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

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 pri-mate 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 autol-ogous blood cooled the targeted brain rapidly to below 34 & DEG;C while the rectal temperature remained around 36 & DEG;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 out-comes. 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. CO 2023 Science China Press. Published by Elsevier B.V. and Science China Press. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Automated summary

This study introduces a novel strategy of selective therapeutic hypothermia in a non-human primate ischemia-reperfusion model, which involves transfusing cooled autologous blood to rapidly cool the targeted brain. The results show that this approach reduces infarct sizes, preserves white matter integrity, and improves functional outcomes. This novel hypothermic modality has potential for acute ischemic stroke treatment in the era of effective reperfusion.