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

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

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1964-1969
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number6
DOIs
StatePublished - Feb 15 2006

Keywords

  • Cerebral blood flow
  • Glycolysis
  • Positron-emission tomography
  • Visual stimulation

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