Extracellular vesicles: mediators and biomarkers of pathology along CNS barriers

Extracellular vesicles (EVs) are heterogeneous, nano-sized vesicles that are shed into the blood and other body fluids, which disperse a variety of bioactive molecules (e.g., protein, mRNA, miRNA, DNA and lipids) to cellular targets over long and short distances. EVs are thought to be produced by nearly every cell type, however this review will focus specifically on EVs that originate from cells at the interface of CNS barriers. Highlighted topics include, EV biogenesis, the production of EVs in response to neuroinflammation, role in intercellular communication and their utility as a therapeutic platform. Researchers from Temple University discuss novel concepts regarding the use of EVs as biomarkers for BBB status and as facilitators for immune neuroinvasion. Future directions and prospective are covered along with important unanswered questions in the field of CNS endothelial EV biology.

Microvesicle (MV) and exosome biogenesis in brain endothelial cells

Upon inflammatory stimuli, brain endothelial cells respond by releasing MVs (microvesicles) and exosomes into the bloodstream and/or in theory perivascularly. For exosomes, stimuli lead to internalization and formation of early endosomes that invaginate to create multivesicular bodies (MVB). For MVs, the vesicle is formed from budding of the plasma membrane.Vesicles are then released either into the blood or the brain parenchyma (theorized)