The Signaling Pathway Regulates The Change In Morphology Of Microglia During Septic Encephalopathy Of Mice

Sepsis is initiated by an uncontrolled infection that causes a severe systemic inflammatory response and multisystem organ failure. Septic encephalopathy(SE) is a serious complication of sepsis that can lead to cerebral atrophy, cognitive impairment, and even mortality. Septic encephalopathy is the pivotal factor determining sepsis mortality. However, the molecular events of SE that lead to the development of encephalopathy remain unclear. To understand the mechanism of septic encephalopathy is so important. Microglia is important immune cell of brain. So, we should know the change of microglia in impairment brain. In this study, we successfully made sepsis model of mice(CLP model), and to study septic encephalopathy. We found the morphology of microglia was changed during septic encephalopathy. We showed that septic injury initiates up regulation of P2X7 and expressed in microglia. We confirmed that using P2X7 inhibitor A438079 can prevent microglia over activation. Objective: To explore which signal effects on microglia activation during SE. Methods: We successfully made sepsis model of mice, and confirm the impossibility of CLP model by using endotoxin test. After CLP 8h, using immunohistochemical staining, we examined microglia morphology change. Using Western Blot and immunohistochemical staining method to detect changes of P2X7 protein level. Then, we examined the morphology change of microglia with P2X7 inhibitor A438079 during CLP 8h. Results: To compared with control, endotoxin level is high in CLP model. It is confirmed that CLP model can be used to study sepsis. After CLP 8h, miroglia were increased, soma area were became bigger. This morphology change showed that microglial cells were activated in cortex of mice brain. After 8 hours of Sepsis, the P2X7 protein levels in cerebral cortex rise significantly, and expressed in activated microglial cells. P2X7 blocker A438079 after processing, the microglia activation were inhibited. Conclusion: This morphology change showed that microglial cells were activated in cortex of mice brain. After CLP, the P2X7 protein levels were increased, and expressed in activated microglial cells. In the process of sepsis in mice, blocking P2X7 expression can prevent the excessive activation of microglia.