Establishment of a mouse model of sepsis associated encephalopathy and preliminary research of cognitive dysfunction in this model

AIM: To establish the mouse model of sepsis-associated encephalopathy (SAE) and the preliminary research of cognitive dysfunction in this model. METHODS: SPF male C57BL/6J mice of 8~10 weeks old were selected. The first part of the experiment divided the mice into 4 groups randomly, namely control group, cecal ligation and puncture (CLP)1 group and CLP2 group (CLP was performed with 7 and 12 syringe needle respectively). The mice in sham operation group were only laparotomy. In the second part of the experiment, the mice were randomly divided into control group, sham operation group and CLP group. The Kaplan-Meier method was used to analyze the postoperative survival rate of the mice in the first part experiment. The neurobehavioral scores were used to evaluate the neurobehavioral changes of the mice. The Morris water maze test and the passive avoidance experiment were used to detect the changes of cognitive memory function in the mice. The pole test and the wire suspension test were used to test the motor coordination of the mice. The serum levels of prostaglandin E2 (PGE₂) were measured by ELISA. RESULTS: In the first part of the experiment, the CLP mice showed obvious symptoms such as lethargy, piloerection, chills and anorexia. The 48 h mortality in CLP1 group and CLP2 group were 20% and 30% respectively. In the 2 parts of the experiments, the neurobehavioral scores of the CLP mice were significantly lower than those in control group and the sham operation group (P<0.01). In CLP mice, the escape latency time of the Morris water maze was significantly prolonged (P<0.01), the target quadrant dwell time and the number of crossing platforms were decreased (P<0.01), the scores in the suspension experiment and the pole test were significantly reduced (P<0.01), the activity of the mice was decreased or even did not enter the darkroom in the step-through test (P<0.05). In the second part of the experiment, the serum level of PGE₂ in the mice after CLP was significantly increased (P<0.01). CONCLUSION: A stable mouse model of sepsis-associated encephalopathy is successfully established by cecal ligation and puncture with 12 syringe needle. The SAE mouse model established by this method is useful for investigating the learning and memory cognitive dysfunction.