David Mikulis
It is well known that blood flow and oxygen consumption increase during neuronal activation. Measurement of these parameters in perhaps the most quoted work has shown a blood flow increase of 45% over baseline but only a 16% increase in oxygen consumption.1 To this day the explanation for the high increase in flow that delivers far more oxygen than the tissue consumes has been elusive. Perhaps it is delivery of other metabolic substrates, removal of the products of metabolism, arterialization of the capillaries to drive oxygen into the tissue, etc, or perhaps it is all of the above. Nevertheless, it is a normal phenomenon and therefore, from a teleologic perspective, must exist for good reason. In fact, the cerebral vasculature has evolved to ensure that flow and functional hyperemia can be preserved even in the setting of varying blood pressure, by controlling vascular resistance via modulation of smooth muscle tone in arteries and arterioles.
But there are conditions in which the normal relationship between neuronal activity and blood flow (neurovascular coupling [NVC]) is disrupted. Acute ischemic stroke is the prime example of this. Blocks in feeding arteries cannot be overcome by collaterals, and the NVC mechanism is incapable of providing increased flow through vasodilation. Tissue death ensues quite rapidly within hours of the acute occlusion. But what would happen to tissue where the NVC mechanism is intact but is close to or has reached its limit to produce vasodilation? There may be enough flow to maintain resting metabolic needs, but if neurons were to begin or to increase signaling, no further vasodilation would occur to support the additional metabolic demand. These neurons would be operating without blood flow support, a condition we have now termed “neurovascular uncoupling” (NVU). This scenario can occur in the setting of advanced arterial steno-occlusive disease and can be associated with TIAs (hemodynamic origin).
The question is, is this an unhealthy condition if left to persist over time in the absence of acute ischemic events? There is building evidence that the answer is “yes,” with the condition termed “neurovascular uncoupling syndrome” (NVUS). It is supported by cortical thinning, decreased fractional anisotropy, and decreased NAA on MRS in areas of maximum vasodilation.2–5 There is also evidence that it is associated with decreased cortical function.6