Intestinal Dysbacteriosis-Propelled T Helper 17 Cells Activation Mediate the Perioperative Neurocognitive Disorder Induced by Anesthesia/Surgery in Aged Rats

Abstract Background: Perioperative neurocognitive disorders (PND) occur frequently in elderly patients after surgery, but the mechanism of PND is not very clear at present. It is reported that anesthesia/surgery could cause intestinal flora imbalance and induce neurocognitive impairment. However, the effect of intestinal flora on PND is poorly understood. We previously found that peripheral interleukin-17A (IL17A) destroyed the blood-brain barrier (BBB), leading to central inflammation and neurocognitive impairment. The small intestine is the main place where Th17 cells are produced. Therefore, we hypothesized that Th17 cells and IL-17 may be an important bridge for intestinal microbes to cause neuroinflammation. Methods: Exploratory laparotomy was performed to establish PND model under sevoflurane anesthesia. 16S rRNA high-throughput sequencing was used to detect the changes of intestinal flora. To explore the relationship between intestinal flora and PND, compound antibiotics were used to eliminate intestinal flora before anesthesia/surgery, and behavior tests, such as open field, Y maze, and fear conditioning tests were applied to detect the changes of memory ability and which was compared with the rats that did not receive compound antibiotics. The number of Th17 cells and Foxp3 cells was detected by flow cytometry in the Peyer's patches (PP), mesenteric lymph nodes (MLN), blood and brain. Hippocampus IL17, IL17RA, IL6 and IL10 were detected by Western blot. Hippocampus IL17, IL17R and IBA1 (ionized calcium binding adaptor molecule1) were detected by immunofluorescence. Results: Anesthesia/surgery caused intestinal flora imbalance and induced neurocognitive impairment, increased the number of Th17 cells in the PP, MLN, blood and brain, up-regulated the lever of IL17, IL17R and inflammatory factor production in the hippocampus. The administration of compound antibiotics before anesthesia/surgery evidently inhibited this effect, including decreased the number of Th17 cells, down-regulated the lever of IL17, IL17R and inflammatory factor production, and improved the memory function. In addition, we found that IL17R was co-labeled with IBA1 in a large amount in the hippocampus through immunofluorescence double-staining. Conclusion: Our study suggested that intestinal dysbacteriosis-propelled T helper 17 cells activation might play an important role in the pathogenesis of PND.