CD47 and hematoma clearance in intracerebral hemorrhage

描述（由申请人提供）：自发性脑出血（ICH）是一种常见且经常致命的中风亚型。如果患者在休克中幸存下来，脑实质内的血肿会引发一系列事件，导致继发性损伤和严重的神经功能缺损。凝块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缺损。我们之前的研究表明血红蛋白及其降解产物（包括铁）从红细胞中释放参与脑出血后的脑损伤。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改善脑出血后的功能结局，CD47在红细胞吞噬中起重要作用。我们的初步研究表明，脑出血后发生红细胞吞噬，红细胞表达CD47。在本应用中，我们拟测试以下具体目的：1)确定CD-47是否介导血肿清除；2)确定增强的凝块清除是否能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申请奠定坚实的基础。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.