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However, there is no information about the role of IRE1\u03b1 inhibitor as well as its molecular mechanisms in preventing neuronal pyroptosis induced by NLRP1 (NOD-, LRR- and pyrin domain-containing 1) inflammasome. In the present study, we hypothesized that IRE1\u03b1 can degrade microRNA-125-b-2-3p (miR-125-b-2-3p) and activate NLRP1\/caspased-1 pathway, and subsequently promote neuronal pyroptosis in HIE rat model.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Ten-day old unsexed rat pups were subjected to hypoxia-ischemia (HI) injury, and the inhibitor of IRE1\u03b1, STF083010, was administered intranasally at 1\u2009h after HI induction. AntimiR-125 or NLRP1 activation CRISPR was administered by intracerebroventricular (i.c.v) injection at 24\u2009h before HI induction. Immunofluorescence staining, western blot analysis, reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR), brain infarct volume measurement, neurological function tests, and Fluoro-Jade C staining were performed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Endogenous phosphorylated IRE1\u03b1 (p-IRE1\u03b1), NLRP1, cleaved caspase-1, interleukin-1\u03b2 (IL-1\u03b2), and interleukin-18 (IL-18) were increased and miR-125-b-2-3p was decreased in HIE rat model. STF083010 administration significantly upregulated the expression of miR-125-b-2-3p, reduced the infarct volume, improved neurobehavioral outcomes and downregulated the protein expression of NLRP1, cleaved caspase-1, IL-1\u03b2 and IL-18. The protective effects of STF083010 were reversed by antimiR-125 or NLRP1 activation CRISPR.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>IRE1\u03b1 inhibitor, STF083010, reduced neuronal pyroptosis at least in part via miR-125\/NLRP1\/caspase-1 signaling pathway after HI.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical Abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1186\/s12974-020-01796-3","type":"journal-article","created":{"date-parts":[[2020,5,6]],"date-time":"2020-05-06T14:03:55Z","timestamp":1588773835000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["IRE1\u03b1 inhibition attenuates neuronal pyroptosis via miR-125\/NLRP1 pathway in a neonatal hypoxic-ischemic encephalopathy rat model"],"prefix":"10.1186","volume":"17","author":[{"given":"Juan","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weitian","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desislava Met","family":"Doycheva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Gamdzyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H.","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiping","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,5,6]]},"reference":[{"key":"1796_CR1","doi-asserted-by":"publisher","unstructured":"Schreglmann M, Ground A, Vollmer B, Johnson MJ. 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