Blood-brain barrier: the protective layer of the brain

In the brain and the entire nervous system it is a fundamental organ for the human being. Therefore, it is strongly protected by bones (the skull and spinal column) and by a system of three layers of membranes called meninges. The security of the different parts of the brain it has been reinforced by millions of years of evolution.

However, although all these elements may be essential when protecting the skull from a blow or trauma, they can not be enough to protect the brain from other types of dangers such as viral infections that could come through the blood. To avoid such dangers as much 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 was previously suspected present in the blood system and the nervous system, the verification of this fact would not arrive until 1885. A researcher named Paul Ehrlich would introduce a dye into an animal's bloodstream and later observe that

the only point that did not stain was the central nervous system, and specifically the brain. The reason for this had to be related to a protection system that surrounded that area as if it were a membrane.

Later another researcher, Edwin Goldman, would try the reverse process by staining 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 body, 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 are part of the wall of blood vessels, located along most of the capillaries that supply the brain. The main characteristic of this layer is its high level of impermeability, not allowing a large number of substances to pass from the blood to the brain and vice versa.

Thus, the BHE acts as a filter between the blood and nervous systems. Despite this, some substances such as water, oxygen, glucose, carbon dioxide, amino acids and some other molecules can pass, with the impermeability being relative.

Its action as a filter is carried out through both its structure, by restricting the union between the cells that make up the passage to the different substances, as through the metabolism of the substances to reach it through the use of enzymes and conveyors. That is, it has a physical facet and another that is chemical.

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

The blind spots of the BHE

Despite the importance of the blood-brain barrier in protecting the nervous system does not cover the entire brain, since the brain needs to receive and be able to emit some substances, like 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 happens in the rest of the Body.

The areas not protected by this barrier are around the third cerebral ventricle 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 sites without blood-brain barrier are mainly of the neuroendocrine system and the 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 postema 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. Regardless of the locations where the blood-brain barrier is not present, there are a series of mechanisms by which essential components for the functioning of cells can pass through it.

The most common and frequently used mechanism in this regard is the use of conveyors, in which the element or substance to be transported binds 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 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 through the blood-brain barrier, acting on the electronic charge and concentration gradient such that substances on both sides of the barrier are attracted to each other.

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

Principal functions

As it has already been possible to glimpse some of the properties that make the blood-brain barrier an element essential for the nervous system, since this layer of endothelial cells mainly fulfills the following functions.

The main function of the blood-brain barrier is to protect the brain from the arrival of external substances, preventing the passage of these elements. In this way, the vast 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 neural environment by keeping constant the composition of the interstitial fluid that bathes and maintains the cells.

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 a way unwanted. Of course, some substances escape this control mechanism.

A 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 your brain function is correct and no medical or medical intervention is required psychiatric. But in cases where external action is necessary at a medical or pharmacological level, this barrier represents a difficulty with which it is difficult to treat.

And it is that a large part of the drugs that are applied at a medical level and that would be used to treat an ailment or infection in another part of the body are not effective in treating the problem in the brain, largely due to the blocking action of the barrier blood brain. Examples of this are found in drugs dedicated to fighting tumors, Parkinson's or dementias.

In order to fix it on many occasions it is necessary to inject the substance directly into the interstitial fluid, use the circumventricular organs as an access route, temporarily break the barrier through the use of microbubbles guided to specific points using ultrasound or using chemical compositions that can cross the blood-brain barrier through some of the mechanisms described above.

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