What is the blood-brain barrier and how can we overcome it?

April 6, 2017 by Jürgen Götz, The Conversation
Brains are precious. We can’t just let any old thing in. Credit: Neil Conway/Flickr, CC BY-SA

The brain is precious, and evolution has gone to great lengths to protect it from damage. The most obvious is our 7mm thick skull, but the brain is also surrounded by protective fluid (cerebrospinal – of the brain and spine) and a protective membrane called the meninges. Both provide further defence against physical injury.

Another protective element is the –brain barrier. As the name suggests, this is a barrier between the brain's (capillaries) and the cells and other components that make up . Whereas the skull, meninges and cerebrospinal fluid protect against physical damage, the blood–brain barrier provides a defence against disease-causing pathogens and toxins that may be present in our blood.

The blood–brain barrier was discovered in the late 19th century, when the German physician Paul Ehrlich injected a dye into the bloodstream of a mouse. To his surprise, the dye infiltrated all tissues except the brain and spinal cord. While this showed that a barrier existed between brain and blood, it wasn't until the 1960s researchers could use microscopes powerful enough to determine the physical layer of the blood–brain barrier.

We now know the key structure of the blood–brain barrier that offers a barrier is the "endothelial tight junction". Endothelial cells line the interior of all blood vessels. In the capillaries that form the blood–brain barrier, endothelial cells are wedged extremely close to each other, forming so-called tight junctions.

The tight gap allows only small molecules, fat-soluble molecules, and some gases to pass freely through the capillary wall and into brain tissue. Some larger molecules, such as glucose, can gain entry through transporter proteins, which act like special doors that open only for particular molecules.

Surrounding the of the blood vessel are other components of the blood–brain barrier that aren't strictly involved in stopping things getting from blood to brain, but which communicate with the cells that form the barrier to change how selective the blood–brain barrier is.

When functioning properly, the blood brain barrier lets the good things in, but prevents nasty pathogens from infecting our brain. Credit: www.shutterstock.com

Why do we need it?

The purpose of the blood–brain barrier is to protect against circulating toxins or pathogens that could cause brain infections, while at the same time allowing vital nutrients to reach the brain.

Its other function is to help maintain relatively constant levels of hormones, nutrients and water in the brain – fluctuations in which could disrupt the finely tuned environment.

So what happens if the blood–brain barrier is damaged or somehow compromised?

One common way this occurs is through bacterial infection, as in meningococcal disease. Meningococcal bacteria can bind to the endothelial wall, causing tight junctions to open slightly. As a result, the blood–brain barrier becomes more porous, allowing bacteria and other toxins to infect the brain tissue, which can lead to inflammation and sometimes death.

It's also thought the blood–brain barrier's function can decrease in other conditions. In multiple sclerosis, for example, a defective blood–brain barrier allows to infiltrate the brain and attack the functions that send messages from one brain cell (neuron) to another. This causes problems with how neurons signal to each other.

When do we need to get through it?

The blood–brain barrier is generally very effective at preventing unwanted substances from accessing the brain, which has a downside. The vast majority of potential drug treatments do not readily cross the barrier, posing a huge impediment to treating mental and neurological disorders.

One possible way around the problem is to "trick" the blood–brain barrier into allowing passage of the drug. This is the so-called Trojan horse approach, in which the drug is fused to a molecule that can pass the blood–brain barrier via a transporter protein.

A different approach is to temporarily open the blood–brain barrier using ultrasound.

In a mouse with Alzheimer's disease, we showed that using ultrasound to open the blood–brain barrier can improve cognition and decrease the amount of toxic plaque that accumulates in the brain. We think this may be due to the ability of ultrasound, in combination with injected gas microbubbles, to temporarily and safely open up the blood–brain barrier to let protective blood-borne factors in. Importantly, this approach didn't damage the brain.

In a new study, we have shown that by temporarily opening the blood–brain barrier, ultrasound allows more of a therapeutic antibody into the brain, improving Alzheimer's-like pathology and cognition more than when using ultrasound or the antibody drug in isolation.

Ultrasound is therefore a promising tool for temporarily and safely overcoming the normally very useful, but sometimes problematic, blood–brain . It can be used to improve delivery of drugs to the brain, and in doing so make treatments for Alzheimer's and other diseases more cost-effective.

Explore further: New research study creates new opportunities for treating brain diseases

Related Stories

New research study creates new opportunities for treating brain diseases

January 16, 2017
Immunotherapy has proven to be effective against many serious diseases. But to treat diseases in the brain, the antibodies must first get past the obstacle of the blood-brain barrier. In a new study, a research group at Uppsala ...

Disruption of brain-blood barrier might influence progression of Alzheimer's

September 29, 2015
More and more data from preclinical and clinical studies strengthen the hypothesis that immune system-mediated actions contribute to and drive pathogenesis in Alzheimer's disease. The team of Roosmarijn Vandenbroucke in the ...

Breaking through the blood-brain barrier

May 11, 2015
The bacteria that sneak past the brain's defenses to cause deadly bacterial meningitis are clever adversaries. Brandon Kim would know. The biology graduate student at San Diego State University investigates the molecular ...

Blood-brain barrier opened noninvasively with focused ultrasound for the first time

November 10, 2015
The blood-brain barrier has been non-invasively opened in a patient for the first time. A team at Sunnybrook Health Sciences Centre in Toronto used focused ultrasound to enable temporary and targeted opening of the blood-brain ...

Understanding how the 'blood-brain barrier' is breached in bacterial meningitis

October 5, 2016
Simon Fraser University researcher Lisa Craig is part of an international team that has uncovered new details about a microbe that invades the brain, sometimes with fatal results. The information is a critical piece of the ...

Recommended for you

Experts devise plan to slash unnecessary medical testing

October 17, 2017
Researchers at top hospitals in the U.S. and Canada have developed an ambitious plan to eliminate unnecessary medical testing, with the goal of reducing medical bills while improving patient outcomes, safety and satisfaction.

New study: Nearly half of US medical care comes from emergency rooms

October 17, 2017
Nearly half of all US medical care is delivered by emergency departments, according to a new study by researchers at the University of Maryland School of Medicine (UMSOM). And in recent years, the percentage of care delivered ...

No evidence that widely marketed technique to treat leaky bladder/prolapse works

October 16, 2017
There is no scientific evidence that a workout widely marketed to manage the symptoms of a leaky bladder and/or womb prolapse actually works, conclude experts in an editorial published online in the British Journal of Sports ...

Ten pence restaurant chain levy on sugary drinks linked to fall in sales

October 16, 2017
The introduction of a 10 pence levy on sugar sweetened drinks across the 'Jamie's Italian' chain of restaurants in the UK was associated with a relatively large fall in sales of these beverages of between 9 and 11 per cent, ...

New exercises help athletes manage dangerous breathing disorder

October 16, 2017
A novel set of breathing techniques developed at National Jewish Health help athletes overcome vocal cord dysfunction and improve performance during high-intensity exercise. Vocal cord dysfunction, now also referred to as ...

Learning and staying in shape key to longer lifespan, study finds

October 13, 2017
People who are overweight cut their life expectancy by two months for every extra kilogramme of weight they carry, research suggests.

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

PPihkala
not rated yet May 05, 2017
So ultrasound can make the BBB to open. There have been reports (*) that cell phone radiation can affect the BBB also. Might this be because it might create ultrasound, when the cell phone radiation is modulated in certain ways? I think cell phone industry is claiming that the energies and wavelengths used in cell phone communications do not have enough energy to excite brain cells, but if it works via induced ultrasound that radiation might not be harmless.
(*) See https://betweenro...d-group/

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.