Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline.
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 ro...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2010
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| _version_ | 1797089820392030208 |
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| author | Terrando, N Monaco, C Ma, D Foxwell, B Feldmann, M Maze, M |
| author_facet | Terrando, N Monaco, C Ma, D Foxwell, B Feldmann, M Maze, M |
| author_sort | Terrando, N |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T03:09:35Z |
| format | Journal article |
| id | oxford-uuid:b3b9b4dd-a622-4ed0-b042-b80e82131355 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:09:35Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | oxford-uuid:b3b9b4dd-a622-4ed0-b042-b80e821313552022-03-27T04:21:18ZTumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b3b9b4dd-a622-4ed0-b042-b80e82131355EnglishSymplectic Elements at Oxford2010Terrando, NMonaco, CMa, DFoxwell, BFeldmann, MMaze, MCognitive 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. |
| spellingShingle | Terrando, N Monaco, C Ma, D Foxwell, B Feldmann, M Maze, M Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline. |
| title | Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline. |
| title_full | Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline. |
| title_fullStr | Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline. |
| title_full_unstemmed | Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline. |
| title_short | Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline. |
| title_sort | tumor necrosis factor alpha triggers a cytokine cascade yielding postoperative cognitive decline |
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