Targeting and Crossing the Blood-Brain Barrier with Extracellular Vesicles

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.

Sarcoidosis exosomes stimulate monocytes to produce pro-inflammatory cytokines and CCL2

“…We and others argue for pathogenic roles of exosomes from the lungs, particularly in inflammatory conditions 6 . Whether exosomes can pass from the lung into systemic circulation, and there interact with circulating cells, remains to be proven but it is highly likely, based on the nature of exosomes to pass other barriers including the blood brain barrier 24 . The current study is based on interactions between pulmonary exosomes and MNPs, which can readily occur within the lungs, but we also hypothesise that www.nature.com/scientificreports/ these exosomes are able to reach systemic circulation, where they encounter blood monocytes, affect activation and potentially subsequent migration to the lungs.…”

A Brief History of Adherons: The Discovery of Brain Exosomes

“…While much of the work has been on exosomes derived from cells that comprise peripheral tissues, they clearly play an important role in brain function as well. However, while their role as potential biomarkers of disease has received a good deal of attention [ 38 , 49 , 50 ], an understanding of their role in normal brain physiology has lagged behind. I hope that this short review describing their early discovery and characterization as adherons will promote more interest in this important and understudied area of research.…”

“…It is likely that exosomes and their HSPGs play a critical role in the construction of the ECM surrounding neurons and glia that dynamically affects their function ( Figure 2 ). Since the ECM and HSPGs are clearly involved in guiding cell migration [ 35 ], providing adhesion loci for cells [ 36 ] and enabling cellular communication [ 37 , 38 ], this suggests a more important role for exosomes in central nervous system (CNS) function than is currently realized.…”

Benzoinum exerts NVU protective effect by inhibiting cell apoptosis in cerebral ischemia rats

“…Pathological mechanism after stroke is complicated. In recent years, NVU has emerged as a new potential target for understanding the occurrence and development of brain disease [22][23][24][25]. In stroke, the function of BBB and the characteristics of neuron are important for repairing injury.…”