In the new paper, the same effects were detected in the rat retina and visual region of the brain during optical stimulation. Williamson and his co-authors have also revealed that the increased NADH/NAD ratio activates a signaling pathway that promotes the creation of nitric oxide, a compound widely recognized for its ability to dilate blood vessels.
"This was the evidence that Marc Raichle's group needed to go ahead and look for this same effect in humans," Williamson says. "They needed some proof that the principle might be applicable to the visual region of the brain in humans, and they found that it is."
For the human research, seven subjects were studied using PET imaging scans. Participants were either asked to close their eyes during the scans or to fix their gaze on an unmoving central crosshair in an animated visual display.
Andrei Vlassenko, M.D., Ph.D., research associate in radiological sciences and an author of the human study, notes that without lactate injections, the blood flow increase to the visual cortex during the visual task was 19 percent. After lactate injections, it was 26 percent.
"That might not seem like a lot if you look strictly at the gain, but if you look at the gain as a percentage of original level of increase, that's fully one-third more," Vlassenko says.
Mark A. Mintun, M.D., professor of radiology and psychiatry, was lead author of the human study. He points out that the mechanism under study isn't the only way the brain controls blood flow. There are other mechanisms to respond to stress, hyperventilation, blood pressure alterations or other dramatic changes.
"What we're doing is isolating the response in blood flow when the brain function itself changes and using that response as a window for investigating brain metabolism," Mintun explains.
Mintun, Raichle and Vlassenko already have a follow-up study using pyruvate injections underway.
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Contact: Michael C. Purdy
purdym@msnotes.wustl.edu
314-286-0122
Washington University School of Medicine
7-Jan-2004