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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Variability in microvessel changes of blood vessel density has prompted us to undertake quantitative morphometric studies of infarcted areas in human brain. In the initial study, brains were obtained at autopsy from 10 patients (ages 45-85). Samples were collected from infarcted hemisphere and controls from the contralateral hemisphere. Formalin fixed, paraffin embedded and thereafter routinely processed sections were stained after Pickworth and with HE. Altogether 6,520 microvessels, representing 10,801 microscopic fields were counted. The Wilcoxon Range test was used for statistical analysis. In 9 of 10 patients in infarcted brain hemispheres, there was a marked increase in microvessel density (p < 0.01), when compared with contralateral brain hemisphere. In addition, a positive correlation was also found between the time of survival and both total density and density of non-perfused blood vessels. To gain a deep insight into the enhanced activity of microvessels, immunocytochemical studies were performed, which have shown, that the vascular endothelial cells in infarcted brain were reactive to two monoclonal antibodies, one, E-9, directed against an activation/proliferation associated endothelial cell specific protein and the other recognizing adhesion molecule VCAM-1. Pan-endothelial Mab PECAM/CD31 was used in those studies for controls and confirmed the obtained results. Our findings strongly support the concept of angiogenesis in the infarcted area. If correlated with morphometric results, it may indicate an important role of microvessels in pathobiology of ischemic stroke.
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PMID:Some remarks on the growth-rate and angiogenesis of microvessels in ischemic stroke. Morphometric and immunocytochemical studies. 750 94

In our studies we used a monoclonal antibody recognizing the vascular adhesion molecule (VCAM-1). Tissue samples were collected at autopsy from human brain infarcts and from brain tumours, removed during surgical procedure (Neurological and Neurosurgical Clinic, Cracow). A novel, unexpected finding were VCAM-1-positive fibrous astrocytes in the stroke tissue, and astrocyte-like cells in the tumours. No staining was obtained either in the contralateral hemisphere or outside of ischemic areas. Likewise, no positive staining of cells was seen outside the tumour tissue. The above findings, taken together, strongly support the concept that astrocytes take part in the immune defense during various pathological processes in the human brain.
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PMID:VCAM-1 expression on reactive and tumour astrocytes. 751 97

The stroke risk factor hypertension may function as a predisposing agent by increasing the vulnerability of blood vessels to thrombosis or hemorrhage. The research here demonstrates that cerebrovascular endothelial cells (EC) from spontaneously hypertensive (SHR) and Wistar-Kyoto normotensive (WKY) rats exhibit similar levels of adhesiveness for syngeneic peripheral blood monocytes (e.g., 22.53 +/- 1.32 and 24.35 +/- 1.16%, respectively). Monocyte adhesion to SHR EC was dramatically increased by treatment of EC with lipopolysaccharide, interferon-gamma, or interleukin-1 beta and tumor necrosis factor-alpha (e.g., 106, 68, and 171%, respectively). Identical treatment of WKY EC also increased adhesion albeit at significantly lower levels than observed on concomitantly tested SHR EC (e.g., 47.8, 12.7, and 60.7%, respectively). Allogeneic combinations of monocytes and EC again demonstrated significantly more upregulation of adhesion by treatment of SHR EC than WKY EC. Characterization of these adhesive interactions revealed the interplay of adhesion pathways, which include lymphocyte functional antigen-1/intercellular adhesion molecule-1 (ICAM-1), Mac-1/ICAM-1, and very late activation antigen-4/vascular adhesion molecule-1 as well as other undetermined mechanisms. In summary, these findings indicate hypertension may enhance responsiveness of endothelium to factors that promote monocyte adhesion.
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PMID:Monocyte adhesion to cerebromicrovascular endothelial cells derived from hypertensive and normotensive rats. 752 99

