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

Inflammation has been implicated as a secondary injury mechanism following ischemia and stroke. A variety of experimental models, including thromboembolic stroke, focal and global ischemia, have been used to evaluate the importance of inflammation. The vasculature endothelium promotes inflammation through the upregulation of adhesion molecules such as ICAM, E-selectin, and P-selectin that bind to circulating leukocytes and facilitate their migration into the CNS. Once in the CNS, the production of cytotoxic molecules may facilitate cell death. The macrophage and microglial response to injury may either be beneficial by scavenging necrotic debris or detrimental by facilitating cell death in neurons that would otherwise recover. While many studies have tested these hypotheses, the importance of inflammation in these models is inconclusive. This review summarizes data regarding the role of the vasculature, leukocytes, blood-brain barrier, macrophages, and microglia after experimental and clinical stroke.
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PMID:Inflammatory mechanisms after ischemia and stroke. 1257 22

The aim of this study was to investigate whether soluble adhesion molecule levels differ by ethnic group. Soluble plasma adhesion molecules [soluble P-selectin (sP-selectin), soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1)] were measured in 261 white (120 females), 188 African origin (99 females) and 215 South Asian (99 females) individuals living in England. All were free from coronary heart disease, stroke and other cardiovascular disease, diabetes, drug therapy for hypertension or high lipids, hormone-replacement therapy or oral contraceptive pill. The results of the study indicated that there were important differences in the levels of adhesion molecules by sex and smoking. However, when adjusting for these and other potential confounders, there were no differences in levels between white subjects and individuals of South Asian origin. In contrast, people of African origin had significantly lower levels of sICAM-1 [Caribbean -30% (-36 to -23%); West African -22% (-29 to -15%), values are means (95% confidence intervals)], sVCAM-1 [Caribbean -14% (-19 to -8%); West African -10% (-17 to -3%)] and sP-selectin [Caribbean -10% (-17 to -2%); West African -24% (-31 to -16%)] than white individuals. In conclusion, circulating levels of some soluble adhesion molecules are lower in individuals of Caribbean or West African origin compared with white or South Asian individuals. These relationships may contribute to the low risk of coronary heart disease seen in people of African origin living in England.
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PMID:Ethnic differences in circulating soluble adhesion molecules: the Wandsworth Heart and Stroke Study. 1267 19

We have demonstrated that induction of mucosal tolerance to E-selectin, a cytokine-inducible adhesion molecule restricted to activating blood vessels, prevents ischemic and hemorrhagic stroke in spontaneously hypertensive, genetically stroke-prone (SHR-SP) rats. We now examine whether mucosal tolerance to E-selectin has protective effects in ischemic brain damage after permanent middle cerebral artery occlusion (MCAO) in SHR-SP rats and whether these effects are related to generation of regulatory T cells. Rats were exposed to intranasal administration of E-selectin every other day for 10 days (single tolerization group) or on two tolerization schedules separated by 11 days (booster tolerization group). Control groups received PBS on corresponding schedules. MCAO was performed 48 h after the last dose of E-selectin or PBS. There were 45.8% and 37.9% (P < 0.05) decreases of infarction volume in the E-selectin booster group compared with the PBS group at 6 and 48 h, respectively. Single tolerization with E-selectin had only a slight trend toward a decrease in infarction volume (6.3%). CD8-positive cells were decreased in brains of E-selectin booster animals (46.6%, P < 0.01) compared with controls; splenocyte-culture supernatant levels of IL-10 were increased (59.3%, P < 0.05) in E-selectin booster animals. A decrease of infarction volume (34%, P < 0.05) was also observed in SHR-SP rats subjected to MCAO after adoptive transfer of splenocytes from E-selectin-tolerized compared with PBS-tolerized donors. The results indicate that, in addition to preventing stroke, mucosal tolerance to E-selectin is cytoprotective. Thus, immunomodulation targeted to activated blood vessel segments can both reduce stroke occurrence and attenuate brain damage if a stroke supervenes.
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PMID:Mucosal tolerance to E-selectin provides cell-mediated protection against ischemic brain injury. 1464 8

Ischemia/reperfusion (I/R) occurs in a number of pathological conditions, including myocardial infarction, stroke, and organ transplantation. During the reperfusion phase, leukocytes are recruited into affected tissues, where they can cause tissue damage and organ failure. Various in vitro models have been developed to study the role of adhesion molecules in I/R-mediated leukocyte recruitment. These models traditionally use isolated leukocytes and static conditions and, therefore, may not recapitulate the in vivo situation. We developed two novel in vitro models of I/R-mediated leukocyte recruitment in which leukocyte recruitment was examined using whole blood under shear conditions. Chemical treatments were used to mimic I/R in the first model, while sequential exposure to hypoxia/reoxygenation (H/R) was used to mimic I/R in the second model. We found that leukocytes were recruited from whole blood under shear conditions to endothelial cells treated with chemically induced I/R or H/R. In both models, mRNA for intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin was upregulated. The role of adhesion molecules in leukocyte recruitment differed slightly between the two models, with E-selectin and VCAM-1 playing approximately equal roles in leukocyte recruitment in the chemically induced I/R model and VCAM-1 being a central mediator of leukocyte recruitment in the H/R model.
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PMID:Ischemia/reperfusion induces the recruitment of leukocytes from whole blood under flow conditions. 1508 64

