CD47 and hematoma clearance in intracerebral hemorrhage

描述(由申请人提供)：自发性脑出血(ICH)是一种常见且往往致命的中风亚型。如果患者在癫痫发作中幸存下来，脑实质内产生的血肿会触发一系列事件，导致二次侮辱和严重的神经功能障碍。血栓溶解在脑出血后继发性脑损伤中起重要作用。确定脑出血后脑损伤的机制是我们实验室的长期目标。脑出血后，血肿中的红细胞溶解，导致脑水肿形成、神经元死亡和神经功能障碍。我们以前的研究表明，红细胞释放血红蛋白及其降解产物，包括铁，与脑出血后的脑损伤有关。最近的研究发现，增强小胶质细胞/巨噬细胞介导的血肿清除可以改善脑出血后的功能转归，而CD47在红细胞吞噬功能中起着重要作用。我们的初步研究表明，脑出血后脑内发生红细胞吞噬作用，红细胞表达CD47。在这一应用中，我们建议测试以下特定目标：1)确定CD-47是否介导血肿清除；以及2)确定增强的血栓清除是否减少脑出血引起的脑损伤并改善脑出血后的行为结局。我们认为，这里提出的试点研究应该为NIH R01的应用奠定坚实的基础。我们研究的长期目标是限制脑出血后的脑损伤。

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. 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.