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

In vitro abnormalities of platelet behaviour have been described in patients with ischemic cerebrovascular disease (ICD) suggesting that changes in platelet receptors and/or platelet a granules may occur in the circulation. We investigated the frequency of such alterations in 95 patients that were studied within a few days after acute stroke. Using specific antibodies to two intrinsic plasma membrane glycoproteins (GPs), the GPIIb-IIIa complex and GPIV, and to thrombospondin (TSP), a a-granular protein that becomes expressed on the platelet surface upon activation, we were able to distinguish two groups of patients: 16 patients presented an increased concentration of TSP on their platelets demonstrating in vivo platelet secretion. These patients could constitute a group with increased risk of thrombosis. In contrast, 20 patients presented a decreased concentration of GPIIb-IIIa and GPIV. This decrease in intrinsic plasma membrane GPs was associated with a decrease in mean platelet volume and may suggest the occurrence of platelet fragmentation in the circulation.
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PMID:Platelet surface glycoprotein changes in patients with cerebral ischemia. 181 6

The effects of hyperthermia on potentially prothrombotic endothelial function were investigated by measuring levels of von Willebrand factor, thrombospondin, tissue plasminogen activator and plasminogen activator inhibitor-1 secreted by unstimulated human umbilical vein endothelial cells cultured at 37 degrees C, 39 degrees C, 41 degrees C and 43 degrees C for 24 h. Endothelial barrier function at 43 degrees C was compared with that at 37 degrees C by measuring permeability to radiolabelled human serum albumin and low density lipoprotein. Thrombospondin levels were unaffected by a temperature of 39 degrees C; they increased after 3 h at 41 degrees C and subsequently declined to values significantly below the 37 degrees C control. At 43 degrees C, secretion exhibited a time-dependent decrease. Secretion of von Willebrand factor was not discernibly affected by exposure to 39 degrees C or 41 degrees C. Its response to 43 degrees C resembled that of thrombospondin to 41 degrees C. In contrast, elevated temperatures markedly increased plasminogen activator inhibitor-1 while decreasing t-PA secretion, though after prolonged exposure to 43 degrees C the levels of both returned to control values. After 12-24 h at 43 degrees C, endothelial permeability to both albumin and low density lipoprotein increased markedly. Vascular endothelium may contribute to the thrombotic tendency associated with heat stroke by increasing access to the prothrombotic subendothelium and reducing fibrinolysis.
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PMID:The effects of hyperthermia on human endothelial monolayers: modulation of thrombotic potential and permeability. 805 50

Platelet activation plays a central role in acute arterial stenosis as has been shown in coronary heart disease. Likewise it can be assumed to be of importance in the evolution of acute cerebral ischemia (ACI), particularly in patients with large vessel disease. Flow cytometric detection of platelet adhesion molecules as a marker of platelet activation in a group of patients with ACI and different etiologies has not been evaluated. In 72 patients with ACI and 72 controls, the exposure of activation-dependent adhesion molecules was determined using flow cytometry after immunostaining with monoclonal antibodies against CD 62, CD 63 and thrombospondin. The extent of platelet activation differed as a function of the etiology of ACI: platelets from patients with atherosclerosis of brain-supplying arteries expressed significantly more activation markers than did controls, whereas patients with cardioembolic stroke did not. By analyzing platelet adhesion molecules it is possible to describe platelet activation profiles in patients with acute cerebral ischemia. This diagnostic procedure will be useful for monitoring individualized anti-platelet therapy and may enable distinguishing different subgroups of stroke patients.
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PMID:Circulating platelets show increased activation in patients with acute cerebral ischemia. 1010 63

After ischemic stroke, there is neovascularization around the infarcted area, which is called penumbra. Angiogenesis and arteriogenesis are responsible for the new vessel formation. Until recently, vasculogenesis has been proved to involve mechanisms in postischemic neovascularization, which was thought to be restricted to embryonic development. New blood vessels' formation is a complex pathologic process after ischemic stroke, in which many factors are properly involved. There are factors stimulating neovascularization, such as vascular endothelial growth factor, platelet-derived growth factor, basic fibroblast growth factor and angiopoietin; there are also factors inhibiting neovascularization, such as thrombospondin. Functional recovery was found after stroke, which may contribute to angiogensis in the periinfarct tissue. Thus, therapeutic angiogenesis has been initially studied in animal models, but there is still a long way to go for therapeutic angiogenesis to be used in the treatment of stroke patient.
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PMID:[Neovascularization after ischemic stroke]. 1525 Jan 70

ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) enzymes are a recently described group of metalloproteinases. The substrates degraded by ADAMTS-1, -4 and -5 suggest that they play a role in turnover of extracellular matrix in the central nervous system (CNS). ADAMTS-1 is also known to exhibit anti-angiogenic activity. Their main endogenous inhibitor is tissue inhibitor of metalloproteinases (TIMP)-3. The present study was designed to investigate ADAMTS-1, -4 and -5 and TIMP-3 expression after experimental cerebral ischaemia and to examine whether cytokines known to be up-regulated in stroke could alter their expression by astrocytes in vitro. Focal cerebral ischaemia was induced by transient middle cerebral artery occlusion in the rat using the filament method. Our results demonstrate a significant increase in expression of ADAMTS-1 and -4 in the occluded hemisphere but no significant change in TIMP-3. This was accompanied by an increase in mRNA levels for interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1ra) and tumour necrosis factor (TNF). ADAMTS-4 mRNA and protein were up-regulated by TNF in primary human astrocyte cultures. The increased ADAMTS-1 and -4 in experimental stroke, together with no change in TIMP-3, may promote ECM breakdown after stroke, enabling infiltration of inflammatory cells and contributing to brain injury. In vitro studies suggest that the in vivo modulation of ADAMTS-1 and -4 may be controlled in part by TNF.
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PMID:ADAMTS-1 and -4 are up-regulated following transient middle cerebral artery occlusion in the rat and their expression is modulated by TNF in cultured astrocytes. 1663 May 94

The ECM (extracellular matrix) is a complex molecular framework that provides physical support to cells and tissues, while also providing signals for cell growth, migration, differentiation and survival. The ECM of the CNS (central nervous system) is unusual in that it is rich in CSPGs (chondroitin sulfate proteoglycans), hyaluronan and tenascins. The CSPGs are widely expressed throughout the developing and adult CNS and have a role in guiding or limiting neurite outgrowth and cell migration. Alterations in the synthesis or breakdown of the ECM may contribute to disease processes. Here, we examine changes in the brain-specific CSPGs, brevican and phosphacan, following transient middle cerebral artery occlusion, a model of stroke in the rat. We have investigated their expression at various time points as well as their spatial relationship with ADAMTS-4 (a disintegrin and metalloprotease with thrombospondin motifs 4). The co-localization of ADAMTS or its activity may indicate a functional role for this matrix-protease pair in degeneration/regeneration processes that occur in stroke.
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PMID:Brevican and phosphacan expression and localization following transient middle cerebral artery occlusion in the rat. 1763 24

Microvascular dysfunction is a critical pathology that underlies the evolution of secondary injury mechanisms after traumatic spinal cord injury (SCI). However, little is known of the molecular regulation of endothelial cell (EC) plasticity observed acutely after injury. One reason for this is the relative lack of methods to quickly and efficiently obtain highly enriched spinal microvascular ECs for high-throughput molecular and biochemical analyses. Adult C57Bl/6 mice received an intravenous injection of fluorescein isothiocyanate (FITC)-conjugated Lycopersicon esculentum lectin, and FITC-lectin-bound spinal microvessels were greatly enriched by fluorescence-activated cell sorter (FACS) purification. This technique allows for rapid (<1.5 h postmortem) isolation of spinal cord microvascular ECs (smvECs). The results from cell counting, reverse-transcription polymerase chain reaction (RT-PCR), and western blot analyses show a high degree of EC enrichment at mRNA and protein levels. Furthermore, a focused EC biology microarray analysis identified multiple mRNAs dramatically increased in the EC compartment 24 h after SCI, which is a time point associated with the pathologic loss of spinal vasculature. These included thrombospondin-1, CCL5/RANTES, and urokinase plasminogen activator, suggesting they may represent targets for therapeutic intervention. Furthermore, these novel methodologic approaches will likely facilitate the discovery of molecular regulators of endothelial dysfunction in a variety of central nervous system (CNS) disorders including stroke and other neurodegenerative diseases having a vascular component.
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PMID:Transcriptomic screening of microvascular endothelial cells implicates novel molecular regulators of vascular dysfunction after spinal cord injury. 1861 14

