• Niccolò Terrando, Claudia Monaco, Daqing Ma, Brian M J Foxwell, Marc Feldmann, and Mervyn Maze.
• Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA 94143-0648, USA.
• Proc. Natl. Acad. Sci. U.S.A. 2010 Nov 23;107(47):20518-22.

AbstractCognitive decline following surgery in older individuals is a major clinical problem of uncertain mechanism; a similar cognitive decline also follows severe infection, chemotherapy, or trauma and is currently without effective therapy. A variety of mechanisms have been proposed, and exploring the role of inflammation, we recently reported the role of IL-1β in the hippocampus after surgery in mice with postoperative cognitive dysfunction. Here, we show that TNF-α is upstream of IL-1 and provokes its production in the brain. Peripheral blockade of TNF-α is able to limit the release of IL-1 and prevent neuroinflammation and cognitive decline in a mouse model of surgery-induced cognitive decline. TNF-α appears to synergize with MyD88, the IL-1/TLR superfamily common signaling pathway, to sustain postoperative cognitive decline. Taken together, our results suggest a unique therapeutic potential for preemptive treatment with anti-TNF antibody to prevent surgery-induced cognitive decline.

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