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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 cytokines are multipotent mediators of inflammation and immunity that can affect key functions of vascular wall cells. Growing evidence suggests that cytokines participate as autocrine or paracrine mediators in atherogenesis, as cells in lesions can both produce and respond to these mediators. The functions of vascular wall cells regulated by cytokines may influence lesion initiation, progression, or complication. For example, cytokines can regulate the expression of adhesion molecules crucial to the recruitment of leukocytes to lesions, including vascular cell adhesion molecule-1 (VCAM-1). Cytokines such as interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) can regulate the production of monocyte chemoattractant protein-1 (MCP-1), a potential signal for directed migration of monocytes into the intima. Cytokines can also regulate genes that encode other growth factors and cytokines themselves. TNF-alpha can induce IL-1 mRNA in human endothelial (EC) and smooth-muscle cells (SMC). IL-1 and TNF-alpha can augment the production by vascular cells of macrophage-colony stimulating factor (M-CSF), which may promote growth and activation of mononuclear phagocytes. Cytokines can exert both pro-and antiatherogenic actions. Activated T cells in human atheroma may secrete the lymphokine IFN-gamma, an inhibitor of SMC proliferation. Cytokines influence vasomotor tone in arteries, e.g., by inducing a form of nitric oxide synthase, the enzyme that synthesizes the vasodilatory nitric oxide radical. The cytokines also modulate endothelial functions that govern the formation and stability of blood thrombi. Finally, in the late stages of the disease, matrix metalloproteinases derived from macrophages or smooth-muscle cells themselves may contribute to weakening of the fibrous cap in the vulnerable shoulder area, promoting plaque rupture and occlusive thrombosis, culminating in the dramatic clinical manifestations of atherosclerosis, including myocardial infarction and stroke. Thus, cytokines can influence multiple aspects of atherogenesis and provide new and interesting targets for therapeutic intervention.
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PMID:Cytokines regulate vascular functions related to stability of the atherosclerotic plaque. 869 71

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

We investigated the role of endothelial cell and leukocyte adhesion in the pathophysiology of acute stroke. The immunocytochemical expression of adhesion molecules in brain tissue from six patients who died following acute ischaemic stroke showed weak endothelial expression of intercellular adhesion molecule-1 (ICAM-1), but intense expression of vascular cell adhesion molecule-1 (VCAM-1) by astrocytes and endothelial cells from the infarcted, but not the non-infarcted areas. We also measured soluble adhesion molecules E-selectin, ICAM-1, VCAM-1 and von Willebrand factor (all by enzyme-linked immunosorbent assay) in 21 patients after an acute ischaemic stroke (ictus < 12 h), and again 3 months later. Blood levels in the stroke patients were compared with 82 healthy controls and 22 subjects with carotid atherosclerosis. Compared with healthy controls, both patient groups had raised levels of von Willebrand factor (P < 0.02) but the level of soluble VCAM-1 was raised only in patients with acute stroke (P < 0.02). Levels of von Willebrand factor and soluble VCAM-1 in the stroke patients were still high at 3 months follow-up. We suggest that there might be changes in adhesion molecule expression and release in the acute and chronic stages of ischaemic stroke, where blood levels are related to immunocytochemical findings on infarcted brain. These changes may perhaps be part of the complex pathophysiological responses to infarction and repair of brain tissue following stroke.
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PMID:Soluble intercelluar adhesion molecule-1, E-selectin, vascular cell adhesion molecule-1 and von Willebrand factor in stroke. 1045 19

Fabry disease is an X-linked recessive disorder resulting in the deposition of globotriaosylceramide in numerous cell types including vascular endothelial cells. Because this disease is associated with vascular injury and a high recurrence rate of thrombotic events, measurements of factors regulating endothelium and leukocyte interaction may provide insight into the mechanisms leading to a prothrombotic state. Twenty-five patients with Fabry disease and 25 control subjects participated in the study. Plasma from all 25 Fabry patients and 15 of the 25 controls were studied for multiple endothelial factors. Leukocyte integrins were measured by flow cytometry in 21 Fabry patients and 10 controls. The concentrations of soluble intercellular adhesion molecule-1, vascular cell adhesion molecule-1, P-selectin, and plasminogen activator inhibitor were significantly higher and thrombomodulin was significantly lower in Fabry patients. Expression of the integrin CD11b on monocytes was also significantly higher in the Fabry patients. This study reveals measurable evidence for endothelium and leukocyte activation that is consistent with a prothrombotic state in Fabry patients compared with controls. Further investigations of these findings may help to understand the mechanism of stroke in Fabry disease and provide indicators (or markers) of efficacy of future therapeutic intervention.
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PMID:Profile of endothelial and leukocyte activation in Fabry patients. 1066 94

Regulation of the adhesion molecules expression by cytokine in vascular endothelial cells was investigated. Human umbilical vein endothelial cells (HUVEC) were stimulated with cytokines, TNF-alpha (1-250 U/ml) or IL-1 beta (0.1-50 U/ml) for 24 h. HUVEC were also cultured with cytokines, TNF-alpha (100 U/ml) or IL-1 beta (10 U/ml), for 4-72 h, cell surface expression of adhesion molecules (ICAM-1 and VCAM-1) were detected and quantitated by immunocytochemical methods and computerized imaging analysis technique. Adhesion molecules expression were up-regulated by TNF-alpha, IL-1 beta in a concentration- and time-dependent manner. Some significant differences were observed between the effects of cytokines on the ICAM-1 and on VCAM-1 expression. Cytokines might directly induce the expression of ICAM-1 and VCAM-1 in vascular endothelial cells. Our observations indicate differential functions of the two adhesion molecules during the evolution of inflammatory responses in stroke.
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PMID:Cytokine-induced cell surface expression of adhesion molecules in vascular endothelial cells in vitro. 1152 54

