The human brain’s immense energy consumption relies heavily on oxygen-dependent metabolism. The efficient delivery and allocation of oxygen are pivotal for maintaining healthy brain function. However, the intricate mechanisms behind this process have largely remained veiled to scientists.

A groundbreaking bioluminescence imaging technique, unveiled in the journal Science, has now provided vivid and detailed insights into the movement of oxygen within the brains of mice. This method, easily replicable by other laboratories, promises to facilitate precise studies on forms of hypoxia, such as those occurring during strokes or heart attacks, offering crucial understanding. Furthermore, it has already begun unraveling the mysteries behind why a sedentary lifestyle heightens the risk of diseases like Alzheimer’s.

Maiken Nedergaard, co-director of the Center for Translational Neuromedicine at the University of Rochester and the University of Copenhagen, emphasized the significance of this research in continuously monitoring changes in oxygen concentration across broad brain areas. This real-time monitoring unveils previously undetected instances of temporary hypoxia, shedding light on changes in blood flow that may trigger neurological deficits.

The novel method employs luminescent proteins, akin to those found in fireflies, which have been harnessed in cancer research. These proteins are introduced into cells via a virus, prompting the production of luminescent enzymes. When these enzymes interact with their substrate, furimazine, a chemical reaction produces light. The accidental discovery of this process’s applicability in imaging brain oxygen dynamics occurred during experiments intended to measure calcium activity in the brain.

Felix Beinlich, Assistant Professor at the Center for Translational Neuroscience at the University of Copenhagen, stumbled upon this breakthrough when an error in protein production caused a delay in research. While awaiting a fresh batch, Beinlich proceeded with experiments using the flawed proteins, leading to the unexpected discovery. By delivering enzyme-producing instructions to astrocytes in the brain and injecting the substrate directly, researchers were able to record fluctuating bioluminescence intensity, indicative of oxygen presence and concentration.

Contrary to existing techniques limited to small brain areas, this method allowed real-time observation of the entire cortex in mice. Changes in bioluminescence intensity correlated with oxygen concentration alterations, as demonstrated by manipulating the animals’ breathing air. Additionally, sensory processing activities, such as whisker stimulation, were visibly reflected in corresponding brain regions’ illumination.

The observation of “hypoxic pockets,” where specific brain areas intermittently experienced oxygen deprivation due to capillary stalling, unveils new avenues for studying diseases associated with brain hypoxia, including Alzheimer’s. These findings suggest that a sedentary lifestyle, aging, hypertension, and other factors may exacerbate such conditions. The technique not only offers a means to understand these diseases better but also provides a platform to test drugs and exercise regimens aimed at improving vascular health and delaying dementia onset.

The collaborative efforts of researchers from various institutions have illuminated new pathways in neuroscience, promising transformative insights into brain oxygen dynamics and associated neurological conditions.

By Impact Lab