title: In vitro effects of dexamethasone on hypoxia-induced hyperpermeability and expression of vascular endothelial growth factor.
abstract: Clinically, dexamethasone is known to reduce cerebral edema. To further investigate the mechanism of this neuroprotection, an in vitro model of brain-derived microvessel endothelial cells (BME cells) was used to investigate the effect of dexamethasone on hypoxia-induced hyperpermeability. Furthermore, the expression of vascular endothelial growth factor (VEGF), which is known to be the mediator of hypoxia-induced hyperpermeability, was evaluated. Dexamethasone (40 microg/ml=100 microM) decreased hypoxia-induced permeability and VEGF expression significantly during time periods of more than 3 h. The time dependence of the dexamethasone effect correlated with a changed mechanism by which hypoxia induced VEGF expression. This was deduced because hypoxia-induced hyperpermeability and VEGF mRNA level were decreased in the presence of an antisense oligonucleotide coding for a region which binds a mRNA stabilizing protein, but only up to 3 h of hypoxia. Furthermore, during this time period the half-life of VEGF mRNA was increased. Results suggest that dexamethasone only decreases transcriptional-induced VEGF expression and that this may be related to the efficacy of dexamethasone to treat brain edema.
authors.affiliation: Kerckhoff-Clinic for Physiological and Clinical Research, 61231 Bad Nauheim, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Fischer
authors.forename: D
authors.initials: D
authors.lastname: Renz
authors.forename: W
authors.initials: W
authors.lastname: Schaper
authors.forename: G F
authors.initials: GF
authors.lastname: Karliczek
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D015687:Cell Hypoxia; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002560:Cerebrovascular Circulation / Q000502:physiology; D003470:Culture Media; D003907:Dexamethasone / Q000494:pharmacology*; D016228:Endothelial Growth Factors / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008222:Lymphokines / Q000096:biosynthesis*; D012313:RNA / Q000096:biosynthesis; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000096:biosynthesis / Q000737:chemistry; D013552:Swine; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D000893:Anti-Inflammatory Agents; D003470:Culture Media; D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D012313:RNA; D003907:Dexamethasone