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.
Bibliographical noteFunding Information:
This work was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (NRF-2017R1A2B4009478 to B-N Koo, NRF-2020R1A2C1012017 to M Suh).
© 2021, The Author(s).
All Science Journal Classification (ASJC) codes
- Cellular and Molecular Neuroscience