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At least 235 records · Page 13Linked to original sources

PubMed2002

Modeling Alzheimer's disease immune therapy mechanisms: interactions of human postmortem microglia with antibody-opsonized amyloid beta peptide.

The induction of an antibody response to amyloid beta (Abeta) peptide has become a strategy for the treatment of Alzheimer's disease (AD). This has proven effective in reducing the plaque burden in transgenic mice that develop Abeta plaques similar to human AD patients. The mechanism for enhanced clearance of Abeta is partly due to the interaction of immunoglobulin Fcgamma receptor-expressing microglia and specific antibody-opsonized Abeta deposits. This interaction can stimulate Fcgamma receptor-mediated phagocytosis, but also results in inflammatory activation of these cells. Consequently, interaction of microglia with antibody-antigen complexes could exacerbate the existing inflammation in the brains of AD patients. In this study, we used substrate-bound Abeta and cultured human microglia from AD and non-demented cases to model interaction of microglia and antibody-opsonized plaques in AD brains. Enhanced production of tumor necrosis factor-alpha, macrophage colony stimulating factor, interleukin-10, and superoxide ions was detected. We also demonstrated enhanced uptake of opsonized Abeta by microglia, which was reduced significantly in the presence of excess IgG, indicative of the involvement of Fcgamma receptor-mediated mechanisms. Human microglia were shown in this study to express mRNA for Fcgamma receptors I, IIa, IIb, and III. The expression of Fcgamma receptor II was augmented by proinflammatory stimulation. These results suggest that initial interactions of human microglia with antibody-opsonized amyloid could result in increased inflammation. The consequence of this on inflammatory pathology in AD brains needs to be considered before immunization is used as a strategy for treating AD.

Alzheimer Disease↗

PubMed2001

Macrophage colony-stimulating factor is expressed in neuron and microglia after focal brain injury.

In a previous study, we have demonstrated that damaged neurons within a boundary area around necrosis fall into delayed neuronal death owing to the cytotoxic effect of microglial nitric oxide (NO), and these neurons are finally eliminated by activated microglia. In this process, microglia are activated to release NO, increase in number, and accumulate toward the damaged area. In this study, we investigated the expression of macrophage colony-stimulating factor (M-CSF, also called colony stimulating factor-1; CSF-1) and other cytokines, which are reported to relate to activation, proliferation, or migration of microglia. The mRNA of M-CSF arose biphasically from 30 min to 1 hr and from 6 to 72 hr after the injury, as demonstrated by semiquantitative RT-PCR. However, another cytokine of granulocyte-macrophage CSF (GM-CSF) or interleukin-3 (IL-3), which causes proliferation of microglia in vitro, was not detected. From immunohistochemical studies, positive staining of M-CSF was observed mainly in neuron-specific enolase (NSE)-positive cells from 1 to 12 hr after the injury, and after that M-CSF became positive in Griffonia simplicifolia isolectin-B4 (GSA-I-B4)-positive cells from 24 to 72 hr in the boundary area around necrosis. These results suggest that neurons around the damaged area express M-CSF in the early phase after injury, which may initially activate microglia, and these activated microglia also express M-CSF later, causing further proliferation or migration of microglia themselves to eliminate damaged neurons or necrotic brain tissue.

Animals↗

PubMed2005

Investigations with cultured human microglia on pathogenic mechanisms of Alzheimer's disease and other neurodegenerative diseases.

Inflammation-mediated mechanisms for human neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD) have evolved from being on the fringe of medical hypotheses to mainstream thinking. Pioneering immunopathology studies with human brain tissues identified microglia associated with neuropathologic hallmarks of these diseases. As activated macrophages were known to produce many potential toxic products, this gave rise to the hypothesis that activated microglia (brain resident macrophages) could be contributing to the degeneration of key target neurons in these diseases, as well as potential vascular dysfunction. Studies with microglia derived from different sources, including human brains, have confirmed that activated microglia can mediate neuronal cell death. Based on these theories, a number of human clinical trials with antiinflammatory agents have been carried out on AD patients. Results to date have indicated a lack of effectiveness at slowing disease progression and have begun to cast doubt on the significance of inflammation in AD. It has been shown recently that activating microglia through immunization of amyloid plaque-developing mice with amyloid beta peptide (Abeta) has promise as a therapeutic strategy and despite some setbacks, has potential as a treatment for AD patients. This article will consider experimental data with microglia to determine whether the additional targets need to be investigated. The use of human microglia cultures, in particular those derived from elderly diseased human brains, offers an experimental system that can closely model the cell type activated in human neurodegenerative diseases. Experimental data produced by our laboratory and others is reviewed to determine the contribution of this unique experimental model to understanding disease mechanisms and possibly discovering new therapeutic targets.

