Metformin mitigates early brain injury after subarachnoid hemorrhage primarily by Sirt1 mediated inflammation and neuroapoptosis

Background: Clinically, early brain injury (EBI) which refers to the acute injuries to the whole brain in the phase of the first 72 h following subarachnoid hemorrhage (SAH), is intensely investigated to improve neurological and psychological function. Apoptosis and inflammation factors are crucial pathophysiological processes in EBI. It had been revealed that metformin (Met) possesses extensive functions, all can be shown in anti-inflammatory, antiapoptotic, and anti-tumor activities. However, the effect has not been clarified in EBI after SAH. Here, the study was performed to evaluate the neuroprotective effects and mechanisms of Met in EBI after SAH. Methods: and results Firstly, we reviewed a clinical retrospective analysis to predict the effect of Met. Secondly, we explored the anti-inflammatory and antiapoptotic effects of Met in vivo. A total of 165 male C57BL/6 were randomly divided into seven groups. SAH grade, Neurological function, Brain edema, and Blood–brain barrier (BBB) permeability were evaluated using a grading system. The apoptosis was observed using the TUNEL assay. The levels of TNF-α, IL-1β, IL-6, and c reaction protein (CRP) as well as the expressions of Bax, Bcl, and Cleaved-Caspase 3 were performed. The results showed that Met reduced brain edema, attenuated BBB permeability, and inhibited apoptosis and inflammation. Conclusions: These results indicate that Met reduces the inflammatory response and alleviates early brain injury after SAH, primarily by increasing SIRT1 levels and inhibiting inflammation factors.