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

爱荷华州大学临床前评估网络（UIowa-SPAN）符合NIH的目标，即最大限度地提高开发和进行中风再灌注背景下神经保护的严格临床前比较研究的效率。目前的提案建立在UIowa作为临床前和临床NINDS赞助的中风研究领导者的丰富传统之上。这一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、共病（例如高脂血症）的经验，结合严格的方法来最大限度地减少偏倚，包括随机化、设盲、意向治疗分析和独立结局裁定。我们的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在未来StrokeNet开发的研究MT平台中进行的II期试验来推进协同神经保护干预领域。具体而言，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）清除剂作用对于减少MT后发生的脑再灌注损伤和缺乏再流至关重要。UA在STAIR/RIGOR指南范围内的动物中具有良好的疗效记录，以及MT治疗患者的安全性和初步疗效的良好记录。将使用SPAN协调中心认为必要的动物模型和合并症，通过设盲、随机、适应性实验，将UA静脉输注与SPAN中的其他候选分子进行比较。该提案可能通过改善那些患有中风并需要机械血栓切除术（MT）治疗的美国人的结果而具有重要的临床意义。

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).