Therapeutic Window for Acute Stroke Therapy

我们建议在加州大学圣地亚哥分校卒中中心（UCSD）建立一个急性卒中转化研究的专门项目（SPOTRIAS）。核心设施和项目将满足SPOTRIAS的目标，增加溶栓治疗患者的数量，特别是卒中后2小时内接受治疗的患者。为了实现这一目标，我们提供了四个相互关联的项目。1)为了找到一个简单的急性脑卒中的血清标志物，我们将描述急性脑卒中患者的游离脂肪酸（FFA）反应，包括时间过程。我们将确定FFA水平是否与各种卒中结局相关，并试图区分缺血和常见的模拟。我们将描述与有效溶栓相关的FFA反应。2)在1期试验中，通过研究卒中发作后3至6小时开始的溶栓，结合24小时的血管内冷却，使用低温延长溶栓的时间窗。我们假设低温对这类患者是安全的。我们将进行一项2期试验，以证明低温可降低出血率，并改善3至6小时溶栓患者的结局。3)使用无创性床边检查-对比增强经颅超声检查在溶栓前后鉴别血管闭塞和灌注缺损。我们将测试超声是否可以区分中风和拟态，并从2小时内出现轻度或波动性缺陷的患者中确定潜在的治疗候选者。4)以确定是否新颖的宽带无线互联网 技术将允许UCSD中风团队的教员通过在圣地亚哥的远程急诊室设置音频/视频咨询功能来指导远程医院的溶栓治疗。急性会诊可能会增加2小时溶栓治疗的次数。这些项目建立在UCSD卒中中心的核心设施之上，其中包括一个国家认可的卒中团队，一个培训计划，一个数据收集和统计分析单位，以及一个标本收集和储存设施。所有需要的团队、协作和设施都已到位。SPOTRIAS计划将使我们能够加强和启动转化研究，最终将通过在2小时内治疗更多患者，并找到治疗更多患者的方法，使中风患者受益。

We propose a Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) at the University of California, San Diego, Stroke Center (UCSD). The Core facilities and projects will meet SPOTRIAS target goals, increasing the number of thrombolytic-treated patients, particularly those treated within 2 hours following stroke. To achieve this, we offer 4 inter-related projects. 1) To find a simple, serum marker of acute stroke, we will characterize the free fatty acid (FFA) response in acute stroke patients, including the time course. We will determine whether FFA levels correlate with various stroke outcomes, and attempt to distinguish ischemia from common mimics. We will characterize the FFA response associated with effective thrombolysis. 2) To use hypotherrnia to prolong the time window for thrombolysis in a Phase 1 trial, by studying thrombolysis beginning 3 to 6 hours following stroke onset, combined with 24 hours of intravascular cooling. We hypothesize that hypothermia will be safe in such patients. We will proceed to a Phase 2 trial to show that hypothermia reduces hemorrhage rates and improves outcomes in 3 to 6 hour thrombolysis patients. 3) To use a non-invasive, bedside test---contrast enhanced transcranial ultrasoundmto identify vascular occlusion and perfusion defects before and after thrombolysis. We will test whether ultrasound may separate stroke from mimics, and identify potential treatment candidates from among patients with mild or fluctuating deficits presenting within 2 hours. 4) To determine whether novel broadband wireless Internet technology will allow UCSD Stroke Team faculty to direct thrombolysis at remote hospitals by placing audio/video consultation capability at remote Emergency Departments in San Diego. Acute consults may increase the number of 2-hour thrombolytic treatments. These projects are built on the core facilities of the UCSD Stroke Center, which include a nationally recognized stroke team, a training program, a data collection and statistical analysis unit, and a specimen collection and storage facility. All of the needed teams, collaborations, and facilities are in place. The SPOTRIAS program will allow us to enhance and initiate translational research that ultimately will benefit stroke patients by treating more patients under 2 hours, and finding ways to treat additional patients later.