increased numbers of p...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/1098-1136(20010315)33:4<314::aid-glia1030>
更新日期:2001-03-15 00:00:00
abstract::The reaction of astroglia was investigated after unilateral destruction of the dorsal lateral geniculate nucleus in the primary visual cortex of adult albino rats. The destruction of the dorsal lateral geniculate nucleus was performed by stereotaxic injections of ibotenic acid, and the location was verified in Nissl s...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.440030410
更新日期:1990-01-01 00:00:00
abstract::The consequences of sublytic terminal complement complex (TCC) assembly on Schwann cell proliferation and apoptosis were examined by using purified complement proteins (C5*-9) or antibody-sensitized Schwann cells in the presence of a serum that was depleted of the seventh component of complement (C7dHS) and reconstitu...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/(sici)1098-1136(200004)30:2<187::aid-glia8
更新日期:2000-04-01 00:00:00
abstract::Extracellular matrix molecules are involved in the cellular functions of proliferation, migration, morphological differentiation, and synaptic plasticity. One candidate molecule of the extracellular matrix is the chondroitin sulfate proteoglycan neurocan. To determine whether neurocan expression is regulated by neuron...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.20329
更新日期:2006-05-01 00:00:00
abstract::Schwann cells (SCs) and olfactory ensheathing glia (OEG) have shown promise for spinal cord injury repair. We sought their in vivo identification following transplantation into the contused adult rat spinal cord at 1 week post-injury by: (i) DNA in situ hybridization (ISH) with a Y-chromosome specific probe to identif...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.20490
更新日期:2007-07-01 00:00:00
abstract::Toll-like receptors 7 (TLR7) and 9 (TLR9) are important mediators of innate immune responses. Both receptors are located in endosomal compartments, recognize nucleic acids, and signal via Myeloid differentiation factor 88 (MyD88). In the current study, we analyzed TLR7 and TLR9 induced activation of astrocytes and mic...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.20952
更新日期:2010-04-15 00:00:00
abstract::In the peripheral nervous system, Schwann cells make myelin, a specialized sheath that is essential for rapid axonal conduction of action potentials. Immature Schwann cells initially interact with many axons, but, through a process termed radial sorting, eventually interact with one segment of a single axon as promyel...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.21175
更新日期:2011-07-01 00:00:00
abstract::The identification of myelin oligodendrocyte glycoprotein (MOG) as a target for autoantibody-mediated demyelination in experimental autoimmune encephalomyelitis (EAE) resulted in the re-evaluation of the role of B cell responses to myelin autoantigens in the immunopathogenesis of multiple sclerosis. MOG is a central n...
journal_title:Glia
pub_type: 杂志文章,评审
doi:10.1002/glia.1111
更新日期:2001-11-01 00:00:00
abstract::Microglia respond rapidly to injury, increasing their synthesis and release of inflammatory mediators, many of which contribute to the maintenance of persistent pain following CNS or PNS injury. We have recently shown that the lysosomal cysteine protease Cathepsin S (CatS) expressed by spinal microglia is vital for th...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.21042
更新日期:2010-11-01 00:00:00
abstract::The mannose receptor is a pattern-recognition receptor involved in innate and adaptive immunity. The receptor is mainly expressed by macrophages and, within the brain, by astrocytes and microglia. This study reports for the first time the effects of two classical proinflammatory (interferon-gamma, IFNgamma) and anti-i...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.10196
更新日期:2003-04-01 00:00:00
abstract::Niemann-Pick disease type C (NPC) is a deadly neurodegenerative disease often caused by mutation in a gene called NPC1, which results in the accumulation of unesterified cholesterol and glycosphingolipids in the endosomal-lysosomal system. Most studies on the mechanisms of neurodegeneration in NPC have focused on neur...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.20563
更新日期:2007-11-15 00:00:00
abstract::Serum is used widely for culturing neurons and glial cells, and is thought to provide essential, albeit undefined, factors such as hormones, growth factors, and trace elements that promote the growth of cells in vitro. Moreover, serum can have profound effects on cell proliferation, differentiation, and cell morpholog...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/(sici)1098-1136(199803)22:3<237::aid-glia3
更新日期:1998-03-01 00:00:00
abstract::We have shown previously that switching of the alpha v-associated beta1 and beta5 integrin subunits during differentiation of myelin-forming oligodendrocytes may regulate important aspects of cell behaviour such as migration (Milner et al., 1996: J Neurosci 16:7240-7252). In this study we have examined the development...
