The mechanism of lipopolysaccharide administration-induced cognitive function impairment caused by glucose metabolism disorder in adult rats

After a major surgery, a central nervous system complication often occurs, which is called as POCD, the Postoperative Cognitive Dysfunction. Clinical manifestations normally include the loss of learning ability, memory, thinking ability and executive and expression ability (Feinkohl et al., 2017a, Needham et al., 2017). POCD may last from a few hours, to a few days or weeks after surgery. In some cases, the disorder may exist for a few months, or even be permanent. Thus, it will result in reducing medication compliance, prolonging hospital stay, and increasing patients’ costs, etc. (Carr et al., 2018). With the rising number of surgery patients; the quantity of patients suffered from POCD is increasing year by year. Therefore, finding effective methods to treat POCD has become a thorny problem. The specific pathogenesis and mechanism of POCD remains unclear. Most scholars believe that POCD is caused by the degeneration of central nervous system in elder patients and induced by surgery and anesthesia. The brain energy metabolism disorder is caused by a combination of various risk factors and leads to neurological dysfunction (Cascella and Bimonte, 2017, Cropsey et al., 2015, Steinmetz and Rasmussen, 2016). Perioperative patients often have fluctuations in blood glucose, which might be accompanied by high and low blood glucose levels, and the postoperative brain glucose uptake rate of POCD patients is significantly reduced. Recent studies have also found that hyperglycemia during extracorporeal circulation is a risk factor for POCD (Feinkohl et al., 2017b, Jones, 2008). Therefore, study on the mechanism of POCD caused by abnormal glucose metabolism is of important guiding significance for perioperative clinical intervention. Studies have shown that glucose metabolism disorder is an important pathological mechanism of cognitive impairment (Diaz-Venegas et al., 2017). McNay et al. found that hippocampal-dependent learning and memory function is related to brain glucose metabolism using brain microdialysis technique (McNay and Recknagel, 2011). The mechanisms of abnormal glucose metabolism leading to POCD involve increased insulin resistance, abnormal insulin signaling pathway, enhanced oxidative stress response, increased advanced glycation end products (AGE), abnormal blood-brain barrier, and glucose transporter-4 metabolic disorders, among which, the insulin signaling pathway IRS-PI3K-AKT-GLUT4 disorder may exert influence on neuronal glucose metabolism and cognitive function changes (Rizzo et al., 2014, Pearson-Leary and McNay, 2016, Yaffe et al., 2011). At present time, diagnosis methods for POCD is insufficient. 18F-FDG (18F-fluorodeoxyglucose) PET/CT is an effective approach in detecting brain glucose metabolism-related damage in neurodegenerative dementia. Normal brain cells have high metabolism rate of 18F-FDG uptake, with standard uptake value. Standard Uptake Value (SUV) is a quantitative indicator that reflects the level of glucose concentration in brain cells, which functionally reflects the metabolic level of brain cells (Banzo et al., 2014, Jimenez-Bonilla et al., 2016). In addition, lipopolysaccharide (LPS) is the main bacterial toll-like receptor 4 (TLR4) ligand that actuates the immune system to respond to infection. Previous studies have shown that surgery in adult rats with intraperitoneal injection of LPS might trigger more serious neurodegenerative diseases, which suggests that adult rats are more prone to cognitive disorders when they have received surgery. This simulates the cognitive function of surgical infection status in young patients in clinical settings (Sochocka et al., 2017, Fischer et al., 2011). In this study, adult rats that have unilateral nephrectomy and have been treated with LPS intraperitoneal injection were used to cause adult rat cognitive dysfunction model. 18F-FDG PET/CT photo copies were used to record and test the changing of brain glucose metabolism of the rats with cognitive dysfunction. Molecular biological techniques were adapted to detect the changes of INSR-PI3K-AKT-GLUT4 of the insulin signaling pathway. Apart from the above, those techniques were helpful to explain the mechanism of glucose metabolism changes of POCD in adult rats, and to provide reference for preventing and treating POCD.