The University of Iowa Stroke Preclinical Assessment Center for Neuroprotection in stroke

爱荷华大学中风临床前神经保护评估中心

• 批准号: 10200920
• 负责人: Anil Kumar Chauhan
• 金额: $ 50.04万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-15 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10200920
• 关键词: Acute; Agreement; American; Animal Experimentation; Animal Experiments; Animal Model; Animals; Antioxidants; Assessment tool; Autologous; Blinded; Blood Vessels; Brain; Brain Injuries; Classification; Clinical; Clinical Trials; Coagulation Process; Comparative Study; Consumption; Data; Development; Drops; Ethics; Exposure to; Female; Free Radical Scavengers; Free Radicals; Future; Goals; Guidelines; Helicopter; Hospitals; Human; Hydroxyl Radical; Hyperlipidemia; IACUC; Infarction; Infrastructure; Institution; Institutional Review Boards; Intention; Interdisciplinary Study; Intervention; Intravenous infusion procedures; Iowa; Ischemia; Ischemic Stroke; Laboratories; Magnetic Resonance Imaging; Mechanics; Mediating; Methodology; Middle Cerebral Artery Occlusion; Modeling; Mus; National Institute of Neurological Disorders and Stroke; Neurologic; Neurologist; Outcome; Outcome Measure; Oxidation-Reduction; Patients; Performance; Peroxonitrite; Phase; Plasma; Positioning Attribute; Protocols documentation; Publications; Randomized; Rattus; Reperfusion Injury; Reperfusion Therapy; Research; Research Infrastructure; Research Personnel; Safety; Scientist; Serum; Severities; Spain; Speed; Stroke; Supplementation; Testing; Thrombectomy; Transportation; United States National Institutes of Health; Universities; Uric Acid; acute stroke; adjudication; animal mortality; cerebrovascular; clinical development; comorbidity; comparative; experience; experimental study; human data; improved outcome; male; neuroprotection; phase II trial; pre-clinical; pre-clinical assessment; stroke intervention; stroke therapy

The University of Iowa Preclinical assessment Network (UIowa-SPAN) meets the goal of the NIH in maximizing efficiencies to develop and conduct rigorous pre-clinical comparative studies of neuroprotection in the context of stroke reperfusion. The current proposal builds on the rich tradition of the UIowa as a leader in preclinical and clinical NINDS-sponsored stroke research. This infrastructure brings together basic cerebrovascular scientists with vascular neurologists and clinical trialists to conduct rigorous animal trials of ischemia-reperfusion. We will capitalize on our experience using both male/female animals, co-morbidities (e.g. hyperlipidemia), combined with a rigorous methodology to minimize biases, including randomization, blinding, intention-to -treat analyses and independent outcome adjudications. Our proposal’s immediate goal is to advance the field of synergistic neuroprotective interventions by allowing uric acid (UA) progress from comparative animal experiments into phase II trials conducted in a future StrokeNet-developed research MT platform. Specifically, this proposal incorporates UA as one of the therapies to be tested through this preclinical assessment network. The free-radical (peroxynitrite) scavenger action of UA is crucial to minimize the brain reperfusion injury and lack of reflow that occurs after MT. UA has a strong record of efficacy in animals within STAIR/RIGOR guidelines, as well as an excellent record of safety and preliminary efficacy in patients treated with MT. Intravenous infusions of UA will be compared against the other candidate molecules in SPAN through blinded, randomized, adaptive experiments using the animals models and co-morbidities deemed necessary by the SPAN coordinating center. The proposal may have significant clinical implications by improving the outcomes of those Americans who suffer a stroke and require treatment with mechanical thrombectomy (MT).

爱荷华大学临床前评估网络（Iowa- span）符合美国国立卫生研究院的目标，即在卒中再灌注的背景下，最大限度地提高效率，开展严格的神经保护临床前比较研究。目前的提案建立在爱荷华大学作为临床前和临床nind资助的中风研究的领导者的丰富传统之上。这个基础设施将基础脑血管科学家与血管神经学家和临床试验学家聚集在一起，进行严格的缺血再灌注动物试验。我们将利用我们使用雄性/雌性动物、合并症（如高脂血症）的经验，结合严格的方法来最大限度地减少偏差，包括随机化、盲法、意向治疗分析和独立结果裁决。我们提议的直接目标是通过允许尿酸（UA）从比较动物实验进展到在未来strokenet开发的研究MT平台上进行的II期试验，推进协同神经保护干预领域。具体来说，该提案将UA纳入临床前评估网络测试的疗法之一。UA的自由基（过氧亚硝酸盐）清除剂作用对于减少MT后发生的脑再灌注损伤和缺乏再流至关重要。在STAIR/RIGOR指南中，UA在动物中有强有力的疗效记录，在接受MT治疗的患者中也有良好的安全性和初步疗效记录。使用动物模型和SPAN协调中心认为必要的合并症进行适应性实验。该建议可能具有重要的临床意义，可以改善美国中风患者需要机械取栓（MT）治疗的结果。