| Summary: | Objective To explore the mitigative effect of metformin on brain damage in mice with lipopolysaccharide (LPS)-induced sepsis. Methods A total of 104 male BALB/c mice were randomly divided into 4 groups (n=26), that is, control, metformin, LPS and LPS+metformin group. LPS of 20 mg/kg was intraperitoneally injected to mice to induce sepsis-like systemic inflammation, and metformin (400 mg/kg) was given intraperitoneally in 0.5 h before LPS injection. Serum and brain samples were harvested 18 h after LPS administration. HE staining was performed for the histological observation in the brain tissues. Evans blue staining was used to evaluate the permeability of the blood-brain barrier (BBB). The activity of Caspase-3, content of malondialdehyde (MDA), and levels of IL-6, TNF-α and myeloperoxidase (MPO) in brain samples, and the levels of neuron-specific enolase (NSE) and soluble protein100-β (S100-β) in serum were determined with corresponding reagent testing kits. Results In the morphological observation on hippocampal CA1 and CA3 regions and cerebral cortex, the results indicated that LPS exposure induced large quantities of widespreading degenerative neurons, and these abnormalities were attenuated in mice receiving metformin administration. The elevated Evans blue content in the brain from LPS-insulted mice was decreased by metformin (P < 0.05). Treatment with metformin suppressed LPS-induced elevation of NSE and S100-β in the serum (P < 0.05). The activity of Caspase-3 was significantly higher in LPS group than the control group (P < 0.01), while the activity of Caspase-3 in LPS+metformin group was lower than in LPS group (P < 0.05), which was higher than that in control group and metformin group (P < 0.05). Metformin treatment decreased the contents of IL-6, TNF-α and MPO in the brain tissue from LPS-insulted mice (P < 0.05). In addition, metformin treatment inhibited LPS-induced increase of MDA in brain tissue (P < 0.01). Conclusion Metformin alleviates LPS-induced brain damage, which may associated with protection of BBB, inhibition of apoptosis, suppressed inflammatory response and attenuated oxidative stress. Metformin might have therapeutic value in sepsis-associated brain damage.
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