Blood-brain barrier: the protective layer of the brain

The BBB is a system of cells that keeps the brain relatively isolated from the blood.

The brain and the nervous system as a whole is a fundamental organ for the human being. It is therefore strongly protected by bones (the skull and the spinal column) and by a system of three layers of membranes called the meninges. The security of the various parts of the brain has been reinforced by millions of years of evolution.

However, while all these elements may be essential to protect the skull from a blow or trauma, they may not be sufficient to protect the brain from other dangers such as viral infections that could reach it through the blood. To avoid such dangers as far as possible, we have another type of protection: the blood-brain barrier (BBB)..

The discovery of the BBB

Although the existence of something that separated the content of the Blood present in the blood system and the nervous system had been suspected before, the confirmation of this fact would not come until 1885. A researcher named Paul Ehrlich would introduce a dye into the blood stream of an animal and subsequently observe that the only point that was not stained was the central nervous system, specifically the encephalon.. The reason for this had to be related to a protective system that surrounded that area as if it were a membrane.

Later another researcher, Edwin Goldman, tried the inverse process by dyeing the cerebrospinal fluid, observing that the only colored parts corresponded to the nervous tissue. These experiments reflect the existence of something that produces a high level of blockage between the nervous system and the rest of the organism.a something that years later would be called the blood-brain barrier by Lewandowski and explored by a large number of experts.

A protection between the blood and the brain

The blood-brain barrier is a small layer of endothelial cells, cells that form part of the wall of blood vessels, located along most of the blood vessels.located along most of the capillaries that supply the brain. The main characteristic of this layer is its high level of impermeability, which prevents a large number of substances from passing from the blood to the brain and vice versa.

Thus, the BBB acts as a filter between the blood and nervous system.. Despite this, some substances such as water, oxygen, glucose, carbon dioxide, amino acids and some other molecules can pass through, but the impermeability is relative.

Its action as a filter is carried out both through its structure, by restricting the union between the cells that compose it the passage to the different substances, and through the metabolism of the substances that reach it through the use of enzymes and transporters. In other words, it has a physical and a chemical facet.

Although the blood-brain barrier itself is a layer of endothelial cells, its correct functioning also depends on other types of cellular structures. Specifically, it is supported by cells called pericytes, which provide structural support and envelop the endothelial cells keeping the blood vessel wall stable, as well as microglia.

The blind spots of the BBB

Despite its importance in protecting the nervous system, the blood-brain barrier (BBB) does not cover the entire brain, as it does not cover the whole of the brain, given that the blood-brain barrier is the only one that protects the nervous system. does not cover the entire brain, since the brain needs to receive and be able to deliver some substancessuch as hormones and neurotransmitters. The existence of this kind of blind spots is necessary to guarantee the proper functioning of the organism, since it is not possible to keep the brain totally isolated from what is happening in the rest of the body.

The areas not protected by this barrier are located around the third ventricle of the brain and are called circumventricular organs. In these areas the capillaries have a fenestrated endothelium, with some openings or accesses that allow the flow of substances from one side of the membrane to the other.

The locations without blood-brain barrier are mainly of the neuroendocrine and autonomic nervous system, some of the structures of this group of circumventricular organs being the neurohypophysis, the pineal gland, some areas of the hypothalamus, the area postrema, the vascular organ of the lamina terminalis and the subfornical organ (below the fornix).

Crossing the blood-brain barrier

As we have seen, the blood-brain barrier is permeable, but in a relative way, since it allows the passage of some substances. In addition to the locations where the blood-brain barrier is not present, there are a number of mechanisms by which a series of mechanisms by which components essential for cell function can cross it..

The most common and frequently employed mechanism is the use of transporters. is the use of transportersIn this process, the element or substance to be transported is bound to a receptor that subsequently enters the cytoplasm of the endothelial cell. Once there, the substance separates from the receptor and is excreted to the other side by the endothelial cell itself.

Another mechanism by which substances cross the blood-brain barrier is transcytosis, a process in which they are formed in the endothelial cell.a process in which a series of vesicles are formed in the barrier through which substances can pass from one side to the other.

Transmembrane diffusion allows ions of different charge to move across the blood-brain barrier, the electronic charge and concentration gradient acting in such a way that substances on either side of the barrier are attracted to each other.

Finally, a fourth mechanism by which some substances pass into the brain without the blood-brain barrier intervening is by bypassing it directly. One way to do this is to use the sensory neurons, forcing a reverse transmission through the axon of the neuron to its soma. This is the mechanism used by such well-known diseases as rabies.

Main functions

As we have already glimpsed some of the properties that make the blood-brain barrier an essential element for the nervous system, since this layer of endothelial cells mainly fulfills the following functions.

The primary function of the blood-brain barrier is to protect the brain from the arrival of external substances, preventing the passage of these substances.by preventing the passage of these elements. In this way, the great majority of molecules external to the nervous system itself cannot affect it, preventing a large part of viral and bacterial infections from affecting the brain.

In addition to this defensive function by blocking the entry of harmful elements, its presence also allows the correct maintenance of the neuronal environment by keeping the composition of the interstitial fluid that bathes and maintains the cells constant.

A final function of the blood-brain barrier is to metabolize or modify elements in order to make them cross between blood and nervous tissues without altering the functioning of the nervous system in an undesirable way. Of course, some substances escape this control mechanism.

Therapeutically problematic protection

The fact that the blood-brain barrier is so impermeable and does not allow the entry of most elements is beneficial when the brain is functioning properly and no medical or psychiatric intervention is required. But in cases where external medical or pharmacological action is necessary, this barrier is a difficulty that is difficult to deal with.

And the fact is that most of the drugs that are applied at the medical level and that would serve to treat an ailment or infection in another part of the organism are not effective in treating the problem in the brain, largely due to the blocking action of the blood-brain barrier. Examples of this can be found in drugs used to treat tumors, Parkinson's disease or dementia.

In order to solve this problem it is often necessary to inject the substance directly into the interstitial fluid.The use of the circumventricular organs as an access route, breaking the barrier temporarily through the use of microbubbles guided to specific points by ultrasound or the use of chemical compositions that can cross the blood-brain barrier through some of the mechanisms described above.

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