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

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

doi:10.1016/j.scib.2023.06.017

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

Sci Bull (Beijing). 2023 Jul 30;68(14):1556-1566. doi: 10.1016/j.scib.2023.06.017. Epub 2023 Jun 20.

Authors

Jian Chen¹, Shuaili Xu², Hangil Lee³, Longfei Wu⁴, Xiaoduo He², Wenbo Zhao⁴, Mo Zhang⁵, Yanhui Ma⁶, Yuchuan Ding³, Yongjuan Fu⁷, Chuanjie Wu⁴, Ming Li⁸, Miuwen Jiang⁹, Huakun Cheng¹⁰, Shengli Li¹¹, Ting Ma¹², Xunming Ji¹³, Di Wu¹⁴

Affiliations

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 Department of Neurosurgery, Xuanwu Hospital, Beijing Institute of Brain Disorders, Capital Medical University, Beijing 100053, China; 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 and Medical 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.
¹² Department of Anesthesiology, Xuanwu Hospital, Beijing Institute of Brain Disorders, Capital Medical University, Beijing 100053, China. Electronic address: maading@sina.com.
¹³ Department of Neurosurgery, 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 and Medical Engineering, Beihang University, Beijing 100083, China. Electronic address: jixm@ccmu.edu.cn.
¹⁴ China-America Institute of Neuroscience, Xuanwu Hospital, Beijing Institute of Brain Disorders, Capital Medical University, Beijing 100053, China. Electronic address: seadi-wu@163.com.

PMID: 37391345
DOI: 10.1016/j.scib.2023.06.017

Abstract

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 °C while the rectal temperature remained around 36 °C 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.

Keywords: Acute ischemic stroke; Autologous blood transfusion; Endovascular hypothermia; Revascularization.