Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline.

Journal Article

Cognitive 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.

Full Text

Duke Authors

Cited Authors

  • Terrando, N; Monaco, C; Ma, D; Foxwell, BMJ; Feldmann, M; Maze, M

Published Date

  • November 2010

Published In

Volume / Issue

  • 107 / 47

Start / End Page

  • 20518 - 20522

PubMed ID

  • 21041647

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.1014557107

Language

  • eng