Circadian rhythms in the blood-brain barrier: impact on neurological disorders and stress responses

Circadian disruption has become more prevalent in society due to the increase in shift work, sleep disruption, blue light exposure, and travel via different time zones. The circadian rhythm is a timed transcription-translation feedback loop with positive regulators, BMAL1 and CLOCK, that interact with negative regulators, CRY and PER, to regulate both the central and peripheral clocks. This review highlights the functions of the circadian rhythm, specifically in the blood-brain barrier (BBB), during both healthy and pathological states. The BBB is a highly selective dynamic interface composed of CNS endothelial cells, astrocytes, pericytes, neurons, and microglia that form the neurovascular unit (NVU). Circadian rhythms modulate BBB integrity through regulating oscillations of tight junction proteins, assisting in functions of the NVU, and modulating transporter functions. Circadian disruptions within the BBB have been observed in stress responses and several neurological disorders, including brain metastasis, epilepsy, Alzheimer's disease, and Parkinson's disease. Further understanding of these interactions may facilitate the development of improved treatment options and preventative measures.