title: 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.
authors: Department of Neurology, Keio University School of Medicine, Tokyo, Japan. yoshiito@sc.itc.keio.ac.jp
authors: Yoshiaki
authors: Y
authors: Itoh
authors: Haruki
authors: H
authors: Toriumi
authors: Satoshi
authors: S
authors: Yamada
authors: Haruhiko
authors: H
authors: Hoshino
authors: Norihiro
authors: N
authors: Suzuki
mesh_terms: D018171:Agrin / Q000378:metabolism; D000704:Analysis of Variance; D000730:Androstadienes / Q000494:pharmacology; D051401:Aquaporin 4 / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D001596:Benzylamines; D001921:Brain / Q000166:cytology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D000080027:Cyclams; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005452:Fluoresceins / Q000378:metabolism; D005782:Gels / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008954:Models, Biological; D009930:Organic Chemicals; D020286:Pericytes / Q000187:drug effects / Q000502:physiology*; D037342:Pertussis Toxin / Q000494:pharmacology; D000077191:Wortmannin
chemical_list: C496030:AQP4 protein, human; D018171:Agrin; D000730:Androstadienes; D051401:Aquaporin 4; D001596:Benzylamines; D000080027:Cyclams; D004791:Enzyme Inhibitors; D005452:Fluoresceins; D005782:Gels; D006571:Heterocyclic Compounds; D007166:Immunosuppressive Agents; D009930:Organic Chemicals; C070080:PKH 26; C083098:calcein green; D037342:Pertussis Toxin; C088327:plerixafor; D000077191:Wortmannin