Breaching the Brain's Security System

By Hunter, Beatrice Trum | Consumers' Research Magazine, February 2001 | Go to article overview

Breaching the Brain's Security System


Hunter, Beatrice Trum, Consumers' Research Magazine


The blood-brain barrier has been described as "an invisible biological shield that isolates the brain from the rest of the body, preventing many substances in the blood from entering brain tissue."

The barrier also protects the brain from fluctuations in its chemical environment that otherwise might cause chaotic firing of nerve cells, with resultant seizures or other health problems. It safeguards the brain from bacteria, viruses, and other harmful substances. It is very selective in what is allowed to pass through. The barrier is the brain's security system.

Billions of capillaries (tiny blood vessels) permeate this biological shield. The capillaries in the brain, like those in the rest of the body, allow oxygen and other nutrients to move from the blood into the cells, and carbon dioxide and other waste products to move out of the cells.

The blood vessels in the brain, as well as in many other organs, are lined with thin, flattened endothelial cells that prevent many substances from diffusing through their walls. The junctures between the cells are extremely tight, and prevent an indiscriminate exchange of substances between the blood and the brain.

Like the placenta, the blood-brain barrier is not an entirely impermeable shield. By nature's design, the barrier is not complete. Otherwise, the brain would starve to death quickly from lack of nutrients, and be poisoned by its own accumulated metabolic waste. Unfortunately, this breaching also permits entry to some food poisons. For example, tetrodotoxin, a blowfish poison, can cross the blood-brain barrier and inhibit neuromuscular function and suppress the brain's cerebral and brainstem functions. Substances such as alcohol and caffeine readily cross the barrier, as do some environmental toxins such as lead, mercury, arsenic, and uranium.

Molecules that are small may pass through the barrier. The tight cellular junctures are loosened only enough to allow the molecules to pass through, then close up again. Larger molecules are barred.

Molecules that are lipophilic (literally "fat loving") substances, soluble in the fat-rich membrane of the endothelial cells, pass readily through the blood-brain barrier. But hydrophilic (literally "water-loving") substances, soluble in water, cannot pass through. However, nature has provided a solution, by allowing the hydrophilic substances to be transported through the barrier by mechanisms operated by the endothelial cells. Thus, vital molecules such as oxygen, glucose, and amino acids are moved in and out of the brain.

Improving Drug Delivery to the Brain. The blood-brain barrier poses an obstacle for drug delivery. In the past, brain tumors and other brain diseases were treated with blunt and invasive measures, such as drilling a skull hole and injecting the drug directly into the brain. Or, a drug would be injected into the cerebrospinal fluid, which bathes the brain as well as the spinal cord. Or, a concentrated sugar solution would be injected into the carotid artery. In this last case, the solution reaching the brain would cause water to leave the endothelial cells, and make them shrink. This succeeded in opening the tight cell structure temporarily so that a drug could pass the blood brain barrier. However, this strategy required general anesthesia, and carried risks such as seizures and blood clotting.

Newer, less risky methods of drug delivery to the brain have been tried by various researchers. One strategy is to use lipophilic "pro-drugs" by disguising medically active molecules so they can sneak through the blood-brain barrier in an inactive form. Once they have been delivered within the brain, the drug is released in an active form. A major drawback is that pro-drugs, after crossing the barrier, tend to diffuse right back out of the brain before they can be effective.

Many useful drugs are based on peptides (large molecules formed by linking two amino acids similar in structure to larger proteins).

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