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)

A number of studies have suggested that hypertension affects the pathogenesis of inflammatory reactions in various organs. The objective of this study was to evaluate the effects of hypertension on leukocyte-endothelial interactions after transient retinal ischemia. Transient retinal ischemia was induced for 60 minutes in spontaneously hypertensive rats (SHR) and in age-matched normotensive Wistar-Kyoto rats (WKY). At 4, 12, 24, 48, and 72 hours after reperfusion, flat-mount retinas were prepared to evaluate the density of leukocytes that had been accumulated in the retina. Intercellular adhesion molecule-1 (ICAM-1) mRNA expression was studied by semiquantitative polymerase chain reaction and ICAM-1 protein levels were studied by enzyme-linked immunosorbent assay. At 14 days after reperfusion, the retinal damage and the effect of superoxide dismutase on the damage were evaluated histologically. In SHR, the number of accumulated leukocytes peaked at 48 hours after reperfusion, and it was upregulated to 5.2-fold, as compared with that of WKY (P<0.001). ICAM-1 mRNA expression and ICAM-1 protein levels were increased significantly in the ischemia-reperfused retina in SHR compared with WKY (P<0.05). Histological examination demonstrated marked increase in the retinal ischemia/reperfusion damage in SHR (P<0.01) and a significant amelioration of the damage by treatment with superoxide dismutase in SHR (P<0.05). Oxidative stress may thus be an important mechanism for the deterioration seen in ischemia/reperfusion injury in the SHR retina.
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PMID:In vivo evaluation of retinal injury after transient ischemia in hypertensive rats. 1500 35

There is evidence that physical activity is associated with decreased brain injury resulting from transient middle cerebral artery (MCA) occlusion. We investigated whether exercise could reduce stroke-induced brain inflammatory injury and its associated mediators. Sprague Dawley rats (3 months old) were subjected to 30 min exercise on a treadmill each day for 1-3 weeks. Stroke, in exercised and non-exercised animals, was then induced by a 2-h MCA occlusion followed by 48 h of reperfusion using an intraluminal filament. Endothelial expression of the intercellular adhesion molecule 1 (ICAM-1) and leukocyte infiltration were determined by immunocytochemistry. Expressions of tumor necrosis factor-alpha (TNF-alpha) and ICAM-1 mRNA were detected using a real-time reverse transcriptase-polymerase chain reaction in ischemic rats with or without exercise, and in non-ischemic control rats following exercise. Expression of TNF-alpha increased after exercise for 2 and 3 weeks. The overexpression of TNF-alpha was not further elevated in 3-week exercised rats subjected to a transient MCA occlusion and 6 or 12 h of reperfusion, as compared to that in non-exercised rats. Furthermore, ICAM-1 mRNA expression remained at significantly (P<0.01) low levels in exercised animals during ischemia/reperfusion. Pre-ischemic exercise significantly (P<0.01) reduced numbers of ICAM-1-positive vessels and infiltrating leukocytes in the frontoparietal cortex and dorsolateral striatum in ischemic rats after 48 h of reperfusion. Exercised ischemic rats demonstrated an 11+/-7% infarct volume of contralateral hemisphere as compared to a 52+/-3% volume in non-exercised ischemic rats. The data suggests that exercise inhibits inflammatory injury (i.e., decreased expression of inflammatory mediators and reduced accumulation of leukocytes) during reperfusion, leading to reduced brain damage. Chronically increased expression of TNF-alpha during exercise prevent the same downstream inflammatory events as does acutely elevated TNF-alpha after ischemia/reperfusion.
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PMID:Exercise preconditioning ameliorates inflammatory injury in ischemic rats during reperfusion. 1561 90

The present study was undertaken to evaluate whether in a neonatal model of stroke a prophylactic neuroprotective treatment with simvastatin modulates hypoxia-ischemia-induced inflammatory and apoptotic signaling. Procaspase-3 and cleaved caspase-3 expression showed a peak at 24 h and returned to control values after 5 days. Caspase-3 activity followed the same pattern of caspase-3 proteolytic cleavage. In simvastatin-treated ischemic animals, the expression of these proteins and caspase-3 activity were significantly lower when compared to that of ischemic animals. alpha-Spectrin and protein kinase C-alpha (PKCalpha) cleavages were not affected by the treatment. Poly (ADP-ribose) polymerase fragmentation, caspase-1 activation, and IL-1beta and ICAM-1 mRNA expression were increased by hypoxia-ischemia and significantly reduced in simvastatin-treated animals. The results indicate that simvastatin-induced attenuation of hypoxia-ischemia brain injury in the newborn rat occurs through reduction of the inflammatory response, caspase-3 activation, and apoptotic cell death.
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PMID:Simvastatin reduces caspase-3 activation and inflammatory markers induced by hypoxia-ischemia in the newborn rat. 1605 75

