Cerebral vasospasm is delayed onset of vasoconstriction occurring days after aneurysmal subarachnoid hemorrhage. It is a major cause of stroke and death after subarachnoid hemorrhage. Hemoglobin and oxidant stress induced by it may be important in the pathogenesis of vasospasm. We found that heme oxygenase-1 messenger ribonucleic acid (mRNA) and protein are increased in smooth muscle cells exposed to hemoglobin. Heme oxygenase-1 protein is also increased in vasospastic arteries. Heme oxygenase-1 expression is known to be induced by oxidative stress and by heme in other types of cells, where it may protect against these cytotoxic stimuli. The long-term objective of this work is to determine the role of heme oxygenase-1 in vasospasm.
The specific aims are: (1) To define the time course and dose-dependence of induction of heme oxygenase-1 and ferritin mRNA and protein in response to hemolysate and purified hemoglobin in cultured cerebrovascular smooth muscle cells. Hypothesis: Heme oxygenase-1 and ferritin are induced by solutions that contain heme, such as hemolysate and purified hemoglobin. (2) To define the time course of induction of heme oxygenase- 1 and ferritin mRNA and protein in the rat basilar artery after subarachnoid hemorrhage. Hypothesis: Vasospasm is associated with hemolysis, exposure of smooth muscle cells to heme, and induction of heme oxygenase-1 and ferritin. The induction of heme oxygenase-1 and ferritin is associated with the resolution of vasospasm. (3) To determine the effects of induction of heme oxygenase-1 and ferritin on vasospasm. Hypothesis: Induction of heme oxygenase-1 and ferritin decrease vasospasm.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08NS001831-04
Application #
2891377
Study Section
NST-2 Subcommittee (NST)
Program Officer
Jacobs, Tom P
Project Start
1996-09-30
Project End
2001-07-31
Budget Start
1999-08-01
Budget End
2001-07-31
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Chicago
Department
Surgery
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637
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