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Neuronal cell damage involving mitochondrial dysfunction plays an important role in the pathogenesis of SCII. Despite the availability of various treatment options, there are currently no mitochondria\u2010targeting drugs that have proven effective against SCII. Polydatin (PD), a glucoside of resveratrol, is known to preserve mitochondrial function in central nervous system (CNS) diseases. The aim of the present study was to explore the neuro\u2010 and mito\u2010protective functions of PD and its underlying mechanisms. An\n                    <jats:italic>in vitro<\/jats:italic>\n                    model of SCII was established by exposing spinal cord motor neurons (SMNs) to oxygen\u2013glucose\u2010deprivation\/reperfusion (OGD\/R), and the cells were treated with different dosages of PD for varying durations. PD improved neuronal viability and protected against OGD\/R\u2010induced apoptosis and mitochondrial injury in a dose\u2010dependent manner. In addition, PD restored the activity of neuronal mitochondria in terms of mitochondrial membrane potential (MMP), intracellular calcium levels, mitochondrial permeability transition pore (mPTP) opening, generation of reactive oxygen species (ROS), and adenosine triphosphate (ATP) levels. Mechanistically, PD downregulated Keap1 and upregulated Nrf2, NQO\u20101, and HO\u20101 in the OGD\/R\u2010treated SMNs. Likewise, PD treatment also reversed the neuronal and mitochondrial damage induced by SCII in a mouse model. Furthermore, the protective effects of PD were partially blocked by the Nrf2 inhibitor. Taken together, PD relieves mitochondrial dysfunction\u2010induced neuronal cell damage by activating the Nrf2\/ARE pathway and is a suitable therapeutic option for SCII.\n                  <\/jats:p>","DOI":"10.1155\/2021\/6687212","type":"journal-article","created":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T18:54:46Z","timestamp":1619031286000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Polydatin Attenuates OGD\/R\u2010Induced Neuronal Injury and Spinal Cord Ischemia\/Reperfusion Injury by Protecting Mitochondrial Function via Nrf2\/ARE Signaling 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