[Frontiers in Bioscience E3, 604-615, January 1, 2011]

[Frontiers in Bioscience E3, 604-615, January 1, 2011]

Sevoflurane preconditioning confers neuroprotection via anti-inflammatory effects

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

1 State Key Laboratory of Medical Neurobiology and Department of Anesthesiology of Huashan Hospital, Fudan University, 138 Yixueyuan Road, Shanghai, China, 200032, ²Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Materials and Methods: 3.1. Animal model of transient focal cerebral ischemia; 3.2. Measurement of infarct volume; 3.3. Assessment of neurological deficits; 3.4. Experimental groups; 3.5. Western blots; 3.6. ELISA; 3.7. Immunofluorescence staining; 3.8. RNA isolation; 3.9. Semi-quantitative real-time RT-PCR; 3.10. Intracerebroventricular injection; 3.11. Statistical analysis
4. Results: 4.1. Physiological variables; 4.2. Sevoflurane preconditioning induced tolerance against focal cerebral ischemia; 4.3. Sevoflurane preconditioning suppressed inflammatory factors after MCAO; 4.4. NF-kappa B was associated with sevoflurane preconditioning-mediated neuroprotection; 4.5. Sevoflurane preconditioning directly attenuated inflammation after MCAO; 4.6. p38 MAPK was involved in neuroprotection induced by sevoflurane preconditioning
5. Discussion
6. Acknowledgements
7. References

1. ABSTRACT

Neuroprotection afforded by volatile anesthetic preconditioning (APC) has been demonstrated in both in vivo and in vitro experiments, yet the underlying mechanism is poorly understood. We therefore investigated whether suppression of p38 MAPK, NF-kappa B and the downstream pro-inflammatory signaling cascade contribute to sevoﬂurane APC-induced neuroprotection. Male Sprague-Dawley rats were exposed for 30min/day on 4 consecutive days to ambient air or to sevoflurane (1.2% or 2.4%). Then rats were subjected to filament occlusion of the middle cerebral artery (MCAO) for 60 min, and euthanized 3 days after MCAO for measuring infarct volume. APC with sevoﬂurane markedly improved neurological performance of stroke rats, significantly decreased infarct volume, and robustly suppressed activation of NF-kappa B and p38 MAPK, and expression of inflammatory cytokines. Furthermore, APC with sevoﬂurane showed a direct inflammation-suppressing effect in rat brain receiving intracerebroventricular infusion of a dose of LPS that doesn't cause overt brain damage. Thus, the data suggest that APC with sevoflurane confers neuroprotection against focal ischemic brain injury, at least in part, by the anti-inflammatory effects of sevoflurane.