Microvascular changes in the brain are significant causes of cerebral edema and ischemia injury. A number of studies suggest that angiotensin (Ang) II may be involved in the initiation and regulation of processes occurring in brain ischemia. We recently reported that Ang II injures brain microvascular endothelial cells (BMEC) partially via stimulating intercellular adhesion molecule-1 (ICAM-1) expression. However, the signaling cascade leading to Ang II-induced ICAM-1 expression in BMEC was unclear. The present study tested the hypothesis that Ang II induces ICAM-1 expression via an AT1 receptor/nuclear factor-kappaB (NF-kappaB) pathway in BMEC. Ang II directly stimulated the expression of ICAM-1 mRNA and protein in primary cultured BMEC. Ang II treatment also resulted in the degradation of IkappaBalpha and increase of NF-kappaB p65 subunit in the nucleus as well as the DNA binding activity of nuclear NF-kappaB. These effects were abolished by pretreatment with the selective AT1 receptor antagonists, losartan and compound EXP-2528, or losartan plus the AT2 receptor antagonist PD123319, but not by PD123319 alone. Moreover, there were no significant differences between the losartan and losartan plus PD123319 groups. These findings indicate that Ang II-induced ICAM-1 upregulation in brain microvascular endothelial cells may be mediated via an AT1 receptor/NF-kappaB pathway.
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PMID:Angiotensin II stimulates intercellular adhesion molecule-1 via an AT1 receptor/nuclear factor-kappaB pathway in brain microvascular endothelial cells. 1634 50

The exact role of inducible NOS (iNOS) in liver ischemia/reperfusion (I/R) injury is controversial. This study was designed to investigate whether donor liver pretreatment with adenovirus encoding iNOS (AdiNOS) ameliorates I/R injury associated with liver transplantation. Orthotopic syngeneic LEW rat liver transplantation (OLT) was performed after 18 or 24 hours' preservation in cold UW. AdiNOS or control gene vector (AdLacZ) was delivered to the liver by donor intravenous pretreatment 4 days before graft harvesting. Uninfected grafts also served as control. Recipients were sacrificed 1 to 48 hours posttransplantation. An abundant hepatic iNOS protein expression and marked serum NO elevation was observed in the AdiNOS-treated group, without affecting endothelial nitric oxide synthase (eNOS) expression, before harvesting and after OLT. AdiNOS pretreatment markedly improved liver function assessed by serum aspartate aminotransferase/alanine aminotransferase levels and reduced liver necrosis formation. AdiNOS treatment also was associated with reduced ICAM-1 mRNA expression and neutrophil accumulation in the liver graft after OLT compared with untransfected or AdLacZ-treated group. Furthermore, AdiNOS delivery significantly improved transplant survival, compared with AdLacZ or saline controls. AdiNOS pretreatment did not attenuate I/R-induced apoptotic cell death in the liver graft. Administration of a selective inhibitor for iNOS abrogated the protection afforded by AdiNOS pretreatment. In conclusion, donor pretreatment with AdiNOS led to improved liver graft injury and posttransplantation survival. Downregulation of ICAM-1 mRNA and neutrophil infiltration may be associated with the mechanisms by which AdiNOS pretreatment confer the protection against transplant-associated hepatic I/R injury.
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PMID:Donor graft adenoviral iNOS gene transfer ameliorates rat liver transplant preservation injury and improves survival. 1649 5

