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The object of our work was to observe whether the Mongolian medicine Eerdun Wurile (EW) improve postoperative cognitive dysfunction (POCD) by affecting the TLR4/NF-κB. Mice (6–8-week-old male C57BL/6 J) were selected to establish an animal model of POCD by combining intracerebroventricular injection of lipopolysaccharide and nephrectomy; EW formulation and EW basic formulation were administered intra-gastrically for 7 consecutive days. The cognitive performance was assessed by Morris water maze test. H&E staining was examined to detect alterations in hippocampal tissue. Immunohistochemical staining was performed to evaluate MyD88, NF-κB, TLR4, iNOS, and IBA-1 expressions; Western blotting and RT-qPCR were performed to evaluate MyD88, NF-κB, and TLR4. The expressions of IL-6, IL-1β, and TNF-α were evaluated by ELISA. Intracerebroventricular injection of lipopolysaccharide combined with nephrectomy induced cognitive dysfunction in mice, stimulated TLR4/NF-κB and microglia, and promoted the secretion of murine TNF-α, IL-1β, and IL-6. EW formulation and EW basic formulation treatment are able to suppress the TLR4/NF-κB pathway activation and microglia, and the serum cytokine secretions related to proinflammation, and restore the cognitive performance. EW formulation and EW basic formulation can improve POCD in mice, and TLR4/NF-κB pathway seems to be one of the important mechanisms in EW’s improvement of POCD.

Background/Objectives: Nutritional status significantly influences cardiac surgery outcomes, with malnutrition contributing to poorer results and increased complications. This study addresses the critical gap in understanding by exploring the relationship between pre-operative nutritional status and post-operative cognitive dysfunction (POCD) in adult cardiac patients. Methods: A comprehensive search across key databases investigates the prevalence of malnutrition in pre-operative cardiac surgery patients, its effects, and its association with POCD. Factors exacerbating malnutrition, such as chronic illnesses and reduced functionality, are considered. The study also examines the incidence of POCD, its primary association with CABG procedures, and the impact of malnutrition on complications like inflammation, pulmonary and cardiac failure, and renal injury. Discussions: Findings reveal that 46.4% of pre-operative cardiac surgery patients experience malnutrition, linked to chronic illnesses and reduced functionality. Malnutrition significantly contributes to inflammation and complications, including POCD, with an incidence ranging from 15 to 50%. CABG procedures are particularly associated with POCD, and malnutrition prolongs intensive care stays while increasing vulnerability to surgical stress. Conclusions: The review underscores the crucial role of nutrition in recovery and advocates for a universally recognized nutrition assessment tool tailored to diverse cardiac surgery patients. Emphasizing pre-operative enhanced nutrition as a potential strategy to mitigate inflammation and improve cognitive function, the review highlights the need for integrating nutrition screening into clinical practice to optimize outcomes for high-risk cardiac surgery patients. However, to date, most data came from observational studies; hence, there is a need for future interventional studies to test the hypothesis that pre-operative enhanced nutrition can mitigate inflammation and improve cognitive function in this patient population.

Numerous results have revealed an association between inhibited function of excitatory amino acid transporter 3 (EAAT3) and several neurodegenerative diseases. This was also corroborated by our previous studies which showed that the EAAT3 function was intimately linked to learning and memory. With this premise, we examined the role of EAAT3 in post-operative cognitive dysfunction (POCD) and explored the potential benefit of riluzole in countering POCD in the present study. We first established a recombinant adeno-associated-viral (rAAV)-mediated shRNA to knockdown SLC1A1/EAAT3 expression in the hippocampus of adult male mice. The mice then received an intracerebroventricular microinjection of 2 μg lipopolysaccharide (LPS) to construct the POCD model. In addition, for old male mice, 4 mg/kg of riluzole was intraperitoneally injected for three consecutive days, with the last injection administered 2 h before the LPS microinjection. Cognitive function was assessed using the Morris water maze 24 h following the LPS microinjection. Animal behavioral tests, as well as pathological and biochemical assays, were performed to clarify the role of EAAT3 function in POCD and evaluate the effect of activating the EAAT3 function by riluzole. In the present study, we established a mouse model with hippocampal SLC1A1/EAAT3 knockdown and found that hippocampal SLC1A1/EAAT3 knockdown aggravated LPS-induced learning and memory deficits in adult male mice. Meanwhile, LPS significantly inhibited the expression of EAAT3 membrane protein and the phosphorylation level of GluA1 protein in the hippocampus of adult male mice. Moreover, riluzole pretreatment significantly increased the expression of hippocampal EAAT3 membrane protein and also ameliorated LPS-induced cognitive impairment in elderly male mice. Taken together, our results demonstrated that the dysfunction of EAAT3 is an important risk factor for POCD susceptibility and therefore, it may become a promising target for POCD treatment.

Post-operative cognitive dysfunction (POCD), especially in elderly patients, has been reported in many studies. Although increasing age, duration of anesthesia, postoperative infections, and respiratory complications were regarded as the risk factors for POCD, no extracerebral diagnostic biomarkers have been identified as indicators of POCD. Ninety-five patients, ages 65–80 years, scheduled for major orthopedic or abdominal surgery were enrolled. Twenty-two patients aged between 20 and 40 years undergoing the same procedures served as controls. Subjects received neuropsychological tests one-day prior and one week post procedure. To determine the presence of POCD, the criteria were used as described in most previous studies. Morning urine samples were obtained one day before surgery and on day 1, day 2 and day 7 post operatively. Urine formaldehyde was determined with high-performance liquid chromatography. The urine formaldehyde level of all patients with and without POCD increased on the first 2 days after surgery. But the formaldehyde concentration (on day 7) in patients with POCD was significantly higher than that in patients without POCD ( p  < 0.01). In the young control group, no patient was diagnosed with POCD. Although the changes in urine formaldehyde of young patients during perioperative period were similar to those in elderly patients without POCD, the formaldehyde concentrations measured at four time points were all significantly lower than those in elderly patients ( p  < 0.05). Levels of urine formaldehyde were elevated in the perioperative period, with the highest levels at day 7 in patients with POCD. This suggests that the increase on day 7 may provide a new physiologic marker along with neuropsychological assessments to assist in the diagnosis of POCD.

Background Post-operative cognitive dysfunction (POCD) is an important complication of cardiac surgeries. Glutamate plays a critical role in physiologic and pathologic conditions in the brain. Due to the role of glutamate in ischemia, this study is designed to identify the effect of memantine in prevention of POCD early and late after cardiac surgeries. Methods In this randomized clinical trial, 172 patients with ages 45–75 years old who underwent elective cardiac surgery were enrolled. For patients in memantine group, 5 mg of memantine per day administered at least 48 h before surgery and increased to 10 mg per day during the first 24 h after surgery and continued for 3 months. A brief Wechsler memory test (WMT) was administered before, three to 5 days after, and 3 months after surgery for both groups. Results Both groups demonstrate standard pattern of cognitive dysfunction after surgery and in follow up. Pre- and post-operative WMT score showed significant improvement in memantine compared to control group ( P  < 0.001) both in unadjusted and adjusted with confounding factor analysis. Unadjusted pre-, post-operative, and follow up WMT score improved significantly after 3 months in memantine group ( P  = 0.006). Conclusion Pre-operative administration of memantine protects patients from POCD following cardiac surgeries. In addition, it improves cognitive function 3 months after surgery. Trial registration The trial was registered in the Iranian Registry of Clinical Trials (registration number: IRCT201303168698N12 ). Graphical abstract Memantin effect on POCD.