Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-18, previously designated interferon gamma-inducing factor, is a proinflammatory cytokine structurally related to interleukin-1beta and is therefore considered a member of the growing family of interleukin-1-like cytokines. Both interleukin-18 and -1beta are synthesized as inactive precursors that necessitate cleavage by caspase-1 for functional activity. In this study, the authors analyzed the expression pattern of interleukin-18, -1beta, and caspase-1 in focal brain ischemia induced in rats either by permanent middle cerebral artery occlusion or by photothrombosis of cortical microvessels. Using reverse transcriptase-polymerase chain reaction, they found a delayed increase of interleukin-18 mRNA starting at 48 hours and reaching its peak between 7 and 14 days after ischemia. In contrast, interleukin-1beta mRNA peaked within 16 hours and was downregulated thereafter. The time course of caspase-1 mRNA expression paralleled that of interleukin-18, but not of interleukin-1beta mRNA. Immunocytochemically, interleukin-18 expression was localized to ED1-positive phagocytic microglia/macrophages infiltrating the necrotic lesion between 3 and 6 days after ischemia. In contrast, interleukin-1beta immunoreactivity was expressed by ramified microglia in the infarct border zone and remote ipsilateral cortex during the first 16 hours postlesion. Induction of interleukin-18 was not accompanied by detectable expression of interferon-gamma mRNA. Their data show spatial and temporal diversity in interleukin-1 and -18 cytokine family expression in brain ischemia, and suggest a role of the interleukin-18/caspase-1 pathway in late-stage inflammatory responses to focal brain ischemia.
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PMID:Interleukin-18 expression after focal ischemia of the rat brain: association with the late-stage inflammatory response. 1180 95

This work aimed to define the spatial expression of endothelin A (ET(A)) and B (ET(B)) receptors in the cerebral cortex after permanent middle cerebral artery occlusion (MCAO) and to identify the phenotype of cells expressing ET(A) and ET(B) receptors. Cortical expression of ET(A) and ET(B) receptors was determined at the mRNA level by semi-quantitative reverse transcription-polymerase chain reaction and at the protein level by immunofluorescence staining, 12, 24 and 72 h after MCAO. Cells expressing endothelin receptors were phenotyped by double labelling with antibodies, anti-protein gene product (PGP9.5) and anti-ED1, towards neurons and activated microglia/macrophages, respectively. Both ET(A) and ET(B) receptor mRNA expressions increased significantly in the ipsilateral cortex in a time-dependent manner after MCAO. Robust expression of ET(A) receptors was noted in most neurons of the ischemic core and in several neurons in laminae 3 and 4 of the peri-infarct region 24 and 72 h after MCAO. ET(B) receptor immunoreactivity was observed in activated microglia/macrophages, beginning 24 h after MCAO. These results provide the first evidence that the action of endothelin during ischemia may be mediated by neuronal ET(A) receptors and activated microglia/macrophage ET(B) receptors. This differential localization of ET(A) and ET(B) receptors suggests that endothelin is involved in some complex neuron-glial interactions in addition to its vascular modulatory activity during ischemia.
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PMID:Cortical expression of endothelin receptor subtypes A and B following middle cerebral artery occlusion in rats. 1208 56

The left and right neocortex of the brain has been shown to exert asymmetrical effects on the immune system. In the present study, we used a middle cerebral artery (MCA) occlusion model in Wistar rats to analyze the influence of unilateral CNS ischemia on spleen cell number and function. The occlusion time was 1 h, followed by reperfusion with survival for 0, 2, 7, 14, and 28 days. Changes in plasma norepinephrine levels were used as an index of peripheral sympathetic activity. Results showed that the total number of spleen cells significantly decreased after 2-28 days of survival in animals with cerebral ischemia compared to sham-operated controls. There was no change in the percentage of CD5(+)-CD4(+) T cells, MHC class II(+) cells, or ED1(+) macrophages. However, the percentage of CD5(+)-CD8(+) T cells decreased at 2 days, resulting in an increased CD4/CD8 ratio, and both parameters returned to control levels after 7 days. Mitogen-induced T and B lymphocyte proliferation increased after 0-28 days post-ischemia independently of the mitogen used. There was no difference in immune response or norepinephrine levels between left and right MCA occlusions. These results are consistent with the notion that cerebral ischemia induces mobilization of certain immune cells from the periphery to the brain, where they may contribute to the local inflammatory response. Additionally, the data indicate that cerebral ischemia is followed by a systemic activation of T and B lymphocytes. Absence of asymmetric effects of left versus right stroke, and failure to demonstrate any suppressive effects of left-sided lesions on lymphocyte proliferation, probably reflects the fact that these large cerebral ischemic lesions affect both cortical and subcortical areas.
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PMID:Temporal effects of left versus right middle cerebral artery occlusion on spleen lymphocyte subsets and mitogenic response in Wistar rats. 1241 24

