PMID- 37295596 OWN - NLM STAT- MEDLINE DCOM- 20230726 LR - 20230726 IS - 1873-7544 (Electronic) IS - 0306-4522 (Linking) VI - 524 DP - 2023 Aug 1 TI - Downregulated Phosphoglycerate Kinase 1 Attenuates Cerebral Ischemia-Reperfusion Injury by Reversing Neuroinflammation and Oxidative Stress through the Nuclear Factor Erythroid 2 Related Factor 2/ARE Pathway. PG - 94-107 LID - S0306-4522(23)00239-7 [pii] LID - 10.1016/j.neuroscience.2023.05.019 [doi] AB - Understanding the role and mechanism of astrocytes in inflammation and oxidative response is crucial for developing therapeutic strategies to reduce inflammation and oxidative injury in cerebral ischemia-reperfusion injury (CIRI). In this study, we investigated the regulatory effects of phosphoglycerate kinase 1 (PGK1) on inflammation and oxidative response after CIRI in male adult Sprague-Dawley (SD) rats and using primary astrocytes obtained from neonatal SD rats, and explored its related mechanisms. We established a rat model of middle cerebral artery occlusion-reperfusion (MCAO/R) by suture occlusion, and an oxygen-glucose deprivation/reoxygenation model of astrocytes using oxygen-free, glucose-free, and serum-free cultures. AAV8-PGK1-GFP was injected into the left ventricle 24 h before modeling. Real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, co-immunoprecipitation (CoIP) assay, fluorescence in situ hybridization (FISH), and western blotting were used to elucidate the in-depth mechanisms of PGK1 in CIRI. PGK1 overexpression significantly exacerbated neurological deficits, increased cerebral infarct volume, and aggravated nerve cell injury in rats after MCAO/R. Using FISH and CoIP assays, we verified the localization of PGK1 and Nrf2 in primary astrocytes. Further rescue experiments showed that Nrf2 knockdown eliminated the protective effect of CBR-470-1 (a PGK1 inhibitor) on CIRI. Lastly, we confirmed that PGK1 aggravates CIRI by inhibiting the Nrf2/ARE pathway. In conclusion, our findings suggest that inhibiting PGK1 attenuates CIRI by reducing the release of inflammatory and oxidative factors from astrocytes by activating the Nrf2/ARE signaling pathway. CI - Copyright (c) 2023 IBRO. Published by Elsevier Ltd. All rights reserved. FAU - Liu, Hua AU - Liu H AD - Department of Neurosurgery, Affiliated Kunshan Hospital of Jiangsu University, Kunshan 215300, China. FAU - Shen, Likui AU - Shen L AD - Department of Neurosurgery, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou 215028, China. FAU - Sun, Zezhi AU - Sun Z AD - Department of Neurosurgery, Affiliated Kunshan Hospital of Jiangsu University, Kunshan 215300, China. FAU - Wu, Wenxi AU - Wu W AD - Department of Neurosurgery, Affiliated Kunshan Hospital of Jiangsu University, Kunshan 215300, China. FAU - Xu, Min AU - Xu M AD - Department of Neurosurgery, Kunshan Hospital of Traditional Chinese Medicine, Kunshan Affiliated Hospital of Nanjing University of Chinese Medicine, Kunshan 215300, China. Electronic address: xumin7788@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230607 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - EC 2.7.2.3 (Phosphoglycerate Kinase) RN - 0 (NF-E2-Related Factor 2) SB - IM MH - Rats MH - Male MH - Animals MH - Rats, Sprague-Dawley MH - Phosphoglycerate Kinase/metabolism/pharmacology MH - Neuroinflammatory Diseases MH - NF-E2-Related Factor 2/metabolism MH - In Situ Hybridization, Fluorescence MH - Oxidative Stress MH - Infarction, Middle Cerebral Artery/metabolism MH - *Reperfusion Injury/metabolism MH - *Brain Ischemia/metabolism OTO - NOTNLM OT - Cerebral ischemia-reperfusion injury OT - Inflammatory response OT - Oxidative response OT - Phosphoglycerate kinase 1 COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/06/10 15:13 MHDA- 2023/07/26 06:43 CRDT- 2023/06/09 19:25 PHST- 2022/12/20 00:00 [received] PHST- 2023/05/15 00:00 [revised] PHST- 2023/05/23 00:00 [accepted] PHST- 2023/07/26 06:43 [medline] PHST- 2023/06/10 15:13 [pubmed] PHST- 2023/06/09 19:25 [entrez] AID - S0306-4522(23)00239-7 [pii] AID - 10.1016/j.neuroscience.2023.05.019 [doi] PST - ppublish SO - Neuroscience. 2023 Aug 1;524:94-107. doi: 10.1016/j.neuroscience.2023.05.019. Epub 2023 Jun 7.