Anti-platelet integrin GPIIIa49-66 antibody (Ab) induces complement-independent platelet oxidative fragmentation and death by generation of platelet peroxide following NADPH oxidase activation. A C-terminal 385-amino acid fragment of ADAMTS-18 (a disintegrin metalloproteinase with thrombospondin motifs produced in endothelial cells) induces oxidative platelet fragmentation in an identical kinetic fashion as anti-GPIIIa49-66 Ab. Endothelial cell ADAMTS-18 secretion is enhanced by thrombin and activated by thrombin cleavage to fragment platelets. Platelet aggregates produced ex vivo with ADP or collagen and fibrinogen are destroyed by the C-terminal ADAMTS-18 fragment. Anti-ADAMTS-18 Ab shortens the tail vein bleeding time. The C-terminal fragment protects against FeCI3-induced carotid artery thrombosis as well as cerebral infarction in a postischemic stroke model. Thus, a new mechanism is proposed for platelet thrombus clearance, via platelet oxidative fragmentation induced by thrombin cleavage of ADAMTS-18.
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PMID:C-terminal ADAMTS-18 fragment induces oxidative platelet fragmentation, dissolves platelet aggregates, and protects against carotid artery occlusion and cerebral stroke. 1952 Aug 14

Extracellular matrix (ECM) and ECM-hydrolytic enzymes play critical roles in reproduction, development, morphogenesis, wound healing, tissue repair, regeneration, and remodeling. They are also involved in pathological processes such as inflammation, arthritis, cardiovascular diseases, stroke, neurodegeneration, metabolic syndrome, and cancer invasion and metastasis. Other reviews summarized the structure and function of ECM-degrading enzymes in cancer and other diseases. This review will focus on current insights of major protease families and other digestive enzymes that play significant roles in ECM remodeling and ECM-related pathologies. For example, the functions of matrix metalloproteinases in modulating adipogenesis, and their subsequent implications in obese patients, are discussed. Recent discovery and characterization of nineteen members of the human disintegrin-metalloproteinase with thrombospondin motif family have revealed new opportunities of investigating these enzymes in human pathologies, especially in the pathogenesis of osteoarthritis. Although kallikrein-3 was discovered many years ago as prostate specific antigen, the biomarker for detecting human prostate cancer and monitoring its recurrence in patients after surgery, fifteen members of the kallikrein family were reported to participate in physiological and pathological processes. Furthermore, exciting research has been carried out on other important ECM-digestive enzymes, including heparanase, cathepsins, hyaluronidases, and matriptases. Research data have suggested that these enzymes are potential therapeutic targets and biomarkers for cancer, arthritis, obesity, diabetic complications, multiple sclerosis, cardiovascular diseases, cerebral vascular diseases, and many other pathological conditions.
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PMID:A fresh prospect of extracellular matrix hydrolytic enzymes and their substrates. 1935 69

Stroke is a leading cause of death and disability. The only therapy available is recombinant tissue plasminogen activator, but side effects limit its use. Platelets play a crucial role during stroke, and the inflammatory reaction promotes neurodegeneration. von Willebrand factor (VWF), an adhesion molecule for platelets, is elevated in patients with acute stroke. The activity of VWF is modulated by ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type I repeats-13) that cleaves VWF to smaller less-active forms. We recently documented that ADAMTS13 negatively regulates both thrombosis and inflammation. We report that deficiency or reduction of VWF reduces infarct volume up to 2-fold after focal cerebral ischemia in mice, thus showing the importance of VWF in stroke injury. In contrast, ADAMTS13 deficiency results in larger infarctions, but only in mice that have VWF. Importantly, infusion of a high dose of recombinant human ADAMTS13 into a wild-type mouse immediately before reperfusion reduces infarct volume and improves functional outcome without producing cerebral hemorrhage. Furthermore, recombinant ADAMTS13 did not enhance bleeding in a hemorrhagic stroke model. Our findings show the importance of VWF in regulating infarction and suggest that recombinant ADAMTS13 could be considered as a new therapeutic agent for prevention and/or treatment of stroke.
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PMID:von Willebrand factor-cleaving protease ADAMTS13 reduces ischemic brain injury in experimental stroke. 1968 10


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