2007 Fiscal Year Final Research Report Summary
A new blood-brain barrier(BBB) model : Specific uses under in vitro conditions of brain diseases
| Project/Area Number |
18590236
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Nagasaki University |
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Principal Investigator |
NIWA Masami Nagasaki University, Graduate School of Bioraedical Sciences, Professor (20136641)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Kunihiko Nagasaki University, Graduate School of Sciences, Assistant Professor (80380955)
NAKAGAWA Shinsuke Nagasaki University, Graduate School of Biomedical Sciences, Research Associate (10404211)
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| Project Period (FY) |
2006 – 2007
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| Keywords | blood-brain barrier / transient cerebral ishemia / prion disease / tight junctions / BBB kit disease model / centrally acting drug |
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| Research Abstract |
Seven different types of blood-brain barrier(BBB)models, mono-culture, double and triple co-cultures, were constructed from primary rat brain endothelial cells, astrocytes and pericytes on culture inserts. The barrier integrity of the models were compared by measurement of transendothelial electrical resistance and permeability for the small molecular weight marker fluorescein. We could confirm that brain endothelial monolayers in mono-culture do not form tight barrier. Pericytes induced higher electrical resistance and lower permeability for fluorescein than type I astrocytes in co-culture conditions. In triple co-culture models the tightest barrier was observed when endothelial cells and pericytes were positioned on the two sides of the porous filter membrane of the inserts and astrocytes at the bottom of the culture dish(BBB kit). With the BBBkit, we investigated effects and permeability on the BBB of centrally acting drugs under in vitro stimulations of prion protein fragment PrP106-126, amyloid-B peptide(1-42), and hypoxia(BBB kit disease models).Edaravone, a clinically-widely used anti-brain edema drug, markedly defended the BBB disruption due to a transient cerebral ischemia. PPS, a candidate drug for prion disease, penetrated more rapidly on the BBB under PrP106-126. Cilostazol increased the activity of P-glycoprotein of the BBB kit under hypoxia and histamine, an in vitro model of the brain edema. Thus, our BBB kit was found to be a suitable in vitro-experimental tool to study drug-permeability on the BBB under pathological conditions.
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Author(s)
Miyazaki, S., Yanagida, T., Nunome, K., Ishikawa, S., Inden, M., Kitamura, Y., Nakagawa, S., Taira, T., Hirota, K., Niwa, M., Iguchi-Ariga S., Ariga, H
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[Journal Article] Pericytes from brain microvessels strengthen the barrier integrity in primary cultures of rat brain endothelial cells2007
Author(s)
Nakagawa, S., Deli, MA., Nakao, S., Hayashi, K., Honda, M., Nakaoke, R., Kataoka, Y., Niwa, M
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Journal Title
Cell Mol Neurobiol 27
Pages: 687-694
Description
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[Journal Article] Pentosan polysulfate protects brain endothelial cells against bacterial lipopolys accharide-induced damages2007
Author(s)
Veszelka, S., Pasztoi, M., Farkas, AE, Krizbai, IA, Dung, NT, Niwa, M., Abraham, CS, Deli, MA
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Journal Title
Neuroohemi Int 50
Pages: 219-228
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[Journal Article] Inhibition of transforming growth factors-B production in brain pericytes contributes to cyclosporin A-induced dysfunction of the blood-blain barrier2007
Author(s)
Takata, F., Dohgu, S., Yamauchi, A., Sumi, N., Nakagawa, S., Naito, M., Tsuruo, T., Shuto, H., Kataoka, Y
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Journal Title
Cell Mol Neurobiol 27
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[Journal Article] Possible protection of sinusoidal endothelial cells by endothelinB receptor during hepatic warm ischemia-reperfusion2007
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Mochizuki, K., Ohni, Y., Kanematsu, T., Sakurai-Yamashita Y., Niwa, M., Hishikawa, Y., Koji, T
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Journal Title
Surg Today 37
Pages: 460-467
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[Journal Article] Adverse effect of cyclosporin A on barrier functions of cerebral microvascular endothelial cells after hypoxia-reoxygenation damage in vitro2007
Author(s)
Dohgu, S., Nishioku, T., Sumi, N., Takata, F., Nakagawa, S., Naito, M., Tsuruo, T., Yamauchi, A., Shuto, H., Kataoka, Y
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Cell Mol Neurobiol 27
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[Journal Article] 14-3-3 protein, total tau and phosphorylated tau in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease and neurodegenerative disease in Japan2006
Author(s)
Satoh, K., Shirabe, S., Eguchi, H., Tsujino, A., Eguchi, K., Satoh, S., Tsujihata, M., Niwa, M., Katamine, S., Kurihara, S., Matsuo, H
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Cell Mol Neurobiol 26
Pages: 45-52
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[Journal Article] Adrenorhedullin improves the blood-brain barrier function through the expression of claudin-52006
Author(s)
Honda, M., Nakagawa, S., Hayashi, K., Kitagawa, N., Tsutsumi, K., Nagata, I., Niwa M
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Journal Title
Cell Mol Neurobiol 26
Pages: 109-118
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[Journal Article] Induction of aquaporin 1 by dexamethasone in lipid rafts in immortalized brain microvascular endothelial cells2006
Author(s)
Kobayashi, H., Yokoo, H., Yanagita, T., Satoh, S., Kis, B., Deli, MA, Niwa, M., Wada A
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Journal Title
Brain Res 1123
Pages: 12-19
Description
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[Presentation] A new BBB model : testing specific functions2007
Author(s)
Nakagawa, S., Deli, MA, Kawaguchi, H., Shimizudani, T., Shimono, T., Yamaguchi, M., Hourai, S., Kataoka, Y., Niwa, M
Organizer
The 10th International symposium on Signal Transduction in the Blood-BrainBarrier
Place of Presentation
Potsdam, Germany
Year and Date
20070913-16
Description
「研究成果報告書概要(欧文)」より
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[Presentation] BBB kit(Blood-Brain Barrier in vitro Reconstruction mode)2007
Author(s)
Nakagawa, S., Deli, MA, Nakao-Nishioku, S., Hayashi, R., Nakaoke, R., Kataoka, Y., Niwa, M
Organizer
The 7th Cerebral Vascular Biology International Conference
Year and Date
20070624-28
Description
「研究成果報告書概要(欧文)」より
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[Presentation] BBB kit(Blood-Brain Barrier in vitro Reconstruction mode)2006
Author(s)
Nakagawa, S., Deli, MA, Nakao-Nishioku, S., Hayashi, R., Nakaoke, R., Kataoka, Y., Niwa, M
Organizer
The 12th International Symposium on SHR-Genetics on Experimental and Human Hypertenson in Relation with Environment Factors-
Place of Presentation
Kyoto
Year and Date
20061020-21
Description
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[Presentation] Effect of pituitary adenylate cyclase activating polypeptide(PACAP) on the tight junctions of the blood-brain barrier2006
Author(s)
Nakagawa, S., Hazama, K., Hourai, S., Yamauchi, A., Kataoka, Y., Deli, MA, Niwa, M
Organizer
The 9th International symposium on Signal Transduction in the Blood-Brain Barrie
Place of Presentation
Salzburg
Year and Date
20060907-10
Description
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