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The focus of the present study is to evaluate the effects of Angiotensin II (Ang II) on neuronal apoptosis after HIE and the potential underlying mechanisms. Methods. Primary neonatal rat cortical neurons were used to study the oxygen-glucose deprivation (OGD) cell model. The expressions of Ang II, AT1R, GSK-3\u03b2, p-GSK-3\u03b2, mTOR, p-mTOR, Bax, Bcl-2, and cleaved caspase-3 were detected via western blot. IF and flow cytometry were used to evaluate neuronal apoptosis. Hypoxic-ischemic encephalopathy (HIE) was established to evaluate the therapeutic effects of Ang II in vivo. Cerebral infarction areas were detected by 2,3,5-Triphenyltetrazolium chloride staining. The righting and geotaxis reflexes were also recorded. In addition, Fluoro-Jade C staining and TUNEL staining were performed to evaluate neuronal degeneration and apoptosis. Results. Ang II significantly increased the rate of neuronal apoptosis, upregulated the expression of cleaved caspase-3, and downregulated Bcl-2\/Bax ratio after OGD insult. For vivo assay, the expressions of endogenous Ang II and AT1R gradually increased and peaked at 24\u2009h after HIE. Ang II increased NeuN-positive AT1R cell expression. In addition, Ang II increased the area of cerebral infarction, promoted neuronal degeneration and apoptosis, aggravated neurological deficits on righting and geotaxis reflexes, and was accompanied by increased expressions of phosphorylated GSK-3\u03b2 and mTOR. The application of valsartan (Ang II inhibitor) or SB216763 (GSK-3\u03b2 inhibitor) reversed these phenomena triggered by Ang II following HIE. Conclusion. Ang II increased neuronal apoptosis through the AT1R\/GSK-3\u03b2\/mTOR signaling pathway after experimental HIE both in vitro and in vivo, and Ang II may serve as a novel therapeutic target to ameliorate brain injury after HIE.<\/jats:p>","DOI":"10.1155\/2020\/8864323","type":"journal-article","created":{"date-parts":[[2020,12,23]],"date-time":"2020-12-23T23:05:08Z","timestamp":1608764708000},"page":"1-14","source":"Crossref","is-referenced-by-count":9,"title":["AT1R\/GSK-3\u03b2\/mTOR Signaling Pathway Involved in Angiotensin II-Induced Neuronal Apoptosis after HIE Both In Vitro and In Vivo"],"prefix":"10.1155","volume":"2020","author":[{"given":"Wei","family":"Si","sequence":"first","affiliation":[{"name":"Department of Neurology, Guizhou Provincial People\u2019s Hospital, Guiyang 550002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Banghui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Guizhou Provincial People\u2019s Hospital, Guiyang 550002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron","family":"Lenahan","sequence":"additional","affiliation":[{"name":"Burrell College of Osteopathic Medicine, Las Cruces, NM 88003, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Guizhou Provincial People\u2019s Hospital, Guiyang 550002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Guizhou Provincial People\u2019s Hospital, Guiyang 550002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Guizhou Provincial People\u2019s Hospital, Guiyang 550002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Guizhou Provincial People\u2019s Hospital, Guiyang 550002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiapeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Guizhou Provincial People\u2019s Hospital, Guiyang 550002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Neurology, Guizhou Provincial People\u2019s Hospital, Guiyang 550002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Guizhou Provincial People\u2019s Hospital, Guiyang 550002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"XikeWang","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Guizhou Provincial People\u2019s Hospital, Guiyang 550002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3216-6094","authenticated-orcid":true,"given":"Xiao","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Guizhou Provincial People\u2019s Hospital, Guiyang 550002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2926-1023","authenticated-orcid":true,"given":"Gang","family":"Zuo","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Taicang Hospital Affiliated to Soochow University, Taicang, Suzhou, Jiangsu 215400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.4103\/1817-1745.205646"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17122078"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-019-02784-7"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2018.01.011"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2018.09.024"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-181000"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1021\/cn500363g"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1111\/1440-1681.12137"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-018-1523-3"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.06-0478"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1023\/B:MCBI.0000038236.59905.8b"},{"issue":"10","key":"12","first-page":"1107","article-title":"Increased AT(2)R protein expression but not increased apoptosis during cardioprotection induced by AT(1)R blockade","volume":"18","author":"R. 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