[Frontiers in Bioscience E3, 978-988, June 1, 2011]

[Frontiers in Bioscience E3, 978-988, June 1, 2011]

Sevoflurane preconditioning protects blood-brain-barrier against brain ischemia

Qiong Yu¹, Min Chu¹, Hailian Wang¹, Shiduo Lu¹, Hui Gao¹, Peiying Li¹, Yu Gan^1,2, Hong Shi¹, Weimin Liang¹, Jun Chen^1,2, Yanqin Gao¹

1Department of Anesthesiology of Huashan Hospital, State Key Laboratory of Medical Neurobiology, and Institute of Brain Science, Fudan University, Shanghai, China, ²Department of Neurology and Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Materials and methods: 3.1. Experimental groups and sevoflurane preconditioning; 3.2. Animal model of transient focal cerebral ischemia; 3.3. Measurement of evans blue extravasation; 3.4. Electron microscopy; 3.5. Assessment of neurological deficits; 3.6. Western blotting; 3.7. Gelatin zymography; 3.8. Immunofluorescence staining; 3.9. Statistical analysis
4. Results: 4.1. Physiological variables; 4.2. Sevoflurane preconditioning improved BBB integrity after MCAO; 4.3. Sevoflurane preconditioning inhibited the activation of astrocytes and microglia cells; 4.4. Sevoflurane preconditioning suppressed up-regulation of cell adhesion molecules; 4.5. Sevoflurane preconditioning inhibited up-regulation of matrix metalloproteinases and tissue inhibitor of matrix metalloproteinases 4.6. Sevoflurane preconditioning suppressed decreases in occludin
5. Discussion
6. Acknowledgements
7. References

1. ABSTRACT

Sevoflurane preconditioning has recently been demonstrated to protect ischemic brain in vivo and in vitro. However, mechanisms underlying this neuroprotection have not been delineated. We therefore assessed the hypothesis that sevoflurane pretreatment protected blood-brain-barrier (BBB) via suppression of cell adhesion molecules (CAMs) and matrix metalloproteinases (MMPs) after ischemia. Repeated sevoflurane preconditioning was administered 24 hours before transient middle cerebral artery occlusion (MCAO). Neurologic deficits and expression of CAMs, MMPs and occludin were examined up to 3 days after ischemia. Evans blue (EB) extravasation and electron microscopy was detected at 2 days after ischemia. The data showed that sevoflurane pretreatment markedly improved BBB integrity and neurological outcomes after ischemia, robustly suppressed ischemia-induced decreases of occludin and increases of intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), MMP-2, MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1). Sevoflurane pretreatment also suppressed the activation of astrocytes and microglias in ipsilateral cortex and corpus callosum. In conclusion, repeated sevoflurane preconditioning confered potent protection against brain ischemia, partly by improving BBB integrity.