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

Human platelets release two major classes of vasoactive mediators during the secretion reaction: arachidonic acid metabolites and biogenic amines. All of these compounds, in particular thromboxane A2, PGF2 alpha, and serotonin (5-HT), are potent constrictors of human cerebral arteries in vitro. This contractile action of platelet-derived vasoconstrictors, as well as their prothrombotic activity, is antagonized by the vascular endothelium. Atherosclerotic alterations of the vessel wall endothelium, typical for cerebral ischemia and stroke, are associated with platelet hyperreactivity and enhanced mediator release during stimulation. Inhibition of platelet (hyper)function by acetylsalicylic acid or ticlopidine has clear protective effects in high-risk patients, underlining the significance of these platelet-derived products for cerebral thromboembolism and vasoconstriction. Whether more selective inhibitors of thromboxane generations or action are equally effective remains to be determined.
Stroke 1990 Dec
PMID:Platelets as a source of vasoactive mediators. 212 87

A method for long-term culture of microvascular endothelial cells from Mongolian gerbil brain and their biologic properties in vitro are described. Microvessels were isolated from Mongolian gerbil brain by a combination of enzymatic treatment, filtration, and centrifugation and were seeded onto a gelatin-coated dish. A morphologically homogeneous cell plaque showing a cobblestone appearance was removed 2 to 3 weeks after the seeding, and the cells were subcultured. The cultured cells grew as monolayers of flat polygonal cells and were carried for more than 20 passages without morphologic change. These cells synthesized prostacyclin and retained an endothelial specific marker, factor VIII-related antigen. When the cells were cultured in a collagen gel, they rapidly formed capillarylike tubular structures without endothelial cell growth factor or special substrata. Long-term culture of purified microvascular endothelial cells derived from Mongolian gerbil brain will facilitate the study of the function of microvascular endothelial cells in human brain under normal and pathologic conditions.
Stroke 1989 Jul
PMID:Long-term culture of microvascular endothelial cells derived from Mongolian gerbil brain. 266 7

Platelet factor 4 (PF4), the platelet antiheparin protein, was isolated from both the supernatant and the cells of recently outdated platelet concentrates. Following purification by affinity chromatography, a competitive binding radioimmunoassay was developed to detect this protein in human plasma. The normal range was determined to be 9.4 +/- 4.7 ng/ml (mean +/- SD for 52 healthy adults). In order to determine whether individuals with transient ischemic attack (TIA) or stroke had measurable increments of PF4 in their plasma, radioimmunoassay studies were performed on 11 patients with well-documented TIA, 10 patients with well-documented stroke and on 16 age-matched controls hospitalized on a neurology service with disorders unrelated to arterial thrombosis. The 16 hospitalized controls had PF4 levels of 10.3 +/- 9.1 ng/ml, a value not significantly different from the 52 normals (P greater than 0.50). Patients with TIA had PF4 levels of 24.6 +/- 12.1 ng/ml, a value significantly higher than both the 52 normals (P less than 0.001) and the 16 hospitalized control patients (P less than 0.005). Patients with stroke had PF4 levels of 35.4 +/- 29.2 ng/ml, a value significantly higher than both the 42 normals (P less than 0.001) and the 16 hospitalized control patients (P less than 0.005). Outdated platelet concentrates facilitate the development of a reproducible radioimmunoassay for PF4. The elevation of this platelet-derived protein in the plasma of patients with stroke and TIA provides evidence for recent or ongoing platelet activation in the cerebral vascular disease population.
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PMID:Human platelet factor 4: preparation from outdated platelet concentrates and application in cerebral vascular disease. 724 39

Antiplatelet therapy has become a useful means of preventing acute thromboembolic artery occlusions in cardiovascular diseases. The rationale for this is an enhanced activity of circulating platelets and release of platelet-derived vasoactive mediators, probably due to endothelial dysfunction. This review discusses the current status of 4 major classes of antiplatelet compounds: (i) aspirin and related drugs active via cyclo-oxygenase product formation; (ii) thienopyridines (ticlopidine and clopidogrel); (iii) direct thrombin inhibitors (e.g. hirudin); and (iv) GPIIb/IIIa receptor antagonists [e.g. abciximab (c7E3 Fab)]. It is concluded that aspirin is the drug of choice for long term oral treatment, specifically for secondary prevention of myocardial infarction, and is also a suitable basic but not maximally efficient drug in percutaneous transluminal coronary angioplasty (PTCA) and platelet activation during clot lysis. Ticlopidine has a similar indication and may be superior to aspirin in prevention of ischaemic stroke and peripheral arterial occlusion. Direct thrombin inhibitors and glycoprotein GPIIb/IIIa receptor antagonists need further investigation in clinical trials. To date, these compounds have a higher bleeding risk and currently they are available only for short term parenteral application. They are superior to aspirin in acute platelet-dependent ischaemic syndromes, such as unstable angina, and in connection with therapeutic PTCA because of their high potency in preventing platelet-dependent reocclusion. Future developments include more selective thromboxane inhibitors, i.e. combined-mode agents; nonpeptide clot-specific thrombin inhibitors with longer lasting action and nonpeptide fibrinogen receptor antagonists.
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PMID:Antiplatelet drugs. A comparative review. 758 91

