The role of Circadian rhythm in blood-brain barrier permeability

Abstract

The blood-brain barrier (BBB) is a crucial structure that regulates the exchange of molecules between the brain and the bloodstream. Recent studies have shown that the BBB permeability exhibits a rhythmic pattern regulated by the circadian rhythm (CR). The CR is regulated by core clock genes that form transcriptional-translational feedback loops, which control the expression of proteins involved in BBB permeability regulation. The diurnal variation in BBB permeability is controlled by tight junction proteins, aquaporin-4, and ion transporters, which exhibit rhythmical expression patterns. Therapeutic approaches targeting rhythmical BBB permeability have important implications for drug delivery and clinical potential in treating disease such as Alzheimer's disease and multiple sclerosis which are two neurological disorders associated with disrupted circadian rhythms and BBB dysfunction. This review aims to introduce the role of CR in BBB permeability regulation, highlighting recent findings on the molecular mechanisms underlying CR regulation of BBB permeability and discussing the potential implications for drug delivery.