Our brain is a really complex and delicate organ. Our body protects it by holding in things that help it and keeping out harmful things like bugs that could cause infections and toxins.
It does this though a protective layer called the blood-brain barrier. Here's how it really works, and what it means for drug design.
First, let's have a look at the circulatory system
Adults have approx 30 trillion cells of their body. Each cell needs several types of nutrients and oxygen, they usually produce waste, which must be removed.
Our circulatory system provides this service, delivering nutrients and removing waste.
Where the circulatory system meets your cells, it branches off into tiny tubes called capillaries. These tiny tubes, about one-tenth the width of a human hair, are also manufactured from cells.
But in most capillaries, there are special features (called fenestrations) that allow Relatively free exchange Nutrients and wastes between the blood and the cells in your tissues.
It's like pizza delivery.
One option to take into consideration how circulation works is sort of a pizza delivery person in an enormous city. Really big streets (pots) have partitions and you possibly can't walk as much as the door and provides someone a pizza.
But when you get right down to the small suburban streets (capellaris), the design of the streets means you possibly can stop, get off your scooter and walk to the door to have a pizza (grocery) delivered.
We often consider the brain as not having much blood. In fact, average is about brains 600 km of blood vessels.
The difference between capillaries in most parts of the brain and elsewhere is that these capillaries are made up of specialised cells which might be tightly packed together and limit the free exchange of anything dissolved in your blood. . They are sometimes called continuous capillaries.
It is the blood brain barrier. It's not a bag around your brain that keeps things from getting into and out but like partitions on all roads, even very small ones.
The only way pizza can enter is thru special slots and these are the right shape for a pizza box.
The blood-brain barrier is established so there are special transporters (like a pizza box slot) for all of the essential nutrients. So mostly, the one things that may enter are things which might be transporters for things that look very similar (on a molecular scale).
The analogy boils down a bit because the pizza box slot applies to nutrients that dissolve in water. Materials which might be highly soluble in grease can often bypass slots within the wall.
Why do we've a blood-brain barrier?
The blood-brain barrier is assumed to exist for a number of reasons.
First, it protects the brain from toxins you would possibly eat (think plant chemicals) and viruses that may often infect the remaining of your body but often don't reach your brain. would find
It provides protection by tightly controlling the movement of nutrients and waste out and in, providing a more stable environment than the remaining of the body.
Finally, it regulates the passage of immune cells, stopping unnecessary inflammation that may damage brain cells.
What does this mean for medicine?
One consequence of this tight regulation of the blood-brain barrier is that for those who desire a drug to succeed in the brain, you have got to contemplate how it is going to enter.
There are a number of points of view. Molecules which might be too fat-soluble can often get into the brain, so you possibly can design your drug to be barely fattier.
Another option is to connect your drug to a different molecule that is often transported into the brain to dam the ride, or a “pro-drug”, just like the normally transported molecule. Think.
Using it to our advantage
You can even profit from the blood brain barrier.
Opioids used for pain relief often cause constipation. They do that because their targets (opioid receptors) are also present within the enteric nervous system, where they act to slow the movement of intestinal contents.
Imodium (loperamide), which is used to treat diarrhea, is definitely an opioid, nevertheless it Specially designed. So it cannot cross the blood brain barrier.
This design means it might act on opioid receptors within the gastrointestinal tract, reducing the motility of the contents, but doesn't act on opioid receptors within the brain.
Unlike Imodium, Ozempic and Victoza (originally designed for type 2 diabetes, but now popular for weight reduction) each contain long fat, to enhance their length of stay within the body.
The results of this long fat attachment is that they will cross the blood-brain barrier, where they work to suppress appetite. This is an element of the rationale why they're so effective as weight reduction drugs.
So while the blood-brain barrier is essential for safeguarding the brain, it presents each a challenge and a chance for brand new drug development.
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