脓毒性脑病是感染后全身炎症反应所致的弥漫性大脑功能障碍和意识改变，是病人早期死亡及中后期认知功能障碍的独立危险因素。但脓毒性脑病的病因和病理机制非常复杂，确切机制尚未完全明确。星形胶质细胞在中枢神经系统信息的传导与处理及损伤的修复发挥重要作用。抑制星形胶质细胞TRPM2通道活性可提高其生存率,推测星形胶质细胞TRPM2通道的诱导表达与星形胶质细胞的凋亡密切相关。本项目拟在建立脓毒性脑病模型基础上，观察野生型和TRPM2基因敲除小鼠海马齿状回神经细胞凋亡及星形胶质细胞活化规律，膜片钳检测海马脑片突触功能，检测TRPM2/AIF/EndoG通路上下游分子表达特点，观察小鼠认知功能改变；并通过离体星形胶质细胞培养，论证TRPM2/TLR-4/NF-κBp65通路在免疫损伤中的作用机制。这将为探索星形胶质细胞TRPM2通道在脓毒性脑病中的作用及发病机制提供理论依据，对脑损伤康复具有重要临床意义。

Sepsis associated encephalopathy (SAE) is a diffuse cerebral dysfunction resulted by systemic inflammatory response.SAE is the most common form of encephalopathy in critical ill patients with poor prognosis. Astrocytes not only constitute the basic skeleton of the central nervous system, and is involved in the conduction of the central nervous system information and processing, important participant in the functional activity of the central nervous system. Biphasic effect of lipopolysaccharide can lead to the astrocytes activation or apoptosis, and activation of astrocytes on neuronal protection and toxicity. Calcium homeostasis and abnormal calcium signaling may be a key factor in the activation of astrocytes. The type of transient receptor potential M2 (TRPM2) channel is a non-selective calcium channel that is highly expressed in the brain. The project intends to observe hippocampus dentate gyrus neuron apoptosis and activation of astrocytes in the LPS induced brain damage model. We are to detect hippocampal slice synaptic function with patch-clamp, detect TRPM2/AIF/EndoG pathway gene and protein expression, and observe changes in cognitive function. Further, the mechanism of TRPM2/TLR-4/NF-κBp65 pathway in LPS induced brain damage will be demonstrated. Both in vitro and in vivo data point to the role of astrocytes as both major source and target of LPS induced brain damage signaling. In this study, understanding the astroglial inflammatory response occurring in brain tissue may provide new strategies for targeting astrocyte-mediated LPS induced brain damage. Inhibition of cell TRPM2 channel activation may improve the survival rate of astrocytes. Lack of specific agonists or blockers is still very limited understanding of the TRPM2 channel, therefore the introduction of TRPM2-/- mice establish LPS sepsis model to study astrocytes TRPM2 LPS induced brain damage mechanism , can provide the basis for the treatment of septic encephalopathy.