Caffeine and the Control of Cerebral Hemodynamics

Abstract

While the influence of caffeine on the regulation of brain perfusion has been the subject of multiple publications, the mechanisms involved in that regulation remain unclear. To some extent, that uncertainty is a function of a complex interplay of processes arising from multiple targets of caffeine located on a variety of different cells, many of which have influence, either directly or indirectly, on cerebral vascular smooth muscle tone. Adding to that complexity are the target-specific functional changes that may occur when comparing acute and chronic caffeine exposure. In the present review, we discuss some of the mechanisms behind caffeine influences on cerebrovascular function. The major effects of caffeine on the cerebral circulation can largely be ascribed to its inhibitory effects on adenosine receptors. Herein, we focus mostly on the A₁, A_2A, and A_2B subtypes located in cells comprising the neurovascular unit (neurons, astrocytes, vascular smooth muscle); their roles in the coupling of increased neuronal (synaptic) activity to vasodilation; how caffeine, through blockade of these receptors, may interfere with the "neurovascular coupling" process; and receptor-linked changes that may occur in cerebrovascular regulation when comparing acute to chronic caffeine intake.