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Orthopedic surgery-induced cognitive dysfunction is mediated by CX3CL1/R1 signaling

 Inja Cho  ;  Jeong Min Kim  ;  Eun Jung Kim  ;  So Yeon Kim  ;  Eun Hee Kam  ;  Eunji Cheong  ;  Minah Suh  ;  Bon-Nyeo Koo 
 JOURNAL OF NEUROINFLAMMATION, Vol.18(1) : 94, 2021-04 
Journal Title
Issue Date
CX3C chemokine receptor 1 ; GABA ; Hippocampus ; Inflammation ; Postoperative cognitive dysfunction ; Postoperative pain
Background: Postoperative pain is a common phenomenon after surgery and is closely associated with the development of postoperative cognitive dysfunction (POCD). Persistent pain and systemic inflammation caused by surgery have been suggested as key factors for the development of POCD. Fractalkine (CX3CL1) and its receptor, the CX3C chemokine receptor 1 (CX3CR1), are known to play a key role in pain and inflammation signaling pathways. Recent studies have shown that the regulation of CX3CR1/L1 signaling influences the development of various diseases including neuronal diseases. We determined whether CX3CR1/L1 signaling is a putative therapeutic target for POCD in a mouse model.

Methods: Adult (9-11 weeks) male mice were treated with neutralizing antibody to block CX3CR1/L1 signaling both before and after surgery. Inflammatory and behavioral responses including pain were assessed postoperatively. Also, CX3CR1 mRNA level was assessed. Hippocampal astrocyte activation, Mao B expression, and GABA expression were assessed at 2 days after surgery following neutralizing antibody administration.

Results: The behavioral response indicated cognitive dysfunction and development of pain in the surgery group compared with the control group. Also, increased levels of pro-inflammatory cytokines and CX3CR1 mRNA were observed in the surgery group. In addition, increased levels of GABA and increased Mao B expression were observed in reactive astrocytes in the surgery group; these responses were attenuated by neutralizing antibody administration.

Conclusions: Increased CX3CR1 after surgery is both necessary and sufficient to induce cognitive dysfunction. CX3CR1 could be an important target for therapeutic strategies to prevent the development of POCD.
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1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
Yonsei Authors
Koo, Bon-Nyeo(구본녀) ORCID logo https://orcid.org/0000-0002-3189-1673
Kim, So Yeon(김소연) ORCID logo https://orcid.org/0000-0001-5352-157X
Kim, Eun Jung(김은정) ORCID logo https://orcid.org/0000-0002-5693-1336
Kim, Jeongmin(김정민) ORCID logo https://orcid.org/0000-0002-0468-8012
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