Post-operative cognitive dysfunction (POCD) is a clinical phenomenon characterized with cognitive decline in patients after anesthesia and surgery. It has been shown that interleukin-1β (IL-1β) contributes to the cognitive impairment of mice after surgery and isoflurane anesthesia. This study is designed to determine whether isoflurane alone increases inflammatory cytokines and causes cell injury and cognitive impairment. Four-month-old male Fisher 344 rats were exposed to or were not exposed to 1.2% isoflurane for 2 h. Two weeks later, rats were subjected to Barnes maze and fear conditioning tests. Although animals exposed to or non-exposed to isoflurane developed spatial learning, animals exposed to isoflurane had significant impairments in long-term spatial memory assessed by Barnes maze. They also had impaired hippocampus-dependent learning and memory in fear conditioning test. IL-1β in the hippocampus was increased at 6 h after isoflurane exposure. Isoflurane also increased activated caspase 3 in the hippocampus and decreased the neuronal density in the CA1 region. However, isoflurane did not change the amount of β-amyloid peptide in the cerebral cortex at 29 days after isoflurane exposure when cognitive impairment was present. These results suggest that isoflurane increases inflammatory cytokine expression and causes cell injury in the hippocampus, which may contribute to isoflurane-induced cognitive impairment in rats.

This meta-analysis examines whether differences in biomarkers, such as programmed cell death ligand 1 (PD-L1) expression and tumor mutation burden, are associated with improved response to immunotherapy and survival in patients with advanced non–small cell lung cancer (NSCLC).

Postoperative cognitive decline is a clinical syndrome. Volatile anesthetics are commonly used during surgery. It is conceivable that volatile anesthetics may contribute to postoperative cognitive decline. Isoflurane can impair cognitive functions of animals under certain conditions. However, the mechanisms for this impairment are not clear. Here, male 18-month old Fisher 344 rats or 10-week old mice were exposed to 1.2 or 1.4% isoflurane for 2 h. Our studies showed that isoflurane impaired the cognitive functions of the rats in Barnes maze. Isoflurane-exposed rats had reduced freezing behavior during the training sessions in the fear conditioning test. This isoflurane effect was attenuated by lidocaine, a local anesthetic with anti-inflammatory property. Rats that had training sessions and were exposed to isoflurane 30 min later had freezing behavior similar to that of control animals. Isoflurane increased the expression of interleukin 1β (IL-1β), interleukin-6 and activated caspase 3 in the hippocampus of the 18-month old rats. IL-1β positive staining was co-localized with that of NeuN, a neuronal marker. The increase of IL-1β and activated caspase 3 but not interleukin-6 was attenuated by lidocaine. Isoflurane also impaired the cognitive functions of 10-week old C57BL/6J mice and increased IL-1β in their hippocampi. However, isoflurane did not affect the cognitive functions of IL-1β deficient mice. Our results suggest that isoflurane impairs the learning but may not affect the recall of the aged rats. IL-1β may play an important role in this isoflurane effect.

Post-operative cognitive dysfunction (POCD) is a clinical phenomenon that has drawn significant attention from the public and scientific community. Age is a risk factor for POCD. However, the contribution of general anesthesia/anesthetics to POCD and the underlying neuropathology are not clear. Here, we showed that 18-month-old male Fisher 344 rats exposed to 1.2% isoflurane, a general anesthetic, for 2 h had significant learning and memory impairments assessed at 2 to 4 weeks after isoflurane exposure. These isoflurane effects were attenuated by intravenous lidocaine (1.5 mg/kg as a bolus and then 2 mg/kg/h during isoflurane exposure), a local anesthetic that has neuroprotective effect. Exposure to isoflurane or isoflurane plus lidocaine did not change the neuronal and synaptic density as well as the expression of NeuN (a neuronal protein), drebrin (a dendritic spine protein), synaptophysin (a synaptic protein), activated caspase 3 and caspase-activated DNase in the hippocampus at 29 days after isoflurane exposure when cognitive impairment was present. Isoflurane and lidocaine did not affect the amount of β-amyloid peptide, total tau and phospho-tau in the cerebral cortex as well as interleukin-1β and tumor necrosis factor-α in the hippocampus at 29 days after isoflurane exposure. Thus, isoflurane induces learning and memory impairment in old rats. Lidocaine attenuates these isoflurane effects. Isoflurane may not cause long-lasting neuropathological changes.

Oral mucosal disease (OMD), which is also called soft tissue oral disease, is described as a series of disorders or conditions affecting the mucosa and soft tissue in the oral cavity. Its etiology is unclear, but emerging evidence has implicated the influence of the composition of the oral mucosa and saliva-resident microbiota. In turn, this dysbiosis effects the immune response balance and epithelial barrier function, followed by the occurrence and progression of OMD. In addition, oral microbial dysbiosis is diverse in different types of diseases and different disease progressions, suggesting that key causal pathogens may exist in various oral pathologies. This narrative literature review primarily discusses the most recent findings focusing on how microbial dysbiosis communicates with mucosal adaptive immune cells and the epithelial barrier in the context of five representative OMDs, including oral candidiasis (OC), oral lichen planus (OLP), recurrent aphthous ulcer (RAU), oral leukoplakia (OLK), and oral squamous cell carcinoma (OSCC), to provide new insight into the pathogenetic mechanisms of OMDs.

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Application of the volatile anesthetic isoflurane during the early phase of reperfusion reduces ischemic heart and brain injury (anesthetic postconditioning). We hypothesize that inhibition of glycogen synthase kinase 3β (GSK3β), a protein whose activation can lead to cell death, participates in anesthetic postconditioning-induced neuroprotection. SH-SY5Y cells, a human neuroblastoma cell line, were induced by retinoic acid to differentiate into terminal neuron-like cells. The cells then were subjected to a 1-h oxygen-glucose deprivation (OGD), a condition to simulate ischemia in vitro, and a 20-h simulated reperfusion. Isoflurane, sevoflurane or desflurane, three commonly used volatile anesthetics, was applied for 1 h during the early phase of simulated reperfusion. Cell injury was quantified by lactate dehydrogenase (LDH) release. Phospho-GSK3β at Ser9 and total GSK3β were quantified at 1 or 3 h after the OGD. OGD increased LDH release, suggesting that OGD induced cell injury. Post-treatment with isoflurane, sevoflurane or desflurane reduced this cell injury. This protection was apparent when 2% isoflurane was applied within 1 h after the onset of reperfusion. Isoflurane post-treatment also significantly increased the phosphorylation of GSK3β at Ser9 at 1 h after the OGD. GSK3β inhibitors reduced OGD and simulated reperfusion-induced LDH release. The combination of GSK3β inhibitors and isoflurane postconditioning did not cause a greater protection than isoflurane postconditioning alone. These results suggest that volatile anesthetic postconditioning reduces OGD and simulated reperfusioninduced cell injury. Since phospho-GSK3β at Ser9 decreases GSK3β activity, our results suggest that volatile anesthetic postconditioning in human neuron-like cells may be mediated by GSK3β inhibition.

HMGB1 A-box, not only EP, can reduce LPS-induced intestinal inflammation through inhibition of the HMGB1/TLR4 signaling pathways.