Everything you always wanted to know about the

blood-brain barrier but were afraid to pass.

Jeff Phillips

Overview

The blood-brain barrier(bbb)is mentioned in several lectures, texts, and articles. However, most of the time it is assumed that the reader/listener is fluent in bbb terminology and understanding.

The key to comprehending what protects the brain from microorganisms, differential drug inter-

actions, and the challenge of breaching this barrier to deliver agents to fight brain disease are a few of the questions and problems connected with the bbb. Capillaries surround and saturate the brain.

Unlike capillaries in other parts of the human body(which are somewhat "leaky"), those in the brain have tight joints. Only a few substances can pass through the bbb. Glucose, salt, water, and

certain nutrients can pass through or be actively transported into the brain. Lipid-soluble substances that are smaller in size are good candidates for passage. The bbb is more for keeping

things out than imprisoning substances within. After over 100 years of research we seem to be

just really beginning to "penetrate" the bbb intellectually and to apply our knowledge!

Biological Concepts

_ capillary action _ diffusion/osmosis

_ viral vectors _ selective permeability

_ neuropharmacology _ neurological disease

Class Time

Exploring the bbb will vary depending on the mode selected. This can be done through illustrated

lecture, handouts, or simulations created. See extensions/variations for other ideas.

Background Information

The capillaries of the brain have endothelial cells that form walls with tight junctions. This creates

the blood-brain barrier. These capillaries are interwoven throughout the human brain, but only make up about five percent of its volume. If you could line up the capillaries end to end, they would stretch out for around 640 kilometers, about the distance from Los Angeles to San

Francisco. If you were able to lay the walls of the capillaries out flat, the surface area would be

about 1000 square feet, or about the size of my 3 + 2 condo! Molecules that are water-soluble are

hindered more by the bbb than fat soluble ones. Substances that have an "intermediate" solubility

will seep through the bbb over time. For example, morphine takes about 20 to 30 minutes to cross

the bbb. However, addicts and others have discovered that if the morphine is soaked in acetic

anhydride and transformed into heroin, it will cross the bbb 100 times faster since it is fat soluble.

The differential passage of drugs into the brain helps explain why some drugs act faster and more

significantly than others, and why even small doses of some can cause rapid overdose. The main

brain "food" is glucose, which unfortunately is not fat soluble. So special active transport systems

pump glucose into the brain. There are various other mechanisms for transport of amino acids,

transferrin(the transport protein for iron), and other nutrients. Even though the bbb keeps out most

of the microorganisms and viruses, a few manage to creep in. For example, the bacteria that cause

meningitis are able to pass through due to their cell wall components. Treatment involved using

massive antibiotics and anti-inflammatory drugs. This reasearch helped to determine how to

deliver various drugs for treatment by introducing viral vectors into tumors, using fat shuttles,

glycopeptides, and monoclonal antibodies. For example, to treat Parkinson’s disease dopa is given along with an inhibitor of dopa decarboxylase. Dopa moves into the brain producing

dopamine. Dopa decarboxylase cannot penetrate the bbb thus dopamine is not formed in the

body. This raises brain dopamine levels and relieves some of the symptoms.

Materials

The materials needed for utilizing this information will vary depending on the approach taken.

For example, students could be used to simulate the blood-brain barrier(bbb)transport process whether it be an active or passive type. Butcher paper, markers, etc., could also be used for student groups to diagram the bbb. Color overheads are another option for lecture format.

A demonstration of diffusion/osmosis could be used to introduce this topic. You need two 1L

beakers, distilled water, cornstarch, iodine crystals or Lugol’s solution, dialysis tubing, twister

ties, glass stir rods or magnetic stirrer(to make solutions), and scissors(see teacher prep).

Teacher Preparation

Search other articles related to the bbb. For example, I scrolled through about 250 sources on Netscape after typing in "blood-brain barrier" on a Yahoo search. In just a few minutes several useable and informative articles were obtained. Watch out for articles that have something to do with barrier only, like "Great Barrier Reef". Teachers should be reminded about throwing around biology lingo to students without adequate disclosure.

Make a saturated starch solution in one beaker and a dilute iodine solution for the other. Use 20cm of dialysis tubing for both beakers. Tie off one end and fill one with iodine solution and the other with starch solution. Tie off other end and place in separate beakers(starch in iodine and vice

versa). Have students predict outcomes and check in 24 hours--can be used for several classes.

Extensions/Variations

Many different types of projects & activities can be performed using the bbb. Teamwork building of models of the bbb; total physical response simulations of substances either passing through the bbb or being blocked by it; CD-ROM or laserdisc simulations of neuropharmacology; or illustrated lecture with student discussion/handouts are some ways that this interesting aspect of neurobiology could be utilized in various classroom settings. Adapt, adopt, and apply the bbb!

Resources

Allton, David, &Tsai, Josephine. Breaching the Blood-Brain Barrier, Michigan State University.

Kalat, James W. Biological Psychology. Brooks/Cole Publishing Company, Inc. 1995.

Leff, David N. Balking the Blood-Brain Barrier. Bioworld Today, 10/17/95.

About The Author

Jeff Phillips is a teacher of an experimental advanced biology course(not AP Biology) and of high

level ability freshmen biology students at Canyon High School in Santa Clarita, California. Jeff

can be reached at Canyon High, 19300 W. Nadal St., Santa Clarita, CA 91351 or by e-mail at

tonyf@smartlink.net. You can also call him from 10-11am or 3pm M-F at (805)252-6110x413.

The Woodrow Wilson National Fellowship Foundation webmaster@woodrow.org
CN 5281, Princeton NJ 08543-5281 Tel:(609)452-7007 Fax:(609)452-0066