Topic Overview
- The Blood Brain Barrier (BBB) limits the flow of molecules, nutrients and solutes from the blood to the brain and from the brain to the blood. It is basically a defensive wall that protects the brain from neurotoxins and other harmful materials, and maintains the brain’s homeostatic environment.
- There are blood vessels in all parts of the body, but the blood vessels inside the brain are unique! They have structural differences with most other blood vessels, characterized by tight junctions and tight junction proteins between the endothelial cells.
- The BBB is formed of several different elements that preserve its function, including astrocytic end-feet, which express specialised molecules designed to communicate directly with the endothelium of the blood vessel.
- The neurons in the brain require an optimal environment to function, which is regulated by the BBB. The neurons also require energy to function properly, and this energy is provided from the blood via several different mechanisms, including passive diffusion and receptor-mediated transport systems.
There are blood vessels in all parts of the body, and what makes the blood vessels inside the brain unique is the appearance of tight junctions and tight junction proteins between the endothelial cells (cells that form the endothelium – the inner cell lining of all blood vessels and lymphatics in the body) that line the brain’s blood vessels. These tight junctions are the main structures responsible for the barrier properties of the blood brain barrier – it limits the flow of molecules, nutrients and solutes from the blood to the brain and from the brain to the blood. It is basically a defensive wall that protects the brain from neurotoxins and other harmful materials, as well as maintains the homeostatic environment of the brain parenchyma i.e. the functional tissue of the brain.
A healthy blood brain barrier is similar to a forest. A forest is comprised of trees and shrubbery that are clumped very close together. The closer the trees are to each other, the harder it is for some animals to traverse through. Some animals, however, have adapted to traverse through it quite easily.
Think of the trees as endothelial cells, the shrubbery as tight junction proteins, and the different animals as different molecules and solutes. The endothelial cells and tight junction proteins protect the brain by only allowing some molecules and solutes to enter the brain, and stop the flow of other molecules and solutes from entering the brain.
Physiology of the Blood Brain Barrier
The blood brain barrier is formed from several different elements. The lumen – or the central space in the blood vessel, is first lined with the endothelium. The endothelial cells that line the blood vessels are tightly sealed by tight junction proteins that bind the cells together and limit the paracellular transport (passage of molecules in the spaces between neigbouring cells, as opposed to passage through a cell) of solutes and molecules into the brain. The endothelial cells share a basement membrane with pericytes. Pericytes are contractile cells, meaning they use active contraction and relaxation along the walls of capillaries. Pericytes cover 60-70% of the endothelial surface and assist with the maintenance of the blood brain barrier, as well are regulate cerebral blood flow with their contractile function (Attwell et al., 2016; Villaseñor et al., 2019). Wrapping around almost 100% of the endothelial surface, overlaying pericytes, are astrocytic end-feet i.e. terminal ends in astrocytes that make connections with other nerve-cells). Astrocytic end-feet express specialised molecules designed to communicate directly with the endothelium to maintain blood brain barrier function (Villaseñor et al., 2019).
The neurons in the brain require an optimal environment to function, which is regulated by the blood brain barrier. The neurons also require energy to function properly, and this energy is provided from the blood. As seen in the graphic above and table below, energy is transported across the blood brain barrier from the blood into the brain, via several different mechanisms.
| Transport Mechanism | Description |
|---|---|
| Diffusion | Oxygen, carbon dioxide, and small lipophilic molecules traverse the endothelium via passive diffusion without the assistance of any receptors, channels or transporters. |
| Paracellular transport | In a healthy blood brain barrier, tight junction proteins limit the flow of solutes and ions from entering the brain between endothelial cells. A loss of tight junction proteins, and therefore an increase in paracellular transport, is associated with blood brain barrier breakdown via an increase of neurotoxins entering the brain, resulting in neurodegenerative diseases in humans (Sweeney et al., 2018). Think back to the forrest analogy – if the shrubbery is not there, the path in the forrest becomes easier to navigate for all sorts of animals, including ones that will cause damage. |
| Protein transport | Carbohydrates, amino acids, vitamins, and other solutes traverse the blood brain barrier via substrate-specific transporters that line the endothelium (Sweeney et al., 2018). Think of the transporters as carry buddies and gate-keepers. They need to identify which substance needs to enter the cell and then either open the door for them or physically move them across the border and into. |
| Receptor-mediated transport | Large macromolecules and proteins are not usually transported into the brain. In some circumstances via receptor mediated transport, these proteins and large macromolecules may traverse the blood brain barrier and enter into the brain (Sweeney et al., 2018). Here we can imagine the receptor as a type of chaperone – it will meet the required molecule and then they will enter the cell together holding hands. Further processes inside the cell make sure that both the receptor and the macromolecule are processed accordingly. |
| Efflux | Transporters that utilise adenosine tri-phosphate as an energy source prevent drugs and xenobiotics (substances not naturally produced or expected to be present in a living organism) from accumulating in the brain. These transporters are located along the endothelial lining and actively efflux or “flow out” drugs from the endothelium back into the blood. |
Check out this short informational video about the structure and function of the BBB by Dr. Marc Dingman – Creator of Neuroscientifically Challenged and 2-Minute Neuroscience
References
Attwell, D., Mishra, A., Hall, C. N., O’Farrell, F. M., & Dalkara, T. (2016). What is a pericyte?. Journal of Cerebral Blood Flow & Metabolism, 36(2), 451-455. https://doi.org/10.1177%2F0271678X15610340
Sweeney, Melanie D., et al. “Blood-brain barrier: from physiology to disease and back.” Physiological reviews 99.1 (2019): 21-78. https://doi.org/10.1152/physrev.00050.2017
Villaseñor, R., Lampe, J., Schwaninger, M., & Collin, L. (2019). Intracellular transport and regulation of transcytosis across the blood–brain barrier. Cellular and Molecular Life Sciences, 76(6), 1081-1092. https://doi.org/10.1007/s00018-018-2982-x
Featured Image Credit decade3d – anatomy online / Shutterstock
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