TY - RPRT A1 - McCarron, R. M. A1 - Doron, D. A. A1 - Sirén, Anna-Leena A1 - Feuerstein, G. Z. A1 - Heldman, E. A1 - Pollard, H. B. A1 - Spatz, M. A1 - Hallenbeck, J. M. T1 - Agonist-stimulated release of von Willebrand factor and procoagulant factor VIII in rats with and without risk factors for stroke [Research Report] N2 - Lipopolysaccharidc (LPS)-induced (i.v. or i.c.v., 1.8 mg/kg) release of von Willebrand factor (vWF) ·was examined in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. SHR rats releascd significantly (P < 0.05) more vWF than WKY rats in response to LPS. LPS also inhibited factor VIII procoagulant activity (FVIII: c) which may indicate an increase in thrombin activity. Cultured cerebrovascular endothelial cells (EC) derived from both SHR and WKY rats, as weil as human umbilical vein EC (HUVEC) cultures constitutively released vWF. Treatment with agonists including LPS, thrombin and tumor necrosis factor-a (TNFa) did not affect the in vitro secretion of vWF by cerebrovascular EC cultures but significantly upregulated vWF release by HUVEC cultur~s. Preincubation of cerebrovascular EC cultures with interleukin-1 OL-l) ± TNFa or co-culturing in the presence of LPS-activated syngeneic monocytes had no effect on vWF secretion. The findings demoostrate that conditions of hypertension may affect endothelial cells and make them more responsive to agonist Stimulation and thereby increase secretion of vWF, an important factqr in hemostasis as weil as thrombosis. The capacity of LPS to significantly affect the in vivo secretion of vWF in SHR and WKY rats but not cultured cerebrovascular EC indicates that observed elevations in plasma vWF were not derived from cerebrovascular EC. lt is suggested that hypertension may function as a risk factor for thrombotic stroke by influencing factors involved in coagulation processes, such as vWF and factor VIII : c. KW - Neurobiologie KW - von Willebrand factor KW - Hypertension KW - Lipopolysaccharide KW - Endothelial cell KW - Stroke KW - Monocyte Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62945 ER - TY - RPRT A1 - Wang, X. A1 - Sirén, Anna-Leena A1 - Liu, Y. A1 - Yue, T-L. A1 - Barone, F. C. A1 - Feuerstein, G. Z. T1 - Upregulation of intercellular adhesion molecule-1 (ICAM-1) on brain microvascular endothelial cells in rat ischemic cortex [Research Report] N2 - The expression of intercellular adhesion molecule 1 (ICAM-1) was studied in rat focal ischemic cortex. A significant increase in ICAM-1 mRNA expression in the ischemic cortex over Ievels in contralateral (nonischemic) site was observed by means of Northern blot analysis following either permanent or temporary occlusion with reperfusion of the middle cerebral artery (PMCAO or MCAO with reperfusion) in spontaneously hypertensive rats. In the ischemic cortex, Ievels of ICAM-1 mRNA increased significantly at 3 h (2.6-fold, n = 3, P < 0.05), peaked at 6 to 12 h (6.0-fold, P < 0.01) and remained elevated up to 5 days (2.5-fold, P < 0.05) after PMCAO. The profile of ICAM-1 mRNA expression in the ischemic cortex following MCAO with reperfusion was similar to that following PMCAO, except that ICAM-1 mRNA was significantly increased as early as 1 h (6.3-fold, n = 3, P < 0.05) and then gradually reached a peak at 12 h (12-fold, P < 0.01) after reperfusion. ICAM-1 mRNA expression in ischemic cortex following PMCAO was significantly greater in hypertensive rats than in two normotensive rat strains. Immunostaining using anti-ICAM-1 antiborlies indicated that upregulated ICAM-1 expressionwas localized to endotheIial cells of intraparenchymal blood vessels in the ischemic but not contralateral cortex. The data suggest that an upregulation of ICAM-1 mRNA and protein on brain capillary endothelium may play an important rote in leukocyte migration into ischemic brain tissue. KW - Neurobiologie KW - Intercellular adhesion molecule 1 KW - Focal brain ischemia KW - Stroke KW - Reperfusion KW - lnflammation Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62952 ER - TY - JOUR A1 - McCarron, R. M. A1 - Wang, L. A1 - Sirén, Anna-Leena A1 - Spatz, M. A1 - Hallenbeck, J. M. T1 - Monocyte adhesion to cerebromicrovascular endothelial cells derived from hypertensive