In the brain, regional changes in neural activity trigger localized alterations in cerebral blood flow1 through astrocyte activation2,3. A rise in intracellular free calcium concentration ([Ca21]i) within astrocyte endfeet, which collectively circumscribe all cerebral vessels4, initiates vasoconstriction5–7 or vasodilation2,6,8–10. Cerebral blood flow couples to the lactate/pyruvate ratio and the related nicotinamide adenine dinucleotide (NADH)/NAD1 ratio11–13, but links between these metabolic substrates and the mechanisms of cerebral blood flow regulation remain unresolved. We tested the hypothesis that the metabolic state of the tissue, altered by oxygen (O2) availability, dictates the type of astrocyte influence on arteriole diameter. At the onset of neural activity dendrites rapidly consume O2 (ref. 14), leading to a reduction in oxygen pressure (pO2)15–17 and oxyhaemoglobin 18,19, which occurs before the increase in cerebral blood flow. Brain metabolism then shifts, whereby glycolysis is enhanced20,21 in astrocytes14 and lactate is released22,23. Lactate is vasoactive12,24 and dynamically alters microvasculature diameter in an O2-dependent manner25. Vasodilation occurs in the brain region experiencing the O2 drop, whereas vasoconstriction ensues in the inactive surrounding area26. Delineating the cellular processes responsible for O2-metabolic effects on cerebral blood flow may be crucial for treating stroke and vascular dementia, as well as aiding in our understanding of neurovascular coupling for the scientific and diagnostic uses of functional magnetic resonance imaging.
Updated on July 22, 2020