The intercellular adhesion of circulating leukocytes to vascular endothelium is a prerequisite for leukocyte emigration from the blood to extravascular tissues. This process is facilitated by adhesion molecules on the surfaces of both the vascular endothelial cells and the leukocytes. The experiments presented here demonstrate for the first time that the leukocyte adhesion receptor, intercellular adhesion molecule-1, is constitutively expressed on cultured cerebromicrovascular endothelial cell lines derived from both spontaneously hypertensive (SHR) rats and normotensive Wistar-Kyoto (WKY) rats. Both cultures contained similar numbers of cells constitutively expressing this adhesion molecule (31.4% and 29.6%, respectively). Adhesion molecule expression was up-regulated by interleukin-1 beta, tumor necrosis factor-alpha, interferon-gamma and lipopolysaccharide in a dose- and time-dependent manner. Both cultures exhibited similar maximum levels of adhesion molecule up-regulation to optimal concentrations of all three cytokines. However, SHR endothelial cells were more sensitive to all three cytokines; significantly higher levels of intercellular adhesion molecule-1 expression were seen on SHR as opposed to WKY endothelial cells cultured with sub-optimal cytokine concentrations. It was also observed that lipopolysaccharide up-regulated intercellular adhesion molecule-1 expression on SHR endothelial cells to a greater extent than on WKY endothelial cells. The findings that intercellular adhesion molecule-1 can be up-regulated to a greater degree on SHR endothelial cells may have important implications for in vivo perivascular leukocyte accumulation under hypertensive conditions. These observations indicate a possible mechanism by which hypertension may predispose to the development of disorders such as atherosclerosis and stroke.
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PMID:Adhesion molecules on normotensive and hypertensive rat brain endothelial cells. 790 12

We evaluated the effect of antibodies directed against a leukocyte adhesion molecule (ICAM-1) in an embolic model of stroke followed by thrombolysis with tissue plasminogen activator (tPA). To test whether reperfusion injury after ischemia was related to white cell adhesion, microclots were injected into carotid circulation. The conditions examined were control, alpha-ICAM 5 min following ischemia, tPA 30 min after ischemia, and the combination of alpha-ICAM and tPA. alpha-ICAM and tPA both increased the amount of clot necessary to produce permanent neurological damage. Combined therapy was no more effective than either substance alone. A similar outcome was obtained when tPA was delayed until 90 min postischemia. When thrombolysis was delayed 3 h following embolism, neither tPA nor the tPA/alpha-ICAM combination reduced neurological damage. Thus, the alpha-ICAM antibody and tPA each effectively reduced neurological damage but the interaction was not significant.
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PMID:Monoclonal antibody to the ICAM-1 adhesion site reduces neurological damage in a rabbit cerebral embolism stroke model. 809 42

Immunoreactivity for SP-40,40, a putative complement inhibitor, adhesion or protective molecule, has been examined in a variety of inflammatory CNS lesions that displayed associations between hypertrophic astrocytes and oligodendrocytes, a phenomenon previously suggested to be related to oligodendrocyte phagocytosis or protection. SP-40,40 staining was common and was predominantly limited to hypertrophic astrocytes within lesion areas and diminished beyond the lesion margin. However, there was no consistent relationship between SP-40,40 immunoreactivity and astrocytes associated with oligodendrocytes. Staining for terminal complement complex (C5b-9/SC5b-9) occurred in association with larger vessel walls and microglial cells in the most active lesions, but was never seen in hypertrophic astrocytes. No association between SP-40,40 and complement deposition could be demonstrated. Staining for tumor necrosis factor-alpha showed a few scattered hypertrophic astrocytes to be positive. The findings confirm the presence of these astrocyte/oligodendrocyte interactions in active CNS lesions of varied etiology (multiple sclerosis, stroke and AIDS encephalitis). SP-40,40 immunoreactivity was common to hypertrophic astrocytes regardless of their associations with oligodendrocytes but showed no colocalization with terminal complement complex. Thus, these glial interactions do not apparently involve protection against complement-mediated lysis. Furthermore, the presence of SP-40,40 in astrocytes lacking association with oligodendrocytes did not support a role for this protein functioning as an adhesion molecule in astrocyte/oligodendrocyte associations.
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PMID:SP-40,40 immunoreactivity in inflammatory CNS lesions displaying astrocyte/oligodendrocyte interactions. 844 Sep 94

