Blood flow control in the brain: possible biphasic mechanism of functional hyperemia.

ABSTRACT

Background: About 120 years ago, Roy and Sherrington hypothesized that the cerebral blood flow (CBF) is closely coupled to metabolism, and metabolism is closely coupled to function. This concept has colored all subsequent inquiries. However, recent studies have revealed a temporal and spatial mismatch between changes in CBF and metabolism. Objective: This article aims to reappraise the nature of functional hyperemia in response to somatosensory stimuli. Method: Firstly, the author discusses what is known and unknown about the control of CBF, reviewing the traditional concepts of autoregulation, neurogenic control, metabolic control and the role of endothelial cells. Secondly, recent papers showing a mismatch or uncoupling between function, metabolism and flow are considered. Thirdly, the reviewer uses his own published and unpublished data to point out the intrinsic and largely unrecognized limitations of spectroscopic techniques for evaluation of oxygen metabolism. Finally, a novel hypothesis is presented concerning the nature of functional hyperemia. Results and conclusion: The reviewer deduces that the initial flow increase in functional hyperemia is elicited by central neural systems, since it is reported that the central cholinergic pathway increases CBF immediately after the onset of somatosensory stimuli. The flow increase occurs concurrently with neuronal activation, but is much faster than the increase of neuronal metabolism. The novel hypothesis is proposed that functional hyperemia is biphasic an initial flow increase under central neural control and a delayed increase is under traditional metabolic control. The metabolic phase may supply more blood than is needed, and may last even after discontinuation of the stimulation (overcompensation). These two phases of hyperemia are suggested to be well mixed, presumably in glial processes, which coordinate blood redistribution in the surrounding microvascular network. Many stimuli from the environment might be managed simply by the neurogenic control of functional hyperemia, without the metabolic change.