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

Abstract

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.

Insulin ameliorating endotoxaemia‐induced muscle wasting is associated with the alteration of hypothalamic neuropeptides and inflammation in rats

“…LPS injection led to an increase in hypothalamic inflammatory cytokines. This was in consistent with other studies . In sepsis, not only the permeability of blood brain barrier was increasing, facilitating circulating cytokine entering into CNS, but also central derived cytokine was upregulated .…”

“…Thus, the anti‐inflammation effect of insulin was likely to be achieved in the brain. This was confirmed in our previous study, which has demonstrated insulin treatment could down‐regulate the inflammation and oxidative stress in cortex, hypothalamus and hippocampus of septic rats . Because hypothalamic inflammation could lead to cachexia, especially muscle atrophy, via the melanocortin system, the stabilization effect of insulin on hypothalamic neuropeptides may account for the alleviated muscle wasting in sepsis.…”

“…However, the exact mechanism of such effect was unclear. In addition to inhibiting peripheral inflammation, our previous study also has demonstrated insulin could alleviate the central inflammation caused by LPS administration . Given the critical role of central inflammation on muscle wasting in sepsis as mentioned before, insulin may ameliorate muscle wasting and promote positive energy balance by reducing central inflammation and modulating hypothalamic neuropeptides.…”

Study of Voluntary Wheel Running on Norepinephrine Mechanism in Striatum in the Rats with Septic Encephalopathy

“…Several recent studies have used S100β as a serum biomarker in the diagnosis of SE (Chen, Q et al 2014). In keeping with the presence of encephalopathy, we showed that there was an increase in S100β level in the CLP and EC groups compared to that of the S group.…”

In Vivo Imaging of Septic Encephalopathy

“…In addition, disseminated blood coagulation [71,72] and oxidative stress [73][74][75] aggravated brain dysfunction of SE. MicroRNA (i.e., noncoding small RNA) involved in RNA silencing and posttranscriptional modification [76].…”