Isoflurane Induces Endothelial Apoptosis of the Post-Hypoxic Blood-Brain Barrier in a Transdifferentiated Human Umbilical Vein Edothelial Cell Model

Dittmar, Michael S. and Petermichl, Walter and Schlachetzki, Felix and Graf, Bernhard M. and Gruber, Michael (2012) Isoflurane Induces Endothelial Apoptosis of the Post-Hypoxic Blood-Brain Barrier in a Transdifferentiated Human Umbilical Vein Edothelial Cell Model. PLOS ONE, 7 (6): e38260. ISSN 1932-6203,

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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.

Item Type: Article
Uncontrolled Keywords: FOCAL CEREBRAL-ISCHEMIA; NEUROVASCULAR UNIT; ARTERY OCCLUSION; NITRIC-OXIDE; RATS; INJURY; STROKE; PERMEABILITY; INHIBITION; ANESTHESIA;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Anästhesiologie
Medicine > Lehrstuhl für Neurologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 12 May 2020 05:42
Last Modified: 12 May 2020 05:42
URI: https://pred.uni-regensburg.de/id/eprint/18571

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