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

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

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 mechanical ventilation on postoperative memory dysfunction in surgical mice. Male C57BL/6 mice were randomly divided into the following 3 groups: control group (group C): anesthetized unventilated animals; surgery group (groups S1h, 3 h and 6 h): underwent surgery under general anesthesia unventilated animals; mechanical ventilation group (groups MV1h, 3 h and 6 h): under mechanical ventilation for 1 h, 3 h and 6 h procedure after surgery. Separate cohorts of animals were tested for memory function with fear conditioning tests, or euthanized at 6 h, 1 d and 3 d post-surgery or post-MV to examined levels systemic and hippocampal IL-1β, IL-6 and TNF-a, and assessed synaptic structure and microglial activation. NF-κB p65, cytochrome c, cleaved caspase-3 and cleaved PARP activation were analyzed by Western blotting. MV6h induced increase CD11b immunopositive Cells, synapse degeneration, cytochrome c release, cleaved caspase-3 and cleaved PARP-1 activation after surgery, decrease in freezing time after surgery. At 6 h and 1 d post-MV, MV6h increased NF-κB activation and levels of systemic and hippocampal IL-1β, IL-6, TNF-a after surgery. Prolonged MV after surgery further aggravates cognitive decline that may stem from upregulation of hippocampal IL-1β, IL-6 and TNF-a, partially via activation of gliocytes in surgical mice hippocampus.