The Blood/Brain Barrier: A Key Factor in Brain Health
The brain has its own protective shield—the blood/brain barrier or BBB. The BBB is a semi-permeable web composed of a stratum of densely-packed brain cells joined with a thin layer of cells lining the tiny capillaries on the surface of the brain. The BBB is highly effective, but it can break down with age and the onslaught of disease, pollution, and other negative factors, impairing its functioning and exposing brain tissue to potential injury.
Sleep deprivation may be one of these negative factors, according to a study published in June 2014 in the Mexican journal Investigation y Desarrollo. Researchers observed that chronic sleep loss in laboratory animals was associated with the weakening and increased permeability of the BBB surrounding the animals’ brains. To test the effects of this BBB degradation, the researchers administered certain drugs that usually do not pass through the barrier. The researchers observed that in chronically sleep-deprived animals, the drugs were able to cross the BBB and reach brain tissue, where they interfered with normal neuronal function and even destroyed brain cells.
“This is a very interesting study, and calls for further research to establish whether long-term sleep deprivation might have the same effects in humans,” says Bradford Dickerson, MD, Director of the Frontotemporal Dementia Unit at Massachusetts General Hospsital (MGH). “Unfortunately, despite the fact that the BBB is so important, there has not been enough research to date into its characteristics and functions in humans.
“Almost any medical condition seems to be associated in some way with abnormalities of the BBB. If we understood this important barrier better, we might be able to use what we learn to devise new and more effective treatments for common diseases, including Alzheimer’s disease (AD) and other brain disorders. It is especially important to identify and publicize strategies individuals can adopt to help ensure the health of the BBB through changes in lifestyle and behavior.” (See What You Can Do.)
WHAT YOU CAN DO
The following strategies may help to strengthen the blood/brain barrier:
- Managing health conditions linked to BBB damage. These conditions include high blood pressure, which can lead to stroke, viral infections, inflammation and cerebrovascular disease.
- Getting regular exercise. Animal research suggests that regular exercise can help protect the BBB by making it less permeable.
- Avoiding chemical toxins and pollutants. A number of toxic chemicals—such as polychlorinated biphenyls (PCBs) and the drug ecstasy (MDMA)—can disrupt BBB integrity and cause leakage.
- Reducing levels of cholesterol. Animal studies have linked high-cholesterol diets with disruptions of the BBB.
- Consuming caffeinated beverages. Research suggests that regular consumption of caffeine may help block disruptions in the BBB caused by a high cholesterol diet.
- Preventing traumatic brain injury. Use vehicular seatbelts, wear helmets while bicycling or playing sports, etc.
- Ensuring healthy sleep by setting aside six to eight hours at night for sleep, establishing good sleep habits, and seeking treatment for sleep disorders.
- Maintaining a healthy body weight.
- Eating a nourishing diet. A deficiency of thiamine (vitamin B-1) is associated with a weakened BBB. A well-balanced diet should include plenty of thiamine-rich foods, such as pork, whole grains, sunflower seeds, kale, beans, and peas.
Defense system
The BBB’s essential function is to wall off the brain and the cerebrospinal fluid from the blood supply. Its tightly sealed cells allow the passage of oxygen, glucose, hormones, immune cells, and other smaller molecules into the brain, but block larger molecules, many of which are potentially neurotoxic or pathogenic agents such as bacteria, inflammatory cells, and chemical compounds. Through its actions, the BBB helps ensure a healthy environment that facilitates neuronal communication and promotes the growth of cerebral blood vessels and new brain cells. It also participates in the process of removing from the brain waste matter and toxic substances—including the beta-amyloid proteins associated with AD.
However, the BBB blocks not only unwanted invaders, but many beneficial molecules as well. Treatment of conditions that affect the brain, such as brain tumors or infections, is complicated by the fact that many drugs cannot pass through the barrier to reach their targets in the brain.
Scientists have identified a number of factors in addition to sleep deprivation that appear to cause the BBB to lose its tight seal and permit the entry of harmful substances to the spinal fluid and brain. These factors include cerebrovascular disease, high blood pressure, traumatic brain injury, obesity, oxidative stress, viral infections, and inflammation. As many as 35 disorders affecting the brain—including AD, multiple sclerosis, AIDS, stroke, tumors, Parkinson’s disease, and psychiatric illnesses, to name a few—are associated with BBB dysfunction.
New developments
In recent years, researchers have begun to look more closely at the BBB, searching not only for ways to strengthen the barrier against the damaging effects of disease and other negative factors, but also for ways to bypass the membrane to allow therapeutic drugs to enter the brain when necessary. It is estimated that currently 98 percent of small-molecule drugs, and 100 percent of large-molecule drugs and antibodies are unable to pass through the BBB.
Among interesting recent findings:
▶ Scientists working with human cells and laboratory animals have discovered a molecule (called microRNA-155) that appears to weaken and create microscopic gaps in the BBB in association with inflammation. The finding is expected to lead to new treatments for neurological conditions.
▶ AD researchers have discovered that administering a steroid-like chemical to mice bred to develop AD increased the production of a BBB protein called P-glycoprotein that is involved in the elimination from the brain of toxic beta-amyloid proteins. One week after receiving the injections, the AD mice in the study had levels of the BBB protein that were similar to levels in mice that did not have AD, and their brain levels of beta-amyloid had dropped to levels comparable to those of healthy mice. A small 2012 study found that AD patients, but not healthy controls, showed signs of defective P-glycoprotein function.
▶ Researchers have made a major advance in their search for ways to bypass the BBB so that needed medicines can be delivered to the brain. In experiments with mice, the scientists found that a molecule called mfsd2a appears to regulate the opening and closing of the BBB. The molecule suppresses a barrier-crossing mechanism called transcytosis, a process by which substances are carried through the BBB in bubbles called vesicles. Blocking the equivalent of this molecule in humans would allow for the selective opening of the BBB to permit delivery of medications via vesicles. Strengthening mfsd2a might also result in a strengthening of the BBB to help prevent disease. MMM
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