journal_title:Glia
pub_type: 杂志文章
doi:
更新日期:1997-12-01 00:00:00
abstract::Within the last few years, the expression of voltage-dependent, TTX-sensitive Na+ channels has been demonstrated in several types of neuroglial cells such as astrocytes and Schwann cells. Recently, we reported the occurrence of such Na+ currents in retinal Müller (glial) cells from dog and cat. This paper deals with t...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.440100304
更新日期:1994-03-01 00:00:00
abstract::Cortical spreading depression (CSD) is a slowly propagating wave of depolarization of gray matter. This phenomenon is believed to underlie the migraine aura and similar waves of depolarization may exacerbate injury in a number of neurological disease states. CSD is characterized by massive ion dyshomeostasis, cell swe...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.23604
更新日期:2019-06-01 00:00:00
abstract::Painful neuropathy is one of the most common complications of diabetes, one hallmark of which is tactile allodynia (pain hypersensitivity to innocuous stimulation). The underlying mechanisms of tactile allodynia are, however, poorly understood. Emerging evidence indicates that, following nerve injury, activated microg...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.20623
更新日期:2008-03-01 00:00:00
abstract::Pharmacological and biochemical data suggest that noradrenaline (NA)-containing fibers not only regulate the activity of cortical neurons but also influence the functional state of non-neuronal elements. In the present study, immunocytochemistry with an antiserum against NA, followed by silver-gold intensification of ...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/(SICI)1098-1136(199606)17:2<133::AID-GLIA5
更新日期:1996-06-01 00:00:00
abstract::Retinoic acid (RA), a metabolite of vitamin A, is required for the regulation of growth and development. Aberrant expression of molecules involved in RA signaling has been reported in various cancer types including glioblastoma multiforme (GBM). Cellular retinoic acid-binding protein 2 (CRABP2) has previously been sho...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.22976
更新日期:2016-06-01 00:00:00
abstract::The effect of cholinergic agonists and antagonists on the intracellular free Ca2+ concentration ([Ca2+]i) of leech neuropile glial cells was investigated by use of iontophoretically injected fura-2. In neuropile glial cells, cholinergic agonists induced a marked increase in [Ca2+]i that was inhibited by d-tubocurarine...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.440150106
更新日期:1995-09-01 00:00:00
abstract::Severe transient focal cerebral ischemia causes brain infarction with a strong glial reaction. We have studied whether postischemic reactive glial cells express epidermal growth factor receptor (EGFR) following middle cerebral artery occlusion in the rat. We have also looked for signs of proliferating activity, as EGF...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/(sici)1098-1136(199806)23:2<120::aid-glia3
更新日期:1998-06-01 00:00:00
abstract::Microglial erythrophagocytosis is crucial in injury response to hemorrhagic stroke. We hypothesized that regulation of microglial erythrophagocytosis via HO-1/CO depends on a pathway involving reactive oxygen species (ROS) and CD36 surface-expression. The microglial BV-2 cell line and primary microglia (PMG) were incu...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.23864
更新日期:2020-11-01 00:00:00
abstract::Neuroprotective M2-skewed microglia appear as promising to alter the course of neurodegenerative diseases and G protein-coupled receptors (GPCRs) are potential targets to achieve such microglial polarization. A common feature of adenosine A2A (A2A R) and cannabinoid CB2 (CB2 R) GPCRs in microglia is that their express...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.23694
更新日期:2019-12-01 00:00:00
abstract::Glioblastoma multiform (GBM) are devastating brain tumors containing a fraction of multipotent stem-like cells which are highly tumorigenic. These cells are resistant to treatments and are likely to be responsible for tumor recurrence. One approach to eliminate GBM stem-like cells would be to force their terminal diff...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.22429
更新日期:2013-02-01 00:00:00
abstract::Rehabilitative therapies after stroke are designed to improve remodeling of neuronal circuits and to promote functional recovery. Only very little is known about the underlying cellular mechanisms. In particular, the effects of rehabilitative training on glial cells, which play an important role in the pathophysiology...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.20632
更新日期:2008-04-01 00:00:00
abstract::Macrophages are critically involved in the pathogenesis of genetically caused demyelination, as it occurs in inherited demyelinating neuropathies. On the basis of the observation that upregulation of the Schwann cell-derived chemokine MCP-1 (CCL2) is a pathologically relevant mechanism for macrophage activation in mic...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.20657
更新日期:2008-06-01 00:00:00
abstract::RhoGTPases are molecular switches that integrate extracellular signals to perform diverse cellular responses. This ability relies on the network of proteins regulating RhoGTPases activity and localization, and on the interaction of RhoGTPases with many different cellular effectors. Myelination is an ideal place for Rh...
journal_title:Glia
pub_type: 杂志文章,评审
doi:10.1002/glia.20752
更新日期:2008-11-01 00:00:00