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.

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ObjectiveThe hippocampal neuron electrophysiology and structure might be the basis of postoperative cognitive function‐related diseases after anesthesia. Here, we examined whether sevoflurane inhalation affected the electrophysiological and ultrastructural morphology of the hippocampal neurons.MethodsThe rats were randomly divided into the air/oxygen and Sevoflurane group (SEV group). The air/oxygen group inhaled carrier gas (1 L/min O2 + 1 L/min air) for 2 hours; The SEV group inhaled 3.4% sevoflurane & carrier gas for 2 hours. After that, the hippocampal electrophysiology signals were observed 1 week after anesthesia. Then, Transmission Electron Microscope was used to observe the neuron cell morphology, structures, and related synaptic morphology in hippocampi.ResultsCompared with the air/oxygen group, the numbers of spontaneous discharge and the values of maximum current significantly decreased in the SEV group, and the neuron cytoplasm edema and organelles also were damaged.ConclusionThe results showed that sevoflurane could weaken the electrophysiological signals of hippocampal neurons and damage the ultrastructure of neurons.

Background: It has been reported that repeated exposure to sevoflurane, a widely used general anesthesia in pediatric surgeries, may lead to brain defect in infant. However, the long-term effect of repeated exposure to sevoflurane during infancy on the learning behavior and neuro-development is less investigated yet.Methods: Sixty-four SD (sprague dawley) rats were randomly divided in to two groups, the experimental group (n=32) was exposed to sevoflurane (2.6%, 2 h) and the control group (n=32) was exposed to carrier gas (1 L/min O2 + 1 L/min Air, 2 h) for three times at infancy (P (postnatal day) 7, P14, and P21). At childhood (P32 to P36), SD rats in each group (n=16) received Morris Water Maze (MWM) test, and then Magnetic Resonance Imaging (MRI) was used to scan their brain and hippocampus at P37. Subsequently, the same NWM test and MRI scanning was conducted for the remaining SD rats in their adulthood (P92 to P97) (n = 16/group).Results: After being exposed to sevoflurane in infancy, the hippocampal volume of SD rats significantly decreased in their childhood and adulthood, their whole brain volume was also shrunken in adulthood; however, MWM test showed there is no obvious change in their spatial learning and memory recall performance either in childhood or in adulthood.Conclusions: Although repeated exposure to sevoflurane in infancy did not affect the spatial learning and memory performance of rats, however, it could result in the decease of hippocampal and brain volume in their adulthood. This study suggests that repetitive sevoflurane exposure in infancy may exert long-term risk in brain development.