{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:27:44Z","timestamp":1793320064427,"version":"4.5.0"},"reference-count":52,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T00:00:00Z","timestamp":1672272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chongqing Yuzhong District Science Technology Commission of China","award":["20210121"],"award-info":[{"award-number":["20210121"]}]},{"name":"Chongqing Yuzhong District Science Technology Commission of China","award":["YXY2021BSH02"],"award-info":[{"award-number":["YXY2021BSH02"]}]},{"name":"Outstanding Researcher Fund of the College of Pharmacology of Chongqing Medical University","award":["20210121"],"award-info":[{"award-number":["20210121"]}]},{"name":"Outstanding Researcher Fund of the College of Pharmacology of Chongqing Medical University","award":["YXY2021BSH02"],"award-info":[{"award-number":["YXY2021BSH02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Endoplasmic reticulum (ER) stress plays an important role in cerebral ischemia\u2013reperfusion injury (CIRI). Geraniol has antioxidant, antibacterial, and anti-inflammatory activities. Studies have shown that geraniol has a protective effect against CIRI in rats, but the exact mechanism is unclear. Purpose: The aim of this study was to investigate the protective mechanism of geraniol against CIRI. We established a middle cerebral artery occlusion reperfusion model in rats and a PC12 cell oxygen\u2013glucose deprivation\/reoxygenation (OGD\/R) model to observe the neuroprotective effects of geraniol. Neurological scoring, 2,3,5-triphenyltetrazolium chloride staining, and hematoxylin and eosin staining were used to evaluate the neuroprotective effects of geraniol against CIRI. ER-stress-related and apoptosis-related protein expression was detected via Western blotting and immunofluorescence. Apoptosis was also detected via TUNEL assays and flow cytometry. The fluorescent detection of intracellular calcium was achieved using fluorescent calcium-binding dyes, and transmission electron microscopy was used to assess the neuronal ultrastructure. Geraniol effectively attenuated cerebral infarction and pathological injury after CIRI, had a protective effect against CIRI, significantly reduced the expression of the ER-stress-related proteins P-PERK, ATF4, CHOP, and GRP78 and the pro-apoptotic protein BAX, increased the expression of the anti-apoptotic protein BCL-2, and reduced the occurrence of apoptosis. In the OGD\/R model in PC12 cells, the protective effect of geraniol was the same as that in vivo. Our results suggest that geraniol has a protective effect against ischemic stroke by a mechanism possibly related to ER stress via the PERK-ATF4-CHOP pathway.<\/jats:p>","DOI":"10.3390\/ijms24010544","type":"journal-article","created":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T02:56:50Z","timestamp":1672282610000},"page":"544","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Geraniol-Mediated Suppression of Endoplasmic Reticulum Stress Protects against Cerebral Ischemia\u2013Reperfusion Injury via the PERK-ATF4-CHOP Pathway"],"prefix":"10.3390","volume":"24","author":[{"given":"Yu","family":"Wu","sequence":"first","affiliation":[{"name":"The Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacology, Chongqing Medical University, Chongqing 400010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Fan","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacology, Chongqing Medical University, Chongqing 400010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sha","family":"Chen","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacology, Chongqing Medical University, Chongqing 400010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Deng","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacology, Chongqing Medical University, Chongqing 400010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Jiang","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacology, Chongqing Medical University, Chongqing 400010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaonan","family":"Yang","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacology, Chongqing Medical University, Chongqing 400010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Dong","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacology, Chongqing Medical University, Chongqing 400010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"119865","DOI":"10.1016\/j.lfs.2021.119865","article-title":"Vortioxetine mitigates neuronal damage by restricting PERK\/eIF2\u03b1\/ATF4\/CHOP signaling pathway in rats subjected to focal cerebral ischemia-reperfusion","volume":"283","author":"Emam","year":"2021","journal-title":"Life Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.neuron.2010.07.002","article-title":"The science of stroke: Mechanisms in search of treatments","volume":"67","author":"Moskowitz","year":"2010","journal-title":"Neuron"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3071","DOI":"10.1161\/STROKEAHA.118.022015","article-title":"Ischemia-reperfusion injury after endovascular thrombectomy for ischemic stroke","volume":"49","author":"Gauberti","year":"2018","journal-title":"Stroke"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"24895","DOI":"10.3390\/ijms161024895","article-title":"MicroRNAs regulate mitochondrial function in cerebral ischemia-reperfusion injury","volume":"16","author":"Hu","year":"2015","journal-title":"Int. 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