Fig. 10

Schematic illustration of the proposed role of cortistatin in regulating physiology and pathology of brain endothelium. Top left, Cort^+/+ BECs under normoxia/normoglycemia (NX/NG) conditions showing homeostatic endothelial barrier integrity. Bottom left, after oxygen–glucose deprivation and reoxygenation (OGD-R) to mimic ischemic damage (red arrow), Cort^+/+ BECs suffered a canonical response (i.e., tight-junctions disruption, immune cell infiltration, proinflammatory mediators release, reorganization of actin in stress fibers, and ECM remodelling), combined with upregulation of protective and reparative transcriptional mechanisms (e.g., anti-inflammatory response or angiogenesis) (zoom for details). Remarkably, these changes were reversed with cortistatin treatment (green arrow). Top right, Cort^−/− BECs in NX/NG conditions presented similar phenotypic changes to Cort^+/+ BECs in OGD-R (except for a decrease in the number of transporters and cortistatin receptors), but a different genetic programming (i.e., exacerbated immune response, deregulated ECM remodelling, and downregulation of angiogenesis and protective pathways related to the response to damage) (zoom for details). Bottom right, after exposing Cort^−/− BECs to OGD-R (red arrow), almost no significant transcriptional changes were observed when compared to Cort^−/− BECs in NX/NG. However, downregulation of metabolites transporters, exacerbated stress fiber formation, and increased immune activity was found. Cortistatin reverted these changes up to physiological conditions (top left, green arrow)