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This article was written by Annabeth Loftman, an undergraduate pursuing a neuroscience degree at Mount Holyoke College.
TL;DR — the complex but important blood-brain barrier is an essential line of defense for the brain and spinal cord (the central nervous system) against harmful substances (e.g., germs) in the blood. The blood-brain barrier is able to select beneficial nutrients and molecules from the blood, allowing them to reach the cells of the brain. The blood-brain barrier keeps unwanted substances in the blood, allowing the brain to be protected and remain healthy.
What is the Blood-Brain Barrier?
Our brains are the most complex organs that we have. Our brains perform functions that impact every single thing that goes on inside our bodies throughout our entire lives, and not even the most advanced researchers fully understand them. Despite being so important, human brains are also incredibly susceptible to small environmental changes, and we would become sick if our brains were exposed to many of the things floating around in the rest of our bodies. So, how do they maintain these specialized conditions? This article will review one of the systems that keeps our brain healthy: the blood-brain barrier.
In order to function at tip-top shape, the brain requires a sort of hazmat suit to protect itself from the rest of the body and the outside environment – a biological system known as the blood-brain barrier.
Instead of being a single physical barrier, the blood-brain barrier is made up of a collection of cells with unique properties. These cells form and surround the small blood vessels throughout the central nervous system (the brain and spinal cord) and are equipped with extra tools to keep unwanted things out. When working properly, these specialized cells act as a sort of gate, allowing only good things through. Blood carries many molecules and nutrients to the brain that are necessary for survival, such as oxygen and glucose. However, blood also contains many ions, molecules, and cells that may be harmless or helpful to the rest of our body but would hurt the brain if allowed access, such as white blood cells. With an intact blood-brain barrier, these potentially harmful substances can be denied access to our brain tissue and transported to the correct destination elsewhere in the body.
What are the Parts of the Blood-Brain Barrier?
The blood-brain barrier is formed by many types of cells working together to create a strong wall against unwanted entities.
In this upcoming diagram, we’re looking at a cross section of a small blood vessel in the central nervous system. This is similar to how you might take an apple and cut it in half to look at the layers on the inside.
Endothelial Cells: cells that line blood vessels
Endothelial cells form the walls of blood vessels. In large vessels, there can be dozens side-by-side and in multiple layers, while the smallest vessels can be as tiny as only one cell wrapped around to form a tube shape.
These cells are the MVPs of the blood-brain barrier. They are the first line of defense and require support from other types of cells to work properly. To achieve a strong barrier, the small spaces between these cells are held together by proteins, creating seams called tight junctions. These spaces are much harder for substances to squeeze through than they are in other places in the body, where the endothelial cells have looser, wider connections. If we imagine the gaps through the blood vessel walls in the rest of the body as the gaps in a chain link fence, the blood vessels in the central nervous system would be closer to a sieve. A chain link fence works to keep large things away, but many small objects can still fit through the gaps. A sieve, on the other hand, does not let much through its gaps at all. This method of crossing the barrier by moving between endothelial cells is called paracellular transport.
Endothelial cells also make it difficult for substances to pass through them. In the body, many ions, molecules, and cells are able to pass to and from the bloodstream by moving directly through the cells that surround the vessels. This is called transcellular transport. In the central nervous system, however, the properties of the blood-brain barrier make this much harder to do (but not impossible).
Pericytes: cells that surround blood vessels
Pericytes sit along the outside of the endothelial tube of the very small blood vessels of the brain. They do not completely cover the blood vessels, but there are many more in the central nervous system than there are in other places in the body. Each cell is big enough to wrap across multiple endothelial cells. They have multiple roles, such as:
- Contracting (i.e. shrinking or tightening) to control the size of the blood vessel
- Regulating the movement of immune cells
- Creating and upholding the blood-brain barrier
The pericytes are held in place within the basement membranes. These are two layers around the blood vessel made up of an assortment of proteins created by the surrounding cells. These layers:
- Act as padding for blood-brain barrier structures
- Help keep the endothelial tight junctions tightly together
- Assist astrocytes with sending signals to the blood vessels
Astrocytes: cells that hold up blood vessels
Astrocytes are multipurpose cells in the central nervous system that perform many functions. One such function is supporting the blood-brain barrier. Each cell has protrusions called endfeet that reach out and almost entirely surround the small blood vessels. These endfeet hold the vessels in place in the brain, similar to scaffolding on a building. In this way, they provide support and an additional physical barrier against anything unwanted trying to cross through.
These cells also serve as a direct link between the central nervous system’s neurons and the blood vessels running through it. Astrocytes can communicate messages from the brain to tell the pericytes or surrounding muscle cells to tighten or relax to control the flow of blood through the vessels.
What Can and Cannot Pass Through the Blood-Brain Barrier?
The cells of the blood-brain barrier are selective in what they allow to enter into the brain tissue. Many small oily molecules are able to pass through without effort with diffusion or paracellular transport (think of an unlocked door – you can simply enter without being invited in).
However, some of the substances that pass through this “unlocked door” aren’t good for the brain and need to be escorted out. This can happen when two molecules are similar sizes but only one of them is wanted in the brain. Unwanted molecules that pass through the blood-brain barrier get kicked out and put back into the blood by efflux pumps.
Water-soluble and large molecules typically need specialized active transport in order to get through. This takes a lot of energy from the cell, since it must create special receptors for the different substances that it wants (like individualized keys for a locked door) and work to pull them through with transport proteins or by transcytosis. Because of this, endothelial cells in the blood-brain barrier have a much higher number of mitochondria (energy-producing parts of the cell) than the rest of the cells in the body to put up with the increased demand.
Let’s put what we’ve just talked about into a diagram like one you’d find in a scientific article.
This level of control over what makes it into the brain and spinal cord tissue and what stays in the blood helps your body maintain homeostasis (a steady environment) in the brain. The blood-brain barrier makes sure that it gets the exact right amount of nutrients and all of the necessary ions. It also is essential for keeping germs out of the central nervous system, protecting from infection.
Conclusion
As you can see, the blood-brain barrier is a complex and important system within the body. It is the brain and spinal cord’s main line of defense against germs and other potentially harmful molecules or cells in the blood. Endothelial cells form the small blood vessels, held together tightly at the seams in tight junctions. Pericytes then hold on to the outside of the tubes, assisting with contracting the vessels to regulate the flow of blood. This system of blood vessels is held up and supported by the endfeet of nearby astrocytes. Only some types of substances are able to make it into the tissue of the central nervous system. There are many types of transport that exist, some of which take more energy than others. This way, the blood-brain barrier can be choosy about what it wants to take in and what will remain in the blood to go to the rest of the body.
Sources
Daneman, R., & Prat, A. (2015). The blood–brain barrier. Cold Spring Harbor Perspectives in Biology, 7(1). https://doi.org/10.1101/cshperspect.a020412
Evans, T. (2020, April 17). How pathogens penetrate the blood-brain barrier. ASM.org. https://asm.org/Articles/2020/April/How-Pathogens-Penetrate-the-Blood-Brain-Barrier#:~:text=The%20blood%2Dbrain%20barrier%20
Know your brain: Blood-brain barrier. Neuroscientifically Challenged. (n.d.). https://neuroscientificallychallenged.com/posts/know-your-brain-blood-brain-barrier
Thomsen, M. S., Routhe, L. J., & Moos, T. (2017). The vascular basement membrane in the healthy and pathological brain. Journal of Cerebral Blood Flow & Metabolism, 37(10), 3300–3317. https://doi.org/10.1177/0271678×17722436
Images were produced using BioRender.com.
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