In order to examine lipid metabolism in relation to neural process following brain ischemia, we investigated temporal and spatial changes of free cholesterol (FC) and neutral lipids (NLs) after 90 min of transient middle cerebral artery occlusion (MCAO). Filipin and Nile Red stainings were performed to detect mainly FC and NLs, respectively. Double stainings for Nile Red plus ED1, MAP2, or GFAP were performed in order to identify cell type of positive stainings. Filipin stanining decreased during 1-7 day and lost at 21 day after transient MCAO in the ischemic core, but did not change in the penumbra. Nile Red positive droplets reached the maximum at 7 day after transient MCAO and gradually decreased in the core, while the peak time delayed in the penumbra. MAP2 immunoreactivity lost at 7 day in the core, and increased in the penumbra during 7-56 day. Most Nile Red positive droplets were double positive for ED1 in the core, and were localized within GFAP positive cells in the penumbra. These results suggest that changes of FC and NLs are different temporally and spatially between the core and penumbra in relation to degenerative and regenerative neural processes following brain ischemia.
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PMID:Temporal and spatial changes of free cholesterol and neutral lipids in rat brain after transient middle cerebral artery occlusion. 1250 28

Apolipoprotein E (ApoE) is a constituent of lipoprotein and plays an important role in the maintenance of neural networks. However, spatiotemporal differences in ApoE expression and its long-term role in neural process after brain ischemia have not been studied. We investigated changes of ApoE immunoreactivity and ApoE mRNA expression both in the core and in the periischemic area at 1, 7, 21, or 56 days after 90 min of transient middle cerebral artery occlusion. Double stainings for ApoE plus NeuN or plus ED1 were performed in order to identify cell type of ApoE-positive stainings. The maximal increase of ApoE expression was observed at 7 days in the core and at 7 and 21 days in the periischemic area. In the core, ApoE plus NeuN double-positive cells increased at 1 and 7 days, without ApoE mRNA expression, whereas they increased in the periischemic area, with a peak at 21 days, with ApoE mRNA expression in glial cells but not in neurons. On the other hand, ApoE plus ED1 double-positive cells increased only in the core, with a peak in number at 7 and 21 days and marked ApoE mRNA expression in macrophages. The present study suggests that ApoE plays various important roles in different type of cells, reflecting spatiotemporal dissociation between degenerative and regenerative processes after brain ischemia, and that ApoE is profoundly involved in pathological conditions, such as brain ischemia.
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PMID:Spatiotemporal changes of apolipoprotein E immunoreactivity and apolipoprotein E mRNA expression after transient middle cerebral artery occlusion in rat brain. 1289 39

This study was aimed to ascertain the effect of sleep deprivation on subsequent cerebral ischemia in the rat hippocampal formation. Seven days after transient global cerebral ischemia induced by four-vessel occlusion method, most of the pyramidal cells in the hippocampal CA1 subfield underwent disruption and pyknosis as detected by cresyl violet staining. With OX-42, OX-18, OX-6 and ED1 immunohistochemistry, robust microglia/macrophage reactions were observed in the CA1 and dentate hilus. The majority of reactive microglia was rod-shaped, bushy or amoeboidic cells bearing hypertrophic processes. Astrocytes also displayed hypertrophic processes, whose immunostaining for glial fibrillary acidic protein was markedly enhanced. The ischemia-induced neuronal damage and glial reactions, however, were noticeably attenuated in rats subjected to pretreatment with sleep deprivation for five consecutive days. The most drastic effect was the diminution of OX-18, OX-6 and ED1 immunoreactivities, suggesting that the immune potentiality and/or phagocytosis of these cells was suppressed by prolonged sleep deprivation prior to ischemic insult. It is postulated that sleep deprivation may have a preconditioning influence on subsequent lethal cerebral ischemia. Hence, sleep deprivation may be considered as a therapeutic strategy in brain ischemic damage.
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PMID:Sleep deprivation prior to transient global cerebral ischemia attenuates glial reaction in the rat hippocampal formation. 1293 51

We investigated temporal and spatial changes of free cholesterol (FC) and neutral lipids (NLs) after brain ischemia with filipin complex staining to detect mainly FC and Nile Red staining for NLs such as cholesteryl ester (CE) and triacylglyceride (TAG). Filipin stainining decreased during 1 to 7 d and lost at 21 d after transient middle cerebral artery (MCA) occlusion in the ischemic core, but did not change in the penumbra. Nile Red positive droplets reached the maximum at 7 d after transient MCA occlusion (MCAO) and gradually decreased in the core, while the peak time delayed in the penumbra. Most Nile Red positive droplets were double positive for ED1 in the core, and were localized within GFAP positive cells in the penumbra. The present study suggests that changes of FC and NLs are different temporally and spatially between the ischemic core and the penumbra in relation to degenerative and regenerative neural processes following brain ischemia. Macrophages and astrocytes are presumed to play important roles in lipid metabolism for neural reorganization of the ischemic brain injury in the ischemic core and the penumbra, respectively.
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PMID:Changes of free cholesterol and neutral lipids after transient focal brain ischemia in rats. 1475 30

