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

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

Journal: Critical care (2015) 19(1):159

Link: https://ccforum.biomedcentral.com/articles/10.1186/s13054-015-0882-0

Comments: Mechanical ventilation (MV) is often a lifesaving intervention in critically ill patients and is frequently used in patients under general anesthesia during surgical operation. However, it is known that patients undergoing surgery develop neuropsychological disturbances, including cognitive decline or memory impairment, and routine clinical procedures such as MV may affect acute-phase brain outcome. Authors aimed to investigate the effect of the prolonged MV on postoperative memory dysfunction as using mice model.

In this study, mice were divided into the following three groups; a control group, a surgery group and a MV group. In the surgery and MV group, surgery consisted of an open tibial fracture with intramedullary fixation in aseptic conditions under general anesthesia. Then, mice were kept on spontaneous breathing under the anesthesia in the surgery group. On the other hand, in the MV group, mice received MV treatment (respiratory rate = 100 breathes/min, mode = pressure control (peak pressure of 12 - 15 cmH2O), fraction of inspiration oxygen (FiO2) = 0.5).

At first, authors revealed that the effect on cognitive alteration among three groups by fear conditioning test. They showed that even surgery reduced fear memory by comparison with control and surgery groups, and that 6-hour exposure to MV treatment significantly reduced fear memory by comparison with surgery and MV groups.

Then, authors tried to address why MV treatment induced cognitive decline from the view point of neuro-inflammatory response. They compared the expression of inflammatory response factors among three groups, and showed that those factors expression level were significantly increased in the plasma and hippocampus in MV groups. Microglial activity in hippocampus was also increased. Next, they revealed hippocanpal synaptic morphometric change after MV treated mice by transmission electron microscopy. In MV group, hippocampal CA1 region showed degenerating presynaptic elements and mitochondrial swelling and vacuolation were conspicuous and the degree of rough endoplasmic reticulum degeranulation. At last, authors indicated that the apoptotic cascades was activated in MV group mice.

Those all data suggest that stress in the lung after MV treatment could promote impaired memory that derived from neuroinflammation, microglial activation, and ultrastructural changes of synapses in the hippocampal CA1 region.