Alzheimer Disease↗

PubMed2005

Perturbations in calcium-mediated signal transduction in microglia from Alzheimer's disease patients.

Calcium-sensitive fluorescence microscopy has been used to study Ca2+-dependent signal transduction pathways in microglia obtained from Alzheimer's disease (AD) patients and non-demented (ND) individuals. Data were obtained from nine AD cases and seven ND individuals and included basal levels of intracellular Ca2+ [Ca2+]i, peak amplitudes (Delta[Ca2+]i) and time courses of adenosine triphosphate (ATP) responses and amplitudes of an initial transient response and a subsequent second component of Ca2+ influx through store-operated channels (SOC) induced by platelet-activating factor (PAF). Overall, AD microglia were characterized by significantly higher (20%) basal Ca2+ [Ca2+]i relative to ND cells. The Delta[Ca2+]i of ATP and initial phase of PAF responses, which reflect rapid depletion of Ca2+ from endoplasmic reticulum stores, were reduced by respective values of 63% and 59% in AD cells relative to amplitudes recorded from ND microglia. Additionally, AD microglia showed diminished amplitudes (reduction of 61%) of SOC-mediated Ca2+ entry induced by PAF and prolonged time courses (increase of 60%) of ATP responses with respect to ND microglia. We have generally replicated these results with exposure of human fetal microglia to beta amyloid (5 microM Abeta1-42 applied for 24 hr). Overall, these data indicate significant abnormalities are present in Ca2+-mediated signal transduction in microglia isolated from AD patients.

Adenosine Triphosphate↗

PubMed2005

Agonists for the peroxisome proliferator-activated receptor-alpha and the retinoid X receptor inhibit inflammatory responses of microglia.

The peroxisome proliferator-activated receptor-alpha (PPAR-alpha) plays a key role in lipid metabolism and inflammation. Recently, we demonstrated that administration of the PPAR-alpha agonists gemfibrozil and fenofibrate, inhibit the clinical signs of experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). In the present study we investigated the effects of PPAR-alpha agonists on primary mouse microglia, a cell type implicated in the pathology of MS and EAE. Our studies demonstrated that the PPAR-alpha agonists ciprofibrate, fenofibrate, gemfibrozil, and WY 14,643 each inhibited NO production by cytokine-stimulated microglia in a dose-dependent manner. However, fenofibrate and WY 14,643 were more potent inhibitors than gemfibrozil and ciprofibrate. In LPS-stimulated microglia, only fenofibrate and WY 14,643 significantly suppressed NO production. Additionally, PPAR-alpha agonists inhibited the secretion of the proinflammatory cytokines IL-1beta, TNF-alpha, IL-6, and IL-12 p40 and the chemokine MCP-1 by LPS-stimulated microglia. Retinoid X receptors (RXRs) physically interact with PPAR-alpha receptors, and the resulting heterodimers regulate the expression of PPAR-responsive genes. Interestingly, the RXR agonist 9-cis retinoic acid (9-cis RA) inhibited NO production by LPS-stimulated microglia. Furthermore, a combination of 9-cis RA and the PPAR-alpha agonist fenofibrate cooperatively inhibited NO production by these cells. A combination of these agonists also selectively inhibited the expression of proinflammatory cytokines including IL-1beta, TNF-alpha, and IL-6 by LPS-stimulated microglia. Collectively, these results raise the possibility that PPAR-alpha and RXR agonists might have benefit as a therapy in MS, where activated microglia are believed to contribute to disease pathology.

Alitretinoin↗

PubMed2006

In vitro proliferation of axotomized rat facial nucleus-derived activated microglia in an autocrine fashion.

