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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Astrocytes are a major cell type in the central nervous system (CNS). They are considered to act in cooperation with neurons and other glial cells and to participate in the development and maintenance of functions of the CNS. Immature astrocytes possess a polygonal shape and have no processes, and continue to proliferate, while mature astrocytes have a stellate cell morphology, increased glial fibrillary acidic protein expression, and proliferate slowly. Stellate astrocytes, which immediately appear at the site of brain lesions by ischemia or other brain injuries, are thought to produce several neurotrophic factors to protect neurons from delayed post-lesion death. Previously we reported that galectin-1, a member of the family of beta-galactoside-binding proteins, induced astrocyte differentiation, and the differentiated astrocytes greatly enhanced their production of brain-derived neurotrophic factor (BDNF). BDNF is known to promote neuronal survival, guide axonal pathfinding, and participate in activity-dependent synaptic plasticity during development. The effect of galectin-1 is astrocyte-specific and does not have any effect on neurons. Prevention of neuronal loss during CNS injuries is important to maintain brain function. Induction of neuroprotective factors in astrocytes by an endogenous mammalian lectin may be a new mechanism for preventing neuronal loss after brain injury, and may be useful for the treatment of neurodegenerative disorders.
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PMID:Glycans and glycan-binding proteins in brain: galectin-1-induced expression of neurotrophic factors in astrocytes. 1602 61

Bilateral common carotid artery occlusion (BCCAO) produces moderate levels of ischemia in the retina of rats, which may simulate the inflow disturbances in severe carotid artery disease. ERG changes following acute BCCAO have been well described, but the effects of chronic BCCAO on the histopathology of the retina remain to be characterized in a reproducible model. Chronic BCCAO was induced in halothane-anaesthetized male Wistar rats and the retina fixed after 3, 6, or 24 hr, 1 week, and 2, 4, or 6 months. Cell counts and measurements of retinal layers were performed in H&E stained paraffin sections. Immunohistochemistry with a panel of fourteen antibodies served to examine the survival of different retinal cell class, astrocytic reactions and the expression of acute stress response proteins. A lectin method was used to label activated microglial cells. Microglial activation, heme oxygenase-1 upregulation and caspase-3 cleavage occurred during the first 24hr in the absence of overt cell death of retinal ganglion cells (RGC). Three waves of neurodegeneration followed. RGCs were affected after 1 week, followed by neurons in the inner nuclear layer at 2 months, and finally photoreceptors at 4 months. Immunomarkers indicated acute damage to horizontal cells and prolonged survival of amacrine cells. In conclusion, chronic BCCAO produced delayed neuronal death in the retina of adult male Wistar rats. The window of moderate changes of at least 1 day may facilitate molecular studies on retinal ganglion cell loss.
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PMID:Complex neurodegeneration in retina following moderate ischemia induced by bilateral common carotid artery occlusion in Wistar rats. 1635 64

To try to determine the cause of hyperintensity of T1-weighted MR images that occurred on and after day 7 following transient cerebral ischemia, dynamic changes in T1-weighted images and histology of rats subjected to 20 min of 4-vessel occlusion were observed. T1-weighted images showed no remarkable alteration on days 1 and 3, although high signal intensity in the striatal region, in which the T1 value was significantly lower than the values on days 1 and 3, was observed on day 7. High signal intensity in T1-weighted images indicates low T1 values. Histological observation revealed accumulation of microglia in the striatal region on day 7 by lectin staining. There was a tight correlation between T1 values and number of lectin-positive cells. Microglia had stout processes and hypertrophic cell bodies on day 7, resembling lipid-laden phagocytes. Sudan black B staining showed the presence of many fatty droplets in the striatal region on day 7. Furthermore, double staining with lectin and Sudan black B revealed the presence of fatty droplets in bodies of lectin-positive cells on day 7. These results suggest that hyperintensity of T1-weighted images on day 7 following transient ischemia and reperfusion indicates accumulation and phagocytic activation of microglia. T1-weighted images seem to represent the progression of non-reversible tissue injury after transient ischemia and reperfusion.
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PMID:Clinical significance of T1-weighted MR images following transient cerebral ischemia. 1766 6

