Human brain has unsuspected oxygen reserve, challenging previous theories

May 28, 2001

St. Louis, May 29, 2001 -- Scientists have discovered that, unlike many other animals, humans have a reserve of oxygen in the brain. This buffer allows the brain to adapt to arduous situations without demanding a sharp increase in blood flow.

"Our finding challenges the previously accepted idea that blood flow increases occur during tasks such as reading to raise oxygen levels in the brain," says study leader Mark A. Mintun, M.D. "That idea has been long assumed in brain imaging studies that attempt to understand how the human brain functions."

Mintun is a professor of radiology and professor of psychiatry at Washington University School of Medicine in St. Louis. His group's findings appear in the June 5 issue of Proceedings of the National Academy of Sciences and will appear on the journal's website May 29.

Imaging has become a critical tool for exploring the brain at work. By measuring changes in blood flow during different tasks, researchers can see which areas of the brain spring into action when, for example, individuals read or memorize words. Because blood supplies cells with oxygen, they assumed that blood flow increases when a particular area of the brain needs more oxygen. The new evidence suggests otherwise.

"I think we're still very safe interpreting increased blood flow as a change in brain activity," says Mintun. "But why flow increases now is unclear. Understanding that will probably change our view of the human brain and alter the way we design studies."

An extensive network of small blood vessels called capillaries feeds the brain. Because every cell is critical to the organ's function, oxygen must diffuse from the capillaries to every nook. Current models suggest that, even if the brain needs only a small amount of extra oxygen, it takes a large increase in blood flow to deliver enough to every cell.

Using positron emission tomography (PET), Mintun and colleagues examined blood flow to the brains of nine healthy volunteers. The subjects were asked to focus on a white cross on a black background and press a button whenever the cross became dim. They performed this task in a normal atmosphere and under oxygen levels resembling those on top of Pike's Peak in Colorado (roughly 14,000 feet).

Current theory suggests that blood flow should increase dramatically if someone tries to perform this task when oxygen levels are very low. And Mintun's team expected that to be the case. Instead, cerebral blood flow failed to relate to the amount of oxygen entering the body.

"The brain appears to have some sort of built-in insurance policy," explains Mintun. "Even when partially deprived of oxygen, it can still take care of itself." Armed with this new information, the team retested current mathematical models of cerebral blood flow. The models assume that, because the brain requires so much oxygen, oxygen from blood diffuses into brain tissue, never to be reabsorbed into blood. But Mintun and colleagues left that assumption out of their equation.

"We allowed the oxygen model to develop on its own without assuming that oxygen flows in only one direction," says Mintun. "That proved to be the critical factor. It turns out that a fair amount of oxygen does go back and forth, creating a dynamic buffer. So when the brain needs more oxygen, it simply taps into this reserve." The researchers also found that the human brain has far more capillaries than it needs. The extra capillaries might serve as a storehouse for delivering surplus oxygen, they suggest.

Other scientists have observed that animals such as rats and even primates are more sensitive to low oxygen levels than humans. Mintun now is determining whether animals' brains have a smaller capillary content than the human brain compared to their use of oxygen. Such a finding might make animal models less useful for exploring the relationship between blood flow and cognition.

The team also is looking for alternative explanations for the increased cerebral blood flow seen during many mental tasks. "We have to take a step back and admit that the blood-flow response we see so crisply when areas of the brain become active may serve some other purpose," he says. "Also, other mechanisms that drive blood flow in the brain may be waiting to be discovered."
Mintun MA, Lundstrom BN, Snyder AZ, Vlassenko AG, Shulman GL, Raichle ME. Blood flow and oxygen delivery to human brain during functional activity: Theoretical modeling and experimental data. Proceedings of the National Academy of Sciences, 98(12), 6859-6864, June 5, 2001.

Funding from the National Institute of Neurological Disorders and Stroke and the National Heart, Lung, and Blood Institute supported this research.

The full-time and volunteer faculty of Washington University School of Medicine are the physicians and surgeons of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC Healthcare.

Washington University School of Medicine

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