Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
School of Engineering, FHNW University of Applied Sciences and Arts Northwestern Switzerland, 5210 Windisch, Switzerland.
Science. 2024 Mar 29;383(6690):1471-1478. doi: 10.1126/science.adn1011. Epub 2024 Mar 28.
Consciousness is lost within seconds upon cessation of cerebral blood flow. The brain cannot store oxygen, and interruption of oxidative phosphorylation is fatal within minutes. Yet only rudimentary knowledge exists regarding cortical partial oxygen tension (o) dynamics under physiological conditions. Here we introduce Green enhanced Nano-lantern (GeNL), a genetically encoded bioluminescent oxygen indicator for o imaging. In awake behaving mice, we uncover the existence of spontaneous, spatially defined "hypoxic pockets" and demonstrate their linkage to the abrogation of local capillary flow. Exercise reduced the burden of hypoxic pockets by 52% compared with rest. The study provides insight into cortical oxygen dynamics in awake behaving animals and concurrently establishes a tool to delineate the importance of oxygen tension in physiological processes and neurological diseases.
意识在脑血流停止后几秒钟内丧失。大脑无法储存氧气，氧化磷酸化中断几分钟内就会致命。然而，关于生理条件下皮质局部氧分压（o）动力学的基本知识尚不存在。在这里，我们引入了 Green 增强纳米灯笼（GeNL），这是一种用于 o 成像的基因编码生物发光氧指示剂。在清醒活动的小鼠中，我们发现了自发的、空间限定的“缺氧口袋”的存在，并证明它们与局部毛细血管流动中断有关。与休息相比，运动使缺氧口袋的负担减少了 52%。该研究深入了解了清醒活动动物的皮质氧动力学，并同时建立了一种工具来描绘氧张力在生理过程和神经疾病中的重要性。
