The chemical lactate has gotten a bad rap. Conventional wisdom considered it to be little more than the bane of runners and other athletes, causing stiff muscles and fatigue, and the "sour" in sour milk. It turns out that view may have been too narrow.
Neuroscientists at UCLA are now looking at lactate with a much more positive eye, considering it a possible replacement "fuel" for the brain in the immediate hours after a traumatic brain injury instead of glucose, the current standard. If they are right, it could change how emergency room physicians and intensive care physicians treat patients with brain injuries in the first critical hours after injury.
Previous work by Dr. Neil Martin, professor and chief of neurosurgery at the David Geffen School of Medicine at UCLA, and Thomas Glenn, a UCLA adjunct assistant professor in the department of neurosurgery, showed that the brain takes up lactate after traumatic injury. Now, thanks to a $275,000 grant from the National Institute for Neurological Diseases and Stroke at the National Institutes of Health, the investigators will determine why the brain does this. Is it actually using lactate to help it recover after injury?
"The prevailing theory for the brain after traumatic injury is that, just as in normal circumstances, glucose is the primary source for energy," Glenn said. "Further, it was thought the brain's metabolic process produces lactate, long considered a harmful waste product of a dysfunctional metabolism, one that causes further cell death via acidosis, an abnormally high buildup of acid in blood and tissue."
Instead, the researchers found that in the first 12 to 48 hours following traumatic injury, the brain takes up and apparently consumes more lactate than at any other time. They discovered this by measuring the levels of lactate in blood entering and leaving the brain. To determine if lactate was being used by the brain, the researchers, in collaboration with George Brooks, a professor in the department of integrative biology at the University of California, Berkeley, labeled lactate with C13, a non-radioactive and stable isotope, then added it to the patient's standard intravenous solution. The isotope served as a marker they could follow to see if the lactate molecule had produced carbon dioxide, the natural byproduct of lactate after use by the brain as fuel.
"Our preliminary tracer-based studies demonstrated the novel and unexpected finding of both lactate uptake and its utilization as fuel in traumatic brain injury," Glenn said. "These results have led us to challenge the current conventional wisdom concerning the type of fuel the brain uses after injury to generate the energy for recovery."
They suspect that following injury the brain may not be able to use glucose because of dysfunction and because the glucose is diverted to other metabolic pathways for other uses. And, Glenn noted, using glucose requires more than 10 enzymatic steps before it generates energy, while lactate requires much fewer steps, making it, under these circumstances, a faster and more efficient source of fuel.
The researchers will seek 20 to 30 additional brain-traumatized patients over the next two years to further confirm their hypothesis, which will require receiving the approval of a patient's family before proceeding. It's a delicate and diplomatic effort under such conditions, and Glenn is grateful that people understand that the bottom line is to improve care after a traumatic brain injury.
"If we can confirm our hypotheses by these studies," said Glenn, "these concepts would force a reconsideration of the standard use of glucose solutions as the foundation for metabolic/nutritional support to the brain in the intensive care unit."