Transection of rat adult facial nerve leads to an increase in the number of activated microglia in the facial nucleus (FN), with a peak in proliferation 3 days after transection. To investigate the characteristics of these activated microglia, we isolated the cells with high purity from axotomized FN (axFN) 3 days after transection according to the previously reported procedure for explant culture. The isolated microglia exhibited immunocytochemical properties similar to those in vivo, and their numbers increased approximately five- to sevenfold over a period of 10 days without the addition of any mitogens, suggesting that self-reproduction was occurring. Actually, the microglia actively incorporated bromodeoxyuridine (BrdU) and strongly expressed an S-phase-specific protein marker, proliferating cell nuclear antigen (PCNA). To examine the mechanism underlying this proliferation, the expression of the mitogens and specific receptors of the microglia were analyzed in conditioned medium (CM) and cells. Macrophage-colony stimulating factor (M-CSF) and granulocyte macrophage-CSF (GM-CSF) were detected in the CM as well as in the cells. Their specific receptor proteins, c-Fms and GMCSFRalpha, were also detected in the cell homogenate. These proliferating microglia were not found to produce deleterious factors for neurons. In summary, the microglia isolated from the axFN were found to be proliferative in an autocrine fashion and to have some cellular properties in common with those observed in vivo.

Animals↗

PubMed1995

Microglia in colony-stimulating factor 1-deficient op/op mice.

Mice that are homozygous for the autosomal recessive mutation osteopetrosis (op) suffer from a general skeletal sclerosis, and the numbers of macrophages in various tissues are significantly decreased. We report that microglia in op/op mice are not affected by the mutation. They have normal morphology and are present in the CNS in normal frequency. In cultures, disaggregated cells of neopallia can form microglia, but such cells from neopallia of op/op mice form microglia only when colony-stimulating factor 1 (CSF-1) is added to the culture medium. The addition of granulocyte/macrophage (GM)-CSF or interleukin (IL)-3 to the culture medium does not stimulate production of microglia. Microglia that form in op/op neopallial cell cultures, in the presence of CSF-1, are capable of Fc-receptor-mediated phagocytosis. Based on our experiments, it seems that microglia are CSF-1 dependent but in op/op mice (in which CSF-1 is absent) microglia may use other locally produced factors.

Animals↗

PubMed2000

p38 map kinase regulates TNF-alpha production in human astrocytes and microglia by multiple mechanisms.

In the vertebrate central nervous system (CNS), tumour necrosis factor-alpha (TNF-alpha) is produced by astrocytes and microglia and mediates cell injury in nerve cells and oligodendrocytes. In the present study, we have used a specific inhibitor of p38 MAP kinase, SB203580 to examine the role of p38 MAP kinase in regulation of TNF-alpha production in human astrocytes and microglia in terms of levels of mRNA and secreted protein. A reverse transcriptase polymerase chain reaction (RT-PCR) analysis showed that increased levels of TNF-alpha mRNA were induced in astrocytes by IL-1beta treatment, and in microglia by bacterial lipopolysaccharide (LPS). In microglia, treatment with SB203580 reduced the level of TNF-alpha mRNA, but in astrocytes it did not. However, the secretion of TNF-alpha by both astrocytes and microglia was markedly inhibited by SB203580 at a low concentration. TNF-alpha secretion was reduced approximately 80% in astrocytes and 85% in microglia. The results demonstrate a key role played by p38 MAP kinase in upregulation of TNF-alpha mRNA levels in LPS-activated human microglia, whereas p38 MAP kinase is involved in post-transcriptional regulation of TNF-alpha production at translational level in IL-1beta-activated human astrocytes.

Astrocytes↗

PubMed2002

Motility and ramification of human fetal microglia in culture: an investigation using time-lapse video microscopy and image analysis.

Microglia are mononuclear phagocytes of the central nervous system and are considered to derive from circulating bone marrow progenitors that colonize the developing human nervous system in the second trimester. They first appear as ameboid forms and progressively differentiate to process-bearing "ramified" forms with maturation. Signals driving this transformation are known to be partly derived from astrocytes. In this investigation we have used cocultures of astrocytes and microglia to demonstrate the relationship between motility and morphology of microglia associated with signals derived from astrocytes. Analysis of progressive cultures using time-lapse video microscopy clearly demonstrates the dynamic nature of microglia. We observe that ameboid microglial cells progressively ramify when cocultured with astrocytes, mirroring the "differentiation" of microglia in situ during development. We further demonstrate that individual cells undergo morphological transformations from "ramified" to "bipolar" to "tripolar" and "ameboid" states in accordance with local environmental cues associated with astrocytes in subconfluent cultures. Remarkably, cells are still capable of migration at velocities of 20-35 microm/h in a fully ramified state overlying confluent astrocytes, as determined by image analysis of motility. This is in keeping with the capacity of microglia for a rapid response to inflammatory cues in the CNS. We also demonstrate selective expression of the chemokines MIP-1alpha and MCP-1 by confluent human fetal astrocytes in cocultures and propose a role for these chemotactic cytokines as regulators of microglial motility and differentiation. The interchangeable morphological continuum of microglia supports the view that these cells represent a single heterogeneous population of resident mononuclear phagocytes capable of marked plasticity.

