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Neuroprotective Effects of Dexmedetomidine Against Hypoxia-Induced Nervous System Injury are Related to Inhibition of NF-κB/COX-2 Pathways

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Abstract

Dexmedetomidine has been reported to provide neuroprotection against hypoxia-induced damage. However, the underlying mechanisms remain unclear. We examined whether dexmedetomidine’s neuroprotective effects were mediated by the NF-κB/COX-2 pathways. Adult male C57BL/6 mice were subjected to a 30-min hypoxic treatment followed by recovery to normal conditions. They received dexmedetomidine (16 or 160 μg/kg) or 25 mg/kg atipamezole, an α2-adrenoreceptor antagonist, intraperitoneally before exposure to hypoxia. The whole brain was harvested 6, 18, or 36 h after the hypoxia to determine the histopathological outcome and cleaved caspase-3, Bax/Bcl, NF-κB, and COX-2 levels. Hypoxia treatment induced significant neurotoxicity, including destruction of the tissue structure and upregulation of the protein levels of caspase-3, the ratio of Bax/Bcl-2, NF-κB, and COX-2. Dexmedetomidine pretreatment effectively improved histological outcome and restored levels of caspase-3, the Bax/Bcl-2 ratio, NF-κB, and COX-2. Atipamezole reversed the neuroprotection induced by dexmedetomidine. Neuroprotection was achieved by PDTC and NS-398, inhibitors of NF-κB and COX-2, respectively. Dexmedetomidine use before hypoxia provides neuroprotection. Inhibition of NF-κB/COX-2 pathways activation may contribute to the neuroprotection of dexmedetomidine.

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Acknowledgments

Supported by grant 2012B031800289 from the science and technology plan projects of Guangdong Province (to Dr. L-Q Mo).

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Authors and Affiliations

  1. Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, No. 58, Zhongshan 2nd Road, Guangzhou, 510080, China

    Wanying Pan, Lin Lin, Nan Zhang, Fuli Yuan, Xiaoxiao Hua, Yueting Wang & Liqiu Mo

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  1. Wanying Pan
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  2. Lin Lin
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Correspondence to Liqiu Mo.

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Pan, W., Lin, L., Zhang, N. et al. Neuroprotective Effects of Dexmedetomidine Against Hypoxia-Induced Nervous System Injury are Related to Inhibition of NF-κB/COX-2 Pathways. Cell Mol Neurobiol 36, 1179–1188 (2016). https://doi.org/10.1007/s10571-015-0315-2

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