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

Journal of Neuroinflammation

Eun Hee Kam¹  Jeong Min Kim¹  Bon-Nyeo Koo¹  Inja Cho¹  Eun Jung Kim¹  So Yeon Kim¹  Minah Suh²  Eunji Cheong³ 

[1] Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, 03722, Seoul, Republic of Korea;Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Korea;Department of Biomedical Engineering, Sungkyunkwan University, 2066, Seobu-ro, Jangan-gu, 16419, Suwon-si, Gyeong gi-do, Republic of Korea;Center for Neuroscience Imaging Research (CNIR), Institute for Basic Science (IBS), Sungkyunkwan University, Suwon, Korea;Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, 16419, Suwon, South Korea;Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, 16419, Suwon, South Korea;Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea;

关键词: Postoperative pain;    Postoperative cognitive dysfunction;    CX3C chemokine receptor 1;    Inflammation;    GABA;    Hippocampus;   

DOI  :  10.1186/s12974-021-02150-x

来源: Springer

【 摘 要 】

BackgroundPostoperative 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.MethodsAdult (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.ResultsThe 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.ConclusionsIncreased 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.

【 授权许可】

CC BY