ObjectivePostoperative cognitive dysfunction (POCD) is common after surgery in elderly patients and is associated with high morbidity. The molecular mechanisms responsible for POCD are unknown. Minocycline, an inhibitor of microglial activation, may be useful in treating and preventing POCD. We explored whether minocycline can inhibit microglial activation and prevent POCD in aged rats as a surgery model.MethodsRats aged 18 to 20 months were randomly allocated to the following groups: naïve, abdominal surgery alone, or minocycline injection before abdominal surgery. Hippocampal cytokine mRNA levels were measured at 3 hours, 1 day, 3 days, and 7 days after surgery, and microglial activation was measured at 3 hours and 7 days after surgery. Memory was assessed using the Morris water maze test.ResultsSurgery resulted in severe cognitive impairment in aged rats and induced a significant neuroinflammatory response and microglial activation. The use of minocycline can prevent microglial activation after surgery, but delayed microglial activation may occur. The use of minocycline may further impair memory after surgery.ConclusionMinocycline can restrain microglial activation and restrict the inflammatory response in the hippocampus early after surgery, but it may induce delayed microglial activation and cannot prevent POCD in aged rats.
acute lung injury (ali) is a serious clinical problem. The present study was performed to investigate the effect of structured triglyceride (STG) on the development of lipopolysaccharide (lPS)-induced ali and its underlying mechanism of action. To establish an lPS-induced ali mouse model, mice were intranasally administered 50 µl lPS. The pathological changes in the lung were observed via haematoxylin-eosin staining. The lung injury score, lung wet/dry weight (W/d) ratio, and myeloperoxidase (MPo) activity were used to evaluate the degree of lung injury. The expression levels of interleukin (il)-1β, il-6 and tumour necrosis factor-α in lung tissues were measured through reverse transcription-quantitative polymerase chain reaction. The enzyme-linked immunosorbent assay was used to measure the levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid. Furthermore, western blotting was performed to detect the activity of the transforming growth factor-α-activated kinase 1 (TAK1)/NF-κB pathway. lPS-induced ali mice were treated with aH7614 [a G-protein coupled receptor 120 (GPR120) inhibitor] to confirm the effect of STG on GPR120. STG treatment decreased the lung pathological changes, lung injury score, lung W/D ratio, and proinflammatory cytokine expression levels and inhibited TAK1/NF-κB pathway activity in the lPS-induced ali mouse model. additionally, aH7614 reversed the inhibitory effects of STG on lung injury, inflammation, and TAK1/NF-κB pathway activity in ali. Moreover, AH7614 weakened the inhibitory effects of STG on inflammation and TAK1/NF-κB pathway activity in lPS-induced raW264.7 cells. collectively, STG may suppress the TAK1/NF-κB pathway activity by enhancing GPr120 expression to alleviate the lung injury and inflammation in ALI.These results suggest the therapeutic potential of STG in the treatment of ali.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.