Effect of long-time mechanical ventilation on early postoperative activation of microglias in hippocampi of mice

Objective To evaluate the effect of long-time mechanical ventilation on early postoperative activation of microglias in the hippocampi of mice. Methods Eighty pathogen-free healthy male C57BL/6 mice, aged 8-10 weeks, weighing 20-25 g, were randomly divided into 2 groups(n=40 each)using a random number table: surgery group(group S)and postoperative mechanical ventilation group(group MV). Open reduction and internal fixation was performed after tibial fracture was induced in both groups.After surgery, the mice were put in the anesthesia chamber containing isoflurane and breathed spontaneously for 6 h in group S, and the mice were mechanically ventilated for 6 h under isoflurane anesthesia in group MV.On 1 day after the end of ventilation, 8 mice were randomly selected, and novel object recognition task was carried out.Testing was performed at 5 min, 2 h and 1 day intervals after the end of training on 4th day, and the preference index was calculated.Contextual fear conditioning test was carried out on 1 and 3 days after the end of ventilation(T1, 2), the mice were sacrificed at T1, 2, and the hippocampi were removed for determination of the activation of microglias(by immunofluorescence), interleukin-6 expression(by enzyme-linked immunosorbent assay)and nuclear factor kappa B p65 expression(by Western blot). Results Compared with group S, the ratio of time spent freezing induced by condition and ratio of time spent freezing induced by context were significantly decreased at T1, the preference index was significantly decreased at 5 min, 2 h and 1 day intervals after the end of training in the novel object recognition task, the activation of microglias was significantly increased at T1, and the expression of interleukin-6 at T1 and nuclear factor kappa B p65 at T1, 2 was significantly up-regulated in group MV(P<0.05). Conclusion Long-time mechanical ventilation induces early postoperative cognitive decline through enhancing activation of microglias in hippocampi and aggravating inflammatory responses in mice. Key words: Respiration, artificial; Hippocampus; Microglia