| Project/Area Number |
08457075
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Sapporo Medical University School of Medicine |
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Principal Investigator |
SAWADA Norimasa Associate Professor Sapporo Medical University Department of Pathology, 医学部, 助教授 (30154149)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 1997: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1996: ¥3,100,000 (Direct Cost: ¥3,100,000)
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| Keywords | Astocyte / Blood-brain barrier / Brain capillary endothelium / Permeability / Tight junction / 7H6 antigen / 7H6 / 細胞電気抵抗 / ZO-1 |
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| Research Abstract |
The capillary endothelium of the central nervous system functions as a highly selective permeability barrier, corresponding to the blood-brain barrier (BBB), but the molecules responsible for the barrier function have not been identified. In the present study, we assessed the roles of the tight junction-associated proteins ZO-1 and 7H6 in the development of brain endothelial barrier function. Capillary endothelial cells were isolated from porcine brain and cultured at a confluent density. Then they were treated with a combination of astrocyte conditioned medium (CM), 8-(4-chlorophenylthio) cyclic AMP (cAMP) and phosphodiesterase inhibitor. More than 10-fold higher barrier function was induced within 10-h, in terms of transendothelial electrical resistance and permeability to inulin and mannitol. Concomitantly, 7H6 antigen, which was not detectable in the control, was induced at the cell border, whereas the expression of ZO-1 did not change significantly between the control and treated cells. These results showed the importance of astrocyte CM and CAMP for the induction of the BBB and suggested the crucial role of 7H6 antigen in the development of the barrier function. This study also suggested that astrocyte CM and cAMP may function differently in the induction of 7H6 antigen in brain capillary endothelial cells.
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