CD47 and hematoma clearance in intracerebral hemorrhage

描述（由申请人提供）：自发性脑内出血（ICH）是一种常见且往往致命的卒中亚型。如果患者在发作后存活，脑实质内产生的血肿会引发一系列事件，导致二次损伤和严重的神经功能缺损。血凝块溶解在脑出血继发性脑损伤中起重要作用。我们实验室的长期目标是确定ICH后脑损伤的机制。 在ICH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。我们以前的研究表明，释放血红蛋白及其降解产物，包括铁从红细胞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ICH后的功能结局，而CD 47在红细胞吞噬作用中具有重要作用。 我们的初步研究表明，脑出血后发生红细胞吞噬作用，红细胞表达CD 47。在本申请中，我们提出测试以下特定目的：1）确定CD-47是否介导血肿清除;和2）确定增强的凝块清除是否减少ICH诱导的脑损伤并改善ICH后的行为结果。 我们认为，这里提出的试点研究应该为NIH R 01的应用奠定坚实的基础。我们研究的长期目标是限制ICH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.