The role of intestinal flora disturbance in perioperative neurocognitive impairment in aged mice

The role of intestinal flora disturbance in perioperative neurocognitive impairment in aged mice

  Perioperative neurocognitive disorder (PND) refers to the changes in mental activity, personality, social ability, and cognitive ability of patients after anesthesia and surgery. It is common in elderly patients. Clarifying its pathophysiological mechanism helps to formulate effective preventive measures. The diversity and stability of intestinal flora in elderly patients is significantly reduced. And surgical operations, especially gastrointestinal surgery, will exacerbate the imbalance of intestinal flora. Recent studies have shown that the "gut-brain dialogue" mediated by the "gut microbiota-gut-brain axis" serves as a two-way communication between the gut microbiota and the brain, which is involved in immune-mediated central nervous system disorders (Guillain-Barre syndrome, Multiple sclerosis and neuromyelitis optica, etc.) and non-immune-mediated central nervous system disorders (depression, anxiety, autism, etc.) play an important role.

In order to evaluate the role of intestinal flora disorder in perioperative neurocognitive impairment in aged mice, Zhengzhou University People’s Hospital Wang Guangzhi, Wu Xiaoying, Han Shuangyin et al. et al. put 60 SPF-grade healthy male C57BL/6J mice, 18 months old, Random number table method was used to divide into 4 groups (n=15): control group (C group), surgery group (O group), surgery + Lactobacillus rhamnosus group (OL group) and surgery + fecal bacteria transplantation group (OF group). The O group, OL group and OF group underwent exploratory laparotomy. In the PL group, 200 μl of Lactobacillus rhamnosus was given by intragastric administration immediately after the operation, once a day, for 10 consecutive days, and the mice could obtain about 0.2×109 CFU of probiotics per day. Seven weeks before the OF group, a broad-spectrum antibiotic mixture (ampicillin and sulbactam 1.5 g/L, vancomycin 500 mg/L, ciprofloxacin 200 mg/L, imipenem and cilastatin 250 mg/L and metronidazole 1 g/L) were added to the drinking water of mice and replaced with sterile tap water 72 h before the operation; 200 μl of fecal bacteria filtrate was given by intragastric administration immediately after the operation, once a day, continuous 10 d. At 10 days postoperatively, 5 mice in each group were sacrificed, and the vascular permeability of the jejunum and ileum was detected by the Evans blue leak test. At 10 days postoperatively, 5 mice in each group were sacrificed, and blood samples of small intestine, hippocampus and orbital vein were collected, and IL-6, IL-17, TNF-α, IFN-γ, IL-4 and IL were detected by ELISA method -10 level. On the 10th day after operation, 5 mice from each group were taken, and the Morris water maze test was used to determine the cognitive function of the mice.

The results showed that compared with group C, the vascular permeability of the jejunum and ileum in group O increased, the levels of IL-6, IL-17, TNF-α and IFN-γ in the small intestine, peripheral blood and hippocampus increased, and IL-4 and The level of IL-10 decreased, the swimming distance and escape latency were prolonged, and the stay time in the target quadrant was shortened (P<0.05 or 0.01). There was no significant difference in the above indicators between the ol group and the of group (p>0.05); compared with the O group In the OL and OF groups, the jejunum and ileum vascular permeability decreased, the levels of IL-6, IL-17, TNF-α and IFN-γ in the small intestine, peripheral blood and hippocampus decreased, and the levels of IL-4 and IL-10 increased. Higher, shorter swimming distance and escape latency, longer stay time in target quadrant (P<0.05).

   Disorders of intestinal flora can mediate hippocampal inflammation, leading to perioperative neurocognitive impairment in aged mice.