Neuroscientists these days regularly make spectacular discoveries about how the brain gets sick. They know much more today about brain cancer, Alzheimer’s disease, Parkinson’s disease, and a host of other neurological disorders than they did just a few years ago. And from such discoveries come all sorts of encouraging possibilities for treating or even curing these diseases. If only we could break down some rogue protein or bind a drug to a troublesome receptor, it seems as if all would be well. There’s just one little hitch: Even if scientists invented the perfect cure, they probably couldn’t get it into the brain to do its work.
Drugs can cross easily out of the bloodstream into most organs of the body. The brain is a glaring exception because it is protected by an intricate shield known as the blood-brain barrier. The blood-brain barrier serves a vital function: It keeps our brains free for the most part from infections or toxins that find their way into other parts of the body. Unfortunately, the brain’s barrier also gets in the way of most medicines that could help heal it. Neurologists sometimes open up the skull and inject drugs directly. That brute-force approach can work in an emergency, but it is hardly a practical solution for people who need to take drugs every day at home.
There is reason for hope that the blood-brain barrier will not block medicine’s path forever, though. Some scientists are working on ways to penetrate it—either by sneaking drugs through the barrier or by temporarily opening channels through which the drugs can pass.
The word barrier sounds formidable, but scientists didn’t even know the blood-brain barrier existed until they discovered it by accident just over a century ago. In the 1800s biologists found they could see the microscopic structure of the body more clearly if they injected tissues with special dyes. In 1885 German biologist Paul Ehrlich (best known for curing syphilis) discovered that if he injected a dye into the abdomen of animals, he could color all their organs—all except the brain. In 1913 one of Ehrlich’s students, Edwin Goldmann, followed up by injecting dye into the nervous system. This time the brain, and only the brain, turned blue. He concluded that there had to be an invisible barrier separating the brain from the rest of the body.
Other researchers discovered that cells lining blood vessels in the brain are welded together, so tightly bound that large molecules cannot slip between them and pass from the blood into the brain. A fatty coating on the cells further prevents most molecules from slipping into the cells themselves. Yet somehow the brain can still manage to get certain large biomolecules, such as hormones, past the barrier.
It wasn’t until 1980 that William Pardridge, a pharmaceutical scientist at the University of California, Los Angeles, found a crucial clue as to how the brain does it. He determined that epithelial cells lining the brain’s blood vessel walls contain a surface protein, or receptor, that can snag insulin, the hormone essential for metabolizing carbohydrates and fats. As Pardridge studied the protein more carefully, he realized that it transports essential insulin into the cell and then out the other side, from which point the hormone travels into the brain to help regulate eating behavior.
Soon scientists were finding other gateways in the blood-brain barrier, which turns out to be less of a barrier than a filter, providing entrée to molecules the brain requires and shutting out most of those that would do it harm. It is a smart filter at that: The cells lining the brain’s blood vessels can build extra proteins for grabbing glucose if the brain needs a boost and can also destroy some of the proteins to dial the flow back down.
Next page: Trojan Horses into the brain
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