Ischemic Stroke Treatment with Microbubbles, a Novel Clot Lysis Therapeutic

微泡治疗缺血性中风，一种新型血栓溶解疗法

• 批准号: 7185787
• 负责人: WILLIAM C CULP
• 金额: $ 38.64万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-15 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7185787
• 关键词: Accounting; Acute; Aftercare; Alteplase; Anatomy; Angiography; Animal Model; Animals; Area; Arterial Fatty Streak; Blood; Blood Circulation; Blood Clot; Blood Vessels; Blood coagulation; Brain; Cause of Death; Cephalic; Cerebrovascular Circulation; Cerebrovascular Disorders; Cessation of life; Chloride Ion; Chlorides; Clinical; Coagulation Process; Combined Modality Therapy; Cytolysis; Data Analyses; Developed Countries; Developing Countries; Disease; Disruption; Dose; Effectiveness; Embolism; Evaluation; Fibrinolytic Agents; Funding; Future; Goals; Guidelines; Hemorrhage; Hour; Human; Imagery; Immersion Investigative Technique; In Vitro; Incidence; Individual; Infarction; Inflammation; Internal carotid artery structure; Intervention; Intravenous; Ischemic Stroke; Life; Measurement; Measures; Mechanics; Methods; Microbubbles; Modeling; Motor; Neuraxis; Neurological outcome; Neurons; Numbers; Oryctolagus cuniculus; Patients; Pharmaceutical Preparations; Pharmacotherapy; Pilot Projects; Protocols documentation; Public Health; Rate; Relative (related person); Research Personnel; Research Project Grants; Safety; Score; Serum; Simulate; Staining method; Stains; Standards of Weights and Measures; Stroke; Surveys; System; Techniques; Testing; Therapeutic; Therapeutic Effect; Therapeutic Embolization; Thrombolytic Therapy; Thrombosis; Thrombus; Time; Ultrasonography; Upper arm; abstracting; aged; base; design; disability; dosage; improved; in vivo; motor impairment; novel; prevent; success; thrombolysis; triphenyltetrazolium

DESCRIPTION (provided by applicant): Cerebrovascular disease is the second leading cause of death in developed countries and accounts for high rates of disability. Current therapies for ischemic stroke [tissue plasminogen activator (tPA)] fail to benefit many victims due to the constraints of time to intervention, the significant incidence of treatment-associated hemorrhage, and the limited therapeutic effect of thrombolysis. Our long-term goal is to improve public health by developing ischemic stroke treatment approaches that overcome the limitations of current treatments. Guidelines for treatment currently focus on either (a) intravenous thrombolytic therapy within 3 hours of stroke onset or (b) intra-arterial mechanical intervention/thrombolysis within 6 hours. It has been recently shown in animal models that thrombolytic therapy may be enhanced by the addition of ultrasound. Furthermore, we hypothesize that combining ultrasound with intravenously injected microbubbles may facilitate mechanical disruption of thrombi in intracranial circulation without resulting in treatment-associated hemorrhage. We propose a pilot study that uses a rabbit model of acute embolic stroke to compare the utility of an intervention consisting of either 1] tPA treatment alone, 2] intravenously injected microbubbles with trans-cranial ultrasound, or 3] tPA treatment combined with microbubbles and ultrasound. We will explore the safety and efficacy of these various treatments for lysing three types of clots: fresh clots that simulate secondary clots associated with acute emboli during the window of therapeutic opportunity in ischemic stroke (Specific Aim 1), aged clots that are more typical of embolic clots that may not be fresh (Specific Aim 2), and insoluble embolic material more typical of atheromata (Specific Aim 3). Our ultimate objective for this pilot study is to test the refinement of novel treatments for embolic stroke that would yield a safe, simple, fast and successful therapy that can be further examined in future funded research projects and eventually applied in the clinical realm. Our proposed pilot study will determine which of these treatments is most successful, and future studies will further explore that treatment. (End of Abstract)

描述（由申请人提供）： 脑血管疾病是发达国家的第二大死亡原因，占残疾率高。当前的缺血性中风[组织纤溶酶原激活剂（TPA）]的疗法由于时间的限制，与治疗相关的出血的显着发生率以及溶栓的治疗作用有限，因此无法使许多受害者受益。我们的长期目标是通过开发缺血性中风治疗方法来改善公共卫生，以克服当前治疗的局限性。目前的治疗指南集中在中风发作后3小时内或（b）6小时内动脉内机械干预/溶​​栓的情况下（a）（a）静脉内溶栓疗法。最近在动物模型中显示，通过添加超声可以增强溶栓疗法。此外，我们假设将超声与静脉注射的微泡相结合可能会促进颅内循环中血栓的机械破坏，而不会导致治疗相关的出血。我们提出了一项试点研究，该研究使用急性栓塞中风的兔模型比较了由单独的1] TPA处理组成的干预措施的实用性，2]静脉注射的微泡中具有跨颅超声波，或3] TPA处理结合了Microbubbles和Microbububbles和UltrasOund。我们将探索这些各种处理的三种类型的凝块的安全性和功效：在缺血性中风的治疗机会窗口中模拟与急性栓子相关的新鲜凝块（特定的目标1），衰老的凝块，这些杂物块的质量更典型，是可能不是新鲜的（特定目标2），以及更典型的emportapt of Propicate of Propicate of Proimate of Propicate of Aim of Aim of Aim of Aimatials的典型材料。我们对这项试验研究的最终目标是测试对栓塞中风的新型治疗方法的改进，该治疗方法将产生一种安全，简单，快速和成功的治疗，可以在未来的资助研究项目中进一步研究，并最终在临床领域中应用。我们提出的试点研究将确定哪种治疗方法最成功，未来的研究将进一步探讨这种治疗方法。 （抽象的结尾）