In the present work, the protective role of metformin on sepsis associated encephalopathy (SAE) using cecal ligation and puncture (CLP) model of sepsis was assessed. Metformin has a potent inhibitory role on inflammation and oxidative stress, which inevitably occur in SAE. The complete mechanisms underlying neuroprotective effects of metformin in SAE are still unclear. In the present study, the role of metformin was evaluated on SAE using CLP model of sepsis.
CLP was performed on Wistar rats and 50 mg/kg metformin was administered immediately. Specific markers of sepsis severity, inflammation, blood brain barrier (BBB) dysfunction, and brain injury were investigated. Specific assay kits and real time polymerase chain reaction (RT-PCR) were used. Histopathological assessment was also carried out.
Treatment with metformin decreased murine sepsis score (MSS), lactate, platelet lymphocyte ratio (PLR), and high mobility group box (HMGB1) levels. The expression of claudin 3 and claudin 5 were increased following treatment with metformin. It also decreased the expression of S100B, neuron specific enolase (NSE), and glial fibrillary acidic protein (GFAP).
Our study suggests that metformin may inhibit inflammation and increase tight junction protein expressions which may improve BBB function and attenuate CLP-induced brain injury. Hence, the potential beneficial effects of metformin in sepsis may be considered in future.