Sepsis-induced brain injuries increase mortality, morbidity, cognitive impairment and lack of effective therapeutic treatment. Previous studies have suggested that metformin provides neuroprotective effects against ischemia, brain trauma and other brain damage, but whether metformin protects a septic brain remains unknown. Thus, the aim of this study is to investigate the possible effects and the mechanism of metformin against septic brain damage using the cecal ligation and puncture (CLP) model. Mice were randomly divided into five groups: the Sham group, CLP group, CLP+ Met group, CLP+ vehicle group and CLP+ Met+ LY group. The survival percentage and brain water content were examined, and the Morris water maze was conducted to determine the protective effect of metformin. Neuronal apoptosis in the cerebral cortex, striatum and hippocampus was examined using TUNEL assay and immunohistochemistry, and western blot was applied to measure the expression of p-Akt. The results indicate that metformin can increase survival percentage, decrease brain edema, preserve the blood-brain barrier (BBB) and improve cognitive function. Metformin also reduced the neuronal apoptosis induced by sepsis and increased the phosphorylation of Akt. However, the protective effect of metformin can be reversed by LY294002, a PI3K inhibitor. In summary, our results demonstrate that metformin can exert a neuroprotective effect by activating the PI3K/Akt signaling pathway.
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and can cause a huge burden to whole families and to society in terms of medical costs. Cognitive disorders induced by sepsis are still exasperating problems in clinical research. This paper examines a new measure of berberine (BBR) in sepsis induced cognitive disorders based on CLP surgery. BBR is one of many extracts from Chinese traditional herbs and exhibits antidiabetic, anticancer and antioxidant activities in treating various clinical disorders. Whether BBR shows efficacy in improving survival rates and inhibiting the extent of cognitive disorders after sepsis was explored in this paper. The result revealed that BBR treatment significantly improved the survival rate and cognitive disorders in septic rats. Increased levels of antioxidant superoxide dismutase (SOD) and reduced levels of lipid peroxidation malondialdehyde (MDA) were exhibited in the serum and brain tissue of the BBR treatment group. Moreover, the inflammatory cytokine (IL-1β, IL-4, IL-6, TNF-α) levels in the brain tissue were all decreased in the BBR treatment group compared to those in the sepsis group. BBR also largely protected the cells from apoptosis in the cerebral cortex and hippocampal CA1 region. Overall, our results indicated that BBR exhibited protective effects on survival rate and cognitive disorders after sepsis by inhibiting the release of inflammatory cytokines, oxidative stress and neuronal apoptosis in brain tissue. Therefore, BBR is a potential drug that shows efficacy in avoiding death rates and cognitive disorder after sepsis.
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