The Blood-Brain Barrier – a Double Edged Sword?

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The blood-brain barrier – a pathological marvel – is a highly selective complex surrounding the brain. It is a phenomenon in its existence, preventing exposure of the various toxins in the bloodstream to the brain. This protective mechanism is crucial for our survival; the brain being such an intricate organ…

The human brain is by far the most complex physical object known to us in the entire cosmos.

Owen Gingerich, Professor at Harvard University

The barrier inhibits diffusion of toxins from blood to brain through the tight packing of endothelial cells in the blood vessels. Elsewhere in the body, blood vessels have small gaps between these endothelial cells, but here, tight junctions make diffusion near-impossible. Furthermore, the selective membrane allows only certain necessities like water, oxygen, and small lipid-soluble substances to pass. Mural cells (namely pericytes) partially cover the outside of endothelial cells to provide a second layer of protection. This is still insufficient, and so glial cells called astrocytes have projections (astrocytic end-feet) that completely surround the blood vessels. All of this offers to brain tissue an unparalleled level of security.

Like everything in nature, there are imperfections in this seemingly airtight system. It is possible for the barrier to become compromised. One way of this is through bacterial infection. Meningococcal bacteria can bind to the endothelial wall, causing the tightly packed cells to slightly open. It follows that small pores allow toxins to infect the brain – leading to inflammation and sometimes death. There are many other disorders arising from problems with the blood-brain barrier; the irony being our body’s most specialised system for protection is sometimes the root of the most deadly diseases.

As well as the risk of compromise, is the problem of drug access. Yes, the barrier prevents unwanted substances from entry, but the brain cannot differentiate between this and drug treatments. So scientists tackle the huge impediment of how to ‘trick’ the brain into accepting medication for neurological disorders. One such approach is the Trojan horse approach.

Molecular Trojan horses are genetically engineered proteins that cross the blood-brain barrier via receptor-mediated transport processes. These transport processes are essentially those where only specific substances can ‘unlock’ entry into something ( like enzymes and substrates ). The horses attach onto the barrier and bind to receptors to gain access. They provide a method of drug delivery that allows for non-invasive means. But this area of research is still an arcane part of medicine. Genetic engineering needs development and funding to become an integral part of drug delivery.

The second approach is ultrasound. Focussed ultrasound is already an established example of how technology compliments medicine in magical ways. But an emerging application is in the opening of the blood-brain barrier. Essentially, multiple beams of ultrasound target the barrier with an unbelievable degree of accuracy to increase permeability. It follows that there is an increase in active transport, thus drugs can cross the formerly closed-off perimeter.

Both approaches tackle the problem in unique ways, and look to redefine the medical industry through a breakthrough that will undoubtedly save millions of lives. More than a quarter of a billion people suffer from neurological disorders – and millions are dying annually. With genius strategies under our sleeve, and many more in the works, scientists strive to change these staggering numbers.


References

  1. NCBI “Blood-brain barrier modelling: challenges and perspectives” (2015) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4498345/
  2. The Conversation “Explainer: what is the blood-brain barrier and how can we overcome it?” (2020) https://theconversation.com/explainer-what-is-the-blood-brain-barrier-ad-how-can-we-overcome-it-75454
  3. Wikipedia “Meningococcal disease” (2020) https://en.wikipedia.org/wiki/Meningococcal_disease
  4. Wikipedia “Multiple sclerosis” (2020) https://en.wikipedia.org/wiki/Blood–brain_barrier#Multiple_sclerosis
  5. NCBI “Molecular Trojan horses for blood-brain barrier drug delivery” (2006) https://www.ncbi.nlm.nih.gov/pubmed/17234133
  6. physicsworld “Focused ultrasound opens the blood-brain barrier” (2018) https://physicsworld.com/a/focused-ultrasound-opens-the-blood-brain-barrier-2/

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