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Stroke is the third main reason of mortality, which is the leading reason for adult disability in the globe. Poststroke inflammation is well known to cause acute ischemic stroke\u2010 (AIS\u2010) induced brain injury (BI) exacerbation. Celastrol (CL) has exhibited anti\u2010inflammatory activities in various inflammatory traits though underlying mechanisms remain unknown. So, the present investigation is aimed at studying CL protective mechanism against AIS\u2010induced BI. <jats:italic>Methods<\/jats:italic>. A mouse model regarding middle cerebral artery occlusion and an oxygen\u2010glucose deprivation (OGD) cell model with or not CL treatment were constructed to study CL protective effects. NF\u2010E2\u2010related factor 2 (Nrf2) was then silenced in BV2 microglia cells (BV2) to study Nrf2 role regarding CL\u2010mediated neuroprotection. <jats:italic>Results<\/jats:italic>. The results showed that CL treatment suppressed AIS\u2010induced BI by inhibiting NLRP3\/caspase\u20101 pathway activations and induction of apoptosis and pyroptosis <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>. NLRP3\/caspase\u20101 pathway blocking activation suppressed OGD\u2010induced cell pyroptosis and apoptosis. Also, CL treatment reversed OGD\u2010induced microglial injury by promoting Nrf2\/heme oxygenase\u20101 (HO\u20101) pathway activations. Nrf2 downregulation reversed CL protective effects against OGD\u2010induced microglial injury, pyroptosis, and apoptosis. <jats:italic>Conclusion<\/jats:italic>. The findings advise that CL treatment ameliorated AIS\u2010induced BI by inhibiting microglial injury and activating the Nrf2\/HO\u20101 pathway.<\/jats:p>","DOI":"10.1155\/2023\/1076522","type":"journal-article","created":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T22:50:07Z","timestamp":1681253407000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Celastrol Treatment Ameliorated Acute Ischemic Stroke\u2010Induced Brain Injury by Microglial Injury Inhibition and Nrf2\/HO\u20101 Pathway 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