Ischemic stroke is a major cause of long-term disability. Neuronal differentiation of neural stem cells (NSCs) is crucial for brain repair after stroke. However, the underlying mechanisms remain unclear. Here, the role and potential mechanisms of phosphofructokinase-1 (PFK-1), the rate-limiting enzyme of glycolysis, was investigated in stroke using middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation models. We found that stroke increased the PFK-1 expression of NSCs. However, PFK-1 inhibition promoted neuronal differentiation of NSCs and facilitated the dendritic maturation of newborn neurons in vitro and in vivo. Moreover, PFK-1 inhibition also improved the spatial memory performance of MCAO rats. Additionally, we proved that the effect of PFK-1 inhibition above might be achieved by promoting β-catenin nuclear translocation and activating its downstream signaling, independent of Wnt signaling. Thus, these observations reveal a critical role of PFK-1 in stroke, which may provide a novel target for regenerative repair after stroke.

缺血性中风是导致长期残疾的主要原因。神经干细胞 (NSC) 的神经元分化对于中风后的大脑修复至关重要。然而，潜在的机制仍不清楚。在这里，使用大脑中动脉闭塞 (MCAO) 和氧-葡萄糖剥夺模型研究了磷酸果糖激酶-1 (PFK-1)（糖酵解的限速酶）在中风中的作用和潜在机制。我们发现中风增加了 NSCs 的 PFK-1 表达。然而，PFK-1抑制促进了NSCs的神经元分化，并促进了新生神经元在体外和体内的树突成熟。. 此外，PFK-1 抑制还改善了 MCAO 大鼠的空间记忆能力。此外，我们证明了上述 PFK-1 抑制作用可能是通过促进β -catenin 核转位和激活其下游信号传导来实现的，而与 Wnt 信号传导无关。因此，这些观察结果揭示了 PFK-1 在中风中的关键作用，这可能为中风后的再生修复提供新的靶点。