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What is the blood-brain barrier?


The brain is very high-maintenance. On the one hand, it uses 20% of the body’s energy (5). On the other hand, it’s sensitive and requires a specific environment to thrive. Somehow the body needs to constantly provide it with nutrients and oxygen while at the same time protecting it from harmful molecules. The oxygen and nutrients are transported to the brain the same way as any other organ - through the blood. That means there are large numbers of capillaries surrounding the brain (also why scalp injuries bleed so much). However, these capillaries and the surrounding cells are very different from everywhere else in the body (4). These differences allow the brain to be shielded from any unwanted molecules. And they’re called the Blood-Brain Barrier (or BBB for short). The BBB was discovered in 1885 when Paul Ehrlich inject dye into the bloodstream of an animal and he noticed that all the organs turned blue except for the brain and spinal cord (6).

How does it work? Capillaries around the brain are lined with special epithelial cells.

In the body, epithelial cells line capillaries with little spaces in between (intercellular space) so molecules can easily pass through.

However, in the brain, the epithelial cells are secured together with tight junctions (1). There’s no space between the cells.

On top of that, specialized brain cells called astrocytes form a layer around the capillary.

Each astrocyte has a specialized extension called a foot process that reaches right up to the capillary. Astrocytes are important for the BBB, but it’s not clear exactly what their role is. Scientists think they are important for the development of the BBB, as well as possibly transporting ions from the brain to the blood (1).

Although the BBB stops most molecules from crossing, it does let some through (i.e. it’s semipermeable). If a molecule is fat-soluble it can diffuse through. Or, if a molecule is just really small, it can use diffusion to cross the barrier. This is how psychoactive drugs have an effect on the brain. Other molecules are actively transported from the blood to the brain through special transport methods. For example, glucose, the main fuel of the brain, is received in this way (1).

So. The BBB is a special layer of protection between capillaries and neurons that protects the brain from dangerous substances and maintains a constant environment. This means that when you hear claims that some substance damages the brain, first you need to ask - can it even cross the BBB? Another common worry is that the BBB is not fully formed at birth, and therefore babies are at risk of toxic substances reaching the brain. However, recent research has found that the tight junctions between the endothelial cells are already formed at birth (9). Although other specific aspects of the BBB change after birth, newborn brains are already protected from toxins (9).

Interestingly, there are actually a few areas of the brain where this special protection is “weaker” or more accurately, specialized. These areas are called circumventricular organs (1,6). Scientists think they have a special purpose: monitoring what’s happening in the blood. Some of these areas produce hormones that will enter the endocrine system through the bloodstream, so it makes sense that they need to know what’s going on in there. These areas have an even more complicated arrangement to allow more molecules to pass back and forth while still protecting the brain from toxic substances. For example, neurons are mostly protected within the BBB, while just one projection (the axon) peeks out to sense the environment and communicate with other cells (6).

Therefore, instead of thinking about the BBB as an impenetrable wall, it’s more accurate to think of it as a dynamic hub, allowing communication between the brain and the rest of the body (7).

The BBB can be weakened or destroyed in a number of ways. Traumatic brain injury, stroke, brain tumors, ischemia (blockage of blood vessels that leads to inadequate blood supply to the brain), and inflammation are just some examples of what can weaken the BBB (10, 11). Drugs like methamphetamine can also temporarily open the BBB (12). Neurodegenerative diseases, like Alzheimer’s, affect neurons as well as endothelial cells, and therefore weaken the BBB (13). On a positive note, a paper just came out showing that, at least in rats, rhubarb helps alleviate the damage done by bleeding on the brain by strengthening the BBB (8).

The BBB is obviously critical for a healthy brain, but there is one downside. The strict rules for what can and cannot cross the BBB makes it a lot harder for scientists to develop treatments for brain diseases. For example, Parkinson’s disease causes death to neurons that produce dopamine. So, individuals need more dopamine than their brain produces. However, instead of prescribing dopamine, doctors must prescribe the precursor to dopamine, called l-DOPA, because it crosses the BBB, while dopamine cannot. Scientists are working on ways to improve drug delivery across the BBB, especially for diseases like brain cancer (14).

The brain makes you who you are, so it needs a special mechanism to keep it protected from toxins, and to maintain a stable environment. As we discover more about this mechanism, the blood-brain barrier, we see it is amazing, complex, dynamic, and effective!

References

1. Chudler, E. H. (2015). Neuroscience For Kids.

2. Laterra J, Keep R, Betz LA, et al. Blood—Brain Barrier. In: Siegel GJ, Agranoff BW, Albers RW, et al., editors. Basic Neurochemistry: Molecular, Cellular and Medical Aspects. 6th edition. Philadelphia: Lippincott-Raven; 1999.

3. Hamilton, N. B., Attwell, D., & Hall, C. N. (2010). Pericyte-mediated regulation of capillary diameter: A component of neurovascular coupling in health and disease. Frontiers in Neuroenergetics.

4. Serlin, Y., Shelef, I., Knyazer, B., & Friedman, A. (2015). Anatomy and physiology of the blood–brain barrier. Seminars in Cell & Developmental Biology, 38, 2-6.

5. Swaminathan, N. (2008, April 29). Why Does the Brain Need So Much Power?

7. Keaney, J. and Campbell, M. (2015), The dynamic blood–brain barrier. FEBS J, 282: 4067–4079.

8. Wang, Y., Peng, F., Xie, G., Chen, Z., Li, H., Tang, T., & Luo, J. (2016). Rhubarb attenuates blood-brain barrier disruption via increased zonula occludens-1 expression in a rat model of intracerebral hemorrhage. Experimental and Therapeutic Medicine Exp Ther Med, 12(1), 250-256.

9. Virgintino, D., Errede, M., Robertson, D., Capobianco, C., Girolamo, F., Vimercati, A., . . . Roncali, L. (2004). Immunolocalization of tight junction proteins in the adult and developing human brain. Histochemistry and Cell Biology, 122(1), 51-59.

10. Alluri, H., Wiggins-Dohlvik, K., Davis, M. L., Huang, J. H., & Tharakan, B. (2015). Blood–brain barrier dysfunction following traumatic brain injury. Metabolic Brain Disease, 30(5), 1093-1104.

11. Strbian, D., Durukan, A., Pitkonen, M., Marinkovic, I., Tatlisumak, E., Pedrono, E., . . . Tatlisumak, T. (2008). The blood–brain barrier is continuously open for several weeks following transient focal cerebral ischemia. Neuroscience, 153(1), 175-181.

12. Turowski, P., & Kenny, B. (2015). The blood-brain barrier and methamphetamine: Open sesame? Frontiers in Neuroscience, 9.

13. Zhao, Z., Nelson, A., Betsholtz, C., & Zlokovic, B. (2015). Establishment and Dysfunction of the Blood-Brain Barrier. Cell, 163(5), 1064-1078.

14. Azad, T. D., Pan, J., Connolly, I. D., Remington, A., Wilson, C. M., & Grant, G. A. (2015). Therapeutic strategies to improve drug delivery across the blood-brain barrier. Neurosurgical Focus, 38(3).

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