Abstract
The blood–brain barrier (BBB) is one of the most complex and selective barriers in the human organism. Its role is to protect the brain and preserve the homeostasis of the central nervous system (CNS). The central elements of this physical and physiological barrier are the endothelial cells that form a monolayer of tightly joined cells covering the brain capillaries. However, as endothelial cells regulate nutrient delivery and waste product elimination, they are very sensitive to signals sent by surrounding cells and their environment. Indeed, the neuro-vascular unit (NVU) that corresponds to the assembly of extracellular matrix, pericytes, astrocytes, oligodendrocytes, microglia and neurons have the ability to influence BBB physiology. Extracellular vesicles (EVs) play a central role in terms of communication between cells. The NVU is no exception, as each cell can produce EVs that could help in the communication between cells in short or long distances. Studies have shown that EVs are able to cross the BBB from the brain to the bloodstream as well as from the blood to the CNS. Furthermore, peripheral EVs can interact with the BBB leading to changes in the barrier’s properties. This review focuses on current knowledge and potential applications regarding EVs associated with the BBB.
Highlights
The brain is protected from the periphery by different barriers including the blood-brain barrier (BBB) and the choroid plexus
In addition to tight junctions (TJs) and Ca2+ -dependent adherens junctions as summarized in Figure 1, the BBB phenotype is composed by efflux pumps such as P-glycoprotein and multidrug-resistance proteins (MRPs), some enzymes, and specific receptors and transporters for transcytosis routes we previously described for the low-density lipoprotein receptor (LDLR) and for the receptor for advanced glycation end-products (RAGE) for amyloid-β (Aβ) peptide entry from the bloodstream into brain [12,13,14,15]
BMEC cultures, Extracellular vesicles (EVs) cargoing CLN-5 protein can bind to leukocytes in vitro, highlighting the possible transfer of a TJ protein from endothelial cells to leukocytes through EVs leading to their transendothelial migration (Paul et al, 2016)
Summary
The brain is protected from the periphery by different barriers including the blood-brain barrier (BBB) and the choroid plexus. Both of these barriers, having important protective roles, have been studied widely over the past few years. The therapeutic compound can be enclosed inside a functionalized capsule made of lipids or polymers [1] Such features allow the drug to be protected at many stages starting with its transport from the digestive tract to the blood stream. With specific structures presented at the surface of the nanoparticles, it is possible to target and penetrate the brain, via transportation through the BBB. As we have recently noticed [3], the information found on the surface of extracellular vesicles (EVs) could be used to functionalize nanoparticles that could travel unharmed and reach the brain
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