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.
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Authors | Michael S Dittmar, Walter Petermichl, Felix Schlachetzki, Bernhard M Graf, Michael Gruber |
Journal | PloS one
(PLoS One)
Vol. 7
Issue 6
Pg. e38260
( 2012)
ISSN: 1932-6203 [Electronic] United States |
PMID | 22723852
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Proto-Oncogene Proteins c-bcl-2
- bcl-2-Associated X Protein
- Isoflurane
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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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