Experimental Cerebral Hemorrhage: Mechanisms and Therapies

实验性脑出血：机制和治疗

• 批准号: 9981857
• 负责人: GUOHUA XI
• 金额: $ 93.82万
• 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/9981857
• 关键词: Address; 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.

自发性脑内出血（ICH）是一种常见且往往致命的卒中亚型。如果患者 在发作中幸存下来，由此产生的脑实质内血肿引发了一系列事件，导致 二次损伤和严重的神经功能缺损虽然人体内的血肿会逐渐消退， 几个月后，功能恢复是分级的，通常是不完全的。脑出血的神经功能缺损 患者是永久性的和残疾的。 在过去的20年里，我一直在研究这样一个假设，即组件的释放（例如， 血红蛋白、铁和凝血酶）导致ICH诱导的脑损伤。我们在铁方面的工作 （从血红蛋白中释放）导致了目前去铁胺治疗ICH的II期临床试验 （NCT02175225）。本提案继续审查这一基本假设。具体而言，它将解决：1） 血肿中早期红细胞溶解的机制; 2）CD 163在血肿清除后血红蛋白清除中的作用 颅内血肿清除机制; 4）脑积水机制 脑室内出血后的发展;和5）ICH的联合治疗。 我们项目的目的是确定脑出血后脑损伤的机制， 开发有效的治疗方法。我们研究的长期目标是限制患者的出血性脑损伤。