Although microglial activation may be an initial beneficial response to a variety of insults, prolonged activation can release toxic substances and lead to cell death. Microglial activation secondary to hypoxia-ischemia and/or infection in immature cerebral white matter is important in the pathogenesis of periventricular leukomalacia (PVL), the major pathological substrate of cerebral palsy in the premature infant. We hypothesize that a transient overexpression in activated microglial density occurs normally in the cerebral white matter of the human fetus during the peak window of vulnerability for PVL. Such an increase could render this region susceptible to insults that cause prolonged microglial activation, as conceptualized in PVL. To examine the developmental profile of microglia in the human fetus and infant brain, immunocytochemistry with microglial specific markers were used in 23 control (non-PVL) cases ranging from 20 to 183 postconceptional (PC) weeks. Tomato lectin, used to identify microglial morphology, revealed that the cerebral white matter of the human fetus and infant is densely populated with intermediate and amoeboid microglia; the latter is indicative of an activated state. Quantitative analysis with CD68 showed increased density of activated microglia in the cerebral white matter of the fetus (<37 PC weeks) relative to the neonate/infant (> or =37 PC weeks) and to the overlying cortex of either age group (P = 0.01). The primary finding of a transient, developmental-dependent overabundance of CD68-activated microglia in the cerebral white matter of the fetus suggests a potential "priming" of this area for diverse brain insults characterized by activation of microglia, particularly PVL. J.
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PMID:Development of microglia in the cerebral white matter of the human fetus and infant. 1670 80

Recent advance in autoimmunity research reveals that the innate immune system is able to recognize self-targets and initiate inflammatory response in a similar way as with pathogens. This review describes one novel example of this innate autoimmunity, ischemia-reperfusion (I/R) injury. Studies of intestinal, skeletal muscle, and heart I/R models showed that reperfusion of ischemic tissues elicits an acute inflammatory response involving serum complement system which is activated by natural IgM. The recent identification of a monoclonal natural IgM that initiates I/R led to the identification of non-muscle myosin heavy chain type II A and C as the self-targets in two different tissues. New evidence further suggests that IgM binds initially to ischemic antigen providing a binding site for mannan binding lectin (MBL) which subsequently leads to activation of complement and results in tissue injury. Therefore, natural IgM mediated innate autoimmunity is likely responsible for the detrimental consequences in ischemic diseases.
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PMID:Natural antibody mediated innate autoimmune response. 1687 47

Reperfusion of ischemic tissues elicits an acute inflammatory response involving serum complement, which is activated by circulating natural IgM specific to self-Ags exposed by ischemia. Recent reports demonstrating a role for the lectin pathway raise a question regarding the initial events in complement activation. To dissect the individual roles of natural IgM and lectin in activation of complement, mice bearing genetic deficiency in early complement, IgM, or mannan-binding lectin were characterized in a mesenteric model of ischemia reperfusion injury. The results reveal that IgM binds initially to ischemic Ag providing a binding site for mannan-binding lectin which subsequently leads to activation of complement and injury.
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PMID:Activation of the lectin pathway by natural IgM in a model of ischemia/reperfusion injury. 1698 12

Inflammation is an important factor for hypoxia-ischemia (HI) brain injury. Interleukin (IL)-18 is a proinflammatory cytokine which may be a contributor to injury in the immature brain after HI. To investigate the effects of post-HI hypothermia on IL-18 in the developing brain, 7-day-old rats were subjected to left carotid artery ligation followed by 8% oxygen for 60 min and divided into a hypothermia group (rectal temperature 32 degrees C for 24 h) and a normothermia group (36 degrees C for 24 h). The IL-18 mRNA was analyzed with real-time RT-PCR, and the protein level was analyzed by Western blot, and the location and source of IL-18 were assessed by immunohistochemistry. The significant increase of the IL-18 mRNA was observed in the ipsilateral hemispheres of the normothermia group at 24 h and 72 h after HI compared with controls, but the level in the ipsilateral hemispheres of the hypothermia group was significantly reduced at both time points, compared with the normothermia group, respectively. The IL-18 protein level in the ipsilateral hemispheres of the normothermia group significantly increased at 72 h after HI compared with controls, however, the protein level of the hypothermia group was significantly decreased, compared with the normothermia group. IL-18-positive cells were observed throughout the entire cortex, corpus callosum (CC) and striatum in the ipsilateral hemispheres of normothermia group at 72 h after HI, however, little positive cells were observed in the hypothermia group. Double labeling immunostaining found that most of the IL-18-positive cells were colocalized with lectin, which is a marker of microglia. The number of ameboid microglia (AM) in the normothermia group was significantly increased in cortex and CC, compared with the number in controls, but there were very few ramified microglia (RM) in these areas. In contrast, the number of AM in the hypothermia group was significantly decreased in cortex and CC, compared with the number in the normothermia group, and there were no significant differences in the number of AM and RM between the hypothermia group and controls. In conclusion, we found that IL-18 mRNA and the protein level were attenuated by post-HI hypothermia and that post-HI hypothermia may decrease microglia activation in the developing brain.
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PMID:Post-ischemic hypothermia reduced IL-18 expression and suppressed microglial activation in the immature brain. 1701 Sep 50

