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Updated: Apr 14, 2026
A Mouse Model of Orthopedic Surgery to Study Postoperative Cognitive Dysfunction and Tissue Regeneration
Published on: February 27, 2018
Prolonged mechanical ventilation-induced neuroinflammation affects postoperative memory dysfunction in surgical mice
Chang Chen1, Zongze Zhang2, Ting Chen3
1Department of Anesthesiology, Zhongnan Hospital, Wuhan University, East Lake Road, Wuhan, 430071, Hubei, China. chang-dream@126.com.
Introduction:
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.
Insights
Prolonged mechanical ventilation (MV) after surgery worsens memory deficits in mice. This cognitive decline is linked to increased inflammation and cellular damage in the hippocampus.
Area of Science:
- Neuroscience
- Surgical Research
- Inflammation Biology
Background:
- Postoperative cognitive dysfunction is a common complication.
- Mechanical ventilation (MV) may impact acute brain outcomes after surgery.
Purpose of the Study:
- To investigate the effect of prolonged mechanical ventilation (MV) on postoperative memory dysfunction in surgical mice.
- To explore the underlying mechanisms involving inflammation and cellular damage.
Main Methods:
- Male C57BL/6 mice underwent surgery and were divided into control, surgery-only, and MV groups for varying durations (1, 3, 6 hours).
- Memory function was assessed using fear conditioning tests.
- Systemic and hippocampal inflammatory markers (IL-1β, IL-6, TNFα), synaptic structure, microglial activation, and apoptotic markers were analyzed.
Main Results:
- Prolonged MV (6 hours) led to synapse degeneration, increased apoptosis markers (cytochrome c, cleaved caspase-3, cleaved PARP-1), and reduced memory performance (decreased freezing time).
- MV induced significant increases in NF-κB activation and levels of IL-1β, IL-6, and TNFα in both systemic circulation and the hippocampus.
Conclusions:
- Prolonged mechanical ventilation exacerbates postoperative cognitive decline.
- This effect is associated with increased hippocampal inflammation (IL-1β, IL-6, TNFα) and glial cell activation.
