Figure 6.

Brain endothelial glycocalyx as a source of circulating biomarkers and therapeutic targets for neurovascular injury. Brain endothelial cell (BEC) glycocalyx is an exceptionally thick layer composed of sugar residues decorating glycolipids, membrane and adsorbed glycoproteins and proteoglycans that cover luminal lining of BECs and participate in essential functions of the neurovascular unit (NVU) (i.e., blood–brain barrier permeability, blood flow control, interactions with inflammatory and immune cells, as a source of adsorbed growth factors, thrombogenesis, and angiogenesis). Through the activation of membrane proteases by hypoxic or inflammatory stimuli, BEC glycocalyx components (proteins, glycosylated fragments of proteins, glycosylated lipids, oligosaccharides, etc.) are promptly ‘shed' into circulatory compartment, creating a pool of unique endothelial-derived biomarkers that could be used to assess NVU and brain pathology. Luminal BEC (glyco)proteins, such are for example adhesion molecules and transporters, are systemically accessible imaging and therapeutic targets for assessing and modifying functions of the NVU in disease.