The hierarchy of endothelial progenitor cells (EPCs) in human umbilical cord blood has been disclosed. In this study we compare, for the first time, the angiogenic potential difference between two types of EPCs. We cultured mononuclear cells (MNCs) isolated from human umbilical cord blood using endothelial cell-conditioned medium and obtained two types of EPCs, referred to as circulating angiogenic cells (CACs) and high proliferative potential endothelial progenitor cells (HPP-EPCs). Both types of cells possess characteristics of EPCs, including expressing CD31, VE-cadherin, KDR and von Willebrand factor, uptake of Ac-LDL and binding to lectin. However, unlike CACs, which express CD14 but not CD133, HPP-EPCs express CD133 but not CD14. Also, unlike CACs, HPP-EPCs display stronger proliferation and clonogenic potential in vitro and show stronger ability to promote vascular growth in the hind-limb model of ischemia in mice (BALB/C-nu) in vivo.
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PMID:Angiogenic potential difference between two types of endothelial progenitor cells from human umbilical cord blood. 1702 Aug 9

C1-inhibitor is increasingly used experimentally and clinically in inflammatory conditions like septicemia and ischemia-reperfusion injury. Several mechanisms may account for the anti-inflammatory effects of C1-inhibitor, including inhibition of complement. The aim of the present study was to investigate and compare the supraphysiologic effect of C1-inhibitor on the three complement pathways. Novel assays for specific evaluation of the classical, lectin and alternative pathways were employed using normal human serum supplemented with increasing concentrations of C1-inhibitor. Solid-phase classical- and lectin pathway activation was dose-dependently and significantly reduced up to 85% in the range of 2-28 times physiologic C1-inhibitor concentration. The lectin pathway was more potently inhibited than the classical at low doses. A functional lectin pathway assay demonstrated a significant reduction of C4 deposition up to 86% even at low concentration of C1-inhibitor and documented the effect to be at the level of MBL/MASPs. In contrast, C1-inhibitor had no effect on solid-phase alternative pathway activation, but significantly reduced cobra venom factor-induced fluid-phase activation up to 88%. The negative controls albumin and IgG had no effect on complement activation. The positive inhibitory controls compstatin (C3 inhibition), EDTA- or MBL-deficient sera reduced complement activation by 82-100%. We conclude that C1-inhibitor in high physiologic doses differentially inhibits all three-complement pathways. The inhibition pattern was strikingly different in the classical and lectin pathway, compared to the alternative. Previous studies interpreting the effects of C1-inhibitor as only due to classical pathway inhibition needs reconsideration. The data has implications for the therapeutic use of C1-inhibitor.
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PMID:Effect of supraphysiologic levels of C1-inhibitor on the classical, lectin and alternative pathways of complement. 1710 Nov 76

The immune response to foreign or self antigens mediates liver damage during viral or autoimmune hepatitis. However, it now appears that also specific antigen-independent liver diseases, where liver damage has been attributed to occur from oxygen radical formation, seem to be mediated by cells of the innate and adaptive immune response. These liver disorders include alcoholic liver disease, non-alcoholic fatty liver disease or non-alcoholic steatohepatitis, and ischemia/reperfusion injury that impairs the function of liver grafts. Here it seems that breakdown of the gastrointestinal barrier might increase the concentration of bacterial toxins in the portal blood, which then activate cells of the innate immune system, e. g., Kupffer cells, but, depending on the nature of the toxin, probably also conventional T cells. Invariant NKT cells which specifically recognize glycolipid antigens were supposed to become activated during metabolic disorders related to obesity. However, both steatohepatitis as well as ischemia/reperfusion injury are associated with a Th1 cytokine response characterized by IFNgamma and TNFalpha elevation, that might reflect an NKT cell response on the one hand, but also conventional T lymphocytes, in particular CD4 (+) T cells, are critical for the pathophysiology of these disorders. In 1992 we described a model of T cell-dependent liver injury inducible by the T cell-mitogenic lectin concanavalin A. This model of immune-mediated liver injury was intensively used to study pathophysiological immune effector mechanisms as well as cytokine signaling important for hepatocellular apoptosis, inhibition of apoptosis and regeneration. Recently it became evident that the inflammatory response in this model is regulated by specific cytokine signals as well as by immune regulator cells. The immune-regulatory functions of the liver are of particular interest with respect to the scavenger function of this organ, being continuously exposed to foreign antigenic material from the gut which should be eliminated without causing chronic disease.
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PMID:Cellular and cytokine-mediated mechanisms of inflammation and its modulation in immune-mediated liver injury. 1723 22


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