Crossing Brain Barriers in Health and Disease: Impact of Circadian Rhythms

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Background

Two brain barriers contribute to maintaining brain homeostasis: the blood-brain barrier (BBB), which separates the systemic circulation from the central nervous system (CNS) and the blood-cerebrospinal fluid barrier (BCSFB) that separates the cerebrospinal fluid from the blood circulation.
Both brain barriers control the microenvironment for proper neural function and protect the tissue from injury and disease, as they provide the appropriate nutrients supply, supervise immune condition and remove waste products from metabolism. Thus, the BBB and BCSFB mediate the communication between the CNS and periphery, protecting the brain from the outside environment while, at the same time, create an obstacle for brain drug delivery to the CNS.

The physiology of most of the organisms is adapted to a 24-hour day-night cycle, anticipating environmental changes imposed by the earth's rotation. Consequently, daily rhythms in multiple physiological processes are subjected to circadian regulation, coming directly or indirectly from the suprachiasmatic nucleus.

The importance of biological clocks on brain barriers and, consequently, on delivery and clearance of drugs to/from the brain has attracted considerable interest and progressed significantly in the last years.
Recently, the BBB permeability was shown to be dynamically regulated by circadian rhythms. In addition, sleep plays an important function in supporting the clearance of metabolites from the brain across the BBB. Similarly, the BCSFB circadian clock might also have some implications in the defense delivery system. Although we already know that brain barriers show biological rhythms in their function, the circadian variation of transport mechanisms and possible implications in several conditions, such as neurodegenerative disorders, is still largely unknown.

This Research Topic aims to collect important data on the mechanisms underlying brain barriers behavior in equilibrium and disease circumstances, and its homeostatic regulation, namely via circadian clock dependent mechanisms. We welcome articles focusing on the following:

• Identification of brain barrier molecules exhibiting daily oscillations
• Effects of circadian fluctuations in the transport of compounds into and out of the brain
• Contribution of disrupted brain barrier circadian clocks to the development/progression of several conditions like neurodegenerative disorders
• Modulation of brain barriers in order to control the penetration/clearance of CNS targeting drugs into/out of the brain
• Optimization of drug delivery with brain barrier circadian changes – chronotherapy

Keywords: Brain barriers, Blood-brain barrier, Blood-cerebrospinal fluid barrier, Circadian rhythm, Chronotherapy

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