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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: kamrang@hotmail.com; 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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References

1.Carden, DL, Granger, DN. Pathophysiology of ischaemia-reperfusion injury. J Pathol 2000; 190: 255–266.3.0.CO;2-6>CrossRefGoogle ScholarPubMed
2.Stanimorovic, DB, Wong, J, Shapiro, A, Durkin, JP. Increase in surface expression of ICAM-1, VCAM and E-selectin in human cerebro-microvascular endothelial cells subjected to ischemia-like insults. Acta Neurochir 1997; 70: 12–16.Google Scholar
3.Neary, P, Redmond, HP. Ischaemia-reperfusion injury and the systemic inflammatory response syndrome. In: Grace, PA, Mathie, RT, eds. Ischemia-Reperfusion Injury. London: Blackwell Science, 1999: 123–136.Google Scholar
4.Wong, D, Dorovini-Zis, K. Upregulation of intercellular adhesion molocule-1 (ICAM-1) expression in primary cultures of human brain microvessel endothelial cells by cytokines and lipopolysaccharide. J Neuroimmunol 1992; 39 1–2: 11–22.CrossRefGoogle Scholar
5.Hess, DC, Zhao, W, Carroll, J, McEachin, M, Buchanan, K. Increased expression of ICAM-1 during reoxygenation in Brain Endothelial Cells. Stroke 1994; 25: 1463–1468.CrossRefGoogle ScholarPubMed
6.Bevilacqua, MP. Endothelial-leukocyte adhesion molecules. Annul Rev Immunol 1993; 11: 767–804.CrossRefGoogle ScholarPubMed
7.Reves, JG, Fragen, RJ, Vinik, HR, Granblatt, DJ. Midazolam: pharmacology and uses. Anaesthesiology 1985; 62: 310–324.CrossRefGoogle ScholarPubMed
8.Ostermann, ME, Keenan, SP, Seiferling, RA, Sibbald, WJ. Sedation in intensive care unit: a systematic review. JAMA 2000; 283 1: 1452–1459.CrossRefGoogle ScholarPubMed
9.Kellbel, Í, Weiss, M. Anaesthetics and immune function. Curr Opin Anaesthesiol 2000; 14: 685–691.CrossRefGoogle Scholar
10.Ghori, K, Harmon, D, Walsh, F, Shorten, G. Effect of midazolam in-vitro cerebral endothelial ICAM-1 expression induced by astrocyte condition media. Eur J Anaesthesiol 2006; 23: 788–792.CrossRefGoogle Scholar
11.Nishina, K, Akamatsu, H, Mikawa, K et al. . The inhibitory effects of thiopental, midazolam, and ketamine on human neutrophil functions. Anesth Analg 1998; 86: 159–165.CrossRefGoogle ScholarPubMed
12.Heller, A, Heller, S, Blecken, S, Urbaschek, R, Koch, T. Effect of intravenous anesthetics on bacterial elimination in human in-vitro. Acta Anaesthesiol Scand 1998; 42 5: 518–526.CrossRefGoogle Scholar
13.Lan, W, Harmon, D, Wang H, J, Ghori, K, Shorten, G, Redmond, HP. The effect of lidocaine on in vitro neutrophil and endothelial adhesion molecule expression induced by plasma obtained during tourniquet-induced ischaemia and reperfusion. Eur J Anaesthesiol 2004; 21 11: 892–897.CrossRefGoogle ScholarPubMed
14.Weiss, M, Mirow, N, Birkhahn, A, Schneider, M, Wernet, P. Benzodiazepines and their solvents influence neutrophil granulocyte function. Br J Anaesth 1993; 70: 317–321.CrossRefGoogle ScholarPubMed
15.Mataki, H, Inagaki, T, Yokoyama, M, Meada, S. ICAM-1 expression and cellular injury in cultured endothelial cells under hypoxia/reoxygenation. Kobe J Med Sci 1994; 40: 49–63.Google ScholarPubMed
16.Winquist, RJ, Kerr, S. Cerebral ischaemia reperfusion injury and adhesion. Neurology 1997; 40 49: 23–26.Google Scholar
17.Zhang, W, Smith, C, Howlett, C, Stanimirovic, D. Inflammatory activation of human brain endothelial cells by hypoxic astrocytes in-vitro is mediated by IL1β. J Cereb Blood Flow Metab 2000; 20 6: 967–978.CrossRefGoogle ScholarPubMed
18.Zhang, W, Smith, C, Shapiro, A et al. . Increased expression of bioactive chemokines in human cerbromicrovascular endothelial cells and astrocytes subjected to simulated ischemia in vitro. J Neuroimmunol 1999; 101 2: 148–160.CrossRefGoogle ScholarPubMed
19.Chopp, M, Zhang, RL, Chen, H, Li, Y, Jiang, N, Rusche, JR. Post ischemic administration of an anti-MAC-1 antibody reduces ischemic cell damage after transient middle cerebral artery occlusion in the rat. Stroke 1994; 25: 869–876.CrossRefGoogle Scholar
20.Goussev, AV, Zhang, ZG, Anderson, DC, Chopp, M. P-selectin antibody reduces haemorrhage and infarct volume resulting from MCA occlusion in the rat. J Neurol Sci 1998; 161 1: 16–22.CrossRefGoogle ScholarPubMed
21.Matsuo, Y, Onodera, H, Shiga, Y et al. . Role of cell adhesion molecules in brain injury after transient middle cerebral artery occlusion in rat. Brain Res 1994; 656: 344–352.CrossRefGoogle Scholar
22.Muhling, J, Gonter, J, Nickolaus, KA. Benzodiazepine receptor-dependent modulation of neutrophil (PMN) free amino- and alpha-keto acid profiles or immune functions. Amino Acid 2005; 28: 85–98.CrossRefGoogle ScholarPubMed
23.Bond, PA, Cundall, RL, Rolfe, B. [3H] Diazepam binding to human granulocytes. Life Sci 1985; 37: 11–16.CrossRefGoogle ScholarPubMed
24.Weizman, R, Gavish, M. Molecular cellular and behavioral aspects of peripheral-type benzodiazepine receptors. Clin Neuropharmacol 1993; 16 15: 401–417.CrossRefGoogle ScholarPubMed