Abstract

The primary objective of the proposed work is to investigate the following hypothesis: Risk factors for stroke create a state in which the probability of an interaction between monocyte/macrophages and endothelial cells which could lead to local thrombosis or hemorrhage in focal regions of the brain vasculature is increased. The general design of the work will compare the activity and functional state of stimulated mononuclear cells and endothelial cells from animals with and without risk factors for stroke and to gauge the interaction between these cells. The analyses will proceed from the whole animal to whole brain to isolated microcirculatory brain vessels to isolated microglia (""""""""brain macrophages"""""""") and isolated brain microcirculatory endothelial cells. Ultrastructural studies and measurement of such cellular products as IL-1, TNF, eicosanoids, and platelet activating factor (PAF), as well as fibrinopeptide A (FPA), B, 15-42 related peptides (110 RPs), CDw 18 receptors on leukocytes and development of procoagulant activity by endothelium in vitro in response to a provocative stimulus, endotoxin (lipopolysaccharide-LPS), should permit direct testing of the above hypothesis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS028225-01
Application #
3414734
Study Section
Neurology A Study Section (NEUA)
Project Start
1989-09-01
Project End
1992-06-30
Budget Start
1989-09-01
Budget End
1990-08-31
Support Year
1
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Henry M. Jackson Fdn for the Adv Mil/Med
Department
Type
DUNS #
City
Rockville
State
MD
Country
United States
Zip Code
20852

  Publications

Sairanen, T R; Lindsberg, P J; Brenner, M et al. (2001) Differential cellular expression of tumor necrosis factor-alpha and Type I tumor necrosis factor receptor after transient global forebrain ischemia. J Neurol Sci 186:87-99
Siren, A L; McCarron, R; Wang, L et al. (2001) Proinflammatory cytokine expression contributes to brain injury provoked by chronic monocyte activation. Mol Med 7:219-29
Sairanen, T R; Lindsberg, P J; Brenner, M et al. (1997) Global forebrain ischemia results in differential cellular expression of interleukin-1beta (IL-1beta) and its receptor at mRNA and protein level. J Cereb Blood Flow Metab 17:1107-20
Liu, Y; Liu, T; McCarron, R M et al. (1996) Evidence for activation of endothelium and monocytes in hypertensive rats. Am J Physiol 270:H2125-31
Lindsberg, P J; Siren, A L; Feuerstein, G Z et al. (1995) Antagonism of neutrophil adherence in the deteriorating stroke model in rabbits. J Neurosurg 82:269-77
McCarron, R M; Wang, L; Siren, A L et al. (1994) Monocyte adhesion to cerebromicrovascular endothelial cells derived from hypertensive and normotensive rats. Am J Physiol 267:H2491-7
McCarron, R M; Doron, D A; Siren, A L et al. (1994) Agonist-stimulated release of von Willebrand factor and procoagulant factor VIII in rats with and without risk factors for stroke. Brain Res 647:265-72
Liu, Y; Jacobowitz, D M; Barone, F et al. (1994) Quantitation of perivascular monocytes and macrophages around cerebral blood vessels of hypertensive and aged rats. J Cereb Blood Flow Metab 14:348-52
Siren, A L; Liu, Y; Feuerstein, G et al. (1993) Increased release of tumor necrosis factor-alpha into the cerebrospinal fluid and peripheral circulation of aged rats. Stroke 24:880-6;discussion 887-8
Siren, A L; Heldman, E; Doron, D et al. (1992) Release of proinflammatory and prothrombotic mediators in the brain and peripheral circulation in spontaneously hypertensive and normotensive Wistar-Kyoto rats. Stroke 23:1643-50;discussion 1650-1

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