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Effect of midazolam on in vitro cerebral endothelial ICAM-1 expression induced by astrocyte-conditioned medium

Published online by Cambridge University Press:  24 May 2006

K. Ghori ,
D. Harmon ,
F. Walsh  and
G. Shorten
K. Ghori
Affiliation:
Cork University Hospital and University College Cork, Department of Anaesthesia and Intensive Care Medicine, Cork, Ireland
D. Harmon
Affiliation:
Cork University Hospital and University College Cork, Department of Anaesthesia and Intensive Care Medicine, Cork, Ireland
F. Walsh
Affiliation:
Cork University Hospital and University College Cork, Department of Anaesthesia and Intensive Care Medicine, Cork, Ireland
G. Shorten
Affiliation:
Cork University Hospital and University College Cork, Department of Anaesthesia and Intensive Care Medicine, Cork, Ireland
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Abstract

Summary

Background and objective: Astrocytes exposed to hypoxia produce pro-inflammatory cytokines and upregulate intercellular adhesion molecule-1 on cerebral endothelium. This study investigated the effects of midazolam on this response. Methods: Mouse astrocytes were exposed to 4 h of hypoxia and 24 h of reoxygenation. Astrocyte-conditioned medium were applied to mouse cerebral endothelial cell cultures for 4 h and 24 h in normoxia. Endothelial cells were pre-incubated for 1 h with midazolam (0, 5, 50 μg L−1). Flow cytometry was used to estimate endothelial ICAM-1 expression. IL-1β concentrations were measured with ELISA. Repeated comparisons were made using ANOVA and post hoc Tukey Test as appropriate. Data are mean (SD). Results: Mouse cerebral endothelial cell ICAM-1 expression was greater after 24 h exposure to hypoxia–reoxygenation astrocyte-conditioned medium compared to normoxic astrocyte-conditioned medium (mean channel flouresence 112.5 (9.5) vs. 81.5 (7.5), P = 0.01). ICAM-1 expression was decreased by midazolam (5 μg L−1) compared to control (mean channel flouresence 81.35 (7.5) vs. 112.5 (9.5), P = 0.01). Supernatant IL-1β concentrations (pg mL−1) in astrocytes exposed to hypoxia–reoxygenation were greater than those exposed to normoxia (16.41 (2.35) vs. 10.5 (2.13), P = 0.01). Conclusion: We conclude that decreased cerebral endothelial ICAM-1 expression in response to activated glial cell compartment by midazolam may decrease post ischaemic brain inflammation and secondary brain injury.

Keywords

INFLAMMATION, ischaemicINTERCELLULAR ADHESION MOLECULE-1MIDAZOLAMMICEASTROCYTES
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 23 , Issue 9 , September 2006 , pp. 788 - 792
Copyright
2006 European Society of Anaesthesiology

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