title: Prolonged mechanical ventilation-induced neuroinflammation affects postoperative memory dysfunction in surgical mice.
abstract: BACKGROUND
  Patients undergoing surgery frequently develop neuropsychological disturbances, including cognitive decline or memory impairment, and routine clinical procedures such as mechanical ventilation (MV) may affect acute-phase brain outcome. We aimed to investigate the effect of the prolonged MV on postoperative memory dysfunction in surgical mice.
  
  
  METHODS
  Male C57BL/6 mice were randomly divided into the following three groups: (1) The control group (group C) comprised anesthetized, unventilated animals; (2) the surgery group (subgroups S1h, S3h and S6h) was unventilated animals that underwent surgery under general anesthesia; and (3) the MV group (subgroups MV1h, MV3h and MV6h) was made up of animals under MV for 1 hour, 3 hours or 6 hours after surgery. Separate cohorts of animals were tested for memory function with fear conditioning tests or were killed at 6 hours, 1 day or 3 days postsurgery or post-MV to examine levels systemic and hippocampal interleukin (IL)-1β, IL-6 and tumor necrosis factor α (TNFα), and assessed synaptic structure and microglial activation. Nuclear factor κB (NF-κB) p65, cytochrome c, cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP) activation were analyzed by Western blotting.
  
  
  RESULTS
  The MV6h group showed increased CD11b-immunopositive cells, synapse degeneration, cytochrome c release, cleaved caspase-3 and cleaved PARP-1 activation after surgery, as well as a decrease in freezing time after surgery. At 6 hours and 1 day post-MV, MV6h increased NF-κB activation and levels of systemic and hippocampal IL-1β, IL-6 and TNFα after surgery.
  
  
  CONCLUSIONS
  Prolonged MV after surgery further aggravates cognitive decline that may stem from upregulation of hippocampal IL-1β, IL-6 and TNFα, partially via activation of gliocytes in the surgical mouse hippocampus.
authors.affiliation: Department of Anesthesiology, Zhongnan Hospital, Wuhan University, East Lake Road, Wuhan, 430071, Hubei, China. chang-dream@126.com.
authors.forename: Chang
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Zhongnan Hospital, Wuhan University, East Lake Road, Wuhan, 430071, Hubei, China. shangrila_cc@yahoo.com.
authors.forename: Zongze
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Zhongnan Hospital, Wuhan University, East Lake Road, Wuhan, 430071, Hubei, China. chenting@whu.edu.cn.
authors.forename: Ting
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Zhongnan Hospital, Wuhan University, East Lake Road, Wuhan, 430071, Hubei, China. sophie_pm@msn.com.
authors.forename: Mian
authors.initials: M
authors.lastname: Peng
authors.affiliation: Department of Anesthesiology, Zhongnan Hospital, Wuhan University, East Lake Road, Wuhan, 430071, Hubei, China. 16089799@qq.com.
authors.forename: Xing
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Anesthesiology, Zhongnan Hospital, Wuhan University, East Lake Road, Wuhan, 430071, Hubei, China. zfluck2002@163.com.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011183:Postoperative Complications / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D012121:Respiration, Artificial / Q000009:adverse effects* / Q000639:trends; D013997:Time Factors
chemical_list: D018836:Inflammation Mediators