{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T03:49:27Z","timestamp":1794368967074,"version":"4.9.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T00:00:00Z","timestamp":1688515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Key Clinical Support Specialty Construction"},{"name":"Shanghai Hongkou District","award":["HKZK2020A10"],"award-info":[{"award-number":["HKZK2020A10"]}]},{"name":"Shanghai Hongkou District Science and Technology Committee"},{"name":"Special Project for Clinical Research in Health Industry of Shanghai Municipal Health Commission","award":["202140259"],"award-info":[{"award-number":["202140259"]}]},{"name":"Medical Scientific Research Project of Shanghai Hongkou District Health Commission","award":["2102-21, 2103-10"],"award-info":[{"award-number":["2102-21, 2103-10"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,7,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Vitamin D supplementation is reported to have anti-inflammatory and neuroprotective effects during cerebral ischemia-reperfusion injury (CIRI), but the protective mechanism has not been fully elucidated. In this study, rats were given prior administrations of 1,25-vitamin D3 (1,25-VitD3) for a week and subjected to 2\u2009hours of middle cerebral artery occlusion (MCAO) followed by 24\u2009hours of reperfusion. Supplementation with 1,25-VitD3 significantly reduced neurological deficit scores and cerebral infarction areas, and increased surviving neurons. Oxygen-glucose deprivation\/reoxygenation (OGD\/R)-induced rat cortical neuron cells (RN-C) were subjected to 1,25-VitD3 treatment. Administration of 1,25-VitD3 improved cell viability and inhibited lactate dehydrogenase (LDH) activity and cell apoptosis in OGD\/R-stimulated RN-C, as assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-h-tetrazolium bromide (MTT) assay, LDH activity assays and TdT-mediated dUTP nick end labeling (TUNEL) staining, respectively. Notably, western blot assay showed that 1,25-VitD3 upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) to alleviate oxidative stress, but reduced proteins and inflammatory cytokines related to NLR pyrin domain containing 3 (NLRP3)-mediated pyroptosis, resulting in decreased pyroptosis and neuroinflammation in vivo and in vitro. Transfection of pcDNA-Nrf2 in RN-C also inhibited pyroptosis and OGD\/R-induced cell death whereas breakdown of Nrf2 signals destroyed the protective effect of 1,25-VitD3 on OGD\/R-stimulated RN-C. In conclusion, 1,25-VitD3 protects neurons against CIRI through activating the antioxidant Nrf2\/HO-1 pathway to restrain NLRP3-mediated pyroptosis.<\/jats:p>","DOI":"10.1093\/jnen\/nlad047","type":"journal-article","created":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T16:50:23Z","timestamp":1688575823000},"page":"722-733","source":"Crossref","is-referenced-by-count":29,"title":["Vitamin D alleviates neuronal injury in cerebral ischemia-reperfusion via enhancing the Nrf2\/HO-1 antioxidant pathway to counteract NLRP3-mediated pyroptosis"],"prefix":"10.1093","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7149-4560","authenticated-orcid":false,"given":"Jinling","family":"Qiao","sequence":"first","affiliation":[{"name":"Neurorehabilitation High Dependency Unit (HDU), Department of Neurology, Jiangwan Hospital , Hongkou District , Shanghai, 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