In 1885, Ehrlich injected blue dye into the bloodstream of mice. The dye stained all of the animals’ organs blue- except their brains. In a follow-up experiment in 1913, one of Ehrlich’s students injected the same dye directly into the brains of mice. This time, the brains turned blue, whereas the other organs did not. Although these experiments suggested a physical barrier between the brain and the bloodstream, no such barrier could be detected with the instruments of the time.
It took until the 1960s before scientists were able to catch a glimpse of the actual barrier standing between the rest of the body and the brain. Using a microscope that was roughly 5,000 times more powerful than the one Ehrlich used, scientists could see the detailed anatomy of the network of blood vessels in the brain comprising what is now known as the blood-brain barrier.
Similar to all other blood vessels in the body, scientists learned that the brain’s blood vessels are lined with endothelial cells, which serve as an interface between circulating blood and the vessel wall. However, unlike other blood vessels in the body, the endothelial cells in the brain are tightly wedged together, creating a nearly impermeable boundary between the brain and bloodstream.
The blood-brain barrier helps block harmful substances, such as toxins and bacteria from entering the brain. But, scientists knew that the brain also depends upon the delivery of hormones and key nutrients, including glucose and several amino acids, from other organs of the body.
Through extensive study, scientists have found that compounds that are very small and/or fat-soluble, including antidepressants, anti-anxiety medications, alcohol, cocaine, and many hormones are able to slip through the endothelial cells that make up the blood-brain barrier without much effort. In contrast, larger molecules, such as glucose or insulin, must be ferried across by proteins. These transporter proteins, located in the brain’s blood vessel walls, selectively snag and pull the desired molecules from the blood into the brain.
Cells within and on either side of the blood-brain barrier are in constant communication about which molecules to let through and when. For instance, if the nerve cells in a region of the brain are working particularly hard, they will signal to the blood vessels to dilate, allowing cell-powering nutrients to quickly travel from the blood to the nerve cells in need.
When the blood-brain barrier breaks down, as is the case in some brain cancers and brain infections or when tiny ruptures to blood vessels occur, some substances that are normally kept out of the brain gain entry and cause problems for the brain.
Some evidence suggests the weakening of the blood-brain barrier may even precede, accelerate, or contribute to a number of neurodegenerative disorders. For instance, studies suggest a leaky blood-brain barrier allows too many white blood cells into the brains of people with multiple sclerosis (MS). With access to the brain, these cells attack myelin, the insulating coating between nerve cells, leading to the disease’s devastating symptoms.