Astrocytes↗

PubMed1994

Relationship of microglia and scrapie amyloid-immunoreactive plaques in kuru, Creutzfeldt-Jakob disease and Gerstmann-Sträussler syndrome.

Kuru, Creutzfeldt-Jakob disease (CJD) and Gerstmann-Sträussler syndrome (GSS) are transmissible dementias affecting humans characterized neuropathologically by intraneuronal vacuolation, spongiform change, astrocytic hypertrophy and hyperplasia and the variable presence of amyloid plaques. It has been suggested that microglia are amyloid-forming cells, which play an essential role in amyloid plaque formation. To study the relationship between microglia and amyloid plaques in kuru, CJD and GSS, cerebellar tissues were examined by the double-immunostaining technique using anti-ferritin antibodies as the microglial marker and anti-scrapie amyloid antibody as plaque marker. Ferritin-immunoreactive microglia were observed interdigitating with and among unicentric, multicentric and diffuse types of scrapie amyloid-immunoreactive plaques and were found to a lesser extent in the neuropil. In kuru and CJD, scrapie amyloid-immunoreactive plaques were predominantly unicentric and were observed in the granular layer. In kuru, 53% of the amyloid plaques were associated with microglia, whereas only 30% of plaques in CJD were. In contrast, scrapie-amyloid-immunoreactive plaques in GSS were of the multicentric type, predominantly observed in the molecular layer, and 90% of these plaques were associated with microglia. Our data indicate that microglia are frequently associated with scrapie amyloid-immunoreactive plaques in GSS, less commonly in kuru and to a much lesser extent in CJD, suggesting that microglia may play a variable but important role in the formation of plaques in the transmissible spongiform encephalopathies.

Adolescent↗

PubMed1994

Dynamics of actin filaments in microglia during Fc receptor-mediated phagocytosis.

The phagocytic ability of mouse microglia during their differentiation in culture and after stimulation with bacterial wall lipopolysaccharide (LPS) has been investigated using Fc receptor-mediated phagocytosis of immunoglobulin (IgG)-coated sheep erythrocytes (SRBCs). We observed that in 10-14 day-confluent neopallial cell cultures some immature microglia are not phagocytic but, on further culturing, they do become phagocytic. LPS-stimulated microglia are able to phagocytose larger numbers of IgG-coated SRBCs and at a faster rate than non-stimulated microglia. Within 5-10 min of phagocytosis the actin filaments of the LPS-stimulated microglia become depolymerized, leaving only bundles of actin filaments around the phagocytosed SRBCs (phagosome cups). At 30 min after the start of phagocytosis the actin filaments of the LPS-stimulated microglia begin to polymerize, and within 2 h the original pre-phagocytosis pattern of the actin filament network is re-established. The non-LPS-stimulated microglia exhibit actin filament depolymerization in only a few lamellipodia and polymerization of actin filaments around engulfed particles, but much later during phagocytosis.

Actins↗

PubMed2001

Microglia promote glioma migration.

Diffuse astrocytic gliomas extensively infiltrate brain tissue and contain numerous microglial cells, but it is unknown whether these two characteristic features are pathogenetically related. We therefore studied the effects of murine microglial cells on motility of GL261 mouse glioma cells using Boyden chamber assays. In the presence of microglia, glioma cell migration occurred earlier, and after 48 h it was threefold higher as compared to incubations without microglia. This effect was mediated by substances released from microglia, because similar effects were observed by microglia-conditioned medium, and it was specific to microglia, because oligodendroglia and endothelial cells only weakly stimulated glioma cell migration. Microglia activating substances (GM-CSF, LPS) led to a further increase of motility. These data support the notion that microglia accumulation in diffuse glial tumors does not merely represent a nonspecific reaction to tissue injury, but reflects participation of these cells in supporting and promoting the invasive phenotype of astrocytoma cells.