Neutrophil elastase, which enhances intercellular adhesion molecule-1 (ICAM-1) expression in endothelial cells, plays an important role in ischemia/reperfusion injury. Here, we investigated signal transduction of ICAM-1 expression in endothelial cells stimulated by neutrophil elastase. Pretreatment of animals with the neutrophil elastase inhibitor, ONO-5046.Na significantly decreased the number of neutrophils or Mac-1(+) (CD11b/CD18) cells in ischemic liver lobes after reperfusion. ICAM-1 expression in the rat endothelial cell line (WK-5) was significantly upregulated after stimulation with neutrophil elastase, but this reaction was inhibited by the neutrophil elastase inhibitor ONO-5046.Na. ICAM-1 mRNA expression, which is induced by neutrophil elastase in a dose-dependent manner, was repressed by the alpha1-protease inhibitor. ICAM-1 expression, stimulated by neutrophil elastase, was partially reduced by a diacylglycerol kinase inhibitor and protein kinase C inhibitor, but was completely inhibited by a phospholipase C inhibitor, cytosolic Ca(2+) chelator, calmodulin antagonist, and nuclear transcription factor kappa B inhibitor. Binding of (125)I-neutrophil elastase to WK-5 cells was competitively inhibited by the addition of unlabeled neutrophil elastase. The neutrophil elastase inhibitor significantly reduces ICAM-1 expression and Mac-1(+) cell accumulation in ischemic liver lobes after reperfusion. Neutrophil elastase stimulates ICAM-1 expression in endothelial cells by intracellular signal transduction via activation of diacylglycerol kinase, protein kinase C, phospholipase C, Ca(2+)-calmodulin, and nuclear transcription factor kappa B.
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PMID:ICAM-1 signal transduction in cells stimulated with neutrophil elastase. 1702 74

We examined whether tumor necrosis factor-alpha (TNF-alpha) promotes postischemic inflammation and myocardial injury via activation of nuclear factor kappa B (NFkappaB) in an in vivo canine model. Isoflurane-anesthetized dogs underwent closed-chest balloon occlusion of the anterior descending coronary artery for 90 minutes, followed by reperfusion for 3 hours. Dogs randomly received a soluble TNF inhibitor (etanercept, 0.5 mg/kg intravenously) or saline before occlusion. Collateral blood flow and risk region size (RISK) were measured with radioactive microspheres, infarct size (INF) was measured by triphenyltetrazolium chloride staining, inflammation was measured by tissue myeloperoxidase (MPO) activity, intercellular adhesion molecular-1 (ICAM-1) messenger ribonucleic acid (mRNA) was measured by Northern blotting, and ICAM-1 protein expression was measured by Western blotting. NFkappaB activation was measured in nuclear extracts by electrophoretic mobility shift assays. INF/RISK was significantly smaller in the etanercept group than in the saline control group after adjusting for collateral flow (P < 0.009 by analysis of covariance, mean reduction in INF/RISK = 40%, 0.32 +/- 0.09 versus 0.53 +/- 0.09). MPO activity, ICAM-1 mRNA and protein expression, and NFkappaB binding activity were all significantly reduced in the etanercept group. Administration of a soluble TNF-alpha inhibitor reduced NFkappaB activation, ICAM-1 upregulation, and myocardial injury following ischemia-reperfusion. TNF-alpha appears to play a significant role in vivo in the genesis of postischemic inflammation.
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PMID:Inhibition of TNF-alpha reduces myocardial injury and proinflammatory pathways following ischemia-reperfusion in the dog. 1720 12

Our previous studies have shown that ferulic acid (4-hydroxy-3-methoxycinnamic acid, FA) inhibits intercellular adhesion molecule-1 (ICAM-1) expression in the ischemic striatum after 2 h of reperfusion in a transient middle cerebral artery occlusion model in rats. The purpose of this study is to further investigate the neuroprotective effects of FA during reperfusion after cerebral ischemia. Rats were subjected to 90 min of ischemia; they were then sacrificed after 2, 10, 24 and 36 h of reperfusion. ICAM-1 and macrophage-1 antigen (Mac-1) mRNA were detected using semi-quantitative RT-PCR at 2 h of reperfusion. Mac-1, 4-hydroxy-2-nonenal (4-HNE), 8-hydroxy-2'-deoxyguanosine (8-OHdG), active caspase 3, neuronal nuclei (NeuN) and TUNEL positive cells were measured at 2, 10, 24 and 36 h of reperfusion. FA (100 mg/kg, i.v.) administered immediately after MCAo inhibited ICAM-1 and Mac-1 mRNA expression in the striatum at 2 h of reperfusion, and reduced the number of Mac-1, 4-HNE and 8-OHdG positive cells in the ischemic rim and core at 10, 24 and 36 h of reperfusion. FA decreased TUNEL positive cells in the penumbra at 10 h, and in the ischemic boundary and core at 24 and 36 h of reperfusion. FA curtailed active caspase 3 expression in the penumbra at 10 h and restored NeuN-labeled neurons in the penumbra and ischemic core at 36 h of reperfusion. FA decreased the level of ICAM-1 mRNA and the number of microglia/macrophages, and subsequently down-regulated inflammation-induced oxidative stress and oxidative stress-related apoptosis, suggesting that FA provides neuroprotection against oxidative stress-related apoptosis by inhibiting ICAM-1 mRNA expression after cerebral ischemia/reperfusion injury in rats.
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PMID:Ferulic acid provides neuroprotection against oxidative stress-related apoptosis after cerebral ischemia/reperfusion injury by inhibiting ICAM-1 mRNA expression in rats. 1840 Feb 11

