Circadian Mechanisms in Brain Fluid Biology

The brain is a complex organ, fundamentally changing across the day to perform basic functions like sleep, thought, and regulating whole-body physiology. This requires a complex symphony of nutrients, hormones, ions, neurotransmitters and more to be properly distributed across the brain to maintain homeostasis throughout 24 hours. These solutes are distributed both by the blood and by cerebrospinal fluid. Cerebrospinal fluid contents are distinct from the general circulation because of regulation at brain barriers including the choroid plexus, glymphatic system, and blood-brain barrier. In this review, we discuss the overlapping circadian (≈24-hour) rhythms in brain fluid biology and at the brain barriers. Our goal is for the reader to gain both a fundamental understanding of brain barriers alongside an understanding of the interactions between these fluids and the circadian timing system. Ultimately, this review will provide new insight into how alterations in these finely tuned clocks may lead to pathology.