Metabolic Reprogramming: Strategy for Ischemic Stroke Treatment by Ischemic Preconditioning

Simple Summary Ischemic preconditioning triggers endogenous neuroprotection to defend against subsequent, more severe cerebral ischemia. However, the underlying biological mechanisms of ischemic preconditioning are still confusing. Here we provide a summary of metabolic mechanism of ischemic preconditioning when it is applied to ischemic stroke. It has been found that metabolic disorder is a determinant of the incidence and progression of stroke. To maintain the cerebral activity transiently, upon ischemia onset, brain tissues enhance their metabolic plasticity, mainly through energy metabolic reprogramming and antioxidant defense. Growing evidence suggests that ischemic preconditioning takes advantage of brain plasticity for its neuroprotective purposes, among which, metabolic reprogramming is crucial to co-ordinate the metabolic imbalance, especially for energy and redox homeostasis. Objectively, the study on metabolic reprogramming of ischemic preconditioning is still in its infancy, such as, there are extremely few studies on the spatiotemporal variation, aging influence, and astrocyte-neuron interactions in metabolic reprogramming of ischemic preconditioning. Further study focus on ischemic preconditioning metabolic reprogramming is needed, and it will be valuable for exploring the mechanisms of ischemic preconditioning, and will be greatly beneficial for the understanding of ischemic stroke treatment and standardized application of ischemic preconditioning. Abstract Stroke is one of the leading causes of death and permanent disability worldwide. Ischemic preconditioning (IPC) is an endogenous protective strategy, which has been reported to exhibit a significant neuroprotective effect in reducing the incidence of ischemic stroke. However, the underlying neuroprotective mechanisms of IPC remain elusive. An increased understanding of the pathogenic mechanisms of stroke and IPC serves to highlight the importance of metabolic reprogramming. In this review, we summarize the metabolic disorder and metabolic plasticity in the incidence and progression of ischemic stroke. We also elaborate how IPC fully mobilizes the metabolic reprogramming to maintain brain metabolic homeostasis, especially for energy and redox homeostasis, and finally protects brain function in the event of an ischemic stroke.