The brain is the only organ that has its own security wall – a network of blood vessels that will let in vital nutrients and compounds but keep out most other substances. One downside of this barrier is that it can often block out medicines that could help to heal brain injuries or cure brain diseases.
This barrier has been investigated for a long time and thanks to advances in image analysis software provider offerings we know that the brain’s blood vessels are lined with densely-packed endothelial cells that create an almost impenetrable barrier.
Research has shown how the blood-brain barrier “decides” which molecules it’ll let through and which ones it won’t. This in turn means that scientists can develop ways to attach drugs to the molecules that are let through.
Getting through the checkpoint
Of course, the blood-brain barrier evolved to keep toxins and bacteria from getting into the brain, but to readily allow hormones and amino acids through.
Researchers found that compounds that have low molecular weights or are fat-soluble (or both) can make it through the endothelial barrier quite easily. Examples of these compounds include hormones, anti-depressants and other medications, alcohol, cocaine and nutrients. Larger-weight molecules like glucose and insulin need to be carried through the endothelial cells by transporter proteins located in the walls of the blood vessels. These transporter proteins “hook” their particular compounds from the blood and move through the wall into the brain.
A lot of chatter
There’s constant chemical communication between the cells in and on both sides of the blood-brain barrier which “decides” which compounds to let through, as well as when and how much. If a group of neurons is working especially hard, signals will “tell” transporter proteins to collect more nutrients, for example.
Leaks
Some types of cancer or infection will cause tiny lesions or ruptures in the blood vessels and their endothelial walls, allowing compounds that would usually be rejected to get through the barrier.
It’s thought that this type of weakening or breakdown precedes or accelerates some degenerative neurological disorders. For example, with multiple sclerosis (MS), the brain has too many white blood cells getting in and these cells start to affect the myelin coating of the nerve cells, which leads to the symptoms of MS.
Making leaks work for the brain
It’s important for these leaks to be prevented or repaired, but creating openings in the blood-brain barrier could also be vital when it comes to treating brain diseases. At present, only 2% of brain disease drugs can actually get into the brain, which means brain tumour patients and people with neurological diseases have few options.
To give patients like these more options, work is going on to find ways to make the barrier more permeable. One method under investigation is a solution that removes water from the tissues around arteries leading into the brain. These cells shrivel up for a few hours, creating gaps though which the meds can travel unhindered until the cells return to their normal size. This method is still experimental, but it’s allowed chemotherapy drugs to reach brain tumours and there are big hopes for it.
Trojan horse
Another trick is to tack drug molecules onto molecules that are recognised and readily transported through the barrier. As yet this “Trojan horse” method has worked well in animal trials, delivering “banned” compounds into the brain, but it’s not been trialled in humans yet.
Photograph by Geralt