What Is the Blood-Brain Barrier?

What is the blood-brain barrier (BBB)?

Phenomenally, the brain has its own built-in security system: the blood-brain barrier (BBB). It allows only certain chemicals into the brain while blocking others by using endothelial cells. Not all areas of the brain have a BBB (most notably, the pituitary and pineal glands), but all areas have endothelial cells in their blood vessels. In the non-BBB areas, the junctions between endothelial cells are discontinuous. This allows molecules, typically hormones, to enter. Endothelial cells perform their barrier function in three main ways:

  1. Restrict: Chemicals cannot pass through the tight spaces in between the cells.
  2. Choose: Certain transport proteins determine which chemicals can cross transcellularly (transported from cell to cell).
  3. Alter: Enzymes can alter chemicals prior to entering the BBB.

What can pass through it?

  • Small compounds
  • Water
  • Gaseous compounds (carbon dioxide, oxygen, helium, xenon, nitrogen, many anesthetics)
  • Many hormones (peptide and steroid hormones)
  • Antidepressants
  • Alcohol
  • Cocaine
  • Caffeine
  • Nicotine

How do we know it exists?

In 1885, scientist Paul Ehrlich injected a blue dye into the bloodstream of mice. He found that all of their organs were dyed blue except for their brains and spinal cords. 28 years later, one of Ehrlich’s associates, Edwin Goldman, injected the same dye into the cerebrospinal fluid of mice and found that the brains turned blue, while the rest of their organs did not. This was profound evidence for the existence of the BBB.

Lewandowsky, in 1898, demonstrated that a certain neurotoxin was only toxic when injected directly into the brain and not into the bloodstream. Upon the invention of the electron microscope, Reese and Karnovsky looked more closely into how the brain was doing this. They peered into the blood vessels in the brain and found densely packed endothelial cells.

Overcoming the BBB

Though it is a wonderfully protective barrier, it becomes a hindrance when trying to administer certain life-saving drugs. Researchers are developing ways to temporarily open the barrier. One method used is to administer a solution that removes some water from the tissues of an artery leading to the brain. The endothelial cells shrivel up and gaps open for drugs to pass through. The cells rehydrate and go back to normal within hours. Brain tumor patients have had chemotherapy drugs delivered to them successfully through this method.


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