Animals↗

PubMed2003

Distribution of major histocompatibility complex class II-positive microglia and cytokine profile of Parkinson's disease brains.

There are numerous observations confirming that microglia expressing major histocompatibility complex (MHC) class II molecules are associated with the central nervous system (CNS) in aging and pathological conditions. In this study, we investigated the distribution of MHC class II-positive microglia in Parkinson's disease (PD) brains. The number of MHC class II-positive microglia in the substantia nigra (SN) and putamen increased as the neuronal degeneration of the SN proceeded. These cells were also ICAM-1 (CD54) and LFA-1 (CD11a) positive. The number of activated microglia not only in the SN and putamen but also in the hippocampus, transentorhinal cortex, cingulate cortex and temporal cortex in PD was significantly higher than that in the normal control. Most activated microglia persisted regardless of the presence or absence of Lewy bodies. They were frequently associated not only with alpha-synuclein-positive Lewy neurites, but also with TH-16-positive dopaminergic and WH-3-positive serotonergic neurites, as well as MAP-2- and SMI-32-positive neurites. These activated microglia were also positive for TNF-alpha and interleukin-6, which are known to have a neuroprotective function. We conclude that MHC class II-positive microglia are a sensitive index of neuropathological change and are actively associated with damaged neurons and neurites.

Aged↗

PubMed2000

Tumor necrosis factor alpha and interleukin-1 alpha inhibit through different pathways interferon-gamma-induced antigen presentation, processing and MHC class II surface expression on astrocytes, but not on microglia.

Astrocytes and microglia, two glial cell populations of the CNS, have been described to be involved in many immune processes. We used defined combinations of cytokines, interferon gamma (IFN-gamma)/interleukin-1 alpha (IL-1 alpha) and IFN-gamma/tumor necrosis factor alpha (TNF alpha), to simulate different in vitro immune environments observed in disease or inflammation. In these conditions, we analyzed and compared the regulating effects of these cytokines on cell surface and total expression of MHC II and on the capacity of murine astrocytes and microglia to present peptide and native antigens to specific primed T cells. Neither IL-1 alpha nor TNF alpha affected the IFN-gamma-induced antigen presentation capacity of microglia. Astrocytes, however, were severely impaired in their capacity to present native antigens and, to a minor extent, a peptide antigen. Total expression of MHC II was not affected by these cytokines in microglia, whereas in astrocytes it was reduced by IL-1 alpha and increased by TNF alpha. Both cytokines downregulated MHC II expression at the surface of astrocytes, but not of microglia. This shows that TNF alpha affects the of IFN-gamma-immunocompetent astrocytes to process and present antigen, probably either by altering membrane traffic of MHC II and of antigen and/or enzymatic activities associated with these mechanisms, while IL-1 alpha does so by downregulating MHC II expression. Altogether, our results illustrate how differently astrocytes and microglia react toward a defined, similar immune environment. One type of cell, the astrocytes, downregulate their T-cell stimulation and MHC II trafficking, and probably also their antigen processing, functions while the other, the microglia, maintain their antigen presentation potential.

Animals↗

PubMed1994

Cellular forms and functions of brain microglia.

Consistent with the recent characterization of microglial cells as macrophages, an overall picture for the unique function of these cells in CNS tissue has developed. The microglia are derived from blood monocytes that migrate into the tissue during fetal development and subsequently remain after complete formation of the blood-brain barrier. These monocytes give rise to the ramified microglia of adult tissue through the developmental intermediate of amoeboid microglia. Ramified microglia appear uniquely adapted in contrast to other tissue macrophages based on their stability or lack of turnover and mitotic capability. The ramified cells, while usually downregulated, can convert into active macrophages termed reactive microglia; this conversion appears to occur nonspecifically in response to any injury. Further, reactive microglial cells can fuse to form giant multinucleated cells during viral infections. Each microglia cell form possesses a characteristic morphology and differing functional state with regard to macrophage activity. In their role as tissue macrophages, microglia are involved in immune responses, tissue transplantation, and AIDS dementia complex, as well as many other neurological mechanisms and diseases.

Animals↗

PubMed2006

Hypoxia-induced iNOS expression in microglia is regulated by the PI3-kinase/Akt/mTOR signaling pathway and activation of hypoxia inducible factor-1alpha.

