Blood is composed of many different materials, including both small and large molecules, fats and bacteria. Activities such as eating and exercise can significantly alter the composition of our blood, which in turn can have an effect on how the body functions. Some of the materials found in the blood following these activities can actually be harmful to certain parts of the body, such as neurons (brain cells). This puts the brain in a tricky situation, because it doesn’t want to absorb these harmful materials, but at the same time the brain requires a steady blood supply which provides the neurons which much-needed oxygen.
In order to minimise the negative effects of these blood components, there exists a sieve-like ‘shield’ called the Blood Brain Barrier, through which only the useful and healthy materials for the brain are allowed to pass.
This barrier was first detected by a German scientists called Paul Ehrlich. He was attempting to discover new compounds to attach disease-causing microbes (and would eventually win the Nobel prize for developing a cure for syphilis). During his research he injected dye into the bloodstream of mice to determine how various tissues absorb chemical dyes. He discovered something very unexpected. Every organ within the body of the mice turned blue except for one; the brain. When Ehrlich reversed the study and injected the brains of the mice, the rest of the organs remained their natural colour. This research, conducted in 1885, was the first example of the blood brain barrier , or BBB, in action.
The blood brain barrier is made of a network of blood vessels. These blood vessels consist of endothelial cells knitted together into a semi-permeable membrane. This means that some materials are allowed to pass, whilst many others are blocked. In normal endothelial tissue, such as that which lines our capillaries, small spaces exist between each individual cell to allow substances to move across the structure. In the brain, however, the endothelial cells which make up the BBB are specialised and fit much more tightly together.
This highly selective material ensures that only a small number of molecules can access the brain through the bloodstream. Many of these molecules are small in size and are hydrophobic, meaning they repel water. Other molecules which cannot pass the structure go on to do other tasks around the body, or are excreted through urine and waste. This mechanism protects the brain from damage due to bacterial infections and viruses (many antibodies have very large molecules).
The BBB is not perfect, of course. Alcohol, for instance, can penetrate the barrier and cause damage to brain structures. The effectiveness of the BBB can also be altered; for instance, inflammation, stress studies in mice (Friedman et al, 1996), lack of sleep (He et al, 2014) can all increase the permeability of the BBB. This, in turn, can increase the risk of dangerous pathogens entering the brain.
Although effective functioning of the BBB is very important, it can at times become a hindrance. Many pharmacological drugs consist of molecules which the brain wants to block out, meaning treatment for a variety of conditions is not as effective as it could be.
Some scientists have developed solutions which bypass the BBB, such as injecting drugs into the cerebrospinal fluid, which encases the brain and flows through the spinal cord. Known as a lumbar puncture or ‘spinal tap’, this risky and painful procedure does not always distribute the drug to the correct location within the brain, and often the spinal fluid is ‘recycled’ too quickly for the drug to be effective.
Another option includes delivering drugs to the cerebrospinal fluid through the olfactory epithelium, an area situated just below the brain, between the nose and eyes. There is no blood brain barrier in this location, and Hanson and Frey (2008) have shown how physicians have successfully harnessed this approach to treat the symptoms of Alzheimer’s Disease.
Alongside the implementation of the ‘intranasal’ approach, many drugs are now in development which ‘trick’ the BBB into allowing the medicine to pass through and access the brain. Nanoparticles, for instance, manipulate the spaces between epithelial cells and create space for drugs to travel across the barrier and into the brain. These drugs come in a ‘controlled-release’ form, which means that a steady concentration of the drug can be delivered to the brain whilst minimising the risk of over-dose or negative side-effects.
For an in-depth look at how the physicians bypass the blood brain barrier, check out this article on Med Merits.