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Mild Hypothermia Protects Brain Injury After Intracerebral Hemorrhage in Mice Via Enhancing the Nrdp1/MyD88 Signaling Pathway

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Abstract

Background

Mild hypothermia has been identified to reduce brain injury following intracerebral hemorrhage (ICH) by protecting neuron cells through several pathways. However, the role of hypothermia in brain function following ICH and the related mechanisms have not been well identified. Ubiquitination-mediated inflammation plays important roles in the pathogenesis of immune diseases. The experiment analyzed anti-inflammatory effects of mild hypothermia following ICH.

Methods

The model of ICH was induced by injecting autologous blood. Neuregulin receptor degradation protein-1 (Nrdp1) and downstream molecule were analyzed. In addition, brain inflammatory response, brain edema, and neurological functions of ICH mice were also assessed.

Results

We found that mild hypothermia attenuated proinflammatory factors production after ICH. Mild hypothermia significantly inhibited BBB injury, water content, and neurological damage following ICH in vivo. Moreover, mild hypothermia also increased Nrdp1/MyD88 levels and thus affect neuronal apoptosis and inflammation.

Conclusions

Taken together, these results suggest that mild hypothermia can attenuate the neuroinflammatory response and neuronal apoptosis after ICH through the regulation of the Nrdp1 levels.

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Funding

The study was supported by the National Natural Science Foundation of China (NSFC No. 81870962), KJQN202000419, cstc2021jcyj-msxm X0552, cstc2021jcyj-msxm X0709 and 2018ZDXM009.

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Author notes

  1. Changlong Zhou and Jinping Wang contributed equally to this study and were regarded as co-first authors.

Authors and Affiliations

  1. Department of Neurosurgery, Yongchuan Hospital, Chongqing Medical University, Chongqing, 402160, China

    Changlong Zhou, Gaohai Shao, Xiaohui Xia, Lirong Wu & Zhao Yang

  2. Department of Neurology, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing, 400014, China

    Jinping Wang

  3. Department of Emergency, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, China

    Anyong Yu

Authors
  1. Changlong Zhou
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  2. Jinping Wang
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  3. Gaohai Shao
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  4. Xiaohui Xia
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  5. Lirong Wu
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  6. Anyong Yu
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  7. Zhao Yang
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Correspondence to Anyong Yu or Zhao Yang.

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All animals received care in compliance with the Principles of Laboratory Animal Care and National Standards.

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Zhou, C., Wang, J., Shao, G. et al. Mild Hypothermia Protects Brain Injury After Intracerebral Hemorrhage in Mice Via Enhancing the Nrdp1/MyD88 Signaling Pathway. Neurotox Res 40, 1664–1672 (2022). https://doi.org/10.1007/s12640-022-00576-6

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  • DOI: https://doi.org/10.1007/s12640-022-00576-6

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