Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1073/pnas.1014557107

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

23/11/2010

Volume

107

Pages

20518 - 20522

Keywords

Animals, Cognition Disorders, Cytokines, Enzyme-Linked Immunosorbent Assay, HMGB1 Protein, Inflammation, Interleukin-1, Mice, Mice, Knockout, Myeloid Differentiation Factor 88, Postoperative Complications, Signal Transduction, Toll-Like Receptor 4, Tumor Necrosis Factor-alpha