title: Deferoxamine regulates neuroinflammation and iron homeostasis in a mouse model of postoperative cognitive dysfunction.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Iron imbalance represents a novel mechanism underlying surgery-induced neuroinflammation and cognitive decline. DFO treatment regulates neuroinflammation and microglia activity after surgery.
authors.affiliation: Department of Anesthesiology, Southwest Hospital, Third Military Medical University, 30 Gaotanyan Road, Chongqing, 400038, China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Southwest Hospital, Third Military Medical University, 30 Gaotanyan Road, Chongqing, 400038, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Pan
authors.affiliation: Department of Anesthesiology, Southwest Hospital, Third Military Medical University, 30 Gaotanyan Road, Chongqing, 400038, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Southwest Hospital, Third Military Medical University, 30 Gaotanyan Road, Chongqing, 400038, China.
authors.forename: Jiao-Lin
authors.initials: JL
authors.lastname: Ning
authors.affiliation: Department of Anesthesiology, Southwest Hospital, Third Military Medical University, 30 Gaotanyan Road, Chongqing, 400038, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Medicine, Division of Nephrology, Duke University Medical Center, Durham, 27710, NC, USA.
authors.forename: Ting
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Basic Science Division, Duke University Medical Center, Durham, 27710, NC, USA.
authors.forename: Niccolò
authors.initials: N
authors.lastname: Terrando
authors.affiliation: Department of Anesthesiology, Southwest Hospital, Third Military Medical University, 30 Gaotanyan Road, Chongqing, 400038, China. jiantenggu@hotmail.com.
authors.forename: Jianteng
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Anesthesiology, Southwest Hospital, Third Military Medical University, 30 Gaotanyan Road, Chongqing, 400038, China. 13908393339@vip.163.com.
authors.forename: Guocai
authors.initials: G
authors.lastname: Tao
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D003213:Conditioning, Psychological / Q000187:drug effects; D003676:Deferoxamine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004660:Encephalitis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D005239:Fear; D006706:Homeostasis / Q000187:drug effects; D007501:Iron / Q000378:metabolism*; D007813:Laparotomy / Q000009:adverse effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011183:Postoperative Complications / Q000188:drug therapy* / Q000503:physiopathology*; D017262:Siderophores / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D017262:Siderophores; D007501:Iron; D003676:Deferoxamine
keywords: Cytokines; Hippocampus; Iron; Microglia; Surgery