and normotensive rats N2 - No abstract available KW - Neurobiologie Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62960 ER - TY - JOUR A1 - Yong, Liu A1 - Jacobowitz, David M. A1 - Barone, Frank A1 - McCarron, Richard A1 - Spatz, Maria A1 - Feuerstein, Giora A1 - Hallenbeck, John M. A1 - Sirén, Anna-Leena T1 - Quantitation of perivascular monocyte / macrophages around cerebral blood vessels of hypertensive and aged rats N2 - The numbers of monocytes and macrophages in the walls of cerebral blood vessels were counted on perfusion-fixed frozen brain sections (16 JLffi) of spontaneously hypertensive rats (SHR), stroke-prone SHR (SHR-SP), normotensive Wistar-Kyoto (WKY) rats, and young (16-week-old) and old (2-year-old) normotensive Sprague-Dawley rats (SD-l6w and SD-2y, respectively) using monoclonal antiborlies against rat macrophages (ED2). The staining was visualized with fluoresceinlabeled second antiborlies. The ED2-specific staining in brain sections was restricted to macrophages in a perivascular location. The number of perivascular cells per square millimeter of high-power field was significantly greater in SHR-SP (8.6 ± 2.1; n = 4) and SHR (6. 7 ± 0.9; n = 6) than in normotensive WKY (4.0 ± 0.5; n = 6; p <0.01). The number of perivascular macrophages was also greater in SD-2y (7.5 ± 2.7; n = 9) than in SD-l6w (2.9 ± 1.8; n = 8; p < 0.01). No ED2 staining was found in the resident microglia or in the endothelial cells, which were identified by double staining with rhodamine-labeled anti-factor VIII-related antigen antiborlies. The results suggest that the stroke risk factors hypertension and advanced age are associated with increased subendothelial accumulation of monocytes and macrophages. This accumulation could increase the tendency for the endothelium to convert from an anticoagulant to a procoagulant surface in response to mediators released from these subendothelial cells. KW - Willebrand-Faktor KW - immunofluorescence KW - ED2 KW - Von Willebrand factor KW - rats KW - brain Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86800 ER - TY - JOUR A1 - McCarron, R. M. A1 - Wang, L. A1 - Sirén, Anna-Leena A1 - Spatz, M. A1 - Hallenbeck, J. M. T1 - Adhesion molecules on normotensive and hypertensive rat brain endothelial cells N2 - The intercellular adhesion of circulating leukocytes to vascular endothellum ls a prerequisite for leukocyte emigration from the blood to extravascular tlssues. This process is facllltated by adhesion molecules on the surfaces of both the vascular endothelial cells and the leukocytes. The experiments presented here demonstrate for the first time that the leukocyte adhesion receptor, intercellular adhesion molecule-1, is constitutively expressed on cultured cerebromicrovascular endothelial cell lines derived from both spontaneously hypertensive (SHR) rats and normotensive WistarKyoto (WKY) rats. Both cultures contained simliar numbers of cells constitutively expressing this adhesion molecule (31.4% and 29.6%, respectlvely). Adhesion molecule expression was up-regulated by interleukin-1 ß, tumor necrosis factor-a, interferon-y and lipopolysaccharide in a dose- and time-dependent manner. Both cultures exhibited similar maximum levels of adhesion molecule up-regulation to optimal concentrations of all three cytokines. However, SHR endothelial cells were moresensitive to all three cytokines; significantly higher levels of intercellular adhesion molecule-1 expresslon were seen on SHR as opposed to WKY endothelial cells cultured with sub-optimal cytokine concentrations. It was also observed that lipopolysaccharide up-regulated intercellular adhesion molecule-1 expression on SHR endothelial cells to a greater extent than on WKY endothelial cells. The findings that intercellular adhesion molecule-1 can be up-regulated to a greater degree on SHR endothelial cells may have important implications for in vivo perivascular leukocyte accumulation under hypertensive conditions. These observations indicate a possible mechanism by which hypertension may predispose to the development of disorders such as atherosclerosis and stroke. KW - Endothelzelle KW - Zell-Adhäsionsmolekül Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86819 ER -