Differential General Anesthetic Effects on Microglial Cytokine Expression

Post-operative cognitive dysfunction has been widely observed, especially in older patients. An association of postoperative 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.