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

Although ischaemic stroke is associated with accentuated platelet function, it remains unclear whether this applies to all sub-types, especially lacunar infarcts, which differ from cortical infarction in their patho-aetiology. Similarly, conflicting evidence suggests that haemorrhagic stroke may, or may not, be associated with a hypothrombotic state. Levels of von Willebrand factor (vWF), fibrinogen, and P-selectin were measured within 48 h of ictus in 163 patients with acute ischaemic stroke and 40 patients with acute primary intracerebral haemorrhage, and 33 age, gender and race matched-controls. vW F (IU/dl) was significantly increased in both cortical and lacunar ischaemic stroke, and haemorrhagic stroke, as compared with controls, median (semiquartile range): 158 (25) vs 144 (19) vs 147 (24) vs 114 (16), respectively. Similarly, fibrinogen (g/litre) was increased: 4.80 (0.90) vs 4.65 (0.70) vs 4.35 (0.83) vs 3.70 (0.70). In contrast, soluble P-selectin (ng/ml) was increased in cortical stroke as compared with lacunar infraction patients or controls: 408 (101) vs 300 (108) vs 324 (121), respectively; P-selectin was not increased in haemorrhagic stroke, 360 (153). Both vW F and fibrinogen correlated with 3-month functional outcome (modified Rankin score): r = 0.371 (2 P = 0.0006), and r = 0.195 (2 P = 0.042), respectively; however, P-selectin was not associated with outcome: r = 0.188 (2 P = 0.084). The results suggest that increases in vW F and fibrinogen in all types of stroke reflect an acute phase response; in contrast, increased soluble P-selectin levels in cortical stroke, but not lacunar infarction, suggest that platelets contribute to the patho-aetiology of some subtypes of ischaemic stroke.
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PMID:Von Willebrand factor, P-selectin and fibrinogen levels in patients with acute ischaemic and haemorrhagic stroke, and their relationship with stroke sub-type and functional outcome. 1679 94

Prolactin and leptin are newly recognised platelet co-stimulators due to potentiation of ADP-induced platelet aggregation. Elevated leptin levels have recently been found to be a risk factor for ischemic stroke in both men and women, and especially in combination with increased blood pressure for hemorrhagic stroke in men. Until now an association between hyperprolactinemia and ischemic stroke has not been investigated systematically. We determined plasma prolactin and leptin levels as well as platelet P-selectin expression in 36 patients with ischemic stroke or transient ischemic attack and detected a significant correlation between increased prolactin values and enhanced ADP stimulated P-selectin expression on platelets. In contrast, no correlation of leptin values with platelet P-selectin expression was found. Next we determined plasma prolactin and leptin as well as acquired and congenital risk factors of thrombophilia in patients with first-ever non-hemorrhagic stroke with or without atrial fibrillation. Excluding patients with such preexisting risk factors, 21 patients with and 59 patients without atrial fibrillation were identified. Patients without atrial fibrillation revealed significantly higher plasma prolactin levels than patients with atrial fibrillation. Furthermore, the influence of aspirin or clopidogrel on prolactin stimulated P-selectin expression in vitro was tested, showing that aspirin was without effect, whereas clopidogrel significantly inhibited platelet P-selectin expression. In conclusion, hyperprolactinemia might be a novel risk factor for stroke mediating its thrombogenic effect through enhanced platelet reactivity, and this might correspond to a higher efficacy of antiplatelet combination therapy with clopidogrel compared to aspirin therapy alone.
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PMID:Enhanced platelet activation by prolactin in patients with ischemic stroke. 1680 49

Several studies have stressed the involvement of inflammation in the pathophysiology of acute brain ischemia, but the role of immunoinflammatory activation in diabetic stroke patients has not yet been fully evaluated. The aim of our study was to evaluate immunoinflammatory activation of acute phase of stroke in relation to time of symptoms onset, diabetic state and diagnostic subtype. We enrolled 60 patients (32 diabetics; 28 non- diabetics) with acute ischemic stroke and 123 subjects without acute ischemic stroke, and measured levels of IL-1beta, TNF-alpha IL-6, IL-10, E-selectin, P-selectin, sICAM-1, sVCAM-1, VWF, 24-72 h and 7-10 days after stroke onset; TPA, PAI-1 plasma levels at 24-72h. Our stroke patients exhibited significantly higher plasma levels of cytokines, selectins, adhesion molecules and PAI-1, and diabetic stroke patients exhibited higher plasma levels of PAI-1 in comparison with non-diabetic ones. Lacunar strokes in comparison with those non-lacunar exhibited significantly lower levels of TNF-alpha and IL1-beta P-selectin and ICAM-1. Moreover, diabetic patients with lacunar strokes exhibited a minor grade of immunoinflammatory activation of the acute phase at 24-72h and 7-10 days after stroke onset. The minor grade of immunoinflammatory activation of patients with lacunar strokes, particularly diabetic ones, could be related to the minor extension of the infarct size, owing to the typical microvascular disease of diabetic subjects which could also explain the reported better outcome of this subtype of ischemic stroke.
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PMID:Immunoinflammatory activation during the acute phase of lacunar and non-lacunar ischemic stroke: association with time of onset and diabetic state. 1702 49

