Protective Effect Of Metformin On Brain Injury In Lipopolysaccharide Induced Sepsis Mice

Background:Inflammation-based brain damage is a serious complication of sepsis,associated with high risk of death and poor prognosis.Metformin is a first-line antidiabetic drug.Recent studies have revealed the profound anti-inflammatory effects of metformin.Objective:To explore the potential effect of metformin on brain damage in mice with LPS-induced systemic inflammation.Methods:Lipopolysaccharide(LPS,20 mg/kg)was intraperitoneally injected to male BALB/c mice to induce sepsis-like systemic inflammation.Metformin(400mg/kg)was given intraperitoneally half an hour before LPS injection.Plasma and brains samples were harvested 18 hours after LPS administration.The levels of neuron-specific enolase(NSE)and soluble protein100-β(S100-β)in plasma and the levels of TNF-α,IL-6,malondialdehyde(MDA)and myeloperoxidase(MPO)in brains samples were determined.Evans blue dye was used to evaluate the permeability of the blood-brain barrier(BBB).Hematoxylin and eosin staining was performed for the histological examination.Results:The results indicated that LPS exposure induced large quantities of degenerative neurons widespreading hippocampal CA1,CA3 regions and cerebral cortex based,these abnormalities were attenuated in mice received metformin administration.Treatment with metformin suppressed LPS induced elevation of NSE and S100-β in plasma and inhibited LPS-induced upregulation of MDA in brain tissue.In addition,the elevated Evans blue content in the brain from LPS-insulted mice was down regulated by metformin.Treatment with metformin decreased the content of TNF-α,IL-6 and MPO in the brain tissue from LPS-insulted mice.Conclusion:These data indicated that metformin alleviated LPS-induced brain damage,these beneficial effects were associated with suppressed inflammatory response and attenuated oxidative stress.These data suggests that metformin might have value in the prevention of sepsis-associated brain damage.