Karmactive Staff
Scientists have uncovered how our brains quickly direct blood to areas that need it most, according to new research published in the journal Cell on July 16, 2025.
A team led by Harvard Medical School researchers found that the brain uses specialized channels in blood vessel linings to communicate where blood is needed in real-time.
“This work helps us understand how you can get that super-important blood supply to the correct areas of the brain on a time scale that is useful,” said Luke Kaplan, a research fellow in neurobiology at Harvard Medical School and co-lead author of the study.
The brain is extremely energy-hungry, making up just 2 percent of body weight but using about 20 percent of the body’s total energy. To manage this high demand efficiently, the brain has developed a system to send blood only to areas actively working.
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The research team discovered that cells lining blood vessels in the brain, called endothelial cells, communicate rapidly through tiny channels known as gap junctions that physically connect neighboring cells.
“The brain essentially uses the inner lining of its blood vessels as a wide-ranging and coordinated signaling highway,” explained Trevor Krolak, a doctoral student and co-lead author.
This communication system allows blood vessels to dilate or contract together, directing blood flow precisely where needed. The team also identified two specific proteins – Connexin37 and Connexin40 – that are crucial for this signaling process.
Understanding this mechanism could improve interpretation of functional MRI (fMRI) brain scans, which measure blood flow to different brain regions as a way to track neural activity.
The findings may also advance our understanding of neurodegenerative diseases like Alzheimer’s, where this blood-allocation process often breaks down, creating a mismatch between blood supply and neuronal activity that contributes to cognitive problems.
“Now that we’ve figured out the mechanism,” said Chenghua Gu, professor of neurobiology at Harvard Medical School and senior author of the study, “we want to apply our knowledge to understanding disease and developing therapies.”
The research was funded by various organizations including the National Institutes of Health, the National Science Foundation, and the Howard Hughes Medical Institute.
Frequently Asked Questions
Harvard researchers discovered that the brain uses specialized channels called gap junctions that connect cells lining blood vessels. These channels form a “signaling highway” that allows endothelial cells to communicate rapidly, telling blood vessels when to expand or contract to direct blood precisely where it’s needed. Two specific proteins – Connexin37 and Connexin40 – are crucial for this process to work properly.
The brain consumes about 20% of the body’s total energy while making up just 2% of body weight because it’s constantly performing energy-intensive tasks like processing information, storing memories, controlling body functions, and managing cognitive processes. Neurons require significant energy to maintain their electrical activity and communication. This high energy demand is why the brain needs an efficient system to direct blood flow precisely where it’s needed at any given moment.
The research shows that the blood-allocation process studied deteriorates in Alzheimer’s disease and other neurodegenerative conditions. When this system breaks down, it creates a mismatch between blood supply and neuronal activity, which can contribute to cognitive problems. Understanding the molecular underpinnings of this process could lead to new approaches for treating Alzheimer’s by potentially restoring proper blood flow regulation in the brain.
Functional MRI (fMRI) relies on measuring changes in blood flow to detect brain activity. This research provides a clearer understanding of the exact mechanisms that connect neural activity to blood flow changes, which could improve how scientists interpret fMRI results. With better knowledge of how neurovascular coupling works at the cellular level, researchers may develop more accurate ways to analyze brain scan data and potentially refine fMRI technology itself.
This discovery reveals a fundamental mechanism in brain function that was previously not well understood. It connects molecular processes (gap junction proteins) to whole-brain activity and blood flow regulation. The findings have broad implications for understanding and potentially treating neurodegenerative diseases, improving brain imaging interpretation, and expanding our knowledge of how the brain manages its energy resources. It provides new targets for therapeutic development and advances our basic understanding of brain physiology.
The research team used a combination of advanced techniques to study the brain’s blood flow mechanisms. They employed optogenetics to precisely activate specific areas of the brain and two-photon microscopy to visualize real-time changes in blood vessels. They also used genetic techniques to remove specific proteins (Connexin37 and Connexin40) in mice to observe how this affected blood flow regulation. These experiments allowed them to map the communication pathway between endothelial cells and determine how signals propagate through blood vessels during neurovascular coupling.