The mechanisms that contribute to inflammatory damage following ischemic stroke are poorly characterized, but studies indicate a role for both complement and P-selectin. In this study, we show that compared with wild-type mice, C3-deficient mice showed significant improvement in survival, neurological deficit, and infarct size at 24 h after middle cerebral artery occlusion and reperfusion. Furthermore, P-selectin protein expression was undetectable in the cerebral microvasculature of C3-deficient mice following reperfusion, and there was reduced neutrophil influx, reduced microthrombus formation, and increased blood flow postreperfusion in C3-deficient mice. We further investigated the use of a novel complement inhibitory protein in a therapeutic paradigm. Complement receptor 2 (CR2)-Crry inhibits complement activation at the C3 stage and targets to sites of complement activation. Treatment of normal mice with CR2-Crry at 30 min postreperfusion resulted in a similar level of protection to that seen in C3-deficient mice in all of the above-measured parameters. The data demonstrate an important role for complement in cerebrovascular thrombosis, inflammation, and injury following ischemic stroke. P-selectin expression in the cerebrovasculature, which is also implicated in cerebral ischemia and reperfusion injury, was shown to be distal to and dependent on complement activation. Data also show that a CR2-targeted approach of complement inhibition provides appropriate bioavailability in cerebral injury to enable complement inhibition at a dose that does not significantly affect systemic levels of serum complement activity, a potential benefit for stroke patients where immunosuppression would be undesirable due to significantly increased susceptibility to lung infection.
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PMID:Complement-dependent P-selectin expression and injury following ischemic stroke. 1708 45

Epidemiological studies have linked levels of particulate matter (PM) in ambient air to cardiovascular mortality and hospitalizations for myocardial infarction (MI) and stroke. Thrombus formation plays a primary role in potentiating acute cardiovascular events, and this study was undertaken to determine whether pulmonary exposure to PM alters hemostasis. PM was collected from the Chapel Hill, NC airshed and was administered to mice by intratracheal instillation at a dose previously shown to exacerbate myocardial ischemia-reperfusion injury. Twenty-four hours after exposure, an increase occurred in the number of circulating platelets and plasma concentrations of fibrinogen and soluble P-selectin. The concentration of tissue factor pathway inhibitor (TFPI) in plasma was decreased, whereas the plasma concentration of plasminogen activator inhibitor (PAI-1) was increased. Consistent with these observations, bleeding time from a tail-tip transection was shortened. These results provide evidence that PM exposure alters hemostasis in otherwise healthy animals and may thereby promote clot formation and impede clot resolution in susceptible individuals. The results also establish definite hemostatic endpoints that can be used to further investigate the effects of dose and particle characteristics on the toxicity of ambient particles.
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PMID:Effect of ambient particulate matter exposure on hemostasis. 1754 51

Recent advances in our understanding of cardiovascular disease have revealed that atherothrombotic events, such as myocardial infarction and ischemic stroke, are the end result of a complex inflammatory response to multifaceted vascular pathology. As well as initiating thrombus formation at the site of a ruptured atherosclerotic plaque, platelets play a key role in vascular inflammation, through release of their own pro-inflammatory mediators and interactions with other relevant cell types (endothelial cells, leukocytes, and smooth muscle cells). An increasing body of literature shows that inflammatory biomarkers can be used to predict atherothrombotic risk and that antiplatelet therapy may reduce the levels of these markers. Acetylsalicylic acid (ASA) has been attributed with reducing levels of the transcription factor nuclear factor kappaB (NF-kappaB), C-reactive protein, and soluble CD40 ligand, although the evidence relating to the latter two markers is conflicting. There is also substantial evidence that therapy with clopidogrel, a specific antagonist of the platelet P2Y12 ADP-receptor, also leads to reductions in serum levels of CD40 ligand, C-reactive protein, P-selectin, and platelet-leukocyte aggregate formation. Beneficial effects of clopidogrel on inflammatory markers have been demonstrated across the spectrum of atherothrombotic disease (acute coronary syndrome patients, patients undergoing percutaneous coronary intervention (PCI), acute ischemic stroke patients, and those with peripheral arterial disease). Oral glycoprotein (GP) IIb/IIIa receptor antagonists, at doses that achieve moderate levels of receptor blockade, may paradoxically be associated with platelet-mediated pro-inflammatory effects. A similar phenomenon has been observed with intravenous GP IIb/IIIa antagonists in vitro, but most often at low doses, and data from clinical studies suggest that these agents may actually attenuate release of inflammatory mediators when administered at doses producing more complete receptor blockade.
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PMID:Clinical evidence for anti-inflammatory effects of antiplatelet therapy in patients with atherothrombotic disease. 1761 99

