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Neuroinflammation Mediated by NLRP3 Inflammasome After Intracerebral Hemorrhage and Potential Therapeutic Targets

Abstract

Intracerebral hemorrhage (ICH) is the most fatal subtype of stroke; there is still a lack of effective treatment. Microglia are a major component of the innate immune system, and they respond to acute brain injury by activating and forming classic M1-like (pro-inflammatory) or alternative M2-like (anti-inflammatory) phenotype. The existence of the polarization indicates that the role of microglia in disease’s progression and recovery after ICH is still unclear, perhaps involving microglial secretion of anti-inflammatory or pro-inflammatory cytokines and chemokines. The NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome is considered to be the main participant in neuroinflammation. Recent evidence has shown that NLRP3 inflammasome can be activated after ICH, resulting in inflammatory cascade reactions and aggravating brain injury. Furthermore, previous studies have reported that NLRP3 inflammasome is mainly present in microglia, so we speculate that its activation may be strongly associated with microglial polarization. Many scholars have investigated the role of brain injury caused by NLRP3 inflammasome after ICH, but the precise operating mechanisms remain uncertain. This review summarized the activation mechanism of NLRP3 inflammasome after ICH and the possible mechanism of NLRP3 inflammasome promoting neuroinflammation and aggravating nerve injury and discussed the relevant potential therapeutic targets.

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Acknowledgments

The support from National Natural Science Foundation of China is gratefully acknowledged.

Funding

This research was funded by the National Natural Science Foundation of China (81701243), the Natural Science Fund of Guangdong Province (2020A1515010038), the Pearl River S&T Nova Program of Guangzhou (201710010047), and the Presidential Foundation of Zhujiang Hospital of Southern Medical University (No. yzjj2018rc03).

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The work presented here was carried out in collaboration among all authors. H. S. and Q. W. conceived and designed the review; L. X., H. Z., and J. L. wrote the paper. All authors read, commented on, and approved this manuscript.

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Correspondence to Qinghua Wang or Haitao Sun.

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Xiao, L., Zheng, H., Li, J. et al. Neuroinflammation Mediated by NLRP3 Inflammasome After Intracerebral Hemorrhage and Potential Therapeutic Targets. Mol Neurobiol 57, 5130–5149 (2020). https://doi.org/10.1007/s12035-020-02082-2

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Keywords

  • NLRP3 inflammasome
  • Intracerebral hemorrhage
  • Neuroinflammation
  • Microglia