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Cordycepin confers neuroprotection in mice models of intracerebral hemorrhage via suppressing NLRP3 inflammasome activation

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Abstract

Neuroinflammation has been recognized as a major contributor to brain injury caused by intracerebral hemorrhage (ICH). Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome acts as an important mediator of inflammatory response in various inflammation-related diseases including hemorrhagic insults. Cordycepin has recently been shown to possess anti-inflammatory effect; however, its role and the possible underlying mechanisms in ICH remain unclear. This study was designed to investigate the neuroprotective effect of cordycepin in mice models of ICH and to elucidate the underlying molecular mechanisms. ICH was induced in male ICR mice by injecting autologous blood infusion stereotactically. Cordycepin was then given intraperitoneally (i.p.) at 30 min after ICH induction. The results demonstrated that NLRP3 inflammasome was activated and exacerbated the inflammatory progression after ICH. Cordycepin treatment significantly alleviated neurological deficits, brain edema, and perihematomal tissue damage following ICH. These changes were accompanied by downregulated NLRP3 inflammasome components expression and a reduction of production and release of inflammasome substrates interleukin-1beta (IL-1β) and interleukin-18 (IL-18). Furthermore, cordycepin ameliorated neuronal death in the perihematomal regions, accompanied by a large reduction in the expression of high-mobility group protein B 1 (HMGB1) post-ICH. In conclusion, this study provides in vivo evidence that cordycepin confers neuroprotective effect in the models of ICH, possibly through the suppression of NLRP3 inflammasome activation.

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Acknowledgements

This research was supported by the Natural Science Fund (No.14ZR1426000; 16ZR14212000) from the Science and Technology Commission of Shanghai Municipality.

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Authors and Affiliations

  1. Department of Neurosurgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China

    Yijun Cheng, Yongxu Wei, Wenlei Yang, Hanbing Shang, Zhebao Wu & Weiguo Zhao

  2. Department of Neurology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China

    Yaying Song

  3. Department of Neurosurgery, North Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201800, People’s Republic of China

    Yu Cai

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  1. Yijun Cheng
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  2. Yongxu Wei
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  3. Wenlei Yang
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  6. Yu Cai
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  7. Zhebao Wu
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Correspondence to Yu Cai, Zhebao Wu or Weiguo Zhao.

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Yijun Cheng and Yongxu Wei contributed equally to this work.

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Cheng, Y., Wei, Y., Yang, W. et al. Cordycepin confers neuroprotection in mice models of intracerebral hemorrhage via suppressing NLRP3 inflammasome activation. Metab Brain Dis 32, 1133–1145 (2017). https://doi.org/10.1007/s11011-017-0003-7

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