Imaging detects transient “hypoxic pockets” in the mouse brain

Using a bioluminescent oxygen indicator, Felix Beinlich and colleagues discovered a spontaneous, spatially defined occurrence of “hypoxic pockets” in the mouse brain. Their technique offers a way to learn more about brain oxygen tension (pO₂), a measure of oxygen delivery and demand in brain tissue that changes dynamically but is not well understood. The findings could have implications for how rest and exercise affect pO₂ in the human brain, including the role of these activities in conditions such as dementia, Beinlich et al. suggest. The researchers used a genetically encoded bioluminescent oxygen indicator called Green NanoLuc in mouse cortical astrocytes to track pO₂ changes. Under resting conditions, pO₂ changed often and included transient but sharply defined events of hypoxia that lasted several seconds to minutes and were spatially confined. Further research confirmed that the hypoxic pockets were caused by circulation changes in the brain’s capillaries. During exercise, the area covered by hypoxic pockets in the mouse brain decreased by 52% compared to the brain during rest. “Our study predicts that physical inactivity has direct effects on tissue pO₂ by favoring capillary occlusions and increasing the number of hypoxic pockets,” they write. “Conversely, simply increasing sensory input or locomotion rapidly suppress the occurrence of hypoxic pockets perhaps explaining the linkage between sedentary lifestyle and an increased risk of dementia.” As pO₂ decreases with age, the researchers also note that their technique might someday be used to determine if hypoxic pockets expand or last longer with age.