Neuropeptide Y (NPY), a sympathetic and platelet-derived vasoconstrictor, acts both directly and by potentiating adrenergic responsiveness and therefore may be beneficial in endotoxic shock, where suppressed vascular responsiveness to adrenergic agents is a key factor. This was studied in anesthetized rats. First, infusion of a nonhypotensive dose of endotoxin (lipopolysaccharide, LPS) markedly suppressed the pressor response to increasing doses of norepinephrine (NE), angiotensin II, and vasopressin but did not suppress the response to NPY. Second, in rats rendered hypotensive by intravenous LPS, continuous NE infusion (0.1-1.0 microgram.kg-1 x min-1 started 5 min after LPS for 1 h) did not alter hemodynamics. In contrast, 5 nmol.kg-1 x min-1 of NPY (equipotent to 0.1 microgram.kg-1 x min-1 of NE in normal rats) increased mean arterial pressure (MAP, from 64 to 114% of baseline), total peripheral resistance index (TPRI, from 64 to 154% of baseline), and left ventricular stroke work index (from 36 to 73% of baseline), without changing cardiac index (CI). Third, in a similar experimental protocol, pretreatment of the hypotensive rats with phentolamine blocked the pressor effect of NE infusion, but only partially attenuated the response to NPY. Finally, addition of low-dose NPY to NE infusion improved survival following a lethal dose of LPS compared with treatment with NE alone (P < 0.01). Thus, unlike other vasoconstrictors tested, NPY-mediated vasoconstriction is preserved during endotoxemia. The beneficial effect of NPY is mediated by increased TPRI without reduction in CI; both NPY receptor-mediated vasoconstriction and potentiation of adrenergic responsiveness may be involved.
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PMID:Neuropeptide Y infusion improves hemodynamics and survival in rat endotoxic shock. 790 7

This year acetylsalicylic acid (aspirin) celebrates its 100-year anniversary. While the drug was previously used mainly as an antipyretic and a pain-killer, aspirin has, during the last 10-15 years, become one of the most important agents in the treatment of cardiovascular and cerebrovascular diseases. In addition to being one of our oldest drugs, aspirin is one of the most interesting and widely used remedies. The antithrombotic property of aspirin is mainly related to its irreversible inhibition of the production of platelet-derived thromboxane A2, which possesses aggregatory and vasoconstrictive properties. Aspirin reduces the risk in patients with overt cardiovascular and cerebrovascular diseases, i.e. chronic stable and unstable angina pectoris. It also reduces the risk in the acute phase of and following a myocardial infarction and after a transient ischemic attack or stroke. The use of the drug is controversial in primary cardiovascular prevention. Overall mortality is not reduced, and side-effects, such as increased bleeding tendency, may be serious. This side-effect is dose-dependent, and smaller doses (75-160 mg) which have the same effect as higher doses should be preferred.
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PMID:[Acetylsalicylic acid in the treatment of cardiovascular and cerebrovascular diseases]. 945 92

Platelet function in whole blood can be comprehensively evaluated by flow cytometry. Flow cytometry can be used to measure platelet reactivity, circulating activated platelets, platelet-platelet aggregates, leukocyte-platelet aggregates, procoagulant platelet-derived microparticles, and calcium flux. Clinical applications of whole blood flow cytometric assays of platelet function in disease states (e.g., acute coronary syndromes, angioplasty, and stroke) may include identification of patients who would benefit from additional antiplatelet therapy and prediction of ischemic events. Circulating monocyte-platelet aggregates appear to be a more sensitive marker of in vivo platelet activation than circulating P-selectin-positive platelets. Flow cytometry can also be used in the following clinical settings: monitoring of GPIIb-IIIa antagonist therapy, diagnosis of inherited deficiencies of platelet surface glycoproteins, diagnosis of storage pool disease, diagnosis of heparin-induced thrombocytopenia, and measurement of the rate of thrombopoiesis.
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PMID:Evaluation of platelet function by flow cytometry. 1087 80

