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

Publication ,  Journal Article
Terrando, N; Monaco, C; Ma, D; Foxwell, BMJ; Feldmann, M; Maze, M
Published in: Proc Natl Acad Sci U S A
November 23, 2010

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.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

November 23, 2010

Volume

107

Issue

47

Start / End Page

20518 / 20522

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Toll-Like Receptor 4
  • Signal Transduction
  • Postoperative Complications
  • Myeloid Differentiation Factor 88
  • Mice, Knockout
  • Mice
  • Interleukin-1
  • Inflammation
  • HMGB1 Protein
 

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Terrando, N., Monaco, C., Ma, D., Foxwell, B. M. J., Feldmann, M., & Maze, M. (2010). Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline. Proc Natl Acad Sci U S A, 107(47), 20518–20522. https://doi.org/10.1073/pnas.1014557107
Terrando, Niccolò, Claudia Monaco, Daqing Ma, Brian M. J. Foxwell, Marc Feldmann, and Mervyn Maze. “Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline.Proc Natl Acad Sci U S A 107, no. 47 (November 23, 2010): 20518–22. https://doi.org/10.1073/pnas.1014557107.
Terrando N, Monaco C, Ma D, Foxwell BMJ, Feldmann M, Maze M. Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline. Proc Natl Acad Sci U S A. 2010 Nov 23;107(47):20518–22.
Terrando, Niccolò, et al. “Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline.Proc Natl Acad Sci U S A, vol. 107, no. 47, Nov. 2010, pp. 20518–22. Pubmed, doi:10.1073/pnas.1014557107.
Terrando N, Monaco C, Ma D, Foxwell BMJ, Feldmann M, Maze M. Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline. Proc Natl Acad Sci U S A. 2010 Nov 23;107(47):20518–20522.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

November 23, 2010

Volume

107

Issue

47

Start / End Page

20518 / 20522

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Toll-Like Receptor 4
  • Signal Transduction
  • Postoperative Complications
  • Myeloid Differentiation Factor 88
  • Mice, Knockout
  • Mice
  • Interleukin-1
  • Inflammation
  • HMGB1 Protein