Astrocytic contributions to blood-brain barrier (BBB) formation by endothelial cells: A possible use of aortic endothelial cell for In vitro BBB model |
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Authors: | Ichiro Isobe Takao Watanabe Toshihisa Yotsuyanagi Norio Hazemoto Kazuo Yamagata Takatoshi Ueki Keiko Nakanishi Kiyofumi Asai Taiji Kato |
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Institution: | 1 Department of Bioregulation Research, Nagoya City University Medical School, Mizuho-Ku, Nagoya 467, Japan 2 Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Nagoya City University, Mizuho-Ku, Nagoya 467, Japan 3 Sumitomo Metal Industries Biomedical Division, Kyoto 619-02, Japan |
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Abstract: | Astrocytic contribution of endothelial cell monolayer permeability was examined in two blood-brain barrier (BBB) models, using the coculture in a double chamber system: rat astrocytes and bovine aortic endothelial cells (BAECs) or bovine brain endothelial cells (BBECs). In system 1, where astrocytes were separated from endothelial cells, a 40% reduction in
-glucose permeability of the BBEC monolayer, but not the BAEC monolayer, was observed by cocultivation with astrocytes. Although several passages of BBEC in culture elicited morphological transformation from spindle-shapes to cobblestone-like features, the passaged BBECs remained responsive to astrocytes in coculture in system 1 (37% reduction of the
-glucose permeability). By contrast, in system 2, where respective endothelial cells and astrocytes layered on the upper and lower surfaces of a membrane, the permeability of both BAEC and BBEC monolayers was reduced by cocultivation with astrocytes (75% reduction for BAEC and 40% reduction for BBEC). BAECs in this contiguous coculture (system 2) with astrocytes showed numerous tight junction-like structures characteristic of the BBB in vivo. These results suggest that primary cultured BBECs, which had been primed by astrocytes in vivo, retain a higher sensitivity to astrocytes possibly through an astrocytic soluble factor (s) to exhibit BBB-specific phenotypes, and that even BAEC from extra-neural tissues, when cultured with astrocytes in close proximity in vitro, may acquire the similar phenotypes and serve for an extensive use of BBB model in vitro. |
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