Cerebral ambiguity

What do we really know about cerebral blood flow (CBF) control? Within the boundaries of our current knowledge, is there an easy test of clinical importance that can eloquently describe the status quo of CBF regulatory processes? Remarkably, the brain alone consumes 20% of the body’s chemical energy, even though it accounts for only 2% of the body’s mass. This high consumption of energy is crucial for the normal functioning of the brain, which needs to be constantly perfused as changes in perfusion lead to an immediate alteration in brain function. If blood glucose and oxygen are not adequately supplied to a region of the brain as in ischemic stroke or cerebral palsy, neurons, and glia become impaired or die. To sustain neuronal function, the brain has evolved very complex regulatory processes to ensure a continuous and constant blood supply (Attwell et al. 2010; Peterson et al. 2011; Willie et al. 2014). The first mechanism is cerebral pressure autoregulation, a process whereby the cerebral arterioles maintain a constant flow despite changes of cerebral perfusion pressure. The second is neurovascular coupling which refers to the brain’s ability to increase the flow of blood to regions where neurons are metabolically active, a response also termed functional hyperemia. Metabolic messengers such as adenosine and lactate and chemical stimuli like carbon dioxide (CO2) contribute to functional hyperemia through glutamateinduced prostaglandin signaling to blood vessels. The effect is a dilatation of the arterioles which leads to a CBF increase; recent data have also suggested the important role of pericytes in regulating CBF through the control of capillary diameter (Itoh and Suzuki 2012). The third mechanism is the neurogenic regulation whereby extensive arborization of perivascular nerves play a role in controlling CBF. Essential to all three regulatory processes is the neurovascular unit, composed of endothelial cells, perivascular nerves, and astrocytes; the endothelium acts through several vasoactive factors (nitric oxide, endothelium-dependent hyperpolarization factor, eicosanoids, endothelins), while astrocytic foot processes directly abut the blood vessels and by glutamate-mediated signaling also play a key role in the regulation of CBF. The interaction of these complex regulatory mechanisms, as well as the mechanisms themselves, are not fully understood. However, their importance is highlighted by the fact that significant brain injury occurs when these regulatory mechanisms are lost as in hypertension, diabetes, stroke, Alzheimer’s disease, spinal cord injury. This underscores the need of research in this field, the results of which might have important implications for the development of new therapeutic approaches. In this issue of Brain and Behavior, Regan and colleagues present a very interesting ultrasonographic study on nine young and healthy subjects, with the aim of elucidating the factors that affect cerebrovascular reactivity (CVR) measurement. In particular they investigated how changes in mean arterial pressure (MAP), different body positions (sitting vs. supine), different stimulus patterns (step vs. ramp) and analysis techniques affect the calculation of CVR. They used CO2 as the stimulus and transcranial Doppler (TCD) measurement of middle cerebral artery velocity (MCAv) as the response. They found that MAP increases with CO2 thus acting as a confounding factor for CVR measurement; hence, they suggest that blood pressure should be monitored during CVR testing. Furthermore, CVR seems to depend also on the stimulus pattern used: lower CVR values were obtained for step response compared to ramp response. Finally, they observed that CVR is not affected by subject’s position