Research review proposes alternative brain blood flow theories

September 19, 2022

By Sarah Small

UNIVERSITY PARK, Pa. — In the brain, neural activity usually is followed by increases in blood flow to the active region, a process known as neurovascular coupling. Scientists know that this process is important for brain health, as the breakdown of this process precedes many neurodegenerative diseases, according to Patrick Drew, Penn State professor of engineering science and mechanics and of biomedical engineering. What scientists don’t know is why neurovascular coupling exists at all.

Drew proposed possible answers to this question in a review article, “Neurovascular coupling: Motive unknown,” published in Trends of Neuroscience.

“Neurovascular coupling is usually attributed to increased oxygen demand of neurons, as the electrical activity of neurons uses energy, and aerobic metabolism can help supply this energy,” said Drew, who is also the associate director of the Penn State Health Neuroscience Institute and affiliated with departments of biology and of neurosurgery, and with the Huck Institute, all at Penn State. “However, that doesn’t seem to be the case, as the brain is over supplied with oxygen, and it’s likely the increases in blood flow serve some other function.”

While the oxygen demand increase is the most popular theory, Drew said there is evidence for other possible functions of neurovascular coupling in the existing scientific literature.

“Possible roles include supplying oxygen for synthesis of neuromodulators, helping regulate brain temperature, carrying signals to neurons, moving or producing cerebrospinal fluid or keeping red blood cells from getting stuck in capillaries,” he said.

According to Drew, the evidence for each of these possibilities is more compelling than the theory that neurovascular coupling exists to supply oxygen for metabolism for neurons.

“Our brain is oversupplied with oxygen, and there is a large safety margin,” he said. “For example, the caffeine in a cup of coffee decreases blood flow to the brain by 30% but doesn’t change the brain’s metabolic rate. Also, when you are at high altitude, the oxygen content in your blood goes down, so less oxygen gets delivered to your brain. If we didn’t have such large safety margins, having a cup of coffee on an airplane flight would cause brain damage.”

The next steps for this area of research include testing some of these possibilities to discover the purpose of neurovascular coupling.

“This will help us understand what it is doing, and what problems result when the normal communication between neurons and blood vessels is interrupted,” Drew said.

The National Institutes of Health supported this work.


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“Our brain is oversupplied with oxygen, and there is a large safety margin. If we didn’t have such large safety margins, having a cup of coffee on an airplane flight would cause brain damage.” — Patrick Drew


Patrick Drew