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

ABSTRACT: 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-1? in the hippocampus after surgery in mice with postoperative cognitive dysfunction. Here, we show that TNF-? is upstream of IL-1 and provokes its production in the brain. Peripheral blockade of TNF-? 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-? 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.

SUBMITTER: Terrando N 

PROVIDER: S-EPMC2996666 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature