Multiple sclerosis (MS) is a chronic disease in which the central nervous system (CNS) is attacked, ultimately leading to irreversible physical damage. Three brain barriers protect the CNS against invading organisms and unwanted substances that are circulating in the peripheral blood. The blood-brain barrier (BBB) occurs along the brain capillaries and separates blood from brain parenchyma. The blood-cerebrospinal fluid (CSF) barrier (BCSFB) is located at the choroid plexus (CP), a structure hanging in the brain ventricles, and restricts passage from the periphery into the CSF. Finally, the meningeal barriers line the outer CNS and separate blood from CSF. The research group previously found that upon systemic inflammation, the CP can secrete extracellular vesicles (EVs) that transfer signals to the brain parenchyma. In this project, we investigate the role of EVs in MS as the lab found an increase in CSF of mice subjected to a mouse MS model. We will study the cellular sources of these EVs, as they can be produced by barrier, inflammatory and brain parenchymal cells or they can come from the periphery upon crossing of the brain barriers. Further, we will analyze their content, identify the recipient cells and study the consequences of this process. Finally, we will determine the effect of (cell-specific) genetic and therapeutic abrogation of EV production on the MS disease course. Conversely, we will administer EVs of MS mice to recipient mice and study the induced effects.