Astrocytes and pericytes cooperatively maintain a capillary-like structure composed of endothelial cells on gel matrix

Abstract

The gliovascular complex (GVC) is a structural and functional unit located at the interface between the cerebral blood flow and neural network. Even though its physiological roles have been partially clarified, the contribution of the astroglia to maintenance of the cerebral vasculature, which is tightly wired with the neuronal network, is only incompletely understood. To elucidate the role of astrocytes and pericytes in maintaining the integrity of the capillaries, we developed a new GVC model in vitro. Human brain microvascular endothelial cells (ECs) plated on a gel matrix developed a capillary-like structure (CLS). Pericytes and astrocytes migrated together and adhered to the CLS to form a GVC-like structure with pericytes between the CLS and astrocytes. Astrocytes together with pericytes suppressed CLS degradation to a greater extent than astrocytes alone. Fumagillin and suramin, angiogenesis inhibitors, suppressed GVC formation. The PDGF receptor inhibitor SU6668 suppressed pericyte/astrocyte migration and accelerated CLS degradation, whereas the VEGF receptor inhibitor SU1498 did not suppress pericyte/astrocyte migration and both types of cells maintained the CLS for a long period of time. Immunohistochemistry revealed aquaporin-4 and agrin expression at the junction of ECs and astrocytes. These results indicate the importance of both astrocytes and pericytes for maintenance of the cerebral microvasculature.