The blood-brain barrier serves to protect the brain from contaminates in the blood. It does this in two primary ways. The physical structure of the blood-brain barrier limits what can pass through it. There are also metabolic barriers, such as enzymes, that limit the permeability of this critical protective barrier. While for the most part, that limitation is a good thing, in the case of pharmaceutical treatment of disease, getting medications across the blood-brain barrier can be a real challenge. A recent study may lead to better navigation of issues relating to the blood-brain barrier, as researchers have found that the circadian rhythm regulates blood-brain barrier and the degree of its permeability.
How the Circadian Rhythm Regulates Blood-Brain Barrier
In a study conducted by researchers from the Perelman School of Medicine at the University of Pennsylvania and published in the peer-reviewed journal Cell, researchers used fruit flies to explore the blood-brain barrier permeability. Fruit flies are highly useful in this sort of research context because they are less complex in design, allowing researchers to gain fundamental information and a better understanding of the basic mechanisms involved in various biological processes.
Using a fluorescent dye to color the fruit fly blood-brain barrier to make it more readily visible, researchers saw that there was time-of-day variation in the permeability of the blood-brain barrier. They noted the existence of a daily permeability variation rhythm, with the blood-brain barrier being most permeable in the evening.
The researchers then tested the pharmaceutical potential of that increased permeability on fruit flies that could be induced to have seizures. They gave the seizure fruit flies phenytoin, an anti-epilepsy drug, treating groups of fruit flies at various times of the day. The researchers found that the fruit flies receiving the medication in the evening had better results, recovering from their seizures faster than did fruit flies receiving medication at other times of the day.
Once the permeability rhythm and its practical treatment use were established, the researchers then turned their attention to the mechanisms involved in that rhythm. Using fruit flies lacking a specific protein linked to circadian rhythm functioning, the researchers were able to demonstrate the role of the circadian rhythm in the daily permeability pattern of the blood-brain barrier. According to the researchers, the perineurial glia cells that make up part of the structure of the blood-brain barrier house a molecular clock that regulates the processes involved in barrier function and permeability rhythm. In turn, molecular clocks are synchronized and otherwise regulated by the circadian rhythm.
Sleep Also Plays a Role
Further research revealed that sleep is also linked to blood-brain barrier permeability patterns. While there is a tight link between sleep and the circadian rhythm in that the circadian rhythm helps regulate the sleep-wake cycle and sleep delays or disruptions can impact the circadian rhythm, there’s more to it than that. According to the researchers involved in this later Perelman School of Medicine at the University of Pennsylvania study, published in Trends in Neurosciences, both sleep and the circadian rhythm help regulate blood-brain barrier activity across species.
The researchers note that sleep helps regulate molecule movement along and through the blood-brain barrier. During sleep, toxins and waste products are flushed out of the blood-brain barrier. The chemical changes that take place during sleep influence a number of deep mechanisms impacting blood-brain barrier functions and permeability, including cellular communications and interactions, as well as the mechanical and chemical processes involved in the movement of molecules through or away from the blood-brain barrier. Sleep disruptions can lead to disruption of these regulatory functions and even, according to the researchers, can lead to structural damage to the blood-brain barrier.
Exciting Therapeutic Implications
Medical science has already established that timing matters for some medications, demonstrating that some medications are more effective at certain times of the day, such as chemotherapy drugs targeting brain cancer. What this new research does is shed light on the mechanisms involved, which has exciting therapeutic potentials when it comes to overcoming the challenge of treating diseases that require drugs to efficiently pass through the blood-brain barrier.
The Importance of Sleep and Circadian Rhythm Health
This research also adds to the rapidly growing body of evidence pointing to the importance of sleep and a healthy circadian rhythm to health and protection from disease. As explained by the researchers, chronically failing to get enough good-quality sleep can actually cause structural damage to the blood-brain barrier, decreasing its ability to perform its vital protective functions.
The circadian rhythm plays a major role in helping to regulate countless essential processes in the body, including those that aid in the functioning of the blood-brain barrier. Make healthy sleep a serious priority and be proactive about your circadian rhythm health. Always address sleep issues promptly.