Platelet activation seems to play a critical role in a number of vascular diseases, including stroke. The aim of our study was whole-blood flow cytometry evaluation of platelet activation markers: P-selectin (CD62), glycoprotein-53 (CD63) and platelet-derived microparticle in vivo in patients with acute cerebral infarction. We investigated 50 patients (29 men and 21 women, mean age 67.8) with acute cerebral infarction. Parameters of platelet activation were measured on the 1st, 3rd and 7th day after stroke onset. Comparisons were made with 20 control patients matched age. Compared to controls (1.6 +/- 0.7%) the stroke patients showed higher expression of CD62 on the 1st (2.6 +/- 1.4%), 3rd (3.5 +/- 2.3%) and 7th (3.0 +/- 2.0%) day after stroke onset. The differences were statistically significant on all days (p < 0.05). Compared to controls (1.5 +/- 0.6%) the stroke patients had also higher expression of CD63 on the 1st (1.9 +/- 0.6%), 3rd (2.0 +/- 0.6%) day and they showed higher level of platelet-derived microparticles on the 3rd (13.0 +/- 3.0%) day after stroke onset. The differences were statistically significant (p < 0.05). Elevated expression of CD62, CD63 and platelet-derived microparticles level indicate platelet activation during the acute phase of ischaemic stroke. Flow cytometry is a useful tool for in vivo assessment of platelet activation.
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PMID:[Blood platelet activation markers in patients with acute cerebral infarction during the earliest stage of the disease--evaluation using flow cytometry methods]. 1125 75

Sphingosine 1-phosphate (S1P) is a platelet-derived bioactive sphingolipid that evokes a variety of biological responses. To understand the role of S1P in the central nervous system, we have examined the effect of S1P on the production of glial cell line-derived neurotrophic factor (GDNF) and growth regulation of cortical astrocytes from rat embryo. Moreover, we examined the possibility that the expression of GDNF is regulated differently in cultured astrocytes from the stroke-prone spontaneously hypertensive rat (SHRSP) than in those from Wistar kyoto rats (WKY). The mRNA expression was quantitated by RT-PCR based on the fluorescent TaqMan methodology. A new instrument capable of measuring fluorescence in real time was used to quantify gene amplification in astrocytes. GDNF protein was investigated by enzyme-linked immunosorbent assay. S1P induced the expression of GDNF mRNA and the production of GDNF protein in a dose-dependent manner in WKY astrocytes. Moreover, S1P increased cell numbers and induced the proliferation of astrocytes. In addition, the level of mRNA expression and protein production of GDNF was significantly lower in SHRSP than WKY astrocytes following exposure to S1P. These findings revealed that S1P augments GDNF protein production and cellular growth in astrocytes. Also, our results indicate that production in SHRSP astrocytes was attenuated in response to S1P compared with that observed in WKY. We conclude that S1P specifically triggers a cascade of events that regulate the production of GDNF and cell growth in astrocytes. Our results also suggest that the reduced expression of GDNF caused by S1P is a factor in the stroke proneness of SHRSP.
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PMID:Sphingosine 1-phosphate induces the production of glial cell line-derived neurotrophic factor and cellular proliferation in astrocytes. 1250 10

The time course of the concentration of active thrombin in clotting plasma (the thrombogram) was measured by subsampling from platelet-rich plasma (PRP) and continuous chromogenic measurement of platelet-poor plasma (PPP) in 41 stroke patients under the age of 50, in whom stroke could not be attributed to cardioembolic disease, arterial dissection or vasculitis. A significant increase in the area under the thrombogram (endogenous thrombin potential, ETP) was seen in 23 patients. In 9 of them, ETP was increased in PRP but normal in PPP. High ETP in PRP was significantly associated with stroke, both in the middle and in the highest tercile of the ETP (odds ratio 5.1, range 1.8-15.1, and 3.7, range 1.3-10.3, respectively). A decreased sensitivity to the inhibitory action of thrombomodulin (TM) on thrombin generation was observed in 5 of 37 cases. No further definition of the cause of increased thrombin generation or TM resistance was attempted, except for the role of von Willebrand factor (vWF). ETP in PRP, platelet-derived procoagulant activity and vWF were correlated and higher in patients than in controls (p=0.002, p=0.045 and p=0.0006, respectively). This confirms the correlation between vWF level and stroke at young age found in epidemiological studies. It suggests that the role of vWF in thrombin generation, which has been demonstrated in vitro, may be the underlying mechanism of this correlation. In summary, hypercoagulability, defined as an increased capacity of the platelet plasma system to form thrombin, is found in over half of the patients under 50 years with an otherwise unexplained stroke. Sometimes it is due to increased plasma factor activity, sometimes to an increased procoagulant activity of the platelets.
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PMID:Thrombin generation in platelet-rich plasma as a tool for the detection of hypercoagulability in young stroke patients. 1285 13


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