Insulin alleviates the inflammatory response and oxidative stress injury in cerebral tissues in septic rats.

Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction that occurs secondary to infection in the body without overt central nervous system (CNS) infection. SAE is frequently encountered in critically ill patients in intensive care units and can be detected in up to 50-70% of septic patients. Previous studies have demonstrated that inflammatory cytokine release and oxidative stress injury are major pathophysiological mechanisms of SAE in critically ill patients. However, there are no effective strategies for the treatment of SAE. Insulin has important immunomodulatory effects and protective effects against oxidative stress injury in the peripheral organs of septic patients. However, very few studies of the possible effects of insulin in cerebral tissues of septic patients have been reported. Therefore, in this study, we aimed to explore whether insulin therapy can inhibit cytokine production (IL-1, IL-6, and TNF-a) and oxidative stress injury of the brain tissue in septic rats. We observed that the protein concentrations of IL-1, IL-6, and TNF-а, in addition to MDA and H2O2 were notably increased, inversely SOD, and GSH were sigificantly decreased in cortex, hippocampus, and hypothalamus of septic rats. Furthermore, the levels of S100 and NSE significantly increased. After 6 hours of insulin therapy, we found that the cytokine concentrations notably decreased and oxidative stress injuries in the cortex, hypothalamus, and hippocampus were alleviated in septic rats. In addition, the S100 and NSE levels significantly decreased. We concluded that insulin can inhibit the production of inflammatory cytokines and the oxidative stress response, thereby improving brain tissue damage.

The effect of extracorporeal membrane oxygenation therapy on systemic oxidative stress injury in a porcine model.

Extracorporeal membrane oxygenation (ECMO) therapy can result in systemic immune inflammation and trigger a hemolytic response, both of which can lead to oxidative stress injury. However, currently, there are few studies about whether ECMO can lead to oxidative stress injury. The objective of this study was to determine the effect of ECMO therapy on systemic oxidative stress. Twelve pigs were randomly divided into control and ECMO treatment groups. Blood samples were collected at -1, 0, 2, 6, 12, and 24 h during ECMO therapy in order to measure the levels of various oxidative stress markers in plasma. All animals included in the study were euthanized after 24 h of ECMO treatment. Malondialdehyde (MDA) was used as a marker of oxidation, and superoxide dismutase (SOD), glutathione (GSH), and total antioxidant capacity (T-AOC) were used as indices for antioxidant activity. The plasma levels of each molecule were similar when measured at -1 and 0 h (P > 0.05). In the control group, MDA, SOD, GSH, and T-AOC remained relatively constant throughout the study period. However, when ECMO was administered for 2 h, plasma levels of MDA increased significantly; conversely, levels of SOD, GSH, and T-AOC decreased. Maximum MDA levels and minimal SOD, GSH, and T-AOC levels were observed after 6 h of ECMO treatment. MDA and SOD levels had returned to baseline at 24 h. At this time-point, levels of MDA and T-AOC in samples from the right frontal cortex and jejunum differed significantly between the control and ECMO treatment groups. These results show that early ECMO treatment can induce significant oxidative stress injury in plasma. However, in the latter stage of the treatment, the oxidative stress injury can be repaired gradually. ECMO treatment can also result in mild oxidative stress injury in the jejunum and brain tissue.

The effect of venovenous extra-corporeal membrane oxygenation (ECMO) therapy on immune inflammatory response of cerebral tissues in porcine model.

BACKGROUND: Extra-Corporeal Membrane Oxygenation (ECMO) therapy is associated with high risk of neurologic injury. But the mechanism of neurologic injury during and/or after ECMO therapy is still unclear. Recent animal experiments confirmed that ECMO treatment increases the immune inflammatory response. The aim of this study is to investigate the effect of VV- ECMO on immune inflammatory response of cerebral tissues and neurological impairment. METHODS: 18 porcine were randomly divided into control, sham and ECMO group (n = 6/group). ECMO was run 24 h in the ECMO group, and serum collected at 0, 2, 6, 12 and 24 h during ECMO treatment for the analysis of cytokine (IL-1ß, IL-6, IL-10, TNF-a) and cerebral injury specific biomarker S100B and NSE. After 24 h ECMO treatment, all animals were euthanized and cerebral tissues (hypothalamus, hippocampus and cortex) were collected for measure of mRNA and protein levels of cytokine (IL-1ß, IL-6, IL-10, TNF-a). RESULTS: The results during ECMO treatment showed that all the pro-inflammation cytokines were increased significantly after 2 h, and anti-inflammation IL-10 showed transient hoist in the first 2 h in serum. After 24 h ECMO therapy, the mRNA levels of pro-inflammation cytokines and anti-inflammation IL-10 were simultaneously up-regulated in cerebral tissues (hypothalamus, hippocampus and cortex). And protein concentrations also showed different increasing levels in cerebral tissues. However, during the ECMO treatment, S100B and NSE protein in serum did not change significantly. CONCLUSION: These findings suggest VV-ECMO treatment can not only lead to immune inflammatory response in blood, but can also produce immune and inflammatory response in cerebral tissues. However the extent of immune inflammation was not sufficient to cause significant neurological impairment in this study. But the correlation between cerebral inflammatory response and cerebral impairment need to further explore.