Migraine is a neurological condition with symptoms such as severe headache which lasts up to 72 hours. 15-25% of adults aged 18-65 experience migraines and accordingly migraine ranks sixth in the diseases that cause the most years lived with disability globally. The mechanisms triggering migraine in a healthy brain are poorly understood but it is thought that the extracellular vesicles released by cells in the brain might help us to understand the molecular events that occur during migraine attacks.
Extracellular vesicles are very small parcels of molecules (including protein and RNA) enclosed in a membrane that are released by cells into their environment. These extracellular vesicles act like a cellular postal service, carrying molecular messages from the original cell through the body’s fluids, then delivering the messages to their target cell. Therefore, if we could intercept and capture these molecular messages in the extracellular vesicles, we could read what the cells are saying to each other and learn why they are behaving in a particular way (e.g. to cause migraine). It is thought that some of the extracellular vesicles from brain cells enter the bloodstream, creating an opportunity in that if we could capture these brain-derived extracellular vesicles from the blood outside the brain (e.g. taken in a standard clinical blood test), we could find out what the cells in the brain are saying to each other and what is happening at the molecular level. This is important because current methods to study the brain during migraine rely on animal models (which may not translate to humans) or imaging techniques, which do not have the resolution to tell us what is happening with molecules in the brain.
One principal challenge of capturing brain-derived extracellular vesicles in the blood is that they are very rare – most extracellular vesicles in the blood actually come from other cells in the body which are also sending out messages. What’s more, all these extracellular vesicles look very similar, so it is difficult to tell which come from the brain or elsewhere. With this crowded environment in the blood, it is still possible to pick out brain-derived extracellular vesicles by targeting specific molecules on the vesicle surface which belong to brain cells but are not found in other parts of the body. However, the body is very complex and there are very few molecules unique to the brain, with most also being found in other areas. Therefore, by using multiple molecules to identify brain-derived extracellular vesicles, we can be more confident that they have come from the brain and not elsewhere, and thus that the brain is the origin of the messages they extracellular vesicles carry.
The main aim of this project is to capture extracellular vesicles (EVs) originating from individual brain cell types (neurons, astrocytes and microglia) from the peripheral blood so that brain-derived EVs (BDEVs) of migraine patients can be analysed. From this, we could gain a better understanding of the cellular and molecular processes during migraine attacks, with possible treatment derivations, as well as if there is a role played by extracellular vesicles in migraine pathology.
