Blood-brain barrier (BBB)

The blood-brain barrier (BBB) is an important mechanism that the body uses to protect the brain and central nervous system (CNS). Through most of the body, endothelium cells are spaced loosely apart, which allows the bloodstream to act as an effective transport service for important molecules. However, near the brain, endothelium cells are spaced particularly closely. Their placement prevents most particles from passing through the blood and into the brain and CNS.

Certain atoms and molecules, such as oxygen, are capable of bypassing the blood-brain barrier. These materials are often necessary for the function of the CNS and thus the barrier allows them to reach the brain. Scientists believe that the blood-brain barrier originally evolved to stop pathogens and toxic substances from passing through the bloodstream and entering the brain. In this way, the blood-brain barrier works to keep the body safe.

However, the blood-brain barrier is sometimes detrimental to a patient’s health. Certain diseases of the brain and CNS are difficult or impossible to treat because the barrier prevents medicine from reaching its intended target. Scientists are currently researching various therapies that could possibly bypass the blood-brain barrier. One method involves using specially designed transport proteins to allow medicine to bypass the barrier. Another method involves temporarily opening the barrier, allowing medicine to pass through uncontested.

Background

During the early twentieth century, researchers Paul Ehrlich and Edwin Goldman conducted experiments using the bloodstream. They injected water soluble dyes into the peripheral circulation system. These dyes temporarily stained the body, allowing the researchers to verify the exact regions of the body that were accessible through the peripheral circulations system. However, they discovered that the stain was unable reach the brain or cerebrospinal fluid.

Researchers Ehrlich and Goldman saw promise in these results and continued experimenting. During follow-up testing, they discovered that if the dye was injected directly into the subarachnoid space, which contained cerebrospinal fluid, it would stain the brain and cerebrospinal fluid. However, the dye was then unable to reach the rest of the body. This showed that certain materials, when injected into the body’s circulatory system, were unable to penetrate the brain. Max Lewandowsky first coined the term “bluthirnschranke,” which translates to blood-brain barrier, in 1900.

In 1942, scientists continued experimenting on the blood-brain barrier. They attempted similar experiments, this time using dyes that were highly lipid-soluble. These tests showed staining in the brain and cerebrospinal fluid, demonstrating that certain materials were able to bypass the barrier. Later research showed that the brain contained two separate barrier systems: the blood-brain barrier and the blood-CSF barrier. In the 1960s, electron microscope cytochemical studies discovered the exact mechanisms that allowed the blood-brain barrier to operate.

Overview

Endothelial tissue is a thin membrane that is found inside the heart and the inner part of blood vessels throughout the body. In most of the body, the cells that make up endothelial tissue are loosely arranged. This allows substances to pass from the blood to other bodily tissues, which lets the blood serve as a mechanism for transporting important substances. Many important substances that enter the body, such as oxygen, are transported to their destination through the blood stream. However, in the brain’s capillaries, the endothelial cells are connected tightly to one another. This stops certain molecules from crossing through the blood and into the brain.

The brain cannot exist in a closed system. It needs certain types of chemicals to function effectively. These essential molecules, including oxygen, are capable of freely passing through the blood-brain barrier. Additionally, fat-soluble substances are often capable of crossing the blood-brain barrier. Common fat-soluble substances to pass into the brain include caffeine and alcohol. Other materials that are necessary for the brain’s function may be transported across the blood-brain barrier with transport proteins.

When functioning correctly, the blood-brain barrier serves as a filter for the brain, keeping foreign materials that enter the bloodstream away from the brain matter. This safeguards the CNS from most forms of infection. However, it is possible for the blood-brain barrier to become compromised. For example, certain traumatic brain injuries or strokes can cause permanent damage to endothelial tissue, resulting in significant damage to the blood-brain barrier. If the blood-brain barrier is damaged, the brain may become vulnerable to toxic compounds from outside the body. Modern research has shown that reduced function of the blood-brain barrier is an early warning sign that cognitive impairment, such as dementia, may occur in older individuals.

While the blood-brain barrier does a remarkable job keeping the brain safe, it sometimes makes it difficult or impossible for doctors to treat patients. For example, sometimes injuries, diseases, or tumors are localized in the brain or the cerebrospinal fluid. If these problems had occurred in other places in the body, doctors might be able to treat them with medication. However, the blood-brain barrier prevents most drugs from passing through to the brain. This can make certain neuro-imaging processes or treatments impossible to carry out.

To combat this problem, doctors are searching for methods of passing foreign substances through the blood-brain barrier. Some researchers are working to develop transport systems that carry them through the blood-brain barrier. These transport systems may require the creation of specialized antibodies that bind to receptors within the endothelial cells. Other proposals involve temporarily opening the blood-brain barrier to allow medicines to pass through. These might utilize microscopic bubbles and ultrasounds to temporarily create openings in the barrier. However, many researchers worry that the medical consequences of temporarily opening the blood-brain barrier have not been thoroughly explored. They worry that such practices might place patients at risk of infections or damage the blood-brain barrier.

Bibliography

“Bypassing the Blood-Brain Barrier.” Harvard Medical School, 2015, hms.harvard.edu/news/bypassing-blood-brain-barrier. Accessed 13 Oct. 2021.

“Bypassing the Blood-Brain Barrier: Delivering Drugs to the Brain.” Newcastle University, 2019, www.technologynetworks.com/drug-discovery/news/bypassing-the-blood-brain-barrier-delivering-drugs-to-the-brain-325149. Accessed 13 Oct. 2021.

Davson, Hugh. “History of the Blood-Brain Barrier Concept.” Springer, link.springer.com/chapter/10.1007/978-1-4613-0701-3‗2. Accessed 13 Oct. 2021.

“History of the Blood-Brain Barrier.” Davis Lab, 2021, davislab.med.arizona.edu/history-blood-brain-barrier. Accessed 13 Oct. 2021.

“How Pathogens Penetrate the Blood-Brain Barrier.” American Society for Microbiology, 17 Apr. 2020, asm.org/Articles/2020/April/How-Pathogens-Penetrate-the-Blood-Brain-Barrier. Accessed 13 Oct. 2021.

Pressman, Peter. “The Anatomy of the Blood-Brain Barrier.” VerywellHealth, 2020, www.verywellhealth.com/what-is-the-blood-brain-barrier-3980707. Accessed 13 Oct. 2021.

Rhea, M. Elizabeth and Banks, William A. “Role of the Blood-Brain Barrier in Central nervous System Insulin Resistance.” Frontiers in Neuroscience, 4 June 2019, www.frontiersin.org/articles/10.3389/fnins.2019.00521/full. Accessed 13 Oct. 2021.

Talegaonkar, S. “Intranasal Delivery: An Approach to Bypass the Blood Brain Barrier.” University of Toronto, tspace.library.utoronto.ca/handle/1807/2344. Accessed 13 Oct. 2021.