Subarachnoid hemorrhage (SAH) affects over 30,000 Americans per year and is one of the major causes of stroke-related potential life-years lost in people age 65 and younger. Despite advances in critical care for SAH patients, more than half of SAH survivors still live with significant disability. Vasospasm, which can occur in up to 70% of SAH survivors, is one of the most important causes for additional brain injury and disability after SAH. Currently, there are no diagnostic tests that can identify SAH patients at risk for developing vasospasm. The diagnosis and treatment of vasospasm are high-risk and often invasive. The causes of vasospasm and secondary brain injury and disability following SAH remain incompletely understood. In this study, we examine specific molecular biomarkers from blood and cerebrospinal fluid samples collected from SAH subjects in order to understand their potential role in causing vasospasm and secondary brain injury following SAH. We will recruit 200 patients with SAH, bank their available blood and cerebrospinal fluid samples, and use advanced molecular techniques to analyze and detect potentially novel molecular biomarkers.
Our first aim i s to examine the relationship between vasospasm seen on angiogram with white blood cells' release of matrix metalloproteinases (MMPs) which can cleave endothelin-1 into fragments that can subsequently cause spasm of cerebral arteries.
Our second aim i s to correlate SAH-related disability with white blood cells' release of MMPs and their interactions with cytokines, plasma gelsolin, and actin - molecules that mediate inflammatory reaction in critical illness such as SAH. Finally, we will use the data generated through our first 2 aims to build a mathematical model aimed to help physicians identify SAH patients who are at high risk for developing vasospasm and further disability. We hope results of this study will advance our understanding on important molecular mechanisms that lead to vasospasm and to secondary brain injuries in SAH. Our work will lay the foundation for potential discovery of new non-invasive bedside tests that can better diagnose and predict vasospasm and patients at risk for greater disability following SAH. Ultimately, we hope advances in understanding of molecular mechanisms of vasospasm and secondary brain injury following SAH will help us identify new therapies that may improve survival and reduce disability in SAH patients.

Public Health Relevance

Subarachnoid hemorrhage (SAH) affects over 30;000 Americans per year and leaves many victims in significant long term disability. This study uses novel technology to search for causes and potential cure of brain injury and disability caused by SAH.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
7K23NS073806-05
Application #
8982262
Study Section
NST-2 Subcommittee (NST)
Program Officer
Koenig, James I
Project Start
2011-04-15
Project End
2015-12-31
Budget Start
2014-09-02
Budget End
2014-12-31
Support Year
5
Fiscal Year
2014
Total Cost
$117,573
Indirect Cost
$8,709
Name
University of Pittsburgh
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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