Dexmedetomidine inhibits inflammatory reaction in the hippocampus of septic rats by suppressing NF-κB pathway

• Published in: PloS one Vol. 13; no. 5; p. e0196897
• Main Authors: Zhang, Xiaobao, Yan, Fang, Feng, Jiying, Qian, Haitao, Cheng, Zhi, Yang, Qianqian, Wu, Yong, Zhao, Zhibin, Li, Aimin, Xiao, Hang
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03.05.2018; Public Library of Science (PLoS)
• Subjects: Anesthesia; Anesthesiology; Animal cognition; Animals; Anti-Inflammatory Agents - pharmacology; Biology and Life Sciences; Brain; Brain research; Central nervous system; Cognitive ability; Cytokines; Dexmedetomidine - pharmacology; Disease Models, Animal; Drug Synergism; Enzyme-linked immunosorbent assay; Experiments; Gene Expression Regulation; Hippocampus; Hippocampus - drug effects; Hippocampus - immunology; Hippocampus - pathology; Inflammation; Injections, Intraperitoneal; Interleukin 6; Interleukin-6 - antagonists & inhibitors; Interleukin-6 - genetics; Interleukin-6 - immunology; Ischemia; Laboratory animals; Lipopolysaccharides; Medical research; Medicine and Health Sciences; Neurodegeneration; Neuroprotection; Neuroprotective Agents - pharmacology; Neurosciences; NF-kappa B - antagonists & inhibitors; NF-kappa B - genetics; NF-kappa B - immunology; NF-κB protein; Proline - analogs & derivatives; Proline - pharmacology; Rats; Rats, Sprague-Dawley; Research and Analysis Methods; Rodents; Sepsis - chemically induced; Sepsis - drug therapy; Sepsis - immunology; Sepsis - pathology; Signal Transduction; Thiocarbamates - pharmacology; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - immunology; Tumor necrosis factor-α; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0196897

Dexmedetomidine (DEX) is known to provide neuroprotective effect in the central nervous system. However, the detailed mechanism remains far more elusive. This study was designed to investigate the relevant mechanisms of DEX's neuroprotective effect. Sprague-Dawley (SD) rats were injected with dexmedetomidine and/or Lipopolysaccharide (LPS) intraperitoneally, and inflammatory cytokines in serum and in the hippocampus were measured by enzyme linked immunosorbent assay (ELISA). NF-κB in the brain tissue extracts was analyzed with western-blot. Then, we investigated whether NF-κB inhibitor prevents the elevation of inflammatory cytokines in rats injected with LPS. Our results indicated that compared with the control group, the rats exposed to LPS showed significant cognitive dysfunction. When compared to controls, the levels of TNF-α and IL-6 in the serum and hippocampus homogenate were increased in rats treated with LPS. DEX pretreatment inhibited the rats' TNF-α, IL-6 and NF-κB levels induced by LPS. In response to LPS, PDTC pretreatment restrains the production of proinflammatory cytokines (TNF-α and IL-6). Rats treated with PDTC and DEX alongside LPS exhibited less TNF-α and IL-6 than the LPS treated group. In combination, PDTC and DEX showed addictive effects. Our data suggest that DEX exerts a neuroprotective effect through NF-κB in part after LPS-induced cognitive dysfunction.