Effect of astroglial cells on hypoxia-induced permeability in PBMEC cells

Am J Physiol Cell Physiol. 2000 Oct;279(4):C935-44. doi: 10.1152/ajpcell.2000.279.4.C935.


An in vitro model of the blood-brain barrier (BBB), consisting of porcine brain-derived microvascular endothelial cells (PBMEC), was used to evaluate the effect of astrocytes in the BBB disruption during hypoxia. Hypoxia-induced hyperpermeability was decreased significantly in a coculture model of astroglia cells, either astrocytes or C6 glioma cells, with PBMEC and, to the same extent, when glia cell-conditioned medium was used. Corresponding to effects on hypoxia-induced hyperpermeability, astrocyte- and C6 cell-conditioned medium diminished hypoxia-induced vascular endothelial growth factor (VEGF) mRNA and protein expression, which recently was shown to be responsible for hypoxia-induced permeability changes in vitro. The effect on hypoxia-induced hyperpermeability and VEGF expression was specific for astroglia cells because conditioned medium from bovine smooth muscle cells (BSMC) did not show any effect. Immunocytochemistry revealed that 24 h of hypoxia disrupted the continuity of the tight junction protein, zonula occludens-1 (ZO-1), which lines the cytoplasmic face of intact tight junctions. These changes were prevented when hypoxia was performed in glia cell-conditioned medium. Results suggest that astrocytes protect the BBB from hypoxia-induced paracellular permeability changes by decreasing hypoxia-induced VEGF expression in microvascular endothelial cells.

MeSH terms

  • Animals
  • Astrocytes / cytology
  • Astrocytes / metabolism*
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / physiology
  • Brain / blood supply*
  • Brain / cytology
  • Cell Hypoxia / physiology*
  • Cell Membrane Permeability / drug effects
  • Cell Membrane Permeability / physiology*
  • Cells, Cultured
  • Coculture Techniques
  • Culture Media, Conditioned
  • Endothelial Growth Factors / biosynthesis
  • Endothelial Growth Factors / genetics
  • Endothelial Growth Factors / pharmacology
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Lymphokines / biosynthesis
  • Lymphokines / genetics
  • Lymphokines / pharmacology
  • Membrane Proteins / metabolism
  • Microcirculation / cytology
  • Microcirculation / metabolism
  • Nitric Oxide / metabolism
  • Phosphoproteins / metabolism
  • RNA, Messenger / biosynthesis
  • Swine
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Zonula Occludens-1 Protein


  • Culture Media, Conditioned
  • Endothelial Growth Factors
  • Lymphokines
  • Membrane Proteins
  • Phosphoproteins
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Zonula Occludens-1 Protein
  • Nitric Oxide