Spontaneous intracerebral hemorrhage (ICH) is a common and often fatal stroke subtype. If the patient survives the ictus, the resulting hematoma within the brain parenchyma triggers a series of events leading to secondary insults and severe neurological deficits. Clot lysis plays an important role in the secondary brain injury following ICH. It is the long-term goal of our laboratory to identify the mechanisms involved in brain damage following ICH. After an ICH, lysis of erythrocytes in the hematoma results in brain edema formation, neuronal death and neurological deficits. Our previous studies demonstrated that the release of hemoglobin and its degradation products including iron from erythrocytes are involved in brain injury following ICH. Recent studies found that enhancing microglia/macrophage-mediated hematoma clearance improves functional outcome after ICH, and CD47 has an important role in erythrophagocytosis. Our preliminary studies have showed that erythrophagocytosis occurs in the brain after ICH and erythrocytes express CD47. In this application, we propose to test the following specific aims: 1) To determine whether CD-47 mediates hematoma clearance;and 2) To determine whether enhanced clot clearance reduces ICH-induced brain injury and improves behavioral outcome following ICH. We believe that the pilot studies proposed here should form a strong basis for a NIH R01 application. The long-term goal of our studies is to limit brain damage following ICH.

Public Health Relevance

After a cerebral hemorrhage, lysis of red blood cells causes a build up of iron in the brain and brain iron accumulation can cause brain cell death and neurological deficits. Recent studies suggest that hematoma clearance is a therapeutic target of brain hemorrhage and enhancing clot clearance reduces hemorrhage- induced neurological deficits. The purpose of this project is to investigate the role of CD47 in clot clearance and brai injury after cerebral hemorrhage. The long-term goal of our studies is to limit brain damage following cerebral hemorrhage.

Agency
National Institute of Health (NIH)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21NS084049-02
Application #
8666825
Study Section
Brain Injury and Neurovascular Pathologies Study Section (BINP)
Program Officer
Koenig, James I
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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