What is the blood-brain barrier?
Blood circulates throughout the body in tubes called blood vessels, delivering oxygen and essential nutrients to different organs. However, not all things that circulate through the body can get into the brain. The blood vessels of the brain are slightly different. Their walls have a unique barrier that allows entry of some substances, but keeps others out of the brain. This unique security feature is known as the blood-brain barrier. This barrier allows passage of some substances, but can block out others. This is important because this provides access to substances that the brain needs to function, while keeping harmful substances at bay. The blood-brain barrier is therefore an important feature that keeps our brains and bodies healthy.
How does the blood-brain barrier work?
The blood-brain barrier is the result of the coordinated effort of several players working together at a microscopic level. These players form physical and functional barriers to select what can enter or exit the brain. Like other blood vessels in the rest of the body, blood vessels in the brain are lined with a thin wall of cells called endothelial cells. Between these endothelial cells, there are gaps that can allow substances to exit the blood to the various organs in the body. However, in the brain, these cells form tight connections between the gaps to restrict large molecules from passing through.
Additionally, brain cells called astrocytes and pericytes wrap around endothelial cells to more strictly block what substances can get through. Very small molecules, such as hormones, can slip through this complex wall. Larger molecules, such as sugars, water, amino acids, and insulin, require help from proteins known as transporters to get through, and are a critical component of the blood-brain barrier.
What happens if the blood-brain barrier is not working properly?
Infections, abnormal inflammation, or prolonged stress in the body can contribute to larger gaps between the tight connections of the blood-brain barrier, seen in diseases such as multiple sclerosis or Alzheimer’s disease or with brain tumours. If the blood-brain barrier is not working properly, harmful substances that are usually kept out of the brain may enter and cause problems, and can start a harmful cycle of more infections and more inflammation.
What challenge does the blood-brain barrier post for brain therapies?
The blood-brain barrier is critical for regulating what enters or exits the brain to maintain a healthy brain. However, the blood-brain barrier also poses a challenge for researchers. Many potentially life-saving drugs developed for treating brain diseases and brain injury cannot pass through this barrier. To overcome this, scientists have devised novel ways to directly or indirectly deliver drugs into the brain. The therapeutic potential of smaller sized drugs (often called “small molecules”) is intentionally being tested as they can more easily pass from the blood to the brain.
Another alternative is making previously impenetrable drugs better at entering the blood-brain barrier. Scientists are trying to do this by attaching chemical modifications that “escort” them into the brain. Finally, direct access to the brain is created by injections that allow access to the brain space. We will talk more about this topic in our Snapshot on Intrathecal Injections next week!
Snapshot written by Claudia Hung and edited by Judit M. Pérez Ortiz