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


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 microg 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 microg 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 microg mL(-1) had the same effect as 5 microg mL(-1).


CONCLUSIONS
Pre-treatment with midazolam diminishes increased expression of cerebral endothelial intercellular adhesion molecule-1 and P-selectin expression following hypoxia-reoxygenation.
Ghori
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Cork University Hospital and University College Cork, Department of Anaesthesia and Intensive Care Medicine, Cork, Ireland. kamrang@hotmail.com
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D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005434:Flow Cytometry; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D002534:Hypoxia, Brain / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D051379:Mice; D008874:Midazolam / Q000494:pharmacology*; D019007:P-Selectin / Q000378:metabolism*; D015424:Reperfusion; D015427:Reperfusion Injury / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D006993:Hypnotics and Sedatives; D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1; D008874:Midazolam