Breaching the Blood-Brain Barrier

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As the organ responsible for controlling and regulating all bodily functions, the brain is highly sensitive and is easily affected by changes in it’s surroundings. That is why it should always be well-protected from injuries, infection, and even from slight fluctuations in the ion levels of the blood. Protecting the brain from invading materials is the role of the blood-brain barrier (BBB).

Functions of BBB
The BBB is a network of capillaries that supplies blood to the brain. Capillaries usually have very thin walls made of endothelial cells, with small spaces between each cell to allow the flow of materials to and from the capillaries. However, the capillaries in the brain are different. They have endothelial cells that are tightly packed together. Star-shaped glial cells called astrocytes also provide support to the endothelial cells by forming a layer around them with their appendages. Because of these, the capillaries in the brain are less permeable.

The BBB prevents the diffusion of large hydrophilic, low-lipid, or highly charged molecules through the cells and into the cerebrospinal fluid (CSF). It also prevents the entry of bacteria, antibodies, and neurotransmitters.

However, the BBB allows small molecules like certain hormones, oxygen, and carbon dioxide to enter. The feet-like projections of astrocytes anchored around the endothelial cells allow the passage of nutrients, like glucose, to the brain, thus, maintaining ion balance in the brain. That way, the brain is almost in a constant state of homeostasis, even if certain illnesses plague the rest of the nervous system.

Problems of the BBB
The BBB is the reason why diseases in the brain rarely occur. But while it offers an effective protection against foreign materials that may attack the brain, it is not perfect and can still be invaded by a number of harmful substances.

Some organisms like the Trypanosoma (a protozoon) and the Treponema pallidum (a bacterium) can go through the BBB by tunneling through the capillary walls. These microorganisms cause sleeping sickness and syphilis, respectively. Certain strains of viruses can also easily pass through the BBB because they are either very small or they attach themselves to immune cells that enter the brain. The rabies virus, for example, starts affecting the peripheral nervous system and continues to travel and proliferate in the brain.

The BBB also “opens up” as a consequence of some diseases and health conditions. Meningitis, hypertension, high concentration of certain substance, microwave radiation, infection, and trauma can open up the BBB or even disrupt it. A disrupted BBB might lead to illness like epilepsy and Alzheimer’s disease. Epileptic seizures are said to be caused by disruptions in the BB. In Alzheimer’s disease, blood plasma with amyloid beta (a peptide) is allowed to flow into the brain and eventually affects the vulnerable neurons in it.

The BBB is formidable barrier but its highly selective permeability also leads to difficulty in treating illnesses in the brain. Therapeutic drugs cannot go through the BBB. However, this technique would lessen a drug’s effectivity. Others tried to develop drugs attached to nanoparticles that are small enough to pass through the BBB, but this was an expensive process. Developing a mechanism or material that can make the BBB more permeable to important treatments remain a constant challenge.

Recently, scientists from Cornell University in the United States reported that they have developed a way to safely and open the BBB during the delivery of drugs. They did this by utilizing a substance called adenosine which has the ability to alter the behavior of the BBB.

An adenosine protein is used to bind to the receptors on the BBB. A pathway in the BBB is then opened and can be used to transfer larger molecules through it. The scientists were successful in transporting macromolecules as big as antibodies and dextran through the BBB. Aside from that, the mechanism can be opened or closed like a switch, so entry to the BBB is controlled.

The only problem now is that this mechanism has only been tried in mice. While the receptors are also found in human BBB, further study is needed to test whether human BBB will exhibit identical effects. Despite that, it cannot be denied that it’s still a wonderful discovery. If tested positively, the process can be used to deliver therapeutic drugs to at last treat Alzheimer’s disease, Parkinson’s disease, and other illness in the brain which have remained untreatable for more than a century.

To understand more about the blood-brain barrier, watch how lead was able to cause extensive damage in the brain despite the presence of the BBB in the video below.

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