Blood-brain Barrier: The Protective Layer Of The Brain
The brain and the entire nervous system are a fundamental organ for the human being. Therefore, it is strongly protected by bones (the skull and spine) and by a three-layer system of membranes called meninges. The safety of the different parts of the brain has been reinforced by millions of years of evolution.
However, while all of these elements may be essential when it comes to protecting the skull from a blow or trauma, they may not be enough to protect the brain from other types of dangers such as viral infections that could reach through the blood. To avoid these types of dangers as much as possible, We have another type of protection: the blood-brain barrier (BBB)
Although the existence of something that separated the blood content present in the blood system and the nervous system was previously suspected, the confirmation of this fact would not come until 1885. A researcher named Paul Ehrlich would introduce a tincture into the blood supply of an animal and would later observe that The only point that was not stained 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 parts with color 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 blood and 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 capillaries that supply the brain. This layer’s main characteristic is its high level of impermeability, not allowing a large number of substances to pass from the blood to the brain and vice versa.
In this way, the BHE 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, with impermeability being relative.
Its action as a filter is carried out through both its structure, by restricting the union between the cells that compose it, the passage of different substances, and through the metabolism of the substances that reach it through the use of enzymes and transporters. 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 cellular structures. Specifically, it is supported by cells called pericytes, which provide structural support and surround the endothelial cells, keeping the blood vessel wall stable, as well as the microglia.
The blind spots of the BBB
Despite the importance of the blood-brain barrier in protecting the nervous system It does not cover the entire brain, since it needs to receive and be able to emit some substances , such as hormones and neurotransmitters. The existence of this type of blind spots is necessary to guarantee the proper functioning of the body, since it is not possible to keep the brain completely isolated from what is happening in the rest of the body.
The areas not protected by this barrier are found 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 locations without a blood-brain barrier are mainly 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 postrema, the vascular organ of the lamina terminalis and the subfornical organ (below the fornix).
As we have seen, the blood-brain barrier is permeable, but in a relative way, since it allows the passage of some substances. Apart from the locations in which 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 sense is the use of conveyors , in which the element or substance to be transported is attached 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 charges to move across the blood-brain barrier, acting on the electronic charge and concentration gradient so 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 sensory neurons, forcing a reverse transmission through the neuron’s axon to its soma. This is the mechanism used by well-known diseases such as rabies.
Principal functions
As has already been seen, 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 main function of the blood-brain barrier is to protect the brain from the arrival of external substances to it , 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 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.
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 the brain is functioning correctly and no type of medical or psychiatric intervention is required. But in cases where external action at a medical or pharmacological level is necessary, this barrier represents a difficulty that is difficult to deal with.
And the fact is that a large part of the drugs that are applied at a medical level and that would serve 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. hematoencephalic. Examples of this are found in medications dedicated to fighting tumors, Parkinson’s or dementia.
In order to solve it In many cases 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 by ultrasound or use chemical compositions that can cross the blood-brain barrier through some of the mechanisms described above.
