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

Agents that inhibit leukocyte adhesion including intercellular adhesion molecule-1 antibodies (anti-ICAM-1) have shown beneficial effects in experimental central nervous system (CNS) ischemia. Doxycycline inhibits leukocyte function in vitro by binding divalent cations and reduces spinal cord reperfusion injury. The authors used a clinically relevant model of focal CNS reperfusion injury to test whether treatment with doxycycline would reduce cerebral ischemic damage and improve functional outcome. Reversible middle cerebral artery occlusion was produced in adult Sprague-Dawley rats by advancing a filament into the internal carotid artery for 2 h. Animals received either i.p. doxycycline (10 mg/kg) (N = 13) or saline (N = 11) 30 min before ischemia, followed by 10 mg/kg every 8 h x 6. Both functional assessment (5 point neurologic scale) and infarct volume was evaluated at 48 h. Functional efficacy: doxycycline 0.5 +/- 0.2 (mean +/- SE) vs control 1.3 +/- 0.3 (p = 0.03). Infarct volume: doxycycline 56 +/- 18 mm3 vs control 158 +/- 44 mm3 (p = 0.03); This protective effect supports the role of doxycycline in reducing CNS reperfusion injury.
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PMID:Doxycycline treatment reduces ischemic brain damage in transient middle cerebral artery occlusion in the rat. 940 91

Secondary ischemic brain injury has been shown to develop as a consequence of inflammation and vasogenic brain edema. In this study we show that inflammatory cytokines and simulated in vitro ischemia stimulate the surface expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelial-leukocyte adhesion molecule-1 (E-selectin) in human cerebromicrovascular endothelial cells (HCEC) in culture. The levels of all three adhesion molecules were dramatically (3 to 10-fold) up-regulated by 4-24 hour exposure to the inflammatory cytokines. IL-1 beta (10-200 u/ml) or TNF alpha (50 200 u/ml), and by a 4 hour exposure to "simulated" in vitro ischemia, as determined by immunocytochemistry and ELISA. Following 24 hours of subsequent reperfusion, the expression of ICAM-1 and VCAM-1 was maintained at ischemia-induced levels, whereas E-selectin was no longer detectable. Both the cytokine- and ischemia-induced up-regulation of adhesion molecules were completely abolished by the transcriptional inhibitor, actinomycin D (10 micrograms/ml), and inhibited by the cycloxygenase (COX) inhibitor, indomethacin (300 microM). These findings implicate HCEC in the processes of leukocyte adhesion and recruitment in the brain during stroke in vivo.
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PMID:Increase in surface expression of ICAM-1, VCAM-1 and E-selectin in human cerebromicrovascular endothelial cells subjected to ischemia-like insults. 941 64

Aging is associated with a progressive decline in renal function and the development of glomerulosclerosis and interstitial fibrosis. Although many studies have addressed the cellular mechanisms of age-related glomerulosclerosis, less is known about the tubulointerstitial fibrosis. In this study, aging (24 mo) rats develop tubulointerstitial fibrosis characterized by tubular injury and focal tubular cell proliferation, myofibroblast activation, macrophage infiltration with increased immunostaining for the adhesive proteins osteopontin and intercellular adhesion molecule-1, and collagen IV deposition. Aging rats demonstrated immunostaining for endothelial nitric oxide synthase (eNOSIII) in renal tubular epithelial cells and infiltrating mononuclear cells in areas of tubulointerstitial injury, with a relative loss of staining of the peritubular capillaries compared with young rats. The aging rats also displayed focal loss of peritubular capillaries (as noted by focally decreased RECA-1 and OX-2 staining) in areas of tubulointerstitial injury. The areas of fibrosis and hypocellularity were associated with increased apoptosis of tubular and interstitial cells compared with young (3 mo) rats (25.4 +/- 5.3 versus 3.5 +/- 2.5 TUNEL-positive cells/0.25 mm2 in old versus young rats, P = 0.0001). It is concluded that tubulointerstitial fibrosis in aging is an active process associated with interstitial inflammation and fibroblast activation. The progressive loss of cells in areas of fibrosis may be due to accelerated apoptosis. Furthermore, the tubulointerstitial injury may be the consequence of ischemia secondary to peritubular capillary injury and altered eNOS expression.
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PMID:Tubulointerstitial disease in aging: evidence for underlying peritubular capillary damage, a potential role for renal ischemia. 952 99

