Research Paper Volume 14, Issue 11 pp 4714—4727

TLR3 deletion inhibits programmed necrosis of brain cells in neonatal mice with sevoflurane-induced cognitive dysfunction

Qi Zhang1,2, *, , Yanan Li1, *, , Jiaxu Yu1, , Chunping Yin1, , Junfei Guo3, , Juan Zhao4, , Qiujun Wang1, ,

  • 1 Department of Anesthesiology, The Third Hospital of Hebei Medical University, Shijiazhuang 050051, Hebei, China
  • 2 Department of Anesthesiology, Children′s Hospital of Hebei Province Affiliated to Hebei Medical University, Shijiazhuang 050031, Hebei, China
  • 3 Department of Orthopedics, The Third Hospital of Hebei Medical University, Shijiazhuang 050051, Hebei, China
  • 4 Experimental Teaching Center of Hebei Medical University, Shijiazhuang 050017, Hebei, China
* Equal contribution

Received: January 19, 2022       Accepted: May 7, 2022       Published: June 6, 2022
How to Cite

Copyright: © 2022 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


This research aimed to explore the influence of TLR deletion on sevoflurane-induced postoperative cognitive dysfunction in neonatal mice. Herein, WT and TLR3 KO neonatal mice, each with 24, were randomly divided into control group, sevoflurane group, and TLR3−/−+sevoflurane group. The hippocampal neurons of WT, TLR3 KO and RIP3 KO neonatal mice in C group, SEV group, TLR3−/−+SEV group and RIP3−/−+SEV group were extracted for in vitro experiments. The results revealed the degeneration and necrosis of nerve cells in SEV group. Microscopic findings indicated that nerve cells showed shrinkage and nuclear hyperchromatism, along with lessening or even disappearance of nuclei and enlargement of cell spaces, and apoptotic cells in the brain tissues were evidently increased. Compared with SEV group, TLR3−/−+SEV group displayed reductions in these phenomena. Additionally, SEV group showed the reduced SHP2 expression and the increased expressions of proteins associated with TLR signaling pathway and apoptosis. Furthermore, there were no obvious differences in the expressions of such proteins in hippocampal neurons between RIP3−/−+SEV and TLR3−/−+SEV groups. The results confirmed that inhibiting RIP3 phosphorylation and suppressing TLR3 expressions exerted the same influence on the expressions of these proteins in the hippocampus of neonatal mice with sevoflurane-induced cognitive dysfunction. Based on these, it is speculated that TLR3 influences neonatal mice with sevoflurane-induced cognitive dysfunction probably by regulating RIP3 phosphorylation.


TLR: toll-like receptor; WT: wild-type; KO: knockout; C group: control group; SEV group: sevoflurane group; TLR3−/−+SEV group: TLR3−/−+sevoflurane group; RIP3: receptor-interacting protein 3; SHP2: Src homology region 2 domain-containing phosphatase-2; TRIF: TIR-domain-containing adapter-inducing interferon-β; p-RIP3: phosphorylated RIP3; CaMKII: calcium/calmodulin-dependent protein kinase II; NLRP3: nucleotide-binding oligomerization domain-like receptor protein 3; GSDMD: gasdermin D; Caspase: cysteinyl aspartate specific proteinase.