IL-33/ST2 axis promotes remodeling of the extracellular matrix and drives protective microglial responses in the mouse model of perioperative neurocognitive disorders

  • Int Immunopharmacol. 2022 Nov 26;114:109479. doi: 10.1016/j.intimp.2022.109479.
Shuming Li  1 ,  Huan Liu  1 ,  Yue Qian  1 ,  Linhao Jiang  2 ,  Shuai Liu  1 ,  Yanling Liu  3 ,  Cihang Liu  4 ,  Xiaoping Gu  5
Affiliations
  • 1. Department of Anesthesiology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China.
  • 2. Medical School, Nanjing University, Nanjing, China.
  • 3. Medical School, Southeast University, Nanjing, China.
  • 4. Department of Anesthesiology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China. Electronic address: [email protected].
  • 5. Department of Anesthesiology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China. Electronic address: [email protected].
PMID: 36446234 DOI: 10.1016/j.intimp.2022.109479
Abstract

Anesthesia and surgery induce cognitive impairment via uncertain mechanisms. Increasing evidence has suggested that microglial activity mediated by IL-33 /ST2 plays a critical role in immune regulation and inflammatory responses. Yet, the implications for microglia activity mediated by IL-33 in perioperative neurocognitive disorders (PND) are not well established. We showed that IL-33 and ST2 were downregulated in the hippocampus after anesthesia and surgery, and the expression of aggrecan, remodeling by microglia, was upregulated. Meanwhile, the expression of pro-inflammatory cytokines (IL-6 and IL-1β) and M1-like microglia marker (iNOS) increased, and the expression of M2-like microglia marker (CD206) decreased. Notably, the administration of IL-33 attenuated neuroinflammation and shifted the polarization of microglia in the hippocampus after anesthesia and surgery. Furthermore, IL-33 treatment rescued the increase of aggrecan, loss of dendritic spines, and impairment of LTP, improving cognitive performance. In conclusion, our study suggests that microglia activity mediated by IL-33/ST2 plays a vital role in cognitive impairments after anesthesia and surgery, which may serve as a therapeutic target for PND.

Keywords
Extracellular matrix; IL-33; Microglia; Neuroinflammation; Perioperative neurocognitive disorders.
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