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Necrostatin-1 Ameliorates Intracerebral Hemorrhage-Induced Brain Injury in Mice Through Inhibiting RIP1/RIP3 Pathway

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Abstract

Necroptosis is a recently discovered programmed necrosis, regulated by receptor interacting protein kinase 1 (RIP1) and RIP3 after death signal stimulation and could be specifically inhibited by necrostatin-1. The aim of this study was to investigate the role of RIP1 and RIP3 signal pathways in a mouse model of collagenase-induced intracerebral hemorrhage (ICH) and assess the effect of necrostatin-1 on brain injury after ICH. We found that RIP1 and RIP3 proteins were abundantly expressed and increased in mice brain after ICH. Necrostatin-1 pretreatment improved neurological function and attenuated brain edema in mice after ICH. Moreover, necrostatin-1 reduced RIP1–RIP3 interaction and propidium iodide (PI) positive cell death, and further inhibited microglia activation and pro-inflammatory mediator genes [tumor necrosis factor-a (TNF-α) and interleukin-1β (IL-1β)] expression after ICH. These findings indicate that RIP1/RIP3-mediated necroptosis is an important mechanism of cell death after ICH. Through inhibiting necroptosis, necrostatin-1 plays a protective role in reducing necrotic cell death after ICH. Necrostatin-1 is a promising therapeutic agent that protects cells from necroptosis and improves functional outcome.

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Acknowledgments

This work was supported by Grants from the National Natural Science Foundation of China No. 81070974 and Youth Project of Fujian Provincial Department of Health (2014-1-59). The authors would like to thank Dr. Gengbao Feng for his technical assistance.

Conflict of interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu Province, People’s Republic of China

    Xingfen Su, Handong Wang, Jianhong Zhu, Qing Sun, Tao Li & Ke Ding

  2. Department of Neurosurgery, The First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou, 350005, Fujian, People’s Republic of China

    Xingfen Su & Dezhi Kang

Authors
  1. Xingfen Su
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  2. Handong Wang
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  3. Dezhi Kang
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  4. Jianhong Zhu
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  5. Qing Sun
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  6. Tao Li
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  7. Ke Ding
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Correspondence to Xingfen Su or Handong Wang.

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Su, X., Wang, H., Kang, D. et al. Necrostatin-1 Ameliorates Intracerebral Hemorrhage-Induced Brain Injury in Mice Through Inhibiting RIP1/RIP3 Pathway. Neurochem Res 40, 643–650 (2015). https://doi.org/10.1007/s11064-014-1510-0

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  • DOI: https://doi.org/10.1007/s11064-014-1510-0

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