Acute neutrophil (PMN) recruitment to postischemic cardiac or pulmonary tissue has deleterious effects in the early reperfusion period, but the mechanisms and effects of neutrophil influx in the pathogenesis of evolving stroke remain controversial. To investigate whether PMNs contribute to adverse neurologic sequelae and mortality after stroke, and to study the potential role of the leukocyte adhesion molecule intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of stroke, we used a murine model of transient focal cerebral ischemia consisting of intraluminal middle cerebral artery occlusion for 45 min followed by 22 h of reperfusion. PMN accumulation, monitored by deposition of 111In-labeled PMNs in postischemic cerebral tissue, was increased 2.5-fold in the ipsilateral (infarcted) hemisphere compared with the contralateral (noninfarcted) hemisphere (P < 0.01). Mice immunodepleted of neutrophils before surgery demonstrated a 3.0-fold reduction in infarct volumes (P < 0.001), based on triphenyltetrazolium chloride staining of serial cerebral sections, improved ipsilateral cortical cerebral blood flow (measured by laser Doppler), and reduced neurological deficit compared with controls. In wild-type mice subjected to 45 min of ischemia followed by 22 h of reperfusion, ICAM-1 mRNA was increased in the ipsilateral hemisphere, with immunohistochemistry localizing increased ICAM-1 expression on cerebral microvascular endothelium. The role of ICAM-1 expression in stroke was investigated in homozygous null ICAM-1 mice (ICAM-1 -/-) in comparison with wild-type controls (ICAM-1 +/+). ICAM-1 -/- mice demonstrated a 3.7-fold reduction in infarct volume (P < 0.005), a 35% increase in survival (P < 0.05), and reduced neurologic deficit compared with ICAM-1 +/+ controls. Cerebral blood flow to the infarcted hemisphere was 3.1-fold greater in ICAM-1 -/- mice compared with ICAM-1 +/+ controls (P < 0.01), suggesting an important role for ICAM-1 in the genesis of postischemic cerebral no-reflow. Because PMN-depleted and ICAM-1-deficient mice are relatively resistant to cerebral ischemia-reperfusion injury, these studies suggest an important role for ICAM-1-mediated PMN adhesion in the pathophysiology of evolving stroke.
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PMID:Cerebral protection in homozygous null ICAM-1 mice after middle cerebral artery occlusion. Role of neutrophil adhesion in the pathogenesis of stroke. 855 Aug 36

Platelet volume is a marker of platelet function and activation. It is readily measured as mean platelet volume (MPV) by clinical haematology analysers using sodium citrate as the anticoagulant. Measurement in EDTA can be unreliable since MPV increases significantly in a time-dependent manner. MPV correlates with platelet function and activation, whether measured as aggregation, thromboxane synthesis, beta-thromboglobulin release, procoagulant function, or adhesion molecule expression. MPV is increased in certain vascular risk factor states, including hypercholesterolaemia and diabetes mellitus, but not essential hypertension. It is increased in acute myocardial infarction, acute ischaemic stroke, pre-eclampsia and renal artery stenosis. Importantly, an elevated MPV predicts a poor outcome following myocardial infarction, restenosis following coronary angioplasty, and the development of pre-eclampsia. Research into the epidemiology of MPV is now required to determine whether thrombomegaly is a risk factor for developing vascular disease. Similarly, the physiological mechanisms which regulate MPV within the megakaryocyte need to be elucidated. Whether MPV ever becomes a routinely requested test remains to be seen but changes in methodology will be required first.
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PMID:Platelet size: measurement, physiology and vascular disease. 873 7

Cytokines which promote emigration of leukocytes from the vascular lumen into the injured brain tissue are produced at the site of incipient cerebral infarction. The blood-borne invaders then accelerate the decomposition of brain cells by their toxic by-products, phagocytic action, and by the immune reaction. Recently accumulated data in our laboratories and other research facilities show that depleting the amount of circulating leukocytes or administering anti-inflammatory chemicals such as cytokine blocking agents, anti-adhesion molecule antibodies, and immunosuppressants effectively minimize the size of ischemia induced cerebral infarction. Based on the fact the leukocyte invasion of the affected brain tissue occurs 6 to 24 hours after onset of ischemia, administration of an anti-inflammatory therapy may widen the therapeutic window against stroke.
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PMID:Inflammation of the brain after ischemia. 878 Jul 95

Once thought as immunologically naive, cells from the central nervous system have been shown to become immunologically reactive and produce various substances including cytokines and adhesion molecules. Recent investigations have revealed that mRNAs of certain cytokines such as tumor necrosis factor, interleukin-1, and interleukin-6 are expressed in the ischemic brain of the animals. Chemokines including CINC, MCP-1, and MIP-1, as well as adhesion molecules such as ICAM-1. ELAM and P-selectin were also found to be expressed. Although identification of the cells producing these cytokines were often difficult, neurons, endothelia, activated astrocytes and microglia/macrophages were the likely sources. The induction of these molecules in ischemic brain is time-locked and appears to be controlled in a highly regulated manner during the process of ischemic cascade. The functional role, interrelationship, and basic mechanism of action of these molecules are being increasingly recognized, while trials such as antiadhesion antibody molecules, growth factors, and anticytokine antibodies have been successful in reducing the neuronal damage in animals subjected to ischemic injury. Furthermore, changes of certain cytokines or adhesion molecules have been detected in the serum or cerebrospinal fluid of patients with stroke and related diseases suggesting that these molecules play a role in the pathogenesis of human stroke. Understanding of these cytokine-adhesion molecule cascades in the ischemic brain may allow us to develop new strategies for the treatment of stroke.
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PMID:Cytokines and adhesion molecules in stroke and related diseases. 878 58


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