The objective of this article is to illustrate both the potential and the limitations of molecular imaging in stroke research. By molecular imaging we mean the visual representation of biological processes at the cellular and molecular level. The use of molecular imaging for stroke diagnosis is still at a very preliminary stage and many of these procedures have only been tested in animals. In rats, stroke therapy using stem cells can be monitored by magnetic resonance imaging (MRI), green fluorescent protein (GFP) or luciferase (LUC) imaging. The migration of macrophages, which take up intravenously administered iron-based contrast agents and then migrate to the area of infarction, can already be observed in stroke patients. With MRI, the new agent Gd-DTPA-sLexA that binds to E- and P-selectin can specifically visualize selectin-mediated early endothelial activation after transient focal ischemia "in vivo". Decreased glial fibrillary acidic protein (GFAP) gene expression can be imaged in vivo by scintigraphy 24 hours after cerebral ischemia using a peptide nucleic acid antisense conjugate labeled with 111In and that hybridizes to the rat GFAP mRNA. Technetium-99m hydrazine nicotinamide-labeled HYNIC-annexin V SPECT can not only detect sites of neuronal injury in stroke patients but also can monitor the effects of neuroprotective therapy with a monoclonal antibody raised against FasLigand (FasL) in rats. Finally, information about cell metabolism in the infarct region can be gained using certain intracellular tracers [e.g. 18F-fluoromisonidazole (FMISO)]. Imaging benzodiazepine receptors with 11C-flumazenil (FMZ) can distinguish between irreversibly damaged and viable penumbra tissue early after stroke.
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PMID:Future contrast agents for molecular imaging in stroke. 1762 9

Inflammation has been implicated as a secondary mechanism underlying neuronal injury induced by ischemia. A variety of experimental models, including thromboembolic stroke, focal and global ischemia, have been used to evaluate contributions of inflammation to neuronal damage. The vasculature endothelium promotes inflammation through upregulation of adhesion molecules such as intercellular adhesion molecule (ICAM), E-selectin, and P-selectin that bind to circulating leukocytes and facilitate migration of leukocytes into the central nervous system (CNS). Once being in the CNS, leukocytes produce cytotoxic molecules that promote cell death. The response of macrophages and microglia to injury may either be beneficial by scavenging necrotic debris or be detrimental by facilitating cell death of neurons that would otherwise recover. While many studies have tested these hypotheses, the significance of inflammation in stroke models is inconclusive. This review summarizes data regarding roles of cell adhesion molecules, astrocytes, microglia and leukocytes in stroke.
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PMID:Inflammatory mechanism in ischemic neuronal injury. 1770 46

Increased ambient air particulate matter (PM) concentrations are associated with risk for myocardial infarction, stroke, and arrhythmia, and ultrafine PM (UFPM) might be particularly toxic to the cardiovascular system. Recent epidemiological studies are beginning to offer mechanistic insights, yet the rodent model remains a valuable tool to explore potential mechanisms. This article reviews a series of studies from our laboratory demonstrating the promise of mouse models to link health effects to biological mechanisms. Specifically, data from 6- to 10-wk-old male ICR mice exposed to intratracheal instillation of 100 microg of UFPM collected from the Chapel Hill, NC airshed are described. Studies of ischemia/reperfusion, vascular function, and hemostasis are described. In summary, UFPM exposure doubles the size of myocardial infarction attendant to an episode of ischemia and reperfusion while increasing postischemic oxidant stress. UFPM alters endothelial-dependent and -independent regulation of systemic vascular tone; increases platelet number, plasma fibrinogen, and soluble P-selectin levels; and reduces bleeding time, implying enhanced thrombogenic potential. Taking these findings together, this model of acute UFPM exposure in the mouse indicates that UFPM induces a prothrombotic state and decreases vasomotor responsiveness, thereby offering insight into how UFPM could contribute to vascular events associated with thrombosis and ischemia and increasing the extent of infarction.
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PMID:Cardiac and vascular changes in mice after exposure to ultrafine particulate matter. 1788 53

Thrombocyte activation and subsequent aggregate formation play a pivotal role in arterio-arterial embolism in high grade carotid artery stenosis. The aim of this study was to test the hypothesis that the amount of activated thrombocytes would differ with the degree of stenosis. In 19 patients with asymptomatic carotid artery stenosis > 70%, 11 patients with low grade carotid disease and a luminal narrowing of < 70%, and 13 healthy controls in vivo thrombocyte activation was determined by the surface thrombocyte expression of P-selectin before and after thrombin stimulation by whole blood flow cytometry. Soluble P (sP)-selectin in serum was measured by ELISA. We found that thrombocyte activation significantly increased with the degree of stenosis in a multiple correlation analysis corrected for age, sex, and cardiovascular risk factors. Only thrombocyte P-selectin expression and sP-selectin serum concentrations were able to discriminate the patient groups in a multivariate analysis, however, only thrombocyte P-selectin expression was an independent variable. In vivo thrombocyte activation, then, increases with the degree of carotid stenosis. Flow cytometry is especially useful in the evaluation of the thrombocyte activation state in patients with cerebrovascular disease.
J Stroke Cerebrovasc Dis
PMID:Thrombocyte activation increases with the degree of carotid artery stenosis. 1790 94


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