Development of circadian neurovascular function and its implications

Abstract

The neurovascular system forms the interface between the tissue of the central nervous system (CNS) and circulating blood. It plays a critical role in regulating movement of ions, small molecules, and cellular regulators into and out of brain tissue and in sustaining brain health. The neurovascular unit (NVU), the cells that form the structural and functional link between cells of the brain and the vasculature, maintains the blood–brain interface (BBI), controls cerebral blood flow, and surveils for injury. The neurovascular system is dynamic; it undergoes tight regulation of biochemical and cellular interactions to balance and support brain function. Development of an intrinsic circadian clock enables the NVU to anticipate rhythmic changes in brain activity and body physiology that occur over the day-night cycle. The development of circadian neurovascular function involves multiple cell types. We address the functional aspects of the circadian clock in the components of the NVU and their effects in regulating neurovascular physiology, including BBI permeability, cerebral blood flow, and inflammation. Disrupting the circadian clock impairs a number of physiological processes associated with the NVU, many of which are correlated with an increased risk of dysfunction and disease. Consequently, understanding the cell biology and physiology of the NVU is critical to diminishing consequences of impaired neurovascular function, including cerebral bleeding and neurodegeneration.

Hypertension: Causes and Consequences of Circadian Rhythms in Blood Pressure

“…249 Although expression of junctional proteins can exhibit a daily rhythm in the retina, relatively little is known regarding potential changes in these proteins at the BBB. 252 A recent study suggested there is less BBB efflux during the dark phase, when mice are more active, and greater efflux during the light phase. 253 BBB efflux transporter expression and function exhibited a diurnal pattern that was inhibited by endothelial-specific knockdown of Bmal1.…”