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The effect of midazolam on cerebral endothelial (P-selectin and ICAM-1) adhesion molecule expression during hypoxia-reperfusion injury in vitro

Published online by Cambridge University Press:  01 March 2008

K. Ghori ,
D. Harmon ,
W. Lan ,
P. Seigne ,
F. Walsh  and
G. D. 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
W. Lan
Affiliation:
Cork University Hospital and University College Cork, Department of Anaesthesia and Intensive Care Medicine, Cork, Ireland
P. Seigne
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. D. Shorten
Affiliation:
Cork University Hospital and University College Cork, Department of Anaesthesia and Intensive Care Medicine, Cork, Ireland
*
Correspondence to: Kamran Ghori, Department of Anaesthesia and Intensive Care Medicine, Cork University Hospital, Wilton Cork, Ireland. E-mail: [email protected]; Tel: +353 214922135; Fax: +353 214546434
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Summary

Background and objective

Hypoxia-reperfusion injury is an important determinant of secondary brain injury. In the acute phase of cerebral reperfusion, pro-inflammatory events enhance expression of cerebral endothelial (intercellular adhesion molecule-1 and P-selectin) adhesion molecules, which play an important role in brain hypoxia-reperfusion injury. Midazolam is the most commonly used sedative in patients with brain injury. The objective of this investigation was to examine the effect of midazolam on the expression of cerebral endothelial intercellular adhesion molecule-1 and P-selectin during hypoxia-reperfusion injury invitro.

Methods

The up-regulation of mouse cerebral endothelial cells intercellular adhesion molecule-1 and P-selectin was assessed following hypoxia-reoxygenation (hypoxia-reperfusion). Cells were pre-treated with three different concentrations of midazolam (0, 5 and 50 μg mL−1) prior to hypoxia. Flow cytometry was used to estimate adhesion molecule expression mean channel fluorescence. Data are presented as mean ± SD.

Results

Mouse cerebral endothelial cell intercellular adhesion molecule-1 and P-selectin expression was greater after exposure to hypoxia-reoxygenation compared to normoxia (mean channel fluorescence) 241 ± 12 vs. 140 ± 7 and 120 ± 14 vs. 46 ± 7, respectively, P < 0.05. Intercellular adhesion molecule-1 and P-selectin expression was decreased by midazolam (5 μg mL−1) pre-incubation compared to control, mean channel fluorescence 184 ± 10 vs. 241 ± 12 and 51 ± 7 vs. 120 ± 14, respectively, P < 0.05. Midazolam at 50 μg mL−1 had the same effect as 5 μg mL−1.

Conclusion

Pre-treatment with midazolam diminishes increased expression of cerebral endothelial intercellular adhesion molecule-1 and P-selectin expression following hypoxia-reoxygenation.

Keywords

HYPOXIA ISCHAEMIABRAINMIDAZOLAMENDOTHELIUMNEUTROPHILS
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 25 , Issue 3 , March 2008 , pp. 206 - 210
Copyright
Copyright © European Society of Anaesthesiology 2008

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