Exposure to hypoxia induced microglia activation and animal studies have shown that neuronal cell death is correlated with microglial activation following cerebral ischemia. Thus, it is likely that toxic inflammatory mediators produced by activated microglia under hypoxic conditions may exacerbate neuronal injury following cerebral ischemia. The hypoxia-inducible factor-1 (HIF-1) is primarily involved in the sensing and adapting of cells to changes in the O(2) level, which is regulated by many physiological functions. However, the role of HIF-1 in microglia activation under hypoxia has not yet been defined. In the current work, we investigate the signaling pathways of HIF-1alpha involved in the regulation of hypoxia-induced overexpression of inducible NO synthase (iNOS) in microglia. Exposure of primary rat microglial cultures as well as established microglial cell line BV-2 to hypoxia induced the expression of iNOS, indicating that hypoxia could lead to the inflammatory activation of microglia. iNOS induction was accompanied with NO production. Moreover, the molecular analysis of these events indicated that iNOS expression was regulated by the phosphatidylinositol 3-kinase (PI3-kinase)/AKT/ mammalian target of rapamycin (mTOR) signaling pathway and activation of hypoxia inducible factor-1alpha (HIF-1alpha). Thus, during cerebral ischemia, hypoxia may not only directly damage neurons, but also promote neuronal injury indirectly via microglia activation. In this study, we demonstrated that hypoxia induced iNOS expression by regulation of HIF-1alpha in microglia.

Animals↗

PubMed2005

Astrocytes and microglia differentially regulate trafficking of lymphocyte subsets across brain endothelial cells.

Feline brain endothelial cells (BECs), astrocytes, and microglia were combined in different configurations in a cell culture insert system to assess the effect of different cell types on the trafficking of peripheral blood mononuclear cell (PBMC) subsets in response to feline immunodeficiency virus (FIV). The addition of astrocytes to BECs significantly increased the adherence of PBMCs. This increase in adherence was suppressed by microglia, whereas microglia alone had no effect on PBMC adherence. FIV exposure of the glial cells did not alter PBMC adherence as compared to same configurations with untreated cells. All PBMC subsets showed some level of trafficking across the endothelial cell layer. The level of trafficking of monocytes and B cells was significantly increased if astrocytes were present. The presence of microglia with the astrocytes reduced transmigration across all PBMC subsets. FIV exposure of astrocytes significantly increased the percentage of CD8 T cell transmigration from 24% to 64% of the total CD4 and CD8 numbers. The presence of microglia significantly reversed the preferential trafficking of CD8 cells in the presence of astrocytes. The results suggested that interaction between the triad of endothelial cells, astrocytes, and microglia played an important, but varying, role in the trafficking of different PBMC subsets. In general, astrocytes had a positive effect on trafficking of PBMCs, while microglia had a suppressive effect. Effects of FIV on trafficking were largely restricted to increases seen in CD8 T cells and monocytes.

Animals↗

PubMed2006

P2X7 receptor immunoreactive profile confined to resting and activated microglia in the epileptic brain.

The purpose of this study was to identify the CNS cellular constituent immunoreactive for specific P2X7 receptor antiserum in the kainate-induced seizure and non-seizure rat brain. Analysis of P2X7 immunocytochemistry (ICC) revealed small immunoreactive cells with processes showing distinct morphological changes as seizures progressed in time. These morphological changes were reminiscent of reactive glia during CNS injury. In order to determine the identity of this non-neuronal cellular constituent, we employed dual ICC techniques using sequential antibody incubations and reacted the sections with contrasting chromagens. Specific glial markers tested in the series included Iba1 (microglia), COX-1 (microglia), and GFAP (astroglia). Results of this study revealed distinct colocalization when sections immunostained for P2X7 were dual immunostained with antisera specific for microglia (Iba1, COX-1). In contrast, no colocalization was evident when sections were dual immunostained with P2X7 and GFAP, an astrocytic marker. In the latter experiment, dual ICC revealed two distinct cell populations with contrasting color demonstrating a population of distinct GFAP immunopositive cells and a population of distinct P2X7 immunopositive cells. We conclude that P2X7 antiserum used in this study is specific for and identifies microglia in rat and that there exists a timeline of progressive changes in microglia morphology that can be demonstrated following kainate-induced seizures. In addition, the morphological changes in microglia following seizure induction that can be identified with P2X7 antisera or with antisera specific for microglia suggest a neuroinflammatory milieu in areas of CNS seizure activity.

Animals↗