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Three-dimensional culture conditions differentially affect astrocyte modulation of brain endothelial barrier function in response to transforming growth factor β1.

Publication ,  Journal Article
Hawkins, BT; Grego, S; Sellgren, KL
Published in: Brain research
May 2015

Blood-brain barrier (BBB) function is regulated by dynamic interactions among cell types within the neurovascular unit, including astrocytes and endothelial cells. Co-culture models of the BBB typically involve astrocytes seeded on two-dimensional (2D) surfaces, which recent studies indicate cause astrocytes to express a phenotype similar to that of reactive astrocytes in situ. We hypothesized that the culture conditions of astrocytes would differentially affect their ability to modulate BBB function in vitro. Brain endothelial cells were grown alone or in co-culture with astrocytes. Astrocytes were grown either as conventional (2D) monolayers, or in a collagen-based gel which allows them to grow in a three-dimensional (3D) construct. Astrocytes were viable in 3D conditions, and displayed a marked reduction in their expression of glial fibrillary acidic protein (GFAP), suggesting reduced activation. Stimulation of astrocytes with transforming growth factor (TGF)β1 decreased transendothelial electrical resistance (TEER) and reduced expression of claudin-5 in co-cultures, whereas treatment of endothelial cells in the absence of astrocytes was without effect. The effect of TGFβ1 on TEER was significantly more pronounced in endothelial cells cultured with 3D astrocytes compared to 2D astrocytes. These results demonstrate that astrocyte culture conditions differentially affect their ability to modulate brain endothelial barrier function, and suggest a direct relationship between reactive gliosis and BBB permeability. Moreover, these studies demonstrate the potential importance of physiologically relevant culture conditions to in vitro modeling of disease processes that affect the neurovascular unit.

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Published In

Brain research

DOI

EISSN

1872-6240

ISSN

0006-8993

Publication Date

May 2015

Volume

1608

Start / End Page

167 / 176

Related Subject Headings

  • Transforming Growth Factor beta1
  • Time Factors
  • Neurology & Neurosurgery
  • Mice
  • Imaging, Three-Dimensional
  • Glial Fibrillary Acidic Protein
  • Endothelial Cells
  • Coculture Techniques
  • Cell Proliferation
  • Cell Membrane Permeability
 

Citation

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Hawkins, B. T., Grego, S., & Sellgren, K. L. (2015). Three-dimensional culture conditions differentially affect astrocyte modulation of brain endothelial barrier function in response to transforming growth factor β1. Brain Research, 1608, 167–176. https://doi.org/10.1016/j.brainres.2015.02.025
Hawkins, Brian T., Sonia Grego, and Katelyn L. Sellgren. “Three-dimensional culture conditions differentially affect astrocyte modulation of brain endothelial barrier function in response to transforming growth factor β1.Brain Research 1608 (May 2015): 167–76. https://doi.org/10.1016/j.brainres.2015.02.025.
Hawkins, Brian T., et al. “Three-dimensional culture conditions differentially affect astrocyte modulation of brain endothelial barrier function in response to transforming growth factor β1.Brain Research, vol. 1608, May 2015, pp. 167–76. Epmc, doi:10.1016/j.brainres.2015.02.025.
Journal cover image

Published In

Brain research

DOI

EISSN

1872-6240

ISSN

0006-8993

Publication Date

May 2015

Volume

1608

Start / End Page

167 / 176

Related Subject Headings

  • Transforming Growth Factor beta1
  • Time Factors
  • Neurology & Neurosurgery
  • Mice
  • Imaging, Three-Dimensional
  • Glial Fibrillary Acidic Protein
  • Endothelial Cells
  • Coculture Techniques
  • Cell Proliferation
  • Cell Membrane Permeability