ANTIPLATELET AGGREGATION THERAPY FOR EMBOLIC STROKE

迫切需要开发补充溶栓治疗急性卒中的疗法。在这个项目中，我们测试的假设，即微血管血栓形成后，中风和血小板聚集有助于发展的暴发性缺血性病变。因此，用GPIIb/IIIa受体拮抗剂治疗栓塞性卒中（GPIIb/IIIa受体将血小板与纤维蛋白原结合，是血小板的末端）和用GPIIb/IIIa受体拮抗剂治疗栓塞性卒中（GPIIb/IIIa受体将血小板与纤维蛋白原结合，是血小板血栓形成的末端）可增强脑灌注，减少血栓形成，补充和增强rtPA对卒中的溶栓治疗。为了实现我们的目标，我们提出了四个具体目标：具体目标1：大鼠将遭受栓塞性中风，并测量组织灌注和血栓形成的时空分布。具体目的2：将大鼠进行栓塞性卒中，并在卒中后的特定时间点（2 h、4 h、6 h）用rtPA治疗。将测量脑梗死体积以及组织灌注和血栓形成的时空分布。具体目标3：大鼠将经历栓塞性中风，并在中风之前和之后的特定时间点用GP IIb/IIIa受体拮抗剂治疗。将测量脑梗死体积以及组织灌注和血栓形成的时空分布。具体目标2：大鼠将遭受栓塞性卒中，并将在卒中后的特定时间点（2 h、4 h、6 h）接受rtPA治疗。将测量脑梗死体积以及组织灌注和血栓形成的时空分布。具体目标3：大鼠将经历栓塞性中风，并在中风之前和之后的特定时间点用GP IIb/IIIa受体拮抗剂治疗。将测量脑梗死体积以及组织灌注和血栓形成的时空分布。具体目标4：大鼠将经历栓塞性中风，并在中风后的特定时间点用GPIIb/IIIa受体拮抗剂和纤维蛋白溶解与rtPA的组合进行治疗。为了验证我们的假设，我们采用了临床相关的大鼠栓塞性卒中模型和最先进的技术，包括定量扫描共聚焦显微镜和MRI。我们开发人体抗血小板聚集治疗的长期目标是在项目3中进行的II期临床试验中启动。本课题为减少血小板介导的脑卒中继发血栓形成提供了实验依据。

There is a compelling need to develop therapies complementary to thrombolysis for the treatment of acute stroke. In this Project, we test the hypothesis that microvascular thrombosis ensues after stroke and that platelet aggregation contributes to progression of the fulminating ischemic lesion. Thus, treatment of embolic stroke with an antagonist to the GPIIb/IIIa receptor, which binds the platelet to fibrinogen and is the terminus of platelet with an antagonist to the GPIIb/IIIa receptor, which binds the platelet to fibrinogen and is the terminus of platelet thrombosis, may enhance cerebral perfusion, reduce thrombosis and complement and enhance thrombolytic therapy of stroke with rtPA. To achieve our goals, we propose four Specific Aims: Specific Aim 1: Rats will be subjected to embolic stroke and the spatiotemporal profiles of tissue perfusion and thrombosis will be measured. Specific Aim 2: Rats will be subjected to embolic stroke and will be treated with rtPA at specific time paints after stroke (2h, 4h, 6h). The volume of cerebral infarction and the spatiotemporal profiles of tissue perfusion and thrombosis will be measured. Specific Aim 3: Rats will be subjected to embolic stroke and will be treated with GP IIb/IIIa receptor antagonist at specific time points before and after stroke. The volume of cerebral infarction and the spatiotemporal profiles of tissue perfusion and thrombosis will be measured. Specific Aim 2: Rats will be subjected to embolic stroke and will be treated with rtPA and specific time points after stroke (2h, 4h, 6h). The volume of cerebral infarction and the spatiotemporal profiles of tissue perfusion and thrombosis will be measured. Specific Aim 3: Rats will be subjected to embolic stroke and will be treated with a GP IIb/IIIa receptor antagonist at specific time points before and after stroke. The volume of cerebral infarction and the spatiotemporal profiles of tissue perfusion and thrombosis will be measured. Specific Aim 4: Rats will be subjected to embolic stroke and will be treated with a combination of GPIIb/IIIa receptor antagonist and fibrinolysis with rtPA at specific time points after stroke. To test our hypotheses, we employ a clinically relevant model of embolic stroke in the rat and state-of-the-art technology, including quantita6tive scanning confocal microscopy and MRI. Our long term objective of developing anti-platelet aggregation therapy in the human is initiated in the Phase II Clinical Trial to be carried out in Project 3. This Project provides the experimental basis for reducing platelet mediated thrombosis secondary to stroke.