The vascular endothelial cell, strategically located at the interface between vascular tissue and the circulating blood, is endowed with unique biological properties which enable it to modulate hemostasis. Studies here will investigate the impact of percussion trauma on selected hemostatic properties of cerebrovascular endothelium ex vivo (arterial and venous) using a human vessel segment model developed in our laboratory. During the course of these studies, a percussion trauma chamber will be developed in which vessels can be subjected to sublethal injury in a controlled experimental setting. The effects of trauma on the fibrinolytic potential (t-PA, u-PA and PAI-1) and procoagulant properties (tissue factor, formation of the prothrombinase complex and Factor X activation) of cerebral endothelial cells will be quantitatively delineated; reversibility of trauma-induced injury will be determined; and the efficacy of intervention with various agents administered to the test system prior to and following injury will be evaluated. It is anticipated that new information will be elucidated regarding the hemostatic response of the cerebrovascular endothelial cell to trauma. Approaches for recovery may be crucial in the development of therapeutic strategies designed to prevent the sequelae of secondary hemostatic complications induced by trauma to the brain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory Grants (P20)
Project #
5P20NS030324-02
Application #
3847139
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Vermont & St Agric College
Department
Type
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405
Shackford, S R; Bourguignon, P R; Wald, S L et al. (1998) Hypertonic saline resuscitation of patients with head injury: a prospective, randomized clinical trial. J Trauma 44:50-8
Shackford, S R (1997) Effect of small-volume resuscitation on intracranial pressure and related cerebral variables. J Trauma 42:S48-53
Chappell, J E; Shackford, S R; McBride, W J (1997) Effect of hemodilution with diaspirin cross-linked hemoglobin on intracranial pressure, cerebral perfusion pressure, and fluid requirements after head injury and shock. J Neurosurg 86:131-8
Gourin, C G; Shackford, S R (1997) Production of tumor necrosis factor-alpha and interleukin-1beta by human cerebral microvascular endothelium after percussive trauma. J Trauma 42:1101-7
Shatos, M A; Doherty, J M; Penar, P L et al. (1996) Suppression of plasminogen activator inhibitor-1 release from human cerebral endothelium by plasminogen activators. A factor potentially predisposing to intracranial bleeding. Circulation 94:636-42
Chappell, J E; McBride, W J; Shackford, S R (1996) Diaspirin cross-linked hemoglobin resuscitation improves cerebral perfusion after head injury and shock. J Trauma 41:781-8
Luh, E H; Shackford, S R; Shatos, M A et al. (1996) The effects of hyperosmolarity on the viability and function of endothelial cells. J Surg Res 60:122-8
Gourin, C G; Shackford, S R (1996) Influence of percussion trauma on expression of intercellular adhesion molecule-1 (ICAM-1) by human cerebral microvascular endothelium. J Trauma 41:129-35
Schmoker, J D; Shackford, S R; Zhuang, J (1996) The effect of lesion volume on cerebral vasomotor tone after focal brain injury and shock. J Neurotrauma 13:67-78
Zhuang, J; Shackford, S R; Schmoker, J D et al. (1995) Colloid infusion after brain injury: effect on intracranial pressure, cerebral blood flow, and oxygen delivery. Crit Care Med 23:140-8

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