Experimental Cerebral Hemorrhage: Mechanisms and Therapies

自发性脑出血(ICH)是一种常见且往往致命的卒中亚型。如果病人 在发病后存活，导致脑实质内的血肿触发一系列事件，导致 二次侮辱和严重的神经缺陷。虽然人的血肿在体内逐渐消退 几个月后，功能恢复是分级的，通常是不完整的。脑出血患者的神经功能障碍 患者是永久性的和致残的。 在过去的20年里，我一直在检验这样一种假设，即组件的释放(例如， 血肿中的血红蛋白、铁和凝血酶)会导致脑出血所致的脑损伤。我们对铁的研究 (从血红蛋白中释放)导致了目前治疗脑出血的去铁胺的第二阶段临床试验 (NCT02175225)。这一提议继续检验这一潜在的假设。具体地说，它将解决：1) 血肿早期红细胞溶解的机制：2)CD163在血肿清除血红蛋白中的作用 ICH；3)内源性血肿清除机制；4)脑积水机制 脑室出血后的进展；5)脑出血的联合治疗。 本项目的目的是确定脑出血后脑损伤的机制，并 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。

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.