Flow cytometric studies suggest that platelets are activated in ischaemic stroke or transient ischaemic attack (TIA). However, few studies have measured circulating leucocyte-platelet complexes in this patient population. Whole blood flow cytometry was used to quantify the expression of CD62P-, CD63-, and PAC1-binding, and the percentages of leucocyte-platelet complexes in acute (1-27 d, n = 79) and convalescent (79-725 d, n = 70) ischaemic cerebrovascular disease (CVD) patients compared with controls without CVD (n = 27). We performed a full blood count, and measured plasma levels of soluble P-selectin, soluble E-selectin, and von Willebrand factor antigen (VWF:Ag) as additional markers of platelet and/or endothelial cell activation. The median percentage CD62P expression and the median percentage monocyte-platelet complexes were higher in both acute and convalescent CVD patients than controls (P </= 0.02). The mean white cell count and mean VWF:Ag levels were significantly elevated in the acute and convalescent phases after ischaemic stroke or TIA (P </= 0.02). Otherwise, there was no significant increase in any other marker of platelet or endothelial activation in CVD patients. There was a positive correlation between the percentage expression of CD62P and the percentages of both neutrophil-platelet and monocyte-platelet complexes in the acute phase, and the percentages of all leucocyte-platelet complexes in the convalescent phase after ischaemic CVD. This study provides evidence for ongoing excessive platelet and/or endothelial activation in ischaemic CVD patients despite treatment with antithrombotic therapy.
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PMID:Platelet degranulation and monocyte-platelet complex formation are increased in the acute and convalescent phases after ischaemic stroke or transient ischaemic attack. 1518 Aug 68

Focal ischemia followed by reperfusion initiates a harmful P- and E-selectin-mediated recruitment of leukocytes in brain microvasculature. In this study, we tested whether a novel magnetic resonance (MR) contrast agent (Gd-DTPA-sLe(x) A), which is designed to bind to activated endothelium could be detected by MR imaging (MRI) in a focal stroke mouse model. MRIs (9.4T) of the brain were acquired 24 hours after transient middle cerebral artery occlusion. T1 maps were acquired repeatedly before and up to 1.5 hours after the intravenous injection of either Gd-DTPA or Gd-DTPA-sLe(x) A. Analysis of images included a pixel-by-pixel subtraction of T1 maps from the precontrast T1 maps and quantification of T1 within the ischemic area. After injection of Gd-DTPA-sLe(x) A, T1 decreased compared with precontrast levels, and an interhemispheric difference between the pre-post contrast T1 developed within the stroke lesion at a mean time of 52 minutes after injection (p < 0.05). Animals injected with Gd-DTPA did not exhibit changes in T1 signal intensity between regions of the ipsilateral and contralateral hemispheres, indicating that the reductions in T1 observed with Gd-DTPA-sLe(x) A were unrelated to blood-brain barrier breakdown. Fluorescent-labeled sLe(x) A administered intravenously was observed to bind to the endothelium of injured but not control brain. The study suggests that the contrast agent Gd-DTPA-sLe(x) A can be used to visualize early endothelial activation after transient focal ischemia in vivo with MRI.
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PMID:MR molecular imaging of early endothelial activation in focal ischemia. 1523 8

To test the hypothesis that the new CHADS2 and Framingham point-based risk stratification scores could be related to plasma vWf (a plasma index of endothelial damage/dysfunction) and soluble E-selectin (an index of endothelial activation) levels in a large cohort of AF patients, we studied 200 consecutive patients (101 male; 72+/-9 years) attending our anti-coagulation clinic for the initiation of anticoagulation treatment with acenocoumarol. AF patients had a median CHADS2 score of 2 (1-2) and a median Framingham point-based risk score of 14 (9-21). Results of research indices in our AF patients were as follows: vWf 142.8+/-41.8 IU/dL and sE-sel 44 (31-62) ng/mL. There were significant correlations between plasma vWf levels and both risk CHADS2 and Framingham risk scores (vWf-CHADS2 risk score: Spearman, r=0.249, p<0.001; vWf-Framingham risk score: r=0.294, p<0.001). sE-sel did not show any significant correlation with both risk scores (sE-sel-CHADS2 risk score: r=-0.054, p=0.460; sE-sel-Framingham risk score: r=0.062, p=0.460). There were no statistically significant correlations between vWf and sE-sel (r=-0.127, p=0.081). Both CHADS2 and Framingham risk scores were significantly correlated with each other, r=0.627, p<0.001. In conclusion, in a wide cohort of non-selected and consecutive AF patients, endothelial damage/dysfunction (assessed by plasma vWf levels) but not endothelial activation (sE-sel) correlated with two new risk stratification scores for stroke in AF. Further prospective studies are needed to assess the prognostic role of prothrombotic indices in AF in relation to stroke and thromboembolic events, and their role in complementing clinical risk stratification schemas.
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PMID:Correlation of plasma von Willebrand factor levels, an index of endothelial damage/dysfunction, with two point-based stroke risk stratification scores in atrial fibrillation. 1603 17

