Uric acid (UA) is a strong endogenous antioxidant that neutralizes the toxicity of peroxynitrite and other reactive species on the neurovascular unit generated during and after acute brain ischemia. The realization that a rapid reduction of UA levels during an acute ischemic stroke was associated with a worse stroke outcome paved the way to investigate the value of exogenous UA supplementation to counteract the progression of redox-mediated ischemic brain damage. The long translational journey for UA supplementation recently reached a critical milestone when the results of the multicenter NIH stroke preclinical assessment network (SPAN) were reported. In a novel preclinical paradigm, 6 treatment candidates including UA supplementation were selected and tested in 6 independent laboratories following predefined criteria and strict methodological rigor. UA supplementation was the only intervention in SPAN that exceeded the prespecified efficacy boundary with male and female animals, young mice, young rats, aging mice, obese mice, and spontaneously hypertensive rats. This unprecedented achievement will allow UA to undergo clinical testing in a pivotal clinical trial through a NIH StrokeNet thrombectomy endovascular platform created to assess new treatment strategies in patients treated with mechanical thrombectomy. UA is a particularly appealing adjuvant intervention for mechanical thrombectomy because it targets the microcirculatory hypoperfusion and oxidative stress that limits the efficacy of this therapy. This descriptive review aims to summarize the translational development of UA supplementation, highlighting those aspects that likely contributed to its success. It includes having a well-defined target and mechanism of action, and an approach that simultaneously integrated rigorous preclinical assessment, with epidemiologic and preliminary human intervention studies. Validation of the clinical value of UA supplementation in a pivotal trial would confirm the translational value of the SPAN paradigm in preclinical research.

尿酸（UA）是一种强内源性抗氧化剂，可以中和急性脑缺血期间和之后产生的过氧亚硝酸盐和其他活性物质对神经血管单元的毒性。认识到急性缺血性中风期间 UA 水平的快速降低与更差的中风结果相关，这为研究外源性 UA 补充剂对抗氧化还原介导的缺血性脑损伤的进展的价值铺平了道路。多中心 NIH 卒中临床前评估网络 (SPAN) 的结果公布后，UA 补充剂的漫长转化之旅最近达到了一个重要的里程碑。在一种新颖的临床前范例中，根据预先确定的标准和严格的方法学严谨性，选择了包括 UA 补充剂在内的 6 种候选治疗方法，并在 6 个独立实验室进行了测试。补充UA是唯一对雄性和雌性动物、幼年小鼠、幼年大鼠、衰老小鼠、肥胖小鼠和自发性高血压大鼠的SPAN超过预设疗效边界的干预措施。这一前所未有的成就将使 UA 能够通过 NIH StrokeNet 血栓切除血管内平台进行关键临床试验的临床测试，该平台旨在评估接受机械血栓切除术治疗的患者的新治疗策略。UA 是一种特别有吸引力的机械血栓切除术辅助干预措施，因为它针对的是限制该疗法疗效的微循环灌注不足和氧化应激。本描述性综述旨在总结 UA 补充剂的转化发展，强调可能有助于其成功的那些方面。它包括制定明确的目标和作用机制，以及同时将严格的临床前评估与流行病学和初步人类干预研究相结合的方法。在关键试验中验证 UA 补充剂的临床价值将证实 SPAN 范式在临床前研究中的转化价值。