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).

爱荷华大学的临床前评估网络（UIOWA-SPAN）符合NIH的目标，以最大程度地提高效率，以在中风再灌注的背景下开发和进行严格的神经保护性临床前比较研究。当前的提案以UIOWA的丰富传统为基础，是临床前和临床Ninds赞助的中风研究的领导者。这种基础设施将基本的脑血管科学家与血管神经科医生和临床试验者汇集在一起​​，以进行严格的局部缺血 - 再灌注试验。我们将利用男性/女性动物，合并症（例如高脂血症）的经验，并结合一种严格的方法，以最大程度地减少偏见，包括随机化，盲目，意图对待分析和独立的结果建议。我们的提议的近期目标是通过允许尿酸（UA）从比较动物实验到在未来的Strotenet开发的MT平台中进行的II期试验来推进协同神经保护干预措施。具体而言，该提案将UA作为通过此临床前评估网络进行测试的疗法之一。 UA的自由基（过氧亚硝酸盐）的清除作用对于最大程度地减少了MT后发生的脑再灌注损伤和缺乏反流至关重要。 UA在楼梯/严格指南中的动物效率有很强的记录，并且在接受MT治疗的患者中具有出色的安全性和初步效率的记录。通过使用动物模型和跨度坐标中心认为必要的合并症，将将UA静脉输注与跨越的其他候选分子进行比较。该提案可能会通过改善遭受中风并需要使用机械血栓切除术（MT）治疗的美国人的结果来具有重大的临床意义。