Figure 9.

Summarizing scheme. (A) Schematic representation of the relative contribution of different brain cell types to the sEV pool in murine brain. Under physiological conditions, microglia appear to be the main contributor to the sEV pool, followed by oligodendrocytes and astrocytes, while neurons contribute relatively little (contribution indicated by thickness of solid arrows). Upon experimental stroke (indicated by the yellow thunderbolt), astrocytic release of sEVs is upregulated and astrocytes appear to be the main contributor 24 h after reperfusion (indicated by the bold dotted arrow). sEVs are depicted as circles and the color refers to their cellular origin. Note that a fraction of sEVs (grey) may also be released by other cell types not assessed here, such as pericytes or endothelial cells. (B) Differential uptake of WT-sEVs and PrP-KO-sEVs may be influenced by PrP. WT-sEVs (on the left) are packed with fl-PrP and its truncated C1 fragment ending with a stretch of hydrophobic amino acids. These sEVs are relatively slowly taken up by neurons and rather seem to fuse with the plasma membrane (PM). In contrast, sEVs lacking PrP (PrP-KO-sEV; on the right) are rapidly endocytosed and transported to lysosomes (red circles). Colocalization (i.e. lysosomes containing sEVs) is indicated in yellow. Similar observations have been made with microglia or astrocytes as recipient cells. Note that other surface proteins and cargo of sEVs, as well as the lipid bilayer of vesicles, lysosomes, and sEVs, are not depicted here to simplify matters.