Esmolol inhibits cognitive impairment and neuronal inflammation in mice with sepsis-induced brain injury

Abstract

Abstract Sepsis is a potentially fatal organ failure resulting from a dysregulated host response to infection. It can be a substantial financial burden on families and society due to the high cost of medical care. The study aims to investigate the protective roles of Esmolol in mice with sepsis-induced brain injuries against cognitive dysfunction and neuronal inflammation. Male C57BL/6J mice were intraperitoneally injected with LPS (10 mg/kg, L2630, Sigma) to establish a septic encephalopathy model. Esmolol (15 mg/kg/h, HY-B1392, MedChemExpress) was subcutaneously infused using osmotic mini-pumps for 6 h before LPS injection. Morris water maze and novel object recognition tests evaluated LPS-induced cognitive impairment and behavioral phenotypes. Cytokines and protein expression were assessed using ELISA assay and RT-qPCR. Esmolol treatment potentially improved cognitive impairment in septic mice. Esmolol administration markedly diminished the abnormal hippocampal neuronal structure, and the expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α was significantly downregulated in the hippocampal tissue. Esmolol treatment significantly reduced apoptotic TUNEL-positive cells and reversed the related gene expression (BAX and BCL-2). The effects of esmolol on the reactive oxidative species and oxidative stress markedly reduce malondialdehyde MDA content and increase superoxide dismutase and catalase in hippocampal tissues. In addition, esmolol significantly reduced the percentage and density of Iba-1 + microglia in septic mice. Our results demonstrated that esmolol potentially improved cognitive impairment and neuronal inflammation in mice with sepsis-induced brain injury.