Atherosclerotic plaques were likened histologically to healing inflammatory lesions by Russell Ross, who proposed a "response to injury" hypothesis for their formation. More recently, intraplaque inflammation has been postulated to play a role in thinning of the fibrous cap, plaque rupture, and superadded thrombosis. Potential causes for vascular injury include mechanical stress, smoke exposure, hypercholesterolemia, hyperhomocysteinemia, and chronic infection (direct, or indirect). Blood levels of inflammatory markers (e.g., C-reactive protein [CRP]; serum amyloid A [SAA]; fibrinogen; plasma viscosity; erythrocyte sedimentation rate [ESR]; leukocyte count, low serum albumin) have been associated with vascular risk factors and with prevalent and incident atherothrombotic cardiovascular disease (CVD) (coronary heart disease, [CHD]; stroke; and peripheral arterial disease). More recently, cytokines (e.g., interleukin-6 [IL-6]) and soluble adhesion molecules (e.g., intercellular adhesion molecule-1, vascular cell adhesion molecule-1) have been associated with both risk factors and disease; and offer potential therapeutic targets for nonspecific "anti-inflammatory" treatment of arterial disease. Infections associated with arterial disease include specific infections (Chlamydia pneumoniae, Helicobacter pylori) and nonspecific infections (periodontal infections, respiratory tract infections). Recent meta-analyses have shown that associations of serum markers of C. pneumoniae and H. pylori with arterial disease, risk factors, or potential intermediary mechanisms for disease are weaker than was first suggested by early reports. Likewise, further studies and meta-analyses are required to evaluate the epidemiologic relationships of CVD to periodontal infection and disease and to chronic pulmonary infections and disease. The weaker the associations between chronic infections and CVD, the larger is the size of randomized controlled trials required to establish (or exclude) a preventive effect of infection treatment. While control of chronic infection in the mouth, stomach or lungs is appropriate for its local effects, proving its efficacy in prevention of CVD presents a continuing challenge to medical science.
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PMID:The relationship between infection, inflammation, and cardiovascular disease: an overview. 1188 52

Stroke-induced inflammatory reaction leads to the accumulation of leukocytes in the brain ischaemic region, where they exert a detrimental effect--promotion and extension of cerebral damage. Intracerebral infiltration of peripheral blood leukocytes requires prior endothelial-leukocyte interactions that are mediated by such cell surface proteins as adhesion molecules. Among adhesion molecules, it is the immunoglobulin gene superfamily (IgSF) that is responsible for strong attachment and transendothelial migration of leukocytes. The principal members of IgSF are: intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and platelet endothelial cell adhesion molecule-1 (PECAM-1). In this review the following issues were described and discussed: an increased expression of ICAM-1 and VCAM-1 in ischaemic brain as well as a detection of their soluble(s) forms in sera of stroke victims. The presented data suggest the involvement of both ICAM-1 and VCAM-1 in the sequence and timing of the infiltration of leukocytes into the brain ischaemic zone after stroke. They have also revealed changes in serum concentrations of sICAM-1 and sVCAM-1 that are characteristic for stroke. Recently, increase in sPECAM-1 levels in serum and cerebrospinal fluid (CSF) has been shown within 24 h of the onset of stroke, having indirectly suggested involvement of the molecule in the inflammatory events during the early phase of stroke.
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PMID:Adhesion molecules of immunoglobulin gene superfamily in stroke. 1190 44

Interleukin-1 (IL-1) is induced immediately after insults to the brain, and elevated levels of IL-1 have been strongly implicated in the neurodegeneration that accompanies stroke, Alzheimer's disease, and multiple sclerosis. In animal models, antagonizing IL-1 has been shown to reduce cell death; however, the basis for this protection has not been elucidated. Here we analyzed the response to penetrating brain injury in mice lacking the type 1 IL-1 receptor (IL-1R1) to determine which cellular and molecular mediators of tissue damage require IL-1 signaling. At the cellular level, fewer amoeboid microglia/macrophages appeared adjacent to the injured brain tissue in IL-1R1 null mice, and those microglia present at early postinjury intervals retained their resting morphology. Astrogliosis also was mildly abrogated. At the molecular level, cyclooxygenase-2 (Cox-2) and IL-6 expression were depressed and delayed. Interestingly, basal levels of Cox-2, IL-1, and IL-6 were significantly lower in the IL-1R1 null mice. In addition, stimulation of vascular cell adhesion molecule-1 mRNA was depressed in the IL-1R1 null mice, and correspondingly, there was reduced diapedesis of peripheral macrophages in the IL-1R1 null brain after injury. This observation correlated with a reduced number of Cox-2+ amoeboid phagocytes adjacent to the injury. In contrast, several molecular aspects of the injury response were normal, including expression of tumor necrosis factor-alpha and the production of nerve growth factor. Because antagonizing IL-1 protects neural cells in experimental models of stroke and multiple sclerosis, our data suggest that cell preservation is achieved by abrogating microglial/macrophage activation and the subsequent self-propagating cycle of inflammation.
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PMID:The type 1 interleukin-1 receptor is essential for the efficient activation of microglia and the induction of multiple proinflammatory mediators in response to brain injury. 1212 68


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