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Melatonin Attenuates Early Brain Injury via the Melatonin Receptor/Sirt1/NF-κB Signaling Pathway Following Subarachnoid Hemorrhage in Mice

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Abstract

Melatonin (Mel) has been reported to alleviate early brain injury (EBI) following subarachnoid hemorrhage (SAH). The activation of silent information regulator 1 (Sirt1), a histone deacetylase, has been suggested to be beneficial in SAH. However, the precise role of Sirt1 in Mel-mediated protection against EBI following SAH has not been elucidated. The present study aims to evaluate the role of melatonin receptor/Sirt1/nuclear factor-kappa B (NF-κB) in this process. The endovascular perforation SAH model was used in male C57BL/6J mice, and melatonin was administrated intraperitoneally (150 mg/kg). The mortality, SAH grade, neurological score, brain water content, and neuronal apoptosis were evaluated. The expression of Sirt1, acetylated-NF-κB (Ac-NF-κB), Bcl-2, and Bax were detected by western blot. To study the underlying mechanisms, melatonin receptor (MR) antagonist luzindole and Sirt1 small interfering RNA (siRNA) were administrated to different groups. The results suggest that Mel improved the neurological deficits and reduced the brain water content and neuronal apoptosis. In addition, Mel enhanced the expression of Sirt1 and Bcl-2 and decreased the expression of Ac-NF-κB and Bax. However, the protective effects of Mel were abolished by luzindole or Sirt1 siRNA. In conclusion, our results demonstrate that Mel attenuates EBI following SAH via the MR/Sirt1/NF-κB signaling pathway.

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Acknowledgments

This study was supported by grants from the National Natural Science Foundation of China (81222015, 81571215), the New Century Talent Supporting Project supported by Chinese Education Ministry (NCET-12-1004), and Leading Talents of Middle-Age and Young in S&T Innovation supported by Chinese Science and Technology Ministry (2013RA2181).

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Authors and Affiliations

  1. Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi’an, China

    Lei Zhao, Haixiao Liu, Liang Yue, Jingbo Zhang, Xia Li, Bodong Wang & Yan Qu

  2. Department of Scientific Research, The Fourth Military Medical University, Xi’an, China

    Yan Lin

  3. Department of Neurosurgery, Tangdu Hospital, No. 1 Xinsi Road, Xi’an, 710038, China

    Yan Qu

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  1. Lei Zhao
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  2. Haixiao Liu
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Lei Zhao, Haixiao Liu, and Liang Yue contributed equally to this work.

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Zhao, L., Liu, H., Yue, L. et al. Melatonin Attenuates Early Brain Injury via the Melatonin Receptor/Sirt1/NF-κB Signaling Pathway Following Subarachnoid Hemorrhage in Mice. Mol Neurobiol 54, 1612–1621 (2017). https://doi.org/10.1007/s12035-016-9776-7

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