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Isoflurane induces endothelial apoptosis of the post-hypoxic blood-brain barrier in a transdifferentiated human umbilical vein endothelial cell model.

Abstract
Isoflurane is a popular volatile anesthetic agent used in humans as well as in experimental animal research. In previous animal studies of the blood-brain barrier (BBB), observations towards an increased permeability after exposure to isoflurane are reported. In this study we investigated the effect of a 2-hour isoflurane exposure on apoptosis of the cerebral endothelium following 24 hours of hypoxia in an in vitro BBB model using astrocyte-conditioned human umbilical vein endothelial cells (AC-HUVECs). Apoptosis of AC-HUVECs was investigated using light microscopy of the native culture for morphological changes, Western blot (WB) analysis of Bax and Bcl-2, and a TUNEL assay. Treatment of AC-HUVECs with isoflurane resulted in severe cellular morphological changes and a significant dose-dependent increase in DNA fragmentation, which was observed during the TUNEL assay analysis. WB analysis confirmed increases in pro-apoptotic Bax levels at 4 hours and 24 hours and decreases in anti-apoptotic Bcl-2 in a dose-dependent manner compared with the control group. These negative effects of isoflurane on the BBB after a hypoxic challenge need to be taken into account not only in experimental stroke research, but possibly also in clinical practice.
AuthorsMichael S Dittmar, Walter Petermichl, Felix Schlachetzki, Bernhard M Graf, Michael Gruber
JournalPloS one (PLoS One) Vol. 7 Issue 6 Pg. e38260 ( 2012) ISSN: 1932-6203 [Electronic] United States
PMID22723852 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Isoflurane
Topics
  • Apoptosis (drug effects)
  • Blood-Brain Barrier (drug effects, physiology)
  • Cell Line, Tumor
  • Cells, Cultured
  • Gene Expression Regulation (drug effects)
  • Human Umbilical Vein Endothelial Cells (drug effects, physiology)
  • Humans
  • Hypoxia
  • In Situ Nick-End Labeling
  • Isoflurane (pharmacology)
  • Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
  • bcl-2-Associated X Protein (genetics, metabolism)

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