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Deferoxamine regulates neuroinflammation and iron homeostasis in a mouse model of postoperative cognitive dysfunction.

dc.contributor.author Chen, L
dc.contributor.author Gu, J
dc.contributor.author Li, X
dc.contributor.author Li, Y
dc.contributor.author Ning, J-L
dc.contributor.author Pan, K
dc.contributor.author Tao, G
dc.contributor.author Terrando, Niccolò
dc.contributor.author Yang, Ting
dc.coverage.spatial England
dc.date.accessioned 2017-03-06T00:57:50Z
dc.date.available 2017-03-06T00:57:50Z
dc.date.issued 2016-10-12
dc.identifier https://www.ncbi.nlm.nih.gov/pubmed/27733186
dc.identifier 10.1186/s12974-016-0740-2
dc.identifier.uri http://hdl.handle.net/10161/13801
dc.description.abstract BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication after surgery, especially amongst elderly patients. Neuroinflammation and iron homeostasis are key hallmarks of several neurological disorders. In this study, we investigated the role of deferoxamine (DFO), a clinically used iron chelator, in a mouse model of surgery-induced cognitive dysfunction and assessed its neuroprotective effects on neuroinflammation, oxidative stress, and memory function. METHODS: A model of laparotomy under general anesthesia and analgesia was used to study POCD. Twelve to 14 months C57BL/6J male mice were treated with DFO, and changes in iron signaling, microglia activity, oxidative stress, inflammatory cytokines, and neurotrophic factors were assessed in the hippocampus on postoperative days 3, 7, and 14. Memory function was evaluated using fear conditioning and Morris water maze tests. BV2 microglia cells were used to test the anti-inflammatory and neuroprotective effects of DFO. RESULTS: Peripheral surgical trauma triggered changes in hippocampal iron homeostasis including ferric iron deposition, increase in hepcidin and divalent metal transporter-1, reduction in ferroportin and ferritin, and oxidative stress. Microglia activation, inflammatory cytokines, brain-derived neurotropic factor impairments, and cognitive dysfunction were found up to day 14 after surgery. Treatment with DFO significantly reduced neuroinflammation and improved cognitive decline by modulating p38 MAPK signaling, reactive oxygen species, and pro-inflammatory cytokines release. CONCLUSIONS: Iron imbalance represents a novel mechanism underlying surgery-induced neuroinflammation and cognitive decline. DFO treatment regulates neuroinflammation and microglia activity after surgery.
dc.language eng
dc.relation.ispartof J Neuroinflammation
dc.relation.isversionof 10.1186/s12974-016-0740-2
dc.subject Cytokines
dc.subject Hippocampus
dc.subject Iron
dc.subject Microglia
dc.subject Surgery
dc.title Deferoxamine regulates neuroinflammation and iron homeostasis in a mouse model of postoperative cognitive dysfunction.
dc.type Journal article
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/27733186
pubs.begin-page 268
pubs.issue 1
pubs.organisational-group Anesthesiology
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group School of Medicine
pubs.publication-status Published online
pubs.volume 13
dc.identifier.eissn 1742-2094


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