Differential effects of propofol and dexmedetomidine on neuroinflammation induced by systemic endotoxin lipopolysaccharides in adult mice

• Published in: Neuroscience letters 2019-08, Vol.707, p.134309-134309, Article 134309
• Main Authors: Huang, Chunxia, Ng, Olivia Tsz-Wa, Chu, John Man-Tak, Irwin, Michael Garnet, Hu, Xianwen, Zhu, Shoufeng, Chang, Raymond Chuen-Chung, Wong, Gordon Tin-Chun
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - pharmacology; Antioxidants - therapeutic use; Brain - drug effects; Brain - metabolism; Brain - pathology; Cognition Disorders - chemically induced; Cognition Disorders - drug therapy; Cognitive dysfunction; Dexmedetomidine; Dexmedetomidine - pharmacology; Dexmedetomidine - therapeutic use; Hippocampus - drug effects; Hippocampus - metabolism; Hypnotics and Sedatives - pharmacology; Hypnotics and Sedatives - therapeutic use; Inflammation - chemically induced; Inflammation - drug therapy; Inflammation - metabolism; Interleukin-1beta - metabolism; Lipopolysaccharides - pharmacology; Male; Maze Learning - drug effects; Mice, Inbred C57BL; Microglia - drug effects; Microglia - metabolism; Neuroinflammation; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Oxidative stress; Propofol; Propofol - pharmacology; Propofol - therapeutic use; Rotarod Performance Test; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2019.134309

•Systemic lipopolysaccharide (LPS) produces cognitive impairment, neuroinflammation and an increase in oxidative stress in the hippocampus.•Dexmedetomidine reduces LPS induced inflammation and oxidative stress without improving cognition.•Propofol decreases microglia activation in the hippocampus following LPS without improving cognition.•The inability of demedetomidine to improve LPS induced cognitive dysfunction may be due to residual inhibition of glutamate neurotransmission.•The inability propofol to improve LPS induced cognitive dysfunction may be due to residual elevation of hippocampal oxidative stress. Propofol and dexmedetomidine are commonly used in clinical situations where neuroinflammation may be imminent or even established but comparative data on their effects on neuroinflammatory and cognitive parameters are lacking. Using a murine model of neuroinflammation induced by systemic lipopolysaccharide (LPS), this study compared the effects of these two agents on cognitive function, neuroinflammatory parameters, oxidative stress and neurotransmission. Male adult C57BL/6 N mice were anaesthetised with propofol or dexmedetomidine prior to intraperitoneal injection of LPS. Cognitive and motor function were assessed by the Y-maze and Rotarod tests respectively. Inflammatory responses were evaluated by relative levels of cytokine mRNA and immunoreactivity of glia cells. LPS caused a marked elevation in IL-1β and TNF-α levels both peripherally and in the brain, together with microglia activation (p