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Published online on January 30, 2006, 10.1073/pnas.0510632103
PNAS | February 7, 2006 | vol. 103 | no. 6 | 1964-1969


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BIOLOGICAL SCIENCES / NEUROSCIENCE
Regulation of blood flow in activated human brain by cytosolic NADH/NAD+ ratio

Andrei G. Vlassenko, Melissa M. Rundle, Marcus E. Raichle*, and Mark A. Mintun*

Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 South Kingshighway Boulevard, St. Louis, MO 63110

Contributed by Marcus E. Raichle, December 14, 2005

It has been known for more than a century that increases in neuronal activity in the brain are reliably accompanied by changes in local blood flow. More recently it has been appreciated that these blood flow increases are accompanied by increases in glycolysis that are much greater than the increases in oxidative phosphorylation. It has been proposed by us and others that this activity-induced increase in glycolysis mediates the increase in blood flow by mechanisms linked through the near-equilibrium relationship between cytosolic NADH/NAD+ and the lactate/pyruvate ratios. Here we show in awake human subjects that by transiently raising blood pyruvate concentration during local increases in functional brain activity, a maneuver designed to reduce the cytosolic NADH/NAD+ ratio, the expected blood flow response measured with positron-emission tomography is significantly attenuated. This result provides critical additional support for the hypothesis that, like in anesthetized rodents, the cytosolic NADH/NAD+ ratio of awake human subjects links activity-induced increases in glycolysis to signaling pathways for the regulation of blood flow.

cerebral blood flow | glycolysis | positron-emission tomography | visual stimulation

Author contributions: A.G.V., M.M.R., M.E.R., and M.A.M. designed research; A.G.V., M.M.R., and M.A.M. performed research; A.G.V., M.M.R., M.E.R., and M.A.M. analyzed data; and A.G.V., M.E.R., and M.A.M. wrote the paper.

Conflict of interest statement: No conflicts declared.

*To whom correspondence may be addressed at: Mallinckrodt Institute of Radiology, Box 8225, Washington University School of Medicine, 510 South Kingshighway Boulevard, St. Louis, MO 63110. E-mail: marc{at}npg.wustl.edu or mintunm{at}mir.wustl.edu

© 2006 by The National Academy of Sciences of the USA


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