Ischemia-reperfusion (IR) injury is a major insult to postcapillary venules. We hypothesized that IR increases postcapillary venular hydraulic conductivity and that IR-mediated changes in hydraulic conductivity result from temporally and mechanistically separate processes. A microcannulation technique was used to determine hydraulic conductivity (Lp) in rat mesenteric postcapillary venules serially throughout ischemia (45 min) and reperfusion (5 h) induced by superior mesenteric artery occlusion and release. Mesenteric IR resulted in a biphasic increase in Lp. White blood cell (WBC) adhesion slowly increased with maximal adhesion corresponding to the second peak (P < 0.005). After IR, tissue was harvested for RT-PCR analysis of ICAM-1, E-selectin, and P-selectin mRNA. Intercellular adhesion molecule-1 (ICAM-1) mRNA in the gut showed the most significant upregulation. Quantitative real-time PCR revealed that ICAM-1 mRNA was upregulated 60-fold in the gut. An ICAM-1 antibody was therefore used to determine the effect of WBC adhesion on Lp during IR. ICAM-1 inhibition attenuated Lp during the first peak and completely blocked the second peak (P < 0.005). When rats were fed a tungsten diet to inhibit xanthine oxidase and then underwent IR, Lp was dramatically attenuated during the first peak and mildly decreased the second peak (P < 0.005). Inhibition of xanthine oxidase by oxypurinol decreased Lp during IR by over 60% (P < 0.002). Tempol, a superoxide dismutase mimetic, decreased Lp during IR by over 30% (P < 0.01). We conclude that IR induces a biphasic increase in postcapillary hydraulic conductivity. Reactive oxygen species impact both the first transient peak and the sustained second peak. However, the second peak is also dependent on WBC-endothelial cell adhesion. These serial measurements of postcapillary hydraulic conductivity may lead the way for optimal timing of pharmaceutical therapies in IR injury.
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PMID:Ischemia-reperfusion injury in rats affects hydraulic conductivity in two phases that are temporally and mechanistically separate. 1879 Aug 38

This study sought to evaluate the effects of selective brain cooling on the expression of intercellular adhesion molecule-1 (ICAM-1) mRNA and infiltration of polymorphonuclear leukocytes (PMNLs) and monocytes/macrophages (MPhi) during global cerebral ischemia/ reperfusion (I/R). Global ischemia of the brain was produced by four-vessel occlusion for 30 min followed by reperfusion for 240 min. Thirty-five SD rats were randomly divided into five groups: group I had no ischemia and reperfusion; groups II, III, IV, and V were subjected to ischemia for 30 min at 37 degrees C and reperfusion for 240 min at 37, 35, 32, and 28 degrees C, respectively. Cerebral tissue samples were taken for pathological examination of the infiltration of PMNLs and MPhi and to detect ICAM-1 mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR). The expression of ICAM-1 mRNA and infiltration of PMNLs and MPhi increased more markedly in group II than in group I (p < 0.01), suggesting that hypothermia evidently inhibited ICAM-1 mRNA expression and PMNL and MPhi infiltration in the damaged cerebral tissue. In addition, significant differences were also found between group III and group II (p < 0.05) and among groups IV, V, and II (p < 0.01). These results suggest that I/R injury induces ICAM-1 mRNA expression and PMNL and MPhi infiltration in SD rats and that selective brain cooling, and especially moderate hypothermia (28-32 degrees C), may provide better cerebral protection by markedly inhibiting the expression of ICAM-1 mRNA while decreasing the infiltration of PMNLs and MPhi in the brain.
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PMID:Influence of selective brain cooling on the expression of ICAM-1 mRNA and infiltration of PMNLs and monocytes/macrophages in rats suffering from global brain ischemia/reperfusion injury. 2010 35


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