Experimental Cerebral Hemorrhage: Mechanisms and Therapies

实验性脑出血：机制和治疗

• 批准号: 10609905
• 负责人: GUOHUA XI
• 金额: $ 107.04万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10609905
• 关键词: Blood; Brain; Brain Edema; Brain Injuries; Brain hemorrhage; Cell Death; Cerebral hemisphere hemorrhage; Coagulation Process; Combined Modality Therapy; Cytolysis; Deferoxamine; Development; Erythrocytes; Event; Excision; Goals; Hematoma; Hemoglobin; Hemorrhage; Human; Hydrocephalus; Iron; Neurologic Deficit; Patients; Phase II Clinical Trials; Role; Secondary to; Series; Stroke; Thrombin; Work; blood-brain barrier disruption; brain cell; brain parenchyma; effective therapy; intraventricular hemorrhage; restoration

Spontaneous intracerebral hemorrhage (ICH) is a common and often fatal stroke subtype. If the patient survives the ictus, the resulting hematoma within brain parenchyma triggers a series of events leading to secondary insults and severe neurological deficits. Although the hematoma in human gradually resolves within several months, restoration of function is graded and usually incomplete. The neurological deficits in ICH patients are permanent and disabling. For the past 20 years, I have been examining the hypothesis that the release of components (e.g., hemoglobin, iron and thrombin) from the hematoma contributes to ICH-induced brain injury. Our work on iron (released from hemoglobin) has led to the current Phase II clinical trial of deferoxamine for ICH (NCT02175225). This proposal continues to examine that underlying hypothesis. Specifically, it will address: 1) the mechanisms of early erythrocyte lysis in the hematoma; 2) the role of CD163 in hemoglobin clearance after ICH; 3) the mechanisms of endogenous hematoma removal; 4) the mechanisms of hydrocephalus development after intraventricular hemorrhage; and 5) combination therapies for ICH. The purpose of our project is to determine mechanisms of brain damage after brain hemorrhage and to develop effective therapies. The long-term goal of our studies is to limit hemorrhagic brain damage in patients.

自发性脑出血（ICH）是一种常见且经常致命的脑卒中亚型。如果病人