our brains have a special feature called the blood brain barrier that selectively lets

good things in and keeps bad things out. And I find this feature fascinating because it

takes advantage of cells and nervous system architecture that don't get a lot of attention

in biology classrooms. Neurons usually get the spotlight since they send nervous impulses

around the body. But the blood brain barrier features a different type of cell, glial cells.

And as we'll see, these underrated cells make up one of the most important aspects

of the central nervous system, and have implications for different diseases. Today, we're talking

about how the blood brain barrier keeps one of our most important organs safe from harm.

A quick circulatory system 101 here — most of our organs receive oxygen and nutrients

the same way. The heart pumps oxygenated blood through arteries into systemic circulation,

then those arteries branch out into tinier and tinier blood vessels called capillaries

that surround different tissues. Capillaries have really thin walls, and oxygen, carbon

dioxide, and other compounds can diffuse through those walls to get in or out of the blood

stream. And just like any other organ, the central nervous system, which includes the

brain and spinal cord, gets oxygen and nutrients from the blood. But these organs are a little

more sensitive to changes in their direct environment, so they need a bit more security

around their blood supply to keep themselves stable. That's where the Blood Brain Barrier

comes in. It's an anatomical separation between the brain's capillaries and the

fluid between brain tissue itself. It's made of a few different structures including

special endothelial cells, a sheath of connective tissue, and nervous tissue that surrounds

those tiny blood vessels in the brain. This thing is purpose built to be a selectively

permeable barrier, so let's take a little tour, starting with the inside of the capillaries.

Their walls are considerably more thin than the blood vessels around muscles. But while

they're thin, the cells that make up the capillary are joined by  tight junctions

which lets almost nothing through. The capillaries around some other organs actually have tiny

pores in them, while the brain capillaries do not, so already they're sealed tighter

by comparison. Surrounding the capillaries are cells called pericytes that wrap around

and support the endothelial cells. They can regulate blood flow by squeezing around the

vessel and help with maintenance of the whole barrier. They sit under a layer of mostly

connective tissue called the basal lamina which surrounds those vessels to give them

some structural integrity. Other tissues have lamina too, but what makes this one unique

is how it's a single, continuous piece throughout the barrier. That makes this endothelium different

from what we see in systemic circulation. As soon as we leave the capillaries, we see

more specialized nervous tissue, but not neurons yet. In particular, we bump up against the

end-feet of astrocytes, star-shaped cells which are bound to the basal lamina layer.

That positioning lets them interact with the blood vessels. For instance, astrocytes can

send signals that contract or dilate the blood vessels that feed the brain. Now, the blood

brain barrier isn't totally impenetrable, it's just more choosy with what it lets

through. And in order to be more selective, the endothelium has a few transporter proteins

embedded within it. These transporters let different nutrients in and waste products

out. Importantly, one of these transporters allows glucose through the barrier and into

the brain. And the brain alone consumes about 20% of our daily glucose, which makes it the

hungriest organ by mass in our bodies. To metabolize all that glucose, the blood brain

barrier needs to let oxygen in. But oxygen doesn't actually use a transporter. Some

things can pass directly through the endothelial cells. Oxygen and Carbon dioxide are lipid

soluble. They diffuse directly across the endothelial cells because the cell's membrane

is made of lipids. But that's more of a chemical properties thing than strictly a

size thing. Like hydrogen is extremely small, but it's hydrophilic, so it can't pass

through the barrier. The issue of what can pass through the membrane becomes an even

bigger challenge when scientists try to design drugs for diseases that affect the brain like

for brain tumors, Alzheimers and multiple sclerosis. So just how do you get something

to sneak past the barrier on purpose? Most molecules that can pass through the blood

brain barrier are small and dissolve in lipids. But many drugs that we'd want to deliver

are comparatively big and insoluble in lipids. So like, the opposite of what we want. One

strategy is to include a special protein with the drug that triggers the transporter proteins

to let it through. Another strategy is focused on packaging known, studied drugs into smaller

packages that can cross the barrier. Same Greek soldiers, different Trojan Horse. These

are the things that neurologists and folks in neuroscience have to deal with for anatomy

as unique as the human brain. If you're interested in more brain videos, I think you'll

like this one on the regions of the brain. As always, make sure you're subscribed and

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