Guardians of the Brain Galaxy
If you had the chance to see brain cells under a microscope, it would appear as if you were gazing into outer space. Cells called astrocytes, named for their resemblance to stars, extend beautiful branches in all directions, like arms of the Milky Way. These cerebral constellations are completed by other branching brain cells like neurons and microglia. But these cell networks do not exist to simply amaze researchers who look at them every day. They are also responsible for sustaining and enriching our lives - letting us listen to and understand music, appreciate a painting’s beauty, run, jump, dance, and dream.
When you have a lot to get accomplished, it can be even more difficult to do so if your workspace is dirty, cluttered, and chaotic with people running around. Similarly, your hardworking brain cells operate within a finely tuned environment with a steady supply of oxygen, sugar and other nutrients from the blood. However, if viruses, toxins, or any other potentially dangerous molecules enter this environment from the blood, the balance can shift and send our brain cells into a frenzy of inflammation. Fortunately, our cerebral galaxy is protected by a team of cells — a group of guardians — that prevent damaging molecules from entering the brain.
Caption: Astrocytes (white) and microglia (pink) fluorescently labeled and imaged with a confocal microscope.
The guardians of our brain galaxy are collectively called the “blood-brain barrier”. This superhero roster includes endothelial cells, pericytes, and astrocytes. Each type of cell contributes special skills and weaknesses in protecting our brain and preventing disease. Endothelial cells are considered the leaders of the guardian team. They link up with one another, creating a wall at the surface of blood vessels and double daring any unfamiliar molecule to step on their brain turf. However, the strength of the barrier created by endothelial cells depends on the other members of this cellular team. Pericytes, like wizards, whip up chemical strength potions for endothelial cells and add another layer to the barrier. Astrocytes are the jack of all trades on this guardian team, from physically supporting the endothelial cell wall, to passing messages between neurons and other cells, and secreting chemicals to help endothelial cells respond to injury.
While this protection is helpful to the brain environment, sometimes these guardians can be unintentionally overprotective. Their watchful tendencies can actually impede good things, like medicines, from entering the brain. This is one of the main reasons it is difficult to develop effective medicines for brain tumors, stroke, infections, Alzheimer's, and other brain diseases. Understanding the ways each of the guardian cells protect the brain can inform how we can use these cell superpowers – and their kryptonite – to help us develop medicines that can get into the brain and to target cells. One method is to disguise these medicine molecules so that the guardians mistake the medicine for something they would normally let in – such as sugar. We can also outfit therapeutic particles with a chemical equivalent of an invisibility shield. With this trick, the guardian cells are unaware there is even a visitor attempting to enter the brain.
Learning more and more about this team and how they work together is helpful to not only target and treat brain disease, but also to appreciate the cells that work every day to protect the galaxy inside our heads.
Caption: Brain vessels in descending length scales surrounded by astrocytes (green), pericytes (purple), and endothelial cells (pink). Created with Biorender.com
References:
Applications and Considerations for Microfluidic Systems To Model the Blood-Brain Barrier, Sydney D. Floryanzia and Elizabeth Nance, ACS Applied Bio Materials 2023 6 (9), 3617-3632, DOI: 10.1021/acsabm.3c00364
Engelhardt, B.; Coisne, C. Fluids and Barriers of the CNS Establish Immune Privilege by Confining Immune Surveillance to a Two-Walled Castle Moat Surrounding the CNS Castle. Fluids and Barriers of the CNS 2011, 8 (1), 4, DOI: 10.1186/2045-8118-8-4
Nance, E.; Pun, S. H.; Saigal, R.; Sellers, D. L. Drug Delivery to the Central Nervous System. Nat. Rev. Mater. 2022, 7 (4), 314– 331, DOI: 10.1038/s41578-021-00394-w
Sydney Floryanzia is a chemical engineering Ph.D. student at the University of Washington, where she works on tools and methods to better investigate how injured brain cells respond to therapeutics. Some of these tools include isolating specific brain cells of interest, using whole hemisphere brain slices, and lots of laser microscopy.