| First Author | Terrando N | Year | 2010 |
| Journal | Proc Natl Acad Sci U S A | Volume | 107 |
| Issue | 47 | Pages | 20518-22 |
| PubMed ID | 21041647 | Mgi Jnum | J:166605 |
| Mgi Id | MGI:4848242 | Doi | 10.1073/pnas.1014557107 |
| Citation | Terrando N, et al. (2010) Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline. Proc Natl Acad Sci U S A 107(47):20518-22 |
| abstractText | 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-1beta in the hippocampus after surgery in mice with postoperative cognitive dysfunction. Here, we show that TNF-alpha is upstream of IL-1 and provokes its production in the brain. Peripheral blockade of TNF-alpha 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-alpha 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. |
