Spontaneous fluctuations in cerebral oxygen supply: An introduction

Spontaneous, low frequency (4-12 cpm) fluctuations, independent of the cardiac and respiratory cycles, in human and animal brains were first recorded with the O₂ polarographic technique in the late 1950s. They were seen in NADH and cytochrome oxidase and associated with spontaneous vasomotion pial and large cerebral arteries. Renewed interest in spontaneous fluctuations was generated by studies with laser-Doppler flowmetry (LDF), reflectance oximetry and functional MRI. Spontaneous fluctuations were consistently produced when cerebral perfusion was challenged by systemic or local manipulations; the fluctuation amplitude reached 30-40% of the mean. The most potent stimuli are hypotension, hyperventilation, cerebral artery occlusion and cerebral vasoconstriction elicited, for example, by a nitric oxide synthase inhibitor but not by indomethacin. The fluctuations are suspended by CO₂ and halothane at concentrations that produce hyperemia. Recently, spontaneous fluctuations were recorded by LDF microprobes in areas as small as 130 μm and by video-microscopy in single capillaries. The fluctuations were absent in severe, focally ischemic brain territories. The dependence of spontaneous fluctuations on intravascular pressure argues for the importance of a myogenic mechanism, however, neuronal modulation may also play a role. Coherence of small vessel vasomotion may be required for the emergence of regional flow fluctuations. There is a need to elucidate the spatial and frequency domains in which fluctuations are present under normal physiological conditions and those in which they may reflect brain injury and pathologies of diagnostic or prognostic value.