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

爱荷华大学临床前评估网络(UIowa-SPAN)符合美国国立卫生研究院的目标，即最大限度地提高效率，开发和进行严格的中风再灌注背景下神经保护的临床前比较研究。目前的提案建立在爱荷华州大学作为临床前和临床NINDS赞助的中风研究领先者的丰富传统之上。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专家聚集在一起，进行严格的缺血-再灌注动物试验。我们将利用我们的经验，既使用雄性/雌性动物，也使用共同疾病(例如高脂血症)，并结合严格的方法将偏见降至最低，包括随机化、盲法、意向治疗分析和独立的结果判断。我们建议的近期目标是通过允许尿酸(UA)从比较动物实验进入第二阶段试验，在未来StrokeNet开发的研究MT平台上进行，从而推动协同神经保护干预领域的发展。具体地说，该提案将尿酸作为通过临床前评估网络进行测试的疗法之一。尿酸的自由基(过氧亚硝酸根)清除作用对于减少移植后的脑再灌注损伤和再灌流的缺乏至关重要。UA在符合STAIR/RIGOR指南的动物身上有很好的疗效记录，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。静脉注射尿酸与SPAN中的其他候选分子将通过盲法、随机、适应性实验，使用SPAN协调中心认为必要的动物模型和共病进行比较。这项建议可能会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大的临床意义。

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).