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Sevoflurane-induced delayed neuroprotection involves mitoKATP channel opening and PKC ε activation

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Abstract

There is an increasing body of evidence that a brief exposure to anesthesia induces ischemic tolerance in rat brain (anesthetic preconditioning). However, it is unknown whether preconditioning with sevoflurane, a commonly used volatile anesthetic in current clinical practice, produces a delayed window of neuroprotection against ischemia and what the mechanisms are for this protection. To address these issues, adult male Sprague–Dawley rats were subjected to middle cerebral arterial occlusion (MCAO) for 2 h. Sevoflurane preconditioning was induced 24 h before brain ischemia by exposing the animals to sevoflurane at 1.0 minimum alveolar concentration (2.4%) in oxygen for 60 min. Animals preconditioned with sevoflurane had lower neurological deficit scores and smaller brain infarct volumes than animals with brain ischemia at 6 and 24 h after MCAO, respectively. Application of a selective antagonist for mitochondrial ATP-sensitive potassium (mitoKATP) channel, 5-hydroxydecanoate (5-HD, 40 mg/kg i.p.) 30 min before sevoflurane exposure attenuated this beneficial effect. Moreover, protein kinase C ε (PKC ε) was translocated to the membrane fraction at 6 h, but not 24 h, after brain reperfusion in animals preconditioned with sevoflurane and this effect was also abolished by 5-HD. We concluded that sevoflurane preconditioning induces a delayed neuroprotection and that mitochondrial KATP channels and PKC ε may be involved in this neuroprotection.

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Abbreviations

MitoKATP channel:

Mitochondrial ATP-sensitive potassium channel

PKC ε:

Protein kinase C epsilon

5-HD:

5-Hydroxydecanoate

MCAO:

Middle cerebral artery occlusion

IPC:

Ischemic preconditioning

VAPC:

Volatile anesthetic preconditioning

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Authors and Affiliations

  1. Department of Anesthesiology, The Affiliated Xiangya Hospital of Center South University, Changsha, 410078, Hunan, China

    Zhi Ye, E. Wang & Qu-lian Guo

  2. Department of Neurosurgery, Affiliated Xiangya Hospital of Center South University, Changsha, 410078, Hunan, China

    Yue-ming Huang

  3. Department of Anesthesiology, Health System Center of University of Virginia, Charlottesville, VA, USA

    Zhi-yi Zuo

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  1. Zhi Ye
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  2. Yue-ming Huang
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Correspondence to Qu-lian Guo.

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Ye, Z., Huang, Ym., Wang, E. et al. Sevoflurane-induced delayed neuroprotection involves mitoKATP channel opening and PKC ε activation. Mol Biol Rep 39, 5049–5057 (2012). https://doi.org/10.1007/s11033-011-1290-4

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  • DOI: https://doi.org/10.1007/s11033-011-1290-4

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