THE RELATIONSHIP OF SERUM PROTEINS TO STROKE SEVERITY

血清蛋白与中风严重程度的关系

• 批准号: 6684329
• 负责人: Edward C Jauch
• 金额: $ 24.09万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6684329
• 关键词: biomarker; blood proteins; cerebral artery; cerebral hemorrhage; cerebral ischemia /hypoxia; cerebrovascular disorder diagnosis; clinical research; computed axial tomography; diagnosis design /evaluation; human subject; magnetic resonance imaging; myelin basic proteins; plasminogen activator; platelet aggregation inhibitors; proteomics; stroke; stroke therapy

The approval of tissue plasminogen activator (tPA) for use in acute ischemic stroke by the FDA in 1996 dramatically changed the treatment of stroke. Yet, many patients who are potential candidates do not receive thrombolytics due to the treating physician's concern of hemorrhage. New diagnostic tests to identify patients at increased risk of tPA-associated hemorrhage, to predict long-term outcome, and to measure therapeutic efficacy would ve very useful to physicians who treat acute stroke patients with tPA or other therapies. This proposal will examine the relationship of serum proteins to baseline stroke severity, clinical and radiographic outcome, response to therapy, and the risk of intracerebral hemorrhage after tPA+/- eptifibatide therapy in the CLEAR Trial. In Aim 1, based on our preliminary findings, two serum proteins, S100 and myelin basic protein (MBP), will be studied over the first 24 hours from presentation. Changes and peaks in S100 and MBP concentrations will be correlated with the severity of neurologic deficit, volume of infarct on CT and magnetic resonance imaging, flow in the middle cerebral artery as measured by magnetic resonance angiography, presence of intracerebral hemorrhage, and long-term outcome. Aim 2 will employ a proteomics approach to identify plasma proteins that are associated with intracerebral hemorrhage following administration of tPA. Pretreatment plasma from patients who do not develop intracerebral hemorrhage. A long-term goal of this study is to develop serum marker assays as independent measures of prognosis and therapeutic efficacy. Such tools would be useful in the design of new clinical therapeutic trials and the selection of therapies in acute stroke. Long-term goals associated with the proteomics study include developing rapid assays that could be used to identify patients at increased risk of hemorrhage to better select patients for thrombolytic therapy. Additionally, the protein library created by this project could help identify new proteins associated with ischemic stroke leading to improved diagnostic assays with increased sensitivity, specificity, and accuracy for cerebral ischemia. Overall, this project in conjunction with Project 3, represents a unique opportunity to compare both a proteomics and genomics approach in a single disease condition, thereby complementing each strategy's strengths. We expect this project will lead to the development of further proteomics and genomics studies of ischemic and hemorrhagic stroke.

1996 年 FDA 批准组织纤溶酶原激活剂 (tPA) 用于治疗急性缺血性中风，极大地改变了中风的治疗。然而，由于治疗医生担心出血，许多潜在候选患者并未接受溶栓治疗。新的诊断测试可识别 tPA 相关出血风险增加的患者、预测长期结果并测量治疗效果，这对于使用 tPA 或其他疗法治疗急性中风患者的医生非常有用。 该提案将检查血清蛋白与基线卒中严重程度、临床和放射学结果、治疗反应以及 CLEAR 试验中 tPA+/- 依替巴肽治疗后脑出血风险的关系。在目标 1 中，根据我们的初步研究结果，将在出现后的前 24 小时内研究两种血清蛋白：S100 和髓磷脂碱性蛋白 (MBP)。 S100 和 MBP 浓度的变化和峰值与神经功能缺损的严重程度、CT 和磁共振成像上的梗塞体积、磁共振血管造影测量的大脑中动脉血流、脑内出血的存在以及长期相关。结果。目标 2 将采用蛋白质组学方法来鉴定与 tPA 给药后脑出血相关的血浆蛋白。 来自未发生脑出血的患者的治疗前血浆。本研究的长期目标是开发血清标志物检测作为预后和治疗效果的独立测量方法。这些工具将有助于设计新的临床治疗试验和选择急性中风的疗法。与蛋白质组学研究相关的长期目标包括开发快速检测方法，可用于识别出血风险增加的患者，以更好地选择患者进行溶栓治疗。此外，该项目创建的蛋白质库可以帮助识别与缺血性中风相关的新蛋白质，从而改进诊断测定，提高脑缺血的敏感性、特异性和准确性。 总体而言，该项目与项目 3 相结合，提供了一个独特的机会，可以在单一疾病条件下比较蛋白质组学和基因组学方法，从而补充每种策略的优势。我们预计该项目将促进缺血性和出血性中风的进一步蛋白质组学和基因组学研究的发展。