文章基本信息

标题：Glycogenolysis Is Crucial for Astrocytic Glycogen Accumulation and Brain Damage after Reperfusion in Ischemic Stroke
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作者：Yanhui Cai ; Haiyun Guo ; Ze Fan 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：5
页码：1-67
DOI：10.1016/j.isci.2020.101136
语种：English
出版社：Elsevier
摘要：SummaryAstrocytic glycogen is an important energy reserve in the brain and is believed to supply fuel during energy crisis. However, the pattern of glycogen metabolism in ischemic stroke and its potential therapeutic impact on neurological outcomes are still unknown. Here, we found extensive brain glycogen accumulation after reperfusion in ischemic stroke patients and primates. Glycogenolytic dysfunction in astrocytes is responsible for glycogen accumulation, caused by inactivation of the protein kinase A (PKA)-glycogen phosphorylase kinase (PhK)-glycogen phosphorylase (GP) cascade accompanied by the activation of glycogen synthase kinase-3β (GSK3β). Genetic or pharmacological augmentation of astrocytic GP could promote astrocyte and neuron survival and improve neurological behaviors. In addition, we found that insulin exerted a neuroprotective effect, at least in part by rescuing the PKA-PhK-GP cascade to maintain homeostasis of glycogen metabolism during reperfusion. Together, our findings suggest a promising intervention for undesirable outcomes in ischemic stroke.Graphical AbstractDisplay OmittedHighlights•Glycogen accumulates upon cerebral reperfusion in humans, primates, and rodents•Impaired glycogenolysis underlies excess glycogen during cerebral reperfusion•Activating glycogenolysis protects against acute and subacute reperfusion insult•Insulin mediates neuroprotection partly by rescuing glycogenolysis upon reperfusionNeuroscience; Molecular Neuroscience; Cellular Neuroscience