Journal Article

Differential General Anesthetic Effects on Microglial Cytokine Expression

Lian, Qingquan, Pan, Jonathan Z., Eckenhoff, Roderic G., Eckenhoff, Maryellen F., Ye, Xuefei

2013

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Activation / Alzheimer Disease - metabolism / Alzheimer Disease - pathology / Alzheimer's disease / Anesthesia / Anesthesiology / Anesthetics / Biology / Cell culture / Cell survival / Cells, Cultured / Central nervous system / Clinical trials / Cognitive ability / Cognitive disorders / Critical care / Cytokines / Cytokines - metabolism / Gene Expression Regulation - drug effects / Humans / Inflammation / Inflammation - drug therapy / Inflammation - metabolism / Isoflurane / Isoflurane - pharmacology / L-Lactate dehydrogenase / Lactate dehydrogenase / Lactic acid / Lipids / Lipopolysaccharides / Lipopolysaccharides - pharmacology / Lysates / Male / Medicine / Methyl Ethers - pharmacology / Microglia / Microglia - drug effects / Microglia - metabolism / Mitogens / Nervous system diseases / Neurodegenerative diseases / Neurological diseases / Neurons - drug effects / Neurons - metabolism / Neurons - pathology / Nitric Oxide - metabolism / Propofol / Propofol - pharmacology / Sevoflurane / Surgery / Tumor necrosis factor-TNF / Variance analysis