Normal adults have very few circulating endothelial cells (CECs) in their blood, but increased levels have been shown in association with conditions associated with endothelial damage such as myocardial infarction and stroke. As atrial fibrillation (AF) is associated with a hypercoagulable state and abnormalities of plasma indices of endothelial damage/dysfunction, we hypothesised that CECs would also be raised in this condition, and would correlate with these plasma markers. We measured CECs (by immunofluoresence) as an indicator of frank endothelial damage, alongside 3 plasma indices of endothelial perturbation: von Willebrand factor (vWf), soluble E-selectin and soluble thrombomodulin (sTM) (all ELISA) in 28 patients with chronic 'stable' AF, 63 patients with AF plus an acute cardiovascular or cerebrovascular event as positive controls, and 20 healthy subjects in sinus rhythm as negative controls. Chronic 'stable' AF patients had significantly higher levels of plasma vWf (p<0.001 ), but comparable numbers of CECs (p=0.1638) in comparison to healthy controls. In patients with AF associated with an acute cardiovascular or cerebrovascular event, levels of CECs (p<0.0001) and sTM (p=0.004), but not vWf or sEsel, were significantly increased in comparison to chronic 'stable' AF patients. Patients with uncomplicated AF have abnormal systemic endothelial damage/dysfunction, as evident by increased plasma vWf levels, but normal numbers of CECs, compared to subjects in sinus rhythm. However, following clinical complications, such as stroke or significant haemodynamic compromise, further endothelial disturbance (as indicated by high levels of sTM and CECs) suggests additional endothelial damage.
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PMID:Circulating endothelial cells in atrial fibrillation with and without acute cardiovascular disease. 1627 Jun 20

Increased numbers of CD146-bearing circulating endothelial cells (CECs) in the peripheral blood probably represent the most direct evidence of endothelial cell damage. As acute ischaemic strokes are associated with endothelial abnormalities, we hypothesised that these CECs are raised in acute stroke, and that they would correlate with the other indices of endothelial perturbation, i.e. plasma von Willebrand factor (vWf) and soluble E-selectin. We studied 29 hypertensive patients (19 male; mean age 63 years) who presented with an acute stroke and compared them with 30 high risk hypertensive patients (21 male; mean age 62 years) and 30 normotensive controls (16 male; mean age 58 years). CECs were estimated by CD146 immunobead capture, vWf and soluble E-selectin by ELISA. Patients with an acute ischaemic stroke had significantly higher numbers of CECs/ml of blood (p<0.001) plasma vWf (p=0.008) soluble E-selectin (p=0.002) and higher systolic blood pressure (SBP) as compared to the other groups. The number of CECs significantly correlated with soluble E-selectin (r=0.432, p<0.001) and vWf (r=0.349, p=0.001) but not with SBP (r=0.198, p=0.069). However, in multivariate analysis, only disease group (i.e. health, hypertension or stroke) was associated with increased CECs. Acute ischaemic stroke is associated with increased numbers of CECs. The latter correlate well with established plasma markers of endothelial dysfunction or damage, thus unequivocally confirming severe vasculopathy in this condition. However, the greatest influence on CECs numbers was clinical group.
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PMID:Circulating endothelial cells in acute ischaemic stroke. 1627 Jun 21

The metabolic syndrome, which is very common in the general population, is defined by the clustering of several classic cardiovascular risk factors, such as type 2 diabetes, hypertension, high triglycerides and low high-density lipoprotein cholesterol (HDL). Central obesity and insulin resistance, which are the two underlying disorders of the syndrome, are further risk factors for cardiovascular disease. Moreover, a panel of novel (non-traditional) risk factors are ancillary features of the metabolic syndrome. They include biomarkers of chronic mild inflammation (e.g. C-reactive protein, CRP), increased oxidant stress (e.g. oxidized low density lipoprotein, LDL), thrombophilia (e.g. plasminogen activator inhibitor-1, PAI-1) and endothelial dysfunction (e.g. E-selectin). Therefore, subjects with the metabolic syndrome are potentially at high risk of developing atherosclerosis and clinical cardiovascular events.In recent years several longitudinal studies have confirmed that subjects with the metabolic syndrome present with atherosclerosis and suffer from myocardial infarction and stroke at rates higher than subjects without the syndrome. The risk of cardiovascular disease (CVD) is particularly high in women with the syndrome and in subjects with pre-existing diabetes, CVD and/or high CRP. However, an increased risk is already present in subjects with a cluster of multiple mild abnormalities. The risk related to the metabolic syndrome is definitely higher when subjects affected are compared to subjects free of any metabolic abnormality.
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PMID:The metabolic syndrome and cardiovascular disease. 1644 90


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