法苏迪尔
医学
冲程(发动机)
缺血性中风
缺血
内科学
物理医学与康复
心脏病学
Rho相关蛋白激酶
化学
信号转导
机械工程
工程类
生物化学
作者
Takahiko Imai,Andreia Morais,Xuyan Jin,Tao Qin,Jessica Lamb,Karisma A. Nagarkatti,Mu‐Hsun Chen,Lígia Simões Braga Boisserand,Rakesh B. Patel,Mariia Kumskova,Anjali Chauhan,Krishnan M. Dhandapani,Mohammad Badruzzaman Khan,Pradip K. Kamat,Yanrong Shi,Suyi Cao,Basavaraju G. Sanganahalli,Joseph B. Mandeville,Patrick D. Lyden,David C. Hess
出处
期刊:Stroke
[Lippincott Williams & Wilkins]
日期:2025-05-27
卷期号:56 (8): 2306-2317
被引量:3
标识
DOI:10.1161/strokeaha.125.050977
摘要
BACKGROUND: The SPAN (Stroke Preclinical Assessment Network) is a confirmatory multicenter trial network to test cerebroprotective interventions in experimental acute stroke. In a first-of-its-kind trial, SPAN tested 6 interventions in a rodent model of transient focal ischemic stroke. Here, we report the efficacy of fasudil, an isoform-nonselective rho-associated kinase inhibitor, on primary and secondary outcomes in the SPAN trial. METHODS: Fasudil was administered at 10 mg/kg intraperitoneally every 12 hours for 6 doses starting 5 minutes before reperfusion in a 60-minute endovascular filament middle cerebral artery occlusion model. The active treatment arm (n=345) was compared with the pooled intraperitoneal and intravenous vehicle arms (n=344). In addition to healthy young mice, the trial included aging mice (16±1 months), diet-induced obese mice, and spontaneously hypertensive rats. The a priori fasudil substudy design stipulated the modified corner test performance on day 28 as the primary end point and separate analyses for mice and spontaneously hypertensive rats using the modified intention-to-treat cohort. RESULTS: =0.022). The effect appeared stronger in aging mice and when ischemia was induced during the active circadian stage. Fasudil did not show any benefit in the spontaneously hypertensive rats. Alternative analyses using the per-protocol population and imputation generally yielded similar conclusions. CONCLUSIONS: Our results reveal a favorable therapeutic profile for fasudil, supporting future translational development of rho-associated kinase inhibitors in ischemic stroke.
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