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 (UIowa-SPAN) 满足 NIH 的目标，即最大限度地提高中风再灌注背景下神经保护的临床前比较研究的效率。当前的提案建立在丰富的传统之上。 UIowa 是 NINDS 资助的临床前和临床中风研究的领导者，该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人员聚集在一起，进行严格的动物试验。我们将利用我们使用雄性/雌性动物、合并症（例如高脂血症）的经验，并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判定。我们提案的近期目标是通过允许尿酸（UA）从比较动物实验进展到未来 StrokeNet 开发的 II 期试验，从而推进协同神经保护干预领域的发展具体来说，该提案将 UA 作为通过该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）清除剂作用对于最大限度地减少脑再灌注损伤和术后回流缺乏至关重要。 MT.UA 在 STAIR/RIGOR 指南中对动物有良好的疗效记录，并且在接受 UA 静脉输注的患者中也有良好的安全性和初步疗效记录。通过使用 SPAN 协调中心认为必要的动物模型和合并症进行盲法、随机、适应性实验，与 SPAN 中的其他候选分子进行比较，该提案可能会通过改善中风和中风的美国人的预后而产生重大的临床意义。需要机械血栓切除术（MT）治疗。