It has been reported that reperfusion is the most important factor in ischemia-reperfusion (I/R) injury. However, causes of I/R injury in the lung are controversial, because oxygen is always supplied if ventilation continues. Therefore, we hypothesized that nonhypoxic ischemia without reperfusion is sufficient for lung injury. To test our hypothesis, we measured both hydrogen peroxide (H2O2) production in the pulmonary circulation, by digital imaging fluorescent dichlorofluorescein, and microvascular permeability (MVP), by the Evans blue extravasation technique in the nonhypoxic ischemia rat lung. We made a nonhypoxic ischemia rat lung by clamping the left pulmonary artery. Both H2O2 production and MVP increased in the nonhypoxic ischemia rat lung. We also determined the effect of oxygen removal by clamping the bronchus in advance of pulmonary artery occlusion, intercellular adhesion molecule-1 (ICAM-1) neutralization with monoclonal antibody 1A29, and platelet-activating factor (PAF) receptor antagonist CV6209 on H2O2 production and MVP. These treatments inhibited both H2O2 production and MVP increase. At high-power viewing of the fluorescent dichlorofluorescein image, H2O2 was detected in the leukocytes within pulmonary capillaries. These data indicate that the nonhypoxic ischemia without reperfusion alone causes radical production and increases MVP. Furthermore, PAF and ICAM-1 contribute to these reactions.
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PMID:Platelet-activating factor mediates intercellular adhesion molecule-1-dependent radical production in the nonhypoxic ischemia rat lung. 965 Nov 91

The nuclear enzyme poly (ADP-ribose) synthetase (PARS) has been shown to play an important role in the pathogenesis of ischemia/reperfusion injury and circulatory shock. The aim of this study was to investigate whether PARS activity may modulate endothelial-neutrophil interaction. We present evidence that genetic disruption of PARS provides protection against myocardial ischemia and reperfusion injury by inhibiting the expression of P-selectin and intercellular adhesion molecule-1 (ICAM-1) and, consequently, by inhibiting the recruitment of neutrophils into the jeopardized tissue. Furthermore, using in vitro studies, we demonstrate that in fibroblasts lacking a functional gene for PARS, cytokine-stimulated expression of ICAM-1 is significantly reduced compared with fibroblasts from animals with a normal genotype. Similarly, in cultured human endothelial cells, oxidative- or cytokine-dependent expression of P-selectin and ICAM-1 is reduced by pharmacological inhibition of PARS by 3-aminobenzamide. These findings provide the first direct evidence that PARS activation participates in neutrophil-mediated myocardial damage by regulating the expression of P-selectin and ICAM-1 in ischemic and reperfused myocardium, and they also provide the basis for a novel therapeutic approach for the treatment of reperfusion injury.
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PMID:Genetic disruption of poly (ADP-ribose) synthetase inhibits the expression of P-selectin and intercellular adhesion molecule-1 in myocardial ischemia/reperfusion injury. 967 Sep 21

The purpose of our study was to determine whether inhibiting the action of tumor necrosis factor-alpha (TNFalpha) attenuates brain injury and reduces inflammatory responses in the mouse during ischemia and reperfusion. Mice underwent middle cerebral artery occlusion (MCAO) for 1 h followed by 23 h reperfusion. Monoclonal neutralizing anti-murine TNFalpha antibody (mAb) was administrated intraventricularly in the mouse with temporary MCAO. Infarct volume in the anti-TNFalpha mAb treated mice was significantly smaller than that in the control group (p < 0.05). The number of intercellular adhesion molecule-1 (ICAM-1)-positive vessels in the ischemic area of the anti-TNFalpha mAb-treated group was significantly less than that in the control group. Our study demonstrated that blocking TNFalpha reduced brain injury and attenuated ICAM-1 expression during transient cerebral ischemia.
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PMID:Inhibition of TNFalpha attenuates infarct volume and ICAM-1 expression in ischemic mouse brain. 967 7

Ischemia-reperfusion injury is a pathogenic factor in the course of many clinical disorders, such as myocardial infarction, stroke, organ transplantation, burns, and circulatory shock. The extent of ischemia-reperfusion injury is dependent on the number of infiltrating leukocytes. With in vivo microscopy, we evaluated the effect of the recombinant form of soluble murine intercellular adhesion molecule-1 (ICAM-1) on ischemia-reperfusion injury in an animal model. A mesenteric vein was occluded with a clamp for 45 min. During a reperfusion period of 30 min, the number of leukocytes rolling along the endothelium and the number of adherent leukocytes were measured with and without pretreatment with recombinant ICAM-1. The number of leukocytes rolling along the endothelial surface increased more than twofold during postischemic perfusion (P < 0.05). Recombinant ICAM-1 had no effect on leukocyte rolling. In the control group, firm adherence of leukocytes was increased 10-fold. Recombinant ICAM-1 dose dependently reduced firm adhesion to the endothelium in response to prior ischemia. After 30 min, reperfusion pretreatment with recombinant ICAM-1 inhibited leukocyte adherence from 512 +/- 123 to 166 +/- 34 leukocytes/mm2 (P < 0.01). We demonstrate here for the first time that soluble recombinant ICAM-1 is able to reduce leukocyte adherence to mesenteric venules in postischemic reperfusion injury dose dependently. Because soluble ICAM-1 is naturally circulating in human serum, the therapeutic use of soluble recombinant forms of ICAM-1 may represent a physiological way to protect against ischemiareperfusion injury.
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PMID:Soluble ICAM-1 reduces leukocyte adhesion to vascular endothelium in ischemia-reperfusion injury in mice. 968 66

