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T0901317, a liver X receptor (LXR) agonist, is widely used to explore the functions of LXRs. T0901317 exerts antiapoptotic effects in many central nervous system disease models. Our aim was to detect the role of T0901317 in neuronal apoptosis in early brain injury after subarachnoid hemorrhage. <jats:italic>Methods<\/jats:italic>. Subarachnoid hemorrhage (SAH) models of Sprague\u2010Dawley rats were established with perforation method. T0901317 was injected intraperitoneally 1\u2010hour post\u2010SAH. GSK2033, an inhibitor of LXRs, and interferon regulatory factor (IRF\u20101) CRISPR activation were injected intracerebroventricularly to evaluate potential signaling pathway. The severity of SAH, neurobehavior test in both short\u2010 and long\u2010term and apoptosis was measured with Western blot and immunofluorescence staining. <jats:italic>Results<\/jats:italic>. Expression of LXR\u2010<jats:italic>\u03b1<\/jats:italic> and IRF\u20101 increased and peaked at 24\u2009h post\u2010SAH, while LXR\u2010<jats:italic>\u03b2<\/jats:italic> remained unaffected in SAH+vehicle group compared with Sham group. Post\u2010SAH T0901317 treatment attenuated neuronal impairments in both short\u2010 and long\u2010term and decreased neuronal apoptosis, the expression of IRF\u20101, P53 upregulated modulator of apoptosis (PUMA), dynamin\u20101\u2010like protein (Drp1), Bcl\u20102\u2010associated X protein (Bax) and cleaved caspase\u20103, and increasing B\u2010cell lymphoma 2 (Bcl\u20102) at 24\u2009h from modeling. GSK2033 inhibited LXRs and reversed T0901317\u2019s neuroprotective effects. IRF\u20101 CRISPR activation upregulated the expression of IRF\u20101 and abolished the treatment effects of T0901317. <jats:italic>Conclusion<\/jats:italic>. T0901317 attenuated neuronal apoptosis via LXRs\/IRF\u20101\/PUMA\/Drp1 pathway in SAH rats.<\/jats:p>","DOI":"10.1155\/2021\/8849131","type":"journal-article","created":{"date-parts":[[2021,5,30]],"date-time":"2021-05-30T21:50:09Z","timestamp":1622411409000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["T0901317, an Agonist of Liver X Receptors, Attenuates Neuronal Apoptosis in Early Brain Injury after Subarachnoid Hemorrhage in Rats via Liver X Receptors\/Interferon Regulatory Factor\/P53 Upregulated Modulator of Apoptosis\/Dynamin\u20101\u2010Like Protein Pathway"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5916-9124","authenticated-orcid":false,"given":"Jiaxing","family":"Dai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1111-2409","authenticated-orcid":false,"given":"Shancai","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2916-9398","authenticated-orcid":false,"given":"Takeshi","family":"Okada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6263-1092","authenticated-orcid":false,"given":"Yu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2926-1023","authenticated-orcid":false,"given":"Gang","family":"Zuo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2392-9280","authenticated-orcid":false,"given":"Jiping","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4319-4285","authenticated-orcid":false,"given":"John H.","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3150-6234","authenticated-orcid":false,"given":"Huaizhang","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,5,30]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)30668-7"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70126-7"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-016-0518-y"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-7091-0353-1_8"},{"key":"e_1_2_10_5_2","first-page":"736","article-title":"Liver X receptors (LXRs). 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