星形胶质细胞和小胶质细胞的糖酵解途径是神经元进行有氧代谢的底物来源，PFKFB3是促进两种胶质细胞糖酵解的关键酶。已报道，增强糖酵解能够缓解缺血性脑卒中引起的能量危机并降低神经元死亡，该过程与PFKFB3表达提升和两种胶质细胞活化状态相关，但具体作用机制不清。我们前期研究也发现，PFKFB3敲除小鼠缺血性脑卒中梗死面积增大，神经元凋亡增多，两种胶质细胞呈现异常活化。结合已有研究，我们推测在缺血性脑卒中发生时，PFKFB3可能通过介导糖酵解途径改变星形胶质细胞和/或小胶质细胞活化状态，进而影响两种胶质细胞对神经元的能量支持作用。因此，本项目将利用两种胶质细胞分别或同时敲除PFKFB3小鼠，在缺血性脑卒中模型下，比较疾病的临床病理特征、神经元凋亡、胶质细胞活化及糖酵解关键调控靶点和产物的差异，揭示PFKFB3在缺血性脑卒中神经保护方面的作用机理，为神经保护药物研究提供理论基础。

Astrocyte and microglia provide the substrate to the aerobic metabolism of neuron by normal glycolysis, PFKFB3 is an important enzyme which modulates the glycolysis in glial cells. Recent reports have shown enhanced glycolysis was neuroprotective in the crisis of energy metabolism caused by cerebral ischemic stroke, the effect is relative to expression of PFKFB3 and activation of glial cells, but the mechanism is still unclear. In our previous study, we found the infarct size of PFKFB3 knockout mice after photochemically induced cerebral ischemia was significantly increased compared to the wild-type mice, the increase of apotosis of neurons and the abnormal activation of astrocytes and microglias were easily observed in the lesion location. Therefore, we speculate PFKFB3-mediated glycolysis participates in regulating activation of glial cells in cerebral ischemic stroke, and then affects energy support of glial cells. In this study, we will utilize astrocyte-specific, microglia-specific and astrocyte-microgila-specific PFKFB3 knockout mice to evaluate clinical and pathological characteristics, apotosis of neuron, activation of glial cells and key targets and products of glycolysis in photothrombotic ischemia mice model. The expected results may reveal neuroprotective mechanism of PFKFB3 in cerebral ischemic stroke, which will provide the theoretical basis for development of neuroprotective drugs.