Tumor necrosis factor (TNF) is released during hepatic ischemia/reperfusion (I/R) and plays an important role in the ensuing neutrophil-mediated lung and liver injury. Since TNF is not a direct neutrophil chemotaxin, we hypothesized that TNF may up-regulate neutrophil adhesion molecules, specifically intercellular adhesion molecule-1 (ICAM-1), following hepatic I/R, and that this molecule then plays an important role in tissue neutrophil influx. Rats underwent 90 min of lobar hepatic ischemia with reperfusion. Pulmonary and hepatic ICAM-1 expression were assessed by reverse transcription-polymerase chain reaction, Western blot analysis, and immunohistochemical staining. Increases in hepatic ICAM-1 were demonstrated within 1 h of reperfusion, while increases in pulmonary ICAM-1 were not seen until 6 h of reperfusion. Next, rats were treated with anti-TNF antibody or control antibody without TNF neutralizing properties prior to hepatic I/R. Pretreatment with anti-TNF antibody significantly decreased pulmonary and hepatic ICAM-1 expression after hepatic I/R. We next investigated the effects of pretreatment with anti-ICAM-1 antibodies on the lung and liver injury that follows hepatic I/R. Lung injury was assessed by changes in pulmonary capillary permeability as estimated by extravasation of Evans Blue dye and pulmonary neutrophil influx as measured by lung myeloperoxidase levels. Liver injury was assessed by hepatic neutrophil morphometrics and plasma liver enzymes (alanine aminotransferase). Pretreatment with anti-ICAM-1 antibodies significantly decreased pulmonary capillary permeability, pulmonary myeloperoxidase, hepatic neutrophil influx, and plasma alanine aminotransferase, as compared to animals pretreated with control antibody. These data suggest that TNF is a proximal trigger for pulmonary and hepatic ICAM-1 up-regulation following hepatic ischemia with reperfusion, and that ICAM-1 is important for pulmonary and hepatic neutrophil influx, with the resultant tissue injury, following hepatic I/R.
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PMID:Tumor necrosis factor up-regulates intercellular adhesion molecule 1, which is important in the neutrophil-dependent lung and liver injury associated with hepatic ischemia and reperfusion in the rat. 974 46

Focal cerebral ischemia elicits a strong inflammatory response involving early recruitment of granulocytes and delayed infiltration of ischemic areas and the boundary zones by T cells and macrophages. Infiltration of hematogenous leukocytes is facilitated by an upregulation of the cellular adhesion molecules P-selectin, intercellular adhesion molecule-1 and vascular adhesion molecule-1 on endothelial cells. Blocking of the leukocyte/endothelial cell adhesion process significantly reduces stroke volume after transient, but not permanent middle cerebral artery occlusion. In the infarct region microglia are activated within hours and within days transform into phagocytes. Astrocytes upregulate intermediate filaments, synthesize neurotrophins and form glial scars. Local microglia and infiltrating macrophages demarcate infarcts and rapidly remove debris. Remote from the lesion no cellular infiltration occurs, but astroglia and microglia are transiently activated. Astrocytic activation is induced by spreading depression. In focal ischemia neurons die acutely by necrosis and in a delayed fashion by programmed cell death, apoptosis. Proinflammatory cytokines such as tumor necrosis factor-alpha and interleukin-1 beta are upregulated within hours in ischemic brain lesions. Either directly or via induction of neurotoxic mediators such as nitric oxide, cytokines may contribute to infarct progression in the post-ischemic period. On the other hand, inflammation is tightly linked with rapid removal of debris and repair processes. At present it is unclear whether detrimental effects of inflammation outweigh neuroprotective mechanisms or vice versa. In global ischemia inflammatory responses are limited, but micro- and astroglia are also strongly activated. Glial responses significantly differ between brain regions with selective neuronal death and neighbouring areas that are more resistent to ischemic damage.
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PMID:Inflammation and glial responses in ischemic brain lesions. 976 Jun 99

Leukocyte-endothelial adhesion molecules, critical to the development of acute inflammation, are expressed in brain as part of the acute inflammatory response to traumatic brain injury (TBI). We measured the concentrations of the adhesion molecules P-selectin, ICAM-1, E-selectin, L-selectin, and VCAM-1 in ventricular cerebrospinal fluid (CSF) from children with severe TBI (Glasgow coma score < 8) and compared these findings with those from children with bacterial meningitis. P-selectin, an adhesion molecule associated with ischemia/reperfusion, was increased in children with TBI versus meningitis and control. Univariate and multivariate regression analyses demonstrated associations between CSF P-selectin and child abuse and age of < 4 years, and a significant, independent association between CSF intercellular adhesion molecule-1 (ICAM-1) and child abuse. These results are consistent with a specific acute inflammatory component to TBI in children. Future studies of secondary injury mechanisms and therapy after TBI should assess on the roles of P-selectin and ICAM-1 in injury and repair processes in brain after TBI.
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PMID:Soluble adhesion molecules in CSF are increased in children with severe head injury. 981 34


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