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What is the blood-brain barrier?

In this article, Dr. Alessandro Cicerale describes what the blood brain-barrier is and how it was discovered.

The discovery of the blood-brain barrier

At the end of the previous video we mentioned the blood-brain barrier – but what is it, exactly?

It is not a structure or an organ that could be seen by the naked eye, or even with a light microscope. The first hint of its existence was found more than 100 years ago by Paul Ehrlich, the discoverer – amongst other things – of the first effective treatment for syphilis. Ehrlich was trying methods to stain the tissues of living organisms, and he found that injecting a dye in the blood vessels of experimental animals he could stain all tissues and organs, but not the brain.

One of his students later found that injecting dyes into the brain could stain the brain, but not the rest of the body. A few decades later – in the early 1940s – other scientists injected into the bloodstream dyes that are soluble in fats, and found out that they could stain the brain tissue, passing through the blood vessels. Even if nothing could be seen, obviously there must have been something that blocked some, but not all, dyes from freely moving into or outside of the brain.

Seeing the barrier for the first time

In the late 1960s, the advances in technology allowed scientists to capture pictures of the blood-brain barrier using electron microscopes. This instrument can see things that are thousands of times smaller than what can be seen with “regular” light microscopes.

The scientists discovered that endothelial cells, that line all blood vessels in the body, in the brain are actually more densely packed, and impede the transit of many classes of molecules

What can pass through the barrier?

Small, fat-soluble molecules are the compounds that can cross the barrier with the greatest ease – it is the case, for instance, of gases like oxygen or nitrous oxide, of ethanol (the alcohol found in alcoholic drinks) or of hormones.

The odds that a compound can cross the barrier decrease as the molecule gets bigger or more water-soluble and, of course, pathogens cannot cross an intact blood-brain barrier. To allow the transit of molecules, such as glucose, that are needed by the brain but could not ‘naturally’ cross the barrier, the membranes of the cells that form the barrier contain transporters. In this way, the environment of the brain can be kept stable, avoiding the accumulation of waste products or the depletion of needed nutrients.

The blood-brain barrier is one of the reasons why what we eat can or cannot directly affect our brain, and we will discuss this topic in more detail in another article at the end of this activity

What happens if the blood-brain barrier breaks down?

Inflammation, some drugs and systemic diseases can affect the blood-brain barrier, making it leaky. In this case, pathogen, toxins and other unwanted molecules can cross into the brain, potentially damaging it. An interesting example is multiple sclerosis: in this illness, the antibodies produced by the body attack the myelin that surrounds the axons, damaging the insulation and impairing the transmission of electrical signals. This then causes the symptoms In normal circumstances, the immune cells cannot cross the blood-brain barrier and therefore could not reach and attack the myelin, but once the barrier is broken, the brain is vulnerable also to the antibodies attack!

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