Free radicals and inflammatory mediators are involved in transient focal cerebral ischemia (FCI). Preadministration of N-acetylcysteine (NAC) has been found to attenuate the cerebral ischemia-reperfusion injury in a rat model of experimental stroke. This study was undertaken to investigate the neuroprotective potential of NAC administered after ischemic events in experimental stroke. FCI was induced for 30 min by occluding the middle cerebral artery (MCA). NAC (150 mg/kg) was administered intraperitoneally at the time of reperfusion followed by another dose 6 hr later. Animals were sacrificed after 24 hr of reperfusion. The cerebral infarct consistently involved the cortex and striatum. Infarction was assessed by staining the brain sections with 2,3,5-triphenyltetrazolium chloride. Animals treated with NAC showed a significant reduction in infarct area and infarct volume and an improvement in neurologic scores and glutathione level. Reduction in infarction was significant even when a single dose of NAC was administered at 6 hr of reperfusion. Immunohistochemical and quantitative real-time PCR studies demonstrated a reduction in the expression of proinflammatory cytokines such as tumor necrosis factor alpha (TNFalpha) and interleukin 1beta (IL-1beta) and inducible nitric oxide synthase (iNOS) in NAC compared to that in vehicle-treated animals. The expression of activated macrophage/microglia (ED1) and apoptotic cell death in ischemic brain was also reduced by NAC treatment. These results indicate that in a rat model of experimental stroke, administration of NAC even after ischemia onset protected the brain from free radical injury, apoptosis, and inflammation, with a wide treatment window.
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PMID:Administration of N-acetylcysteine after focal cerebral ischemia protects brain and reduces inflammation in a rat model of experimental stroke. 1511 24

Carbon monoxide (CO), a product of heme metabolism by heme oxygenases, is known to impart protection against oxidative stress. We hypothesized that CO would protect ischemia-reperfusion (I/R) injury of transplanted organs, and the efficacy of CO was studied in the rat kidney transplantation model. A Lewis rat kidney graft, preserved in University of Wisconsin solution at 4 degrees C for 24 h, was orthotopically transplanted into syngeneic rats. Recipients were maintained in room air or exposed to CO (250 ppm) in air for 1 h before and 24 h after transplantation. Animals were killed 1, 3, 6, and 24 h after transplantation to assess efficacy of inhaled CO. Rapid upregulation of mRNA for IL-6, IL-1beta, TNF-alpha, ICAM-1, heme oxygenase-1, and inducible nitric oxide synthase was observed within 3 h after transplantation in the control grafts of air-exposed recipients, associating with histopathological evidences of acute tubular necrosis, interstitial hemorrhage, and edema. In contrast, the increase of inflammatory mediators was markedly inhibited in kidney grafts of CO-treated recipients, which correlated with improved renal cortical blood flow. Further detailed morphological analyses revealed that CO preserved the glomerular vascular architecture and podocyte viability with less apoptosis of tubular epithelial cells and less ED1(+) macrophage infiltration. CO inhalation resulted in improved serum creatinine levels and clearance, and animal survival was significantly improved with CO to 60.5 from 25 days in untreated controls. The study demonstrates that exposure of kidney graft recipients to CO at a low concentration can impart significant protective effects against renal I/R injury and improve function of renal grafts.
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PMID:Protection of transplant-induced renal ischemia-reperfusion injury with carbon monoxide. 1529 46

Immunophilin ligands, such as cyclosporin A and FK506, have neuroprotective effects in experimental stroke models, although the precise mechanism is unclear. Cyclophilin C-associated protein (CyCAP) is a natural cellular ligand for the immunophilin, cyclophilin C, and has a protective effect against endotoxins by downmodulating the proinflammatory response. Expressions of CyCAP and cyclophilin C mRNA in a rat middle cerebral artery (MCA) occlusion ischemia model were investigated by Northern blotting and in situ hybridization. Both CyCAP and cyclophilin C mRNAs were ubiquitously distributed in the neurons of the normal brain. Expression increased in neurons of the periinfarct zone up to 7 days after MCA occlusion. The neuronal distribution was confirmed by counterimmunostaining of NeuN. Both mRNAs were predominantly expressed in microglia of the ischemic core at 7 days, confirmed by immunostaining with the microglial marker, ED1. The quantification of CyCAP and cyclophilin C mRNAs at 7 days by Northern blot analysis showed the 8.5-fold increase (P<0.005, n=6) and 6.8-fold increase (P<0.005, n=6), respectively, in ischemic core compared with control. The coincidence of CyCAP and cyclophilin C expression in neurons and microglia suggests distinct roles in each cellular population. In particular, the early increase in penumbral neurons might be related to protection in periinfarct neurons.
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PMID:Cyclophilin C-associated protein and cyclophilin C mRNA are upregulated in penumbral neurons and microglia after focal cerebral ischemia. 1564 40


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