Metformin Attenuates Brain Injury By Inhibiting Inflammation And Regulating Tight Junction Proteins In Septic Rats

Document Type : Original Article


1 Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran

2 School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

3 . Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, Ardabil, Iran

4 . Faculty of Pharmacy, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran


Objective: Metformin has a potent inhibitory activity against inflammation and oxidative stress, which inevitably occur
in sepsis-associated encephalopathy (SAE). The precise mechanisms underlying neuroprotective effects of metformin in SAE, are still unclear. In the present work, the protective effect of metformin on SAE using cecal ligation and puncture (CLP) model of sepsis, was assessed.
Materials and Methods: In this experimental study, CLP procedure was performed in 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.
Results: Treatment with metformin decreased murine sepsis score (MSS), lactate, platelet lymphocyte ratio (PLR), and high mobility group box (HMGB1) levels. The expression levels of claudin 3 (Cldn3) and claudin 5 (Cldn5) were increased following treatment with metformin. Metformin decreased the expression of S100b, neuron specific enolase (Nse), and glial fibrillary acidic protein (Gfap).
Conclusion: 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, should be considered in future.