Dietary Restriction Improves Perioperative Neurocognitive Disorders by Inhibiting Neuroinflammation and Gut Microbial Dysbiosis.

ABSTRACT

Anesthesia/surgery have been identified as potential factors contributing to perioperative neurocognitive disorders, with a notably heightened risk observed in aging populations. One of the primary drivers of this impairment is believed to be neuroinflammation, specifically inflammation of hippocampal microglia. Dietary restriction has demonstrated a favorable impact on cognitive impairment across various disorders, primarily by quelling neuroinflammation. However, the precise influence of dietary restriction on perioperative neurocognitive disorders remains to be definitively ascertained. This investigation aims to explore the effects of dietary restriction on perioperative neurocognitive disorders and propose innovative therapeutic strategies for their management. The model of perioperative neurocognitive disorder was induced through exploratory laparotomy under isoflurane anesthesia. Cognitive performance was evaluated using the open field test, Barnes maze test, and fear conditioning test. The enzyme-linked immunosorbent assay (ELISA) was employed to quantify concentrations of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in both serum and hippocampal samples. The Western blot technique was utilized to assess expression levels of hippocampal PSD 95, Synaptophysin, TLR4, MyD88, and NF-kB p65. Microglial polarization was gauged using a combination of reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence labeling techniques. We conducted 16S rRNA sequencing to investigate the impact of dietary restriction on the intestinal flora of aged mice following anesthesia/surgery. Our findings indicate that dietary restrictions have the potential to ameliorate anesthesia/surgery-induced cognitive dysfunction. This effect is achieved through the modulation of gut microbiota, suppression of inflammatory responses in hippocampal microglia, and facilitation of neuronal repair and regeneration.