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

  • K. Ghori (a1), D. Harmon (a1), F. Walsh (a1) and G. Shorten (a1)

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.

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Corresponding author

Correspondence to: Kamran Ghori, Department of Anaesthesia and Intensive Care Medicine, Cork University Hospital, Wilton Cork, Ireland. E-mail: kamrang@hotmail.com; Tel: +353 214 546 400; Fax: +353 214 546 434

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Keywords

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

  • K. Ghori (a1), D. Harmon (a1), F. Walsh (a1) and G. Shorten (a1)

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