title: Differential general anesthetic effects on microglial cytokine expression.
abstract: Post-operative cognitive dysfunction has been widely observed, especially in older patients. An association of post-operative cognitive dysfunction with the neurodegenerative diseases, such as Alzheimer's disease, has been suggested. Neuroinflammation contributes to Alzheimer pathology, through elevated pro-inflammatory cytokines and microglial activation in the CNS leading to neuronal damage, synaptic disruption and ultimately cognitive dysfunction. We compare the effects of three different, clinically-used, anesthetics on microglial activation with, and without, the prototypical inflammatory trigger, lipopolysaccharide (LPS). Microglial BV-2 cell cultures were first exposed to isoflurane, sevoflurane (each at 2 concentrations) or propofol for 6 h, and cytokine levels measured in lysates and media. The same experiments were repeated after 1 h LPS pre-treatment. We found; 1) anesthetics alone have either no or only a small effect on cytokine expression; 2) LPS provoked a large increase in microglia cytokine expression; 3) the inhaled anesthetics either had no effect on LPS-evoked responses or enhanced it; 4) propofol nearly eliminated the LPS pro-inflammatory cytokine response and improved cell survival as reflected by lactate dehydrogenase release. These data suggest that propofol may be a preferred anesthetic when it is desirable to minimize neuroinflammation.
authors: Department of Anesthesiology and Critical Care, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Xuefei
authors: X
authors: Ye
authors: Qingquan
authors: Q
authors: Lian
authors: Maryellen F
authors: MF
authors: Eckenhoff
authors: Roderic G
authors: RG
authors: Eckenhoff
authors: Jonathan Z
authors: JZ
authors: Pan
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000777:Anesthetics; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D007530:Isoflurane / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009569:Nitric Oxide / Q000378:metabolism; D015742:Propofol / Q000494:pharmacology; D000077149:Sevoflurane
chemical_list: D000777:Anesthetics; D016207:Cytokines; D008070:Lipopolysaccharides; D008738:Methyl Ethers; D009569:Nitric Oxide; D000077149:Sevoflurane; D007530:Isoflurane; D015742:Propofol
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