It goes without saying, but you really don’t want toxic chemicals in your brain. Luckily,
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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