Abstract | BACKGROUND: Astrocytic glycogen works as an essential energy reserve for surrounding neurons and is reported to accumulate excessively during cerebral ischemia/reperfusion (I/R) injury. Our previous study found that accumulated glycogen mobilization exhibits a neuroprotective effect against I/R damage. In addition, ischemia could transform astrocytes into A1-like (toxic) and A2-like (protective) subtypes. However, the underlying mechanism behind accumulated glycogen mobilization-mediated neuroprotection in cerebral reperfusion injury and its relationship with the astrocytic A1/A2 paradigm is unknown. METHODS: RESULTS: Here, we observed that astrocytic glycogen mobilization inhibited A1-like astrocytes and enhanced A2-like astrocytes after reperfusion in an experimental ischemic stroke model in vivo and in vitro. In addition, glycogen mobilization could enhance the production of NADPH and glutathione by the pentose phosphate pathway (PPP) and reduce ROS levels during reperfusion. NF-κB inhibition and STAT3 activation caused by a decrease in ROS levels were responsible for glycogen mobilization-induced A1-like and A2-like astrocyte transformation after I/R. The astrocytic A1/A2 paradigm is closely correlated with glycogen mobilization-mediated neuroprotection in cerebral reperfusion injury. CONCLUSIONS: Our data suggest that ROS-mediated NF-κB inhibition and STAT3 activation are the key pathways for glycogen mobilization-induced neuroprotection and provide a promising metabolic target for brain reperfusion injury in ischemic stroke.
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Authors | Haiyun Guo, Ze Fan, Shiquan Wang, Lina Ma, Jin Wang, Doutong Yu, Zhen Zhang, Lin Wu, Zhengwu Peng, Wenming Liu, Wugang Hou, Yanhui Cai |
Journal | Journal of neuroinflammation
(J Neuroinflammation)
Vol. 18
Issue 1
Pg. 230
(Oct 13 2021)
ISSN: 1742-2094 [Electronic] England |
PMID | 34645472
(Publication Type: Journal Article)
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Copyright | © 2021. The Author(s). |
Chemical References |
- Reactive Oxygen Species
- Glycogen
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Topics |
- Animals
- Animals, Newborn
- Astrocytes
(metabolism, pathology)
- Brain Ischemia
(metabolism, pathology, prevention & control)
- Coculture Techniques
- Female
- Glycogen
(metabolism)
- Ischemic Stroke
(metabolism, pathology, prevention & control)
- Male
- Mice
- Mice, Inbred C57BL
- Neuroprotection
(physiology)
- Reactive Oxygen Species
(metabolism)
- Reperfusion Injury
(metabolism, pathology, prevention & control)
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