Title |
Stimulation of the α7 Nicotinic Acetylcholine Receptor Protects against Neuroinflammation after Tibia Fracture and Endotoxemia in Mice
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Published in |
Molecular Medicine, October 2014
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DOI | 10.2119/molmed.2014.00143 |
Pubmed ID | |
Authors |
Niccolò Terrando, Ting Yang, Jae Kyu Ryu, Phillip T. Newton, Claudia Monaco, Marc Feldmann, Daqing Ma, Katerina Akassoglou, Mervyn Maze |
Abstract |
Surgery and critical illness often associate with cognitive decline. Surgical trauma or infection can lead independently 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 d 3 and this was associated with further neuroinflammation (CD11b and CD68 immunoreactivity) in the hippocampus in mice compared with those receiving surgery or LPS alone. Administration of a selective α7 subtype nicotinic acetylcholine receptor (α7 nAChR) agonist 2 h after LPS significantly improved neuroinflammation and hippocampal-dependent memory dysfunction. Modulation of nuclear factor-kappa B (NF-κB) 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 antiinflammatory pathway. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United States | 2 | 4% |
Unknown | 51 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Master | 9 | 17% |
Student > Ph. D. Student | 8 | 15% |
Student > Bachelor | 5 | 9% |
Professor | 5 | 9% |
Student > Doctoral Student | 5 | 9% |
Other | 10 | 19% |
Unknown | 11 | 21% |
Readers by discipline | Count | As % |
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Neuroscience | 11 | 21% |
Medicine and Dentistry | 8 | 15% |
Agricultural and Biological Sciences | 8 | 15% |
Biochemistry, Genetics and Molecular Biology | 4 | 8% |
Immunology and Microbiology | 2 | 4% |
Other | 7 | 13% |
Unknown | 13 | 25% |