Human cerebrovascular function in health and disease: insights from integrative approaches

Background: The marked increase in the size of the brain, and consequently, in neural processing capability, throughout human evolution is the basis of the higher cognitive function in humans. However, greater neural, and thus information processing capability, comes at a significant metabolic cost; despite its relatively small size, the modern human brain consumes almost a quarter of the glucose and oxygen supply in the human body. Fortunately, several vascular mechanisms ensure sufficient delivery of glucose and oxygen to the active neural tissue (neurovascular coupling), prompt removal of neural metabolic by-products (cerebral vasoreactivity), and constant global blood supply despite daily variations in perfusion pressure (cerebral autoregulation). The aim of this review is to provide an integrated overview of the available data on these vascular mechanisms and their underlying physiology. We also briefly review modern experimental approaches to assess these mechanisms in humans, and further highlight the importance of these mechanisms for humans' evolutionary success by providing examples of their healthy adaptations as well as pathophysiological alterations. Conclusions: Data reviewed in this paper demonstrate the importance of the cerebrovascular function to support humans' unique ability to form new and different interactions with each other and their surroundings. This highlights that there is much insight into the neural and cognitive functions that could be gleaned from interrogating the cerebrovascular function.