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Lipocalin-2 and Intracerebral Hemorrhage-induced Brain Injury

Lipocalin-2 与脑出血引起的脑损伤

基本信息

批准号：
8865750
负责人：
YA HUA
金额：
$ 19.4万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-02-01 至 2017-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8865750
关键词：
Acute Affect Apoptosis Astrocytes Binding Binding Proteins Blood Blood - brain barrier anatomy Brain Brain Edema Brain Injuries Carrier Proteins Cell Death Cells Cerebral hemisphere hemorrhage Cessation of life Chelating Agents Clinical Data Coagulation Process Contralateral Cytolysis Data Deferoxamine Edema Erythrocytes Event Family Family suidae Ferritin Figs - dietary Gelatinase A Goals Heart Hematoma Homeostasis Human Infusion procedures Injection of therapeutic agent Ipsilateral Iron Iron Overload Knock-out Knockout Mice Laboratories Mediating Mediator of activation protein Names Neurologic Neurons Outcome Pathway interactions Patients Phase Pilot Projects Play Production Protein Export Pathway Proteins Rattus Role Secondary to Series Serum Siderophores Stroke Subarachnoid Hemorrhage Supportive care Testing Thrombin Time Tissues Toxic effect Transferrin United States National Institutes of Health Up-Regulation Wild Type Mouse X-Ray Computed Tomography aged base brain cell brain tissue cerebral atrophy member new therapeutic target public health relevance uptake white matter injury

项目摘要

DESCRIPTION (provided by applicant): 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. Brain iron overload 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 iron overload. Lipocalin 2 (LCN2), also known as neutrophil gelatinase associated lipocalin or 24p3, is a siderophore-binding protein. LCN2 mediates iron uptake. The role of LCN2 in ICH is unclear, but LCN2 upregulation in the brain after ICH may affect iron homeostasis. Our preliminary studies showed: 1) brain LCN2 levels are markedly increased after ICH; 2) most LCN2 positive cells after ICH are astrocytes; 3) iron can upregulate brain LCN2; and 4) deferoxamine reduces ICH-induced LCN2 upregulation; 5) subarachnoid hemorrhage results in less white matter injury in LCN2 knockout mice; and 6) intracerebral injection of iron causes less brain swelling in LCN2 knockout mice. These findings suggest an important role of iron in brain LCN2 upregulation after ICH and potentially a role of LCN2 in handling iron that is released from the hematoma after ICH. In this application, we propose to test the following specific aims: 1) To determine whether or not ICH results in less brain edema, blood-brain barrier disruption, neuronal death and neurological deficits in lipocalin 2 knockout mice compared to wild type mice; and 2) To determine whether or not lipocalin 2 modulates intracerebral hemorrhage-induced brain iron overload. 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.