低温自体血靶向回输对于非人灵长类脑卒中模型的神经保护作用  

Hypothermic neuroprotection by targeted cold autologous blood transfusion in a non-human primate stroke model

作　　者：陈健 徐率立 Hangil Lee 吴隆飞 何小夺 赵文博 张默 马艳辉 丁玉川 付永娟 吴川杰 李明 姜缪文 程化坤 李胜利 马挺 吉训明 吴迪 Jian Chen;Shuaili Xu;Hangil Lee;Longfei Wu;Xiaoduo He;Wenbo Zhao;Mo Zhang;Yanhui Ma;Yuchuan Ding;Yongjuan Fu;Chuanjie Wu;Ming Li;Miuwen Jiang;Huakun Cheng;Shengli Li;Ting Ma;Xunming Ji;Di Wu(Department of Neurosurgery,Xuanwu Hospital,Beijing Institute of Brain Disorders,Capital Medical University,Beijing 100053,China;China-America Institute of Neuroscience,Xuanwu Hospital,Beijing Institute of Brain Disorders,Capital Medical University,Beijing 100053,China;Department of Neurological Surgery,Wayne State University School of Medicine,Detroit MI 46801,USA;Department of Neurology,Xuanwu Hospital,Beijing Institute of Brain Disorders,Capital Medical University,Beijing 100053,China;Department of Radiology,Xuanwu Hospital,Capital Medical University,Beijing 100053,China;Department of Anesthesiology,Xuanwu Hospital,Beijing Institute of Brain Disorders,Capital Medical University,Beijing 100053,China;Department of Pathology,Xuanwu Hospital,Beijing Institute of Brain Disorders,Capital Medical University,Beijing 100053,China;Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine,Beijing 100053,China;Interdisciplinary Innovation Institute of Medicine and Engineering,Beijing Advanced Innovation Center for Big Data-Based Precision Medicine,School of Biological Science andMedical Engineering,Beihang University,Beijing 100083,China;Department of Neurosurgery,Heilongjiang Provincial Hospital,Harbin 1500036,China;Department of Laboratory Animal Science,Capital Medical University,Beijing 100069,China)

机构地区：[1]Department of Neurosurgery,Xuanwu Hospital,Beijing Institute of Brain Disorders,Capital Medical University,Beijing 100053,China [2]China-America Institute of Neuroscience,Xuanwu Hospital,Beijing Institute of Brain Disorders,Capital Medical University,Beijing 100053,China [3]Department of Neurological Surgery,Wayne State University School of Medicine,Detroit MI 46801,USA [4]Department of Neurology,Xuanwu Hospital,Beijing Institute of Brain Disorders,Capital Medical University,Beijing 100053,China [5]Department of Radiology,Xuanwu Hospital,Capital Medical University,Beijing 100053,China [6]Department of Anesthesiology,Xuanwu Hospital,Beijing Institute of Brain Disorders,Capital Medical University,Beijing 100053,China [7]Department of Pathology,Xuanwu Hospital,Beijing Institute of Brain Disorders,Capital Medical University,Beijing 100053,China [8]Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine,Beijing 100053,China [9]Interdisciplinary Innovation Institute of Medicine and Engineering,Beijing Advanced Innovation Center for Big Data-Based Precision Medicine,School of Biological Science andMedical Engineering,Beihang University,Beijing 100083,China [10]Department of Neurosurgery,Heilongjiang Provincial Hospital,Harbin 1500036,China [11]Department of Laboratory Animal Science,Capital Medical University,Beijing 100069,China

出　　处：《Science Bulletin》2023年第14期1556-1566,M0004,共12页科学通报（英文版）

基　　金：supported by the National Natural Science Foundation of China(82027802,82171304,82071466,81771260,81871022,82071468,and 82201618);“Sail Plan”Key Medical Specialty(ZYLX202139);“Mission”Talent Project of Beijing Municipal Administration of Hospitals(SML20150802);Beijing Municipal Science and Technology Project(Z181100001918026);Technological Innovation and Service Capability Construction Project From Beijing Municipal Commission of Education(11000023T000002157177)。

摘　　要：近几十年来,虽然研究已经证明治疗性低温在啮齿类动物脑卒中模型中有神经保护作用,但其临床转化却未能成功.可能的原因是不同物种之间的生物学差异以及转化研究中治疗性低温诱导难以有效实施.本研究介绍了一种基于非人灵长类动物缺血再灌注模型的选择性治疗性低温疗法,即将自体血于体外循环中冷却,在血管再通后立即通过微导管向缺血区域回输低温自体血.低温自体血将目标脑区迅速冷却至34℃以下,而核心温度可以维持在36℃左右.低温自体血回输减少了梗死面积,保留了白质完整性,改善了神经功能且未引发低温相关并发症.本研究结果表明,在非人灵长类动物脑卒中模型中,通过冷自体输血诱导治疗性低温是一种可行、快速和安全的方法.这提示低温自体血靶向回输是一种具有临床转化潜力的新型低温脑保护疗法.Over decades,nearly all attempts to translate the benefits of therapeutic hypothermia in stroke models of lower-order species to stroke patients have failed.Potentially overlooked reasons may be biological gaps between different species and the mismatched initiation of therapeutic hypothermia in translational studies.Here,we introduce a novel strategy of selective therapeutic hypothermia in a non-human primate ischemia-reperfusion model,in which autologous blood was cooled ex vivo and the cool blood transfusion was administered at the middle cerebral artery just after the onset of reperfusion.Cold autologous blood cooled the targeted brain rapidly to below 34℃while the rectal temperature remained around 36℃with the assistance of a heat blanket during a 2-h hypothermic process.Therapeutic hypothermia or extracorporeal-circulation related complications were not observed.Cold autologous blood treatment reduced infarct sizes,preserved white matter integrity,and improved functional outcomes.Together,our results suggest that therapeutic hypothermia,induced by cold autologous blood transfusion,was achieved in a feasible,swift,and safe way in a non-human primate model of stroke.More importantly,this novel hypothermic approach conferred neuroprotection in a clinically relevant model of ischemic stroke due to reduced brain damage and improved neurofunction.This study reveals an underappreciated potential for this novel hypothermic modality for acute ischemic stroke in the era of effective reperfusion.

关 键 词：自体血 非人灵长类动物 缺血区域 血管再通 神经保护作用 自体输血 微导管 核心温度 

分 类 号：R743.3[医药卫生—神经病学与精神病学]