Rupture of an intracranial aneurysm, causing subarachnoid hemorrhage (SAH), afflicts about 30,000 North Americans per year. An important cause of stroke and death in patients with ruptured aneurysms is cerebral vasospasm which is narrowing of the major cerebral arteries developing from 4 to 14 days after aneurysm rupture. Vasospasm causes morbidity and mortality in about 15% of patients with SAH although angiograms taken during the time of vasospasm will disclose its presence in about two-thirds of cases. Treatment of vasospasm, that includes calcium-channel antagonists, hemodynamic therapy and tissue plasminogen activator, accounts for some of the discrepancy between the number of patients with vasospasm seen angiographically compared to those who develop stroke from it. The long-term objectives of our laboratory are (1) to determine the compound(s) in subarachnoid blood that cause vasospasm, (2) to determine the mechanisms by which they do so, and (3) to develop effective treatments for vasospasm.
The specific aims of this grant are (1) to determine how the time course and degree of vasospasm in monkeys depends on subarachnoid blood and to analyze the blood for spasmogens, (2) to determine the component(s) of erythrocytes that cause vasospasm in rats, (3) to characterize the vasoactive compound in cerebrospinal fluid (CSF) and subarachnoid blood removed from patients with SAH, (4) to determine whether adenosine triphosphate (ATP) and pure hemoglobin can cause vasospasm in monkeys, (5) to determine the concentrations and time course of changes-in CSF levels of adenine nucleotides and hemoglobins in humans after SAH, (6) to determine the effects of P2-purinoceptor antagonists against vasospasm in monkeys, (7) to determine if synthesis of endothelin (ET) and ET receptor messenger ribonucleic acids (mRNAs) and secretion of ET and ET receptor proteins are increased in cultured cerebral smooth muscle and endothelial cells exposed to erythrocyte hemolysate or purified hemoglobin, (8) to determine the time course of changes in ET and ET receptor mRNAs and proteins following SAH in rats and (9) to determine the effects of an ET antagonist on vasospasm in monkeys.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS025946-12
Application #
2891721
Study Section
Neurology A Study Section (NEUA)
Program Officer
Jacobs, Tom P
Project Start
1988-04-01
Project End
2001-03-31
Budget Start
1999-04-01
Budget End
2000-03-31
Support Year
12
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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Zhang, Zhen-Du; Macdonald, R Loch (2006) Contribution of the remodeling response to cerebral vasospasm. Neurol Res 28:713-20

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