Journal
BRAIN RESEARCH
Volume 1147, Issue -, Pages 39-50Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2007.02.029
Keywords
brain endothelial cell; astrocyte; astrocyte -conditioned medium; in vitro BBB model; permeability; tight junction
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Funding
- NIAAA NIH HHS [R21 AA013858, R21 AA013858-03] Funding Source: Medline
- NIAID NIH HHS [R01 AI047225, R01 AI047225-05] Funding Source: Medline
- NIMH NIH HHS [R21 MH076650-02, R21 MH076650] Funding Source: Medline
- NINDS NIH HHS [R01 NS026310, R01 NS026310-21] Funding Source: Medline
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The blood-brain barrier (BBB) is a structural and functional barrier that regulates the passage of molecules into and out of the brain to maintain the neural microenvironment. We have previously developed the in vitro BBB model with human brain microvascular endothelial cells (HBMEC). However, in vivo HBMEC are shown to interact with astrocytes and also exposed to shear stress through blood flow. In an attempt to develop the BBB model to mimic the in vivo condition we constructed the flow-based in vitro BBB model using HBMEC and human fetal astrocytes (HFA). We also examined the effect of astrocyte-conditioned medium (ACM) in lieu of HFA to study the role of secreted factor(s) on the BBB properties. The tightness of HBMEC monolayer was assessed by the permeability of dextran and propidium iodide as well as by measuring the transendothelial electrical resistance (TEER). We showed that the HBMEC permeability was reduced and TEER was increased by non-contact, co-cultivation with HFA and ACM. The exposure of HBMEC to shear stress also exhibited decreased permeability. Moreover, HFA/ACM and shear flow exhibited additive effect of decreasing the permeability of HBMEC monolayer. in addition, we showed that the HBMEC expression of ZO-1 (tight junction protein) was increased by co-cultivation with ACM and in response to shear stress. These findings suggest that the non-contact co-cultivation with HFA helps maintain the barrier properties of HBMEC by secreting factor(s) into the medium. our in vitro flow model system with the cells of human origin should be useful for studying the interactions between endothelial cells, glial cells, and secreted factor(s) as well as the role of shear stress in the barrier property of HBMEC. (c) 2007 Elsevier B.V. All rights reserved.
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