Stimulation of the alpha 7 nicotinic acetylcholine receptor protects against neuroinflammation after tibia fracture and endotoxemia in mice.
Surgery and critical illness often associate with cognitive decline. Surgical trauma or infection can independently lead to learning and memory impairments via similar, but not identical, cellular signaling of the innate immune system that promotes neuroinflammation. In this study we explored the pu...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2014
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| _version_ | 1797072161214562304 |
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| author | Terrando, N Yang, T Ryu, J Newton, P Monaco, C Feldmann, M Ma, D Akassoglou, K Maze, M |
| author_facet | Terrando, N Yang, T Ryu, J Newton, P Monaco, C Feldmann, M Ma, D Akassoglou, K Maze, M |
| author_sort | Terrando, N |
| collection | OXFORD |
| description | Surgery and critical illness often associate with cognitive decline. Surgical trauma or infection can independently lead to learning and memory impairments via similar, but not identical, cellular signaling of the innate immune system that promotes neuroinflammation. In this study we explored the putative synergism between aseptic orthopedic surgery and infection, the latter reproduced by postoperative lipopolysaccharide (LPS) administration. We observed that surgery and LPS augmented systemic inflammation up to postoperative day 3 and this was associated with further neuroinflammation (CD11b and CD68 immunoreactivity) in the hippocampus in mice compared to those received surgery or LPS alone. Administration of a selective alpha 7 subtype nicotinic acetylcholine receptor (α7 nAChR) agonist 2 hours after the LPS significantly improved neuroinflammation and hippocampal-dependent memory dysfunction. Modulation of nuclear factor-kappa B (NFκB) activation in monocytes and regulation of the oxidative stress response through nicotinamide adenine dinucleotide phosphate (NADPH) signaling appear to be key targets in modulating this response. Overall, these results suggest that it may be conceivable to limit and possibly prevent postoperative complications, including cognitive decline and/or infections, through stimulation of the cholinergic anti-inflammatory pathway. |
| first_indexed | 2024-03-06T23:03:42Z |
| format | Journal article |
| id | oxford-uuid:630dc873-5e87-4e32-8355-cc7067a51e67 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:03:42Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | oxford-uuid:630dc873-5e87-4e32-8355-cc7067a51e672022-03-26T18:10:20ZStimulation of the alpha 7 nicotinic acetylcholine receptor protects against neuroinflammation after tibia fracture and endotoxemia in mice.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:630dc873-5e87-4e32-8355-cc7067a51e67EnglishSymplectic Elements at Oxford2014Terrando, NYang, TRyu, JNewton, PMonaco, CFeldmann, MMa, DAkassoglou, KMaze, MSurgery and critical illness often associate with cognitive decline. Surgical trauma or infection can independently lead to learning and memory impairments via similar, but not identical, cellular signaling of the innate immune system that promotes neuroinflammation. In this study we explored the putative synergism between aseptic orthopedic surgery and infection, the latter reproduced by postoperative lipopolysaccharide (LPS) administration. We observed that surgery and LPS augmented systemic inflammation up to postoperative day 3 and this was associated with further neuroinflammation (CD11b and CD68 immunoreactivity) in the hippocampus in mice compared to those received surgery or LPS alone. Administration of a selective alpha 7 subtype nicotinic acetylcholine receptor (α7 nAChR) agonist 2 hours after the LPS significantly improved neuroinflammation and hippocampal-dependent memory dysfunction. Modulation of nuclear factor-kappa B (NFκB) activation in monocytes and regulation of the oxidative stress response through nicotinamide adenine dinucleotide phosphate (NADPH) signaling appear to be key targets in modulating this response. Overall, these results suggest that it may be conceivable to limit and possibly prevent postoperative complications, including cognitive decline and/or infections, through stimulation of the cholinergic anti-inflammatory pathway. |
| spellingShingle | Terrando, N Yang, T Ryu, J Newton, P Monaco, C Feldmann, M Ma, D Akassoglou, K Maze, M Stimulation of the alpha 7 nicotinic acetylcholine receptor protects against neuroinflammation after tibia fracture and endotoxemia in mice. |
| title | Stimulation of the alpha 7 nicotinic acetylcholine receptor protects against neuroinflammation after tibia fracture and endotoxemia in mice. |
| title_full | Stimulation of the alpha 7 nicotinic acetylcholine receptor protects against neuroinflammation after tibia fracture and endotoxemia in mice. |
| title_fullStr | Stimulation of the alpha 7 nicotinic acetylcholine receptor protects against neuroinflammation after tibia fracture and endotoxemia in mice. |
| title_full_unstemmed | Stimulation of the alpha 7 nicotinic acetylcholine receptor protects against neuroinflammation after tibia fracture and endotoxemia in mice. |
| title_short | Stimulation of the alpha 7 nicotinic acetylcholine receptor protects against neuroinflammation after tibia fracture and endotoxemia in mice. |
| title_sort | stimulation of the alpha 7 nicotinic acetylcholine receptor protects against neuroinflammation after tibia fracture and endotoxemia in mice |
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