Extracellular Vesicles at CNS barriers: Mode of action.

The exchange of molecules between the brain and periphery is limited by cellular barriers such as the blood-brain barrier (BBB) and the blood-CSF barrier (BCB). Extracellular vesicles (EVs) secreted by brain cells or circulating in the blood stream interact with these barriers and provide a pathway for brain-periphery communication. This review briefly summarizes the main current concepts of EVs signaling over the BBB/BCB. EVs can either be released by barrier cells upon stimulation, act on barrier cells modulating barrier properties, or cross the barrier transferring cargo between the circulation and the brain. The mechanisms of EV signaling and passage over the BBB are increasingly being explored, with inflammation being a main driver. EVs acting at or through the barriers possess wide-ranging effects on brain-periphery communication in both healthy and pathological states. A deeper understanding of the mechanisms of action is important for translation into biomedical applications for brain diseases.