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.

FDA在1996年在FDA中批准在急性缺血性中风中批准，急剧改变了中风的处理。然而，由于医生对出血的关注，许多潜在候选者的患者没有接受血栓溶液。进行新的诊断测试，以鉴定患有TPA相关的出血风险增加的患者，以预测长期结局并测量治疗疗效对治疗TPA或其他疗法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中风严重程度，临床和放射学结局，对治疗的反应以及TPA +/- eptibibibatide治疗后脑出血的风险。在AIM 1中，基于我们的初步发现，将在介绍后的前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浓度的变化和峰将与神经系统缺陷的严重程度，CT上的梗塞体积和磁共振成像，中部动脉中的流动相关，如磁共振血管造影，存在脑血管造影，脑部出血的存在以及长期结局。 AIM 2将采用一种蛋白质组学方法来鉴定给予TPA后与脑内出血相关的血浆蛋白。 未发生脑出血的患者的预处理血浆。这项研究的一个长期目标是开发血清标志物分析作为预后和治疗功效的独立测量。此类工具对于设计新的临床治疗试验和急性中风的疗法的选择将很有用。与蛋白质组学研究相关的长期目标包括开发快速测定，可用于鉴定出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文库可以帮助鉴定与缺血性中风相关的新蛋白质，从而改善诊断测定，并提高敏感性，特异性和对脑缺血的准确性。 总体而言，该项目与项目3结合使用，这是一个独特的机会，可以在单个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。我们预计该项目将导致进一步的蛋白质组学和缺血性和出血性中风的基因组学研究。