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Rat and cellular model of SAH were introduced in this study, and betulin, an activator of DJ\u20101 protein, was administered to reveal the effect. Gross assessment regarding mortality, neurofunctions, SAH grade, brain water content (BWC) along with multiple cellular and molecular studies in\u00a0vivo or\/and in\u00a0vitro such as immunofluorescence (IF) staining, western blot (WB), reactive oxygen species (ROS) assay, and flow cytometry (FCM) were all conducted after SAH induction to verify the protective effect and the relevant mechanisms of DJ\u20101 in diverse levels. In addition, MK2206 (selective inhibitor of Akt) and iRNA<jats:italic>Dj\u20101<\/jats:italic> (interfering RNA to <jats:italic>Dj\u20101<\/jats:italic>) were utilized to confirm the mechanisms of the effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The data from our study showed that DJ\u20101 protein was moderately expressed in neurons, microglia, and astrocytes; its level in brain tissue elevated and peaked at 24\u201372\u2009h after SAH induction. Betulin could efficaciously induce the expression of DJ\u20101 which in turn activated Akt and Bcl\u20102, and anti\u2010oxidative enzymes SOD2 and HO\u20101, functioning to reduce the activation of cleaved caspase\u20103 (c\u2010Casp\u20103) and reactive oxygen species (ROS). The induced DJ\u20101 could upregulate the expression of Nrf2. However, Akt seemed no direct effect on elevating the expression of Nrf2. DJ\u20101 alone could as well activate Akt\u2010independent antiapoptotic pathway via suppressing the activation of caspase\u20108 (Casp\u20108).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Betulin which was a potent agonist of DJ\u20101 had the ability to induce its expression in brain tissue. DJ\u20101 had neuroprotective effect on EBI through comprehensive mechanisms, including facilitating intrinsic and extrinsic antiapoptotic pathway, and reducing oxidative injury by upregulating the expression of redox proteins. Betulin as an inexpensive drug showed the potential for SAH treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.70019","type":"journal-article","created":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T04:29:08Z","timestamp":1725596948000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Betulin ameliorates neuronal apoptosis and oxidative injury via <scp>DJ<\/scp>\u20101\/Akt\/Nrf2 signaling pathway after subarachnoid hemorrhage"],"prefix":"10.1111","volume":"30","author":[{"given":"Xiaoyang","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, The First People's Hospital of Yunnan Province The Affiliated Hospital of Kunming University of Science and Technology  Kunming Yunnan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First People's Hospital of Yunnan Province The Affiliated Hospital of Kunming University of Science and Technology  Kunming Yunnan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qixiong","family":"Lu","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Kunming University of Science and Technology. 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