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Keira Ramirez

Biochemistry

02/1/2012

The Blood Brain Barrier

The Blood Brain Barrier is anatomically produced by specialized blood vessels. All blood

vessels are made of a basal membrane and surrounding endothelial cells. Throughout the body

endothelial cells are fenestrated meaning that they have large openings between blood cells which

allow big molecules or polarized molecules to move freely through and from the blood into

surrounding tissue. This is important because the blood stream supplies our body with necessary

nutrients and sugars. However there is a danger of poisons, toxins, and heavy metals which can thus get

into our tissue through the fenestrated endothelial cells. This is bad for organs such as the liver and

kidney, not to mention the brain. In fact, it would be drastically worse for the brain than for any other

organs. Because, in the brain nerve cells are not constantly regenerated as in the rest of the body,

meaning that we are stuck with the same brains cells with which we are born for our entire life span.

With the conclusion that if they are poisoned once, they are gone forever, bringing with them the

function associated with these cells.

Why is the brain so special and doesnt regenerate like, for example skin? The brain is

extremely complex. In the brain it matters which cell is connected to other cells. There are trillions of

very very specific connections to very specific nerve cells in particular sections of the brain. When cells

are lost it is impossible for another cell to be regenerated with the right partners and right strength of

connection. In some cases bad connections could be worse than no connection at all. That is why,

simpler animals, like goldfish, can regenerate brain cells where we can not. For all these reasons the

brain needs to be protected. And that is what the Blood Brain Barrier is for.

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The Blood Brain Barrier does this with specialized blood vessels. In these blood vessels the

endothelial cells are tightly sealed by tight junctions. Tight junctions are very helpful in keeping out

dangerous molecules and toxins, the only problem is, how does the brain receive the nutrients and other

necessities necessary, through these blood vessels? The brain needs more nutrients and energy than any

other organ in our body and to get them the brain has specialized proteins that can transport molecules

into the brain tissue, or that can open gates so that ions or polar substances are able to flow into the

brain.

However, what I just described is not true for all bigger molecules because the biochemistry

between molecules dictates what molecules can flow through the membrane of the endothelial cell into

the membrane of the brain cell. Because, while the tight junctions can avoid molecules from traveling

into those holes a molecule that is hydrophobic can simply diffuse through the lipid membrane and

does not need an opening. All cells are surrounded by lipid bilayers, which are composed of

phospholipids that have a polar phosphate group as a head (a polar cap) and two hydrophobic chains,

consisting of many carbohydrate bonds.

Because the blood and the internal milieu of cells are aequos and contains polar charges the

polar caps face the internal and external cell while sandwiching the hydrophobic carbohydrate chains in

between. For this reason hydrophobic molecules can penetrate through the blood into the brain.

This is the reason why, for example heroin, gets you high. This molecule is hydrophobic,

allowing an easy pass to the brain. The easier a substance passes to the brain, the faster it has a reaction,

and is more likely to produce a high. In this context it is important to note that a substance, like cocain

(codein) and ritalin (metalphenedote) act on very similar sides of the brain, yet they have slightly

different hydrophobic and/or hydrophilic properties. Ritalin is a little more hydrophilic, causing it to go

into the brain slower than cocain and thus not generating a high like cocain. However, there are cases

where ritalin is injected directly into the bloodstream to get a high, abusing the substance. A similar

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story can be made for codein and heroin. Codein is more hydrophilic than heroin and thereby doesnt

enter the brain as fast. That is why codein is commonly prescribed as a cough medicine and doesnt

produce highs, whereas heroin does enter fast and is therefor a highly addicting drug. Interestingly,

people in the 30s didnt know about all this and heroin was a widely used and prescribed cough

medicine.

To create commonly used drugs Biochemists make substances more hydrophobic or hydrophilic

by binding polar molecules to the carbohydrates. Thus making substances either more or less soluble in

the brain by avoiding polar molecules. For example if you want an antibiotic that can fight brain

bacteria you want to make it more hydrophobic whereas if you want an antibiotic that is for the

stomach you make it hydrophilic. In the case of chemotherapy, a therapy used for the brain, substances

are made more hydrophobic. However, in some diseases the brain blood vessels become leaky and

thereby let too much water into the brain in addition to poisoning the brain molecules and effecting

brain function. This causes symptoms such as nausea, confusion, and in the worst case coma. Another

problem occurs when brain tumor cells make their own leaky blood vessels because the tumor wants

sugar to enhance its growth; which is one of the problems that make brain tumors so dangerous.

However, I only talked about the hydrophobic substances that go into the brain, but how do

hydrophilic substances enter the brain? For example, our brain constantly needs glucose, a hydrophilic

substance. For this reason the cells in the brain have glucose transporters that transport the glucose into

the cell from the blood. These transporters are extremely specific and, for example, the glucose

transporter transports only glucose into the brain and nothing else. In addition there are other

transporters for other molecules. For example, glutamate transporters or GABA transporters; both are

very important neurotransmitters that fulfill very important and very specific regulatory functions.

GABA causes inhibition in the brain and glutamate excitation. In the case of any neurological disorders

such as epilepsy the flow of these molecules across the membrane is effected. Another good example is

the precursor, (which is a molecule that is needed to produce a transmitter) of dopamine, which is

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called L-DOPA. L-DOPA is transported through the blood and is recognized by a very specific

transporter that transports L-DOPA into the brain and produces dopamine. Dopamine is a very

important neurotransmitter, which when dis-regulated or out of balance causes neurological disorders.

Dopamine for example is disturbed in ADHD and causes hyperactivity and Attention Deficit. Cocain

and Ritalin act on a dopamine transporter. And thereby help save patients that suffer from ADHD.

However due to drug abuse it can become very addictive for people without ADHD. Too much

dopamine in the brain can lead to schizophrenia; which is why people with a drug history become

psychotic which can last for the rest of their life. On the other hand, too little dopamine leads to tremor

and rigidity in addition to the inability to initiate a movement or act. Which happens in Parkinson's

disease. In the case of Parkinson's a set of nerve cells that produce dopamine are dying. These cells sit

in the substantia negra. The only way to restore functions in these patients is to increase the

concentration of dopamine in the brain. The problem, however, is that dopamine is polar and charged,

and the brain lacks a dopamine transporter. Which means that you can give a patient as much dopamine

as you want and it wont affect the brain.

These are the subjects I still need to discuss, however, they are all connected so it shouldnt be too

much more.

Area Postrema

Vomiting center

Median Eminents

Also, as I said before I haven't worked on this since I started it so it's not very well written; I especially

have a problem with comma splices and run on sentences! Sorry!

Thank you so much for all your help and understanding!