» Articles » PMID: 36138980

IL-33 Alleviates Postoperative Cognitive Impairment by Inhibiting Hippocampal Inflammation and Upregulating Excitatory Synaptic Number in Aged Mice

Overview
Journal Brain Sci
Publisher MDPI
Date 2022 Sep 23
PMID 36138980
Authors
Affiliations
Soon will be listed here.
Abstract

Delayed neurocognitive recovery (dNCR), a postoperative complication that occurs in elderly patients, still lacks effective treatment. Interleukin-33 (IL-33) has been proved to modulate neuroinflammation and synaptic plasticity, among other effects, but the role of IL-33 in dNCR is not clear. We established a dNCR model in aged mice by laparotomy under sevoflurane anesthesia. Cognition was evaluated by Morris water maze (MWM) and fear conditioning test (FCT). Immunofluorescence was used to detect the density of IL-33 and glial fibrillary acidic protein (GFAP) co-localization, ionized calcium-binding adapter molecule 1, vesicular glutamate transporter 1 (vGlut1) and postsynaptic density protein-95 (PSD95) co-localization in the hippocampus. IL-33, GFAP, vGlut1 and PSD95 were tested by Western blotting. Enzyme-linked immunosorbent assay was used to detect the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and IL-10. Surgery/anesthesia reduced the level of IL-33 in the hippocampus. Intraperitoneal injection of 200 ng IL-33 per mouse significantly decreased the latency to the platform and increased the number of platform crossings and the target quadrant dwell time in MWM, while increasing the freezing time in the context test of FCT. Furthermore, IL-33 inhibited microglial activation and the release of TNF-α and IL-1β while upregulating the markers of excitatory synapses vGlut1 and PSD95. Our findings indicated that IL-33 improved cognition by inhibiting the hippocampal inflammatory response and upregulating the number of excitatory synapses. Therefore, IL-33 is a potential drug for the treatment of dNCR.

Citing Articles

Nanoarchitectonics of tannic acid based injectable hydrogel regulate the microglial phenotype to enhance neuroplasticity for poststroke rehabilitation.

Liu Z, Zhang S, Ran Y, Geng H, Gao F, Tian G Biomater Res. 2023; 27(1):108.

PMID: 37908012 PMC: 10617113. DOI: 10.1186/s40824-023-00444-0.


Siglec-E Ligand Downregulation on Hippocampus Neurons Induced Inflammation in Sevoflurane-Associated Perioperative Neurocognitive Disorders in Aged Mice.

Zhang X, Wang X, Xu Z, Sun F, Jia Y, Tian Y Inflammation. 2023; 47(1):30-44.

PMID: 37603227 DOI: 10.1007/s10753-023-01888-1.

References
1.
Yasuoka S, Kawanokuchi J, Parajuli B, Jin S, Doi Y, Noda M . Production and functions of IL-33 in the central nervous system. Brain Res. 2011; 1385:8-17. DOI: 10.1016/j.brainres.2011.02.045. View

2.
Deiner S, Silverstein J . Postoperative delirium and cognitive dysfunction. Br J Anaesth. 2009; 103 Suppl 1:i41-46. PMC: 2791855. DOI: 10.1093/bja/aep291. View

3.
Newman S, Stygall J, Hirani S, Shaefi S, Maze M . Postoperative cognitive dysfunction after noncardiac surgery: a systematic review. Anesthesiology. 2007; 106(3):572-90. DOI: 10.1097/00000542-200703000-00023. View

4.
Vorhees C, Williams M . Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc. 2007; 1(2):848-58. PMC: 2895266. DOI: 10.1038/nprot.2006.116. View

5.
Khodadadi H, Lopes Salles E, Jarrahi A, Costigliola V, Khan M, Yu J . Cannabidiol Ameliorates Cognitive Function via Regulation of IL-33 and TREM2 Upregulation in a Murine Model of Alzheimer's Disease. J Alzheimers Dis. 2021; 80(3):973-977. DOI: 10.3233/JAD-210026. View