ANTIPLATELET AGGREGATION THERAPY FOR EMBOLIC STROKE

迫切需要开发补充溶栓治疗的治疗方法来治疗急性中风。在这个项目中，我们测试了中风后微血管血栓形成和血小板聚集有助于暴发性脑缺血损害进展的假设。因此，用结合血小板与纤维蛋白原的GPIIb/IIIa受体拮抗剂和结合血小板与纤维蛋白原的GPIIb/IIIa受体拮抗剂治疗栓塞性卒中，可增强脑血流灌注，减少血栓形成和补体，加强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：大鼠将受到栓塞性卒中，并将测量组织灌注和血栓形成的时空分布。具体目的2：建立栓塞性卒中大鼠模型，于卒中后特定时间(2小时、4小时、6小时)给予rtPA治疗。将测量脑梗塞体积以及组织灌注和血栓形成的时空分布。具体目的3：建立栓塞性卒中大鼠模型，在卒中前后的特定时间点给予GP IIb/IIIa受体拮抗剂治疗。将测量脑梗塞体积以及组织灌注和血栓形成的时空分布。具体目的2：建立栓塞性卒中大鼠模型，给予rtPA及卒中后特定时间点(2小时、4小时、6小时)治疗。将测量脑梗塞体积以及组织灌注和血栓形成的时空分布。具体目标3：大鼠将进行栓塞性卒中，并在卒中前后的特定时间点使用GP IIb/IIIa受体拮抗剂进行治疗。将测量脑梗塞体积以及组织灌注和血栓形成的时空分布。具体目的4：建立栓塞性卒中大鼠模型，在卒中后特定时间点给予GPIIb/IIIa受体拮抗剂联合rtPA纤溶治疗。为了验证我们的假设，我们使用了一个与临床相关的大鼠栓塞性中风模型和最先进的技术，包括定量扫描共聚焦显微镜和磁共振成像。我们在人类中开发抗血小板聚集疗法的长期目标是在项目3中进行的第二阶段临床试验中启动。该项目为减少继发于中风的血小板介导的血栓形成提供了实验基础。

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.