Prolonged mechanical ventilation-induced neuroinflammation affects postoperative memory dysfunction in surgical mice.

Chang Chen,Zongze Zhang,Ting Chen,Xing Xu,Yanlin Wang,Mian Peng

doi:10.1186/s13054-015-0882-0

Chang Chen, Zongze Zhang + Show 4 more

Open Access

https://doi.org/10.1186/s13054-015-0882-0

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Abstract

IntroductionPatients 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.MethodsMale 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.ResultsThe 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.ConclusionsProlonged 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.

Highlights

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
Six-hour exposure to MV after surgery dramatically increased the levels of IL-1β, IL-6 and tumor necrosis factor α (TNFα) in the hippocampus and plasma at 6 hours and 1 day post-MV compared with the surgery-only group (P
We found that MV group at 6 hours (MV6h) induced cognitive decline following surgery and increased activation of microgliosis and apoptotic cascades after surgery, supporting the hypothesis that detrimental effects of prolonged MV after surgery may affect the brain

Summary

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. Intubation and positive pressure ventilation increase the incidence of delirium by up to 74% to 83% compared with 20% to 48% in nonintubated patients [3]. Critical care patients who undergo long-term MV show distinctive neurological impairment, including memory and cognitive decline [4]. During the past few years, an increasing amount of evidence has supported the view that the excessive release of proinflammatory cytokines, including tumor necrosis factor α (TNFα), interleukin (IL)-1β and IL-6, is involved in cognitive impairment after surgery [9]. The pathogenesis of MVincreased, surgery-induced cognitive impairment is poorly understood, including early neurological effects related to

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