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Background: The aim of the study was to determine the effects of repeated anesthesia exposure across postnatal development., Methods: Seventy-two newborn Sprague-Dawley rats were randomly divided into Sev group and Con-aged group. Sev groups were exposed to 2.6% sevoflurane for 2 h on postnatal day (P) 7, P14, and P21; the Con groups only received carrier gas for 2 h. Learning and memory were evaluated using the MWM test at P31 (juvenile), P91 (adult), and 18 months postnatally (aged). The relative expression of APP and Mapt mRNA was detected by RT-PCR, while Aβ, tau, and P-tau protein levels were analyzed by immunohistochemistry., Results: After repeated inhalation of sevoflurane, MWM test performance was significantly decreased in the Sev-aged group compared to the Con-aged group (P > 0.05). The relative expression of APP and Mapt mRNA was not significantly different between groups in each growth period (P > 0.05). The tau expression in the juvenile hippocampal CA1, CA3, and dentate gyrus regions increased markedly in the Sev group, while P-tau only increased in the hippocampal CA3 region in the Sev-adult group. The expression of tau, P-tau, and Aβ in the hippocampal regions was upregulated in the Sev-aged group., Conclusions: Multiple exposures to sevoflurane across postnatal development can induce or aggravate cognitive impairment in old age., Impact: Whether multiple sevoflurane exposures across postnatal development cause cognitive impairment in childhood, adulthood, or old age, as well as the relationship between sevoflurane and the hippocampal Aβ, tau, and P-tau proteins, remains unknown. This study's results demonstrate that multiple exposures to sevoflurane across postnatal development do not appear to affect cognitive function in childhood and adulthood; however, multiple exposures may lead to a cognitive function deficit in old age. The underlying mechanism may involve overexpression of the tau, P-tau, and Aβ proteins in the hippocampus., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Neuroinflammation is the main pathological mechanism of cognitive dysfunction caused by neurodegenerative diseases, and effective preventive and therapeutic measures are not available. We predicted the key targets of gastrodin's effects upon neuroinflammation through Network Pharmacology and molecular docking. Then the predicted targets were used to study how gastrodin affected cognitive dysfunction triggered by lipopolysaccharide-induced neuroinflammation in rats and its mechanisms. Three-month-old male rats were intraperitoneally injected with lipopolysaccharide for 3 days (d), 7 d and 14 d respectively. Gastrodin improved learning and memory ability of rats with neuroinflammation. Lipopolysaccharide enhanced the levels of pro-inflammatory cytokines, such as TNF-α, IL-1β and IL-6, in rat hippocampus, which could be reversed by gastrodin. Gastrodin also inhibited the activation of microglia. Our findings suggested that gastrodin exerted neuroprotective effects in rats with neuroinflammation by impacting the TLR4-NF-kB-NLRP3 pathway. Therefore, gastrodin may be a potential therapeutic agent for neuroinflammation-induced cognitive dysfunction., (© 2022. The Author(s).)