Intraperitoneal hypertension, a novel risk factor for sepsis-associated encephalopathy in sepsis mice

Abstract

Sepsis associated encephalopathy (SAE), appears often indicates the deterioration of the sepsis disease and which have high risk of death. Although several mechanism and hypotheses have been proposed and studied, there is no breakthrough in the treatment of SAE. We performed a systematic research to evaluate the effect of intraperitoneal pressure on SAE. A mice model of sepsis was established by intraperitoneal injection of endotoxin. A total of 48 female BALB/c mouse (30 days old) were randomly divided into a control group (n = 12) and an injection of endotoxin referred to bacterial lipopolysaccharide (LPS) group (n = 12). Intraperitoneal hypertension (IAH) referred to IAH group (n = 12), and LPS + IAH group (n = 12). Following sepsis induction, diagnosis, the brains were analyzed for both function and ultrastructural morphology.We determined that IAH exacerbated sepsis induces sepsis-associated encephalopathy when examining low score of neurological function and more delta wave in EEG, increased neuronal edema in LPS + IAH group, as well as an escalation of Bax and Cleaved-caspase-3, Cleaved-parp, and reduction of Bcl-2 and Mfsd2a in LPS + IAH group. Therefore, IAH can exacerbate and increase incident rate of sepsis-related encephalopathy in sepsis mice by promoting neuronal apoptosis and destruction of the blood-brain barrier.