{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:14:54Z","timestamp":1791220494543,"version":"4.1.0"},"reference-count":44,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971769 and 81871063"],"award-info":[{"award-number":["81971769 and 81871063"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Hypoxia-inducible factor 1 can sufficiently control the progress of neurological symptoms after ischemic stroke owing to their actions associated with its downstream genes. In this study, we evaluated the role of HIF-1\u03b1 in attenuating brain damage after endothelin-1 injection. Focal cerebral ischemia in mice were induced by endothelin-1 microinjection. Hypoxia-inducible factor 1 activator, dimethyloxalylglycine (DMOG), and HIF-1\u03b1 inhibitor, acriflavine (ACF), were used to evaluate the hypoxia-inducible factor 1 activity during cerebral ischemia. The expression levels of HIF-1\u03b1, glial fibrillary acidic protein (GFAP), interleukin-10 (IL-10), inducible nitric oxide synthase (iNOS), phosphorylated I-kappa-B-alpha\/total I-kappa-B-alpha (p-I\u03baB\u03b1\/I\u03baB\u03b1) and nuclear factor kappa B (NF-kB) were assessed. Besides, mRNA levels of IL-10, tumor necrosis factor- alpha (TNF-\u03b1), and NF-kB were also analyzed. Results showed a noticeable increase in hypoxia-inducible factor 1 and IL-10 levels in the DMOG group with a decline in iNOS, TNF-\u03b1, and NF-kB levels, implying the anti-inflammatory role of hypoxia-inducible factor 1 activator following stroke. These findings were further corroborated by GFAP immunostaining that showed astrocytic activation to be inhibited 12 days post-ischemia, as well as histological and TEM analyses that demonstrated hypoxia-inducible factor 1 induction to alleviate neuronal soma damage and cell death. Based on our study, HIF-1\u03b1 could be a potential therapeutic target for ischemic stroke.<\/jats:p>","DOI":"10.3390\/cells10061359","type":"journal-article","created":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T15:58:44Z","timestamp":1622563124000},"page":"1359","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Hypoxia Inducible Factor-1\u03b1 Attenuates Ischemic Brain Damage by Modulating Inflammatory Response and Glial Activity"],"prefix":"10.3390","volume":"10","author":[{"given":"Nashwa","family":"Amin","sequence":"first","affiliation":[{"name":"Institute of Neuroscience, School of Medicine, Zhejiang University, Hangzhou 310058, China"},{"name":"Department of Zoology, Faculty of Science, Aswan University, Aswan 81521, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijia","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, School of Medicine, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiannan","family":"Ren","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, School of Medicine, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoning","family":"Tan","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, School of Medicine, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9732-7904","authenticated-orcid":false,"given":"Benson O. A.","family":"Botchway","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, School of Medicine, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiying","family":"Hu","sequence":"additional","affiliation":[{"name":"Obstetrics & Gynecology Department, Zhejiang Integrated Traditional and Western Medicine Hospital, Hangzhou 310003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengpei","family":"Chen","sequence":"additional","affiliation":[{"name":"The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Ye","sequence":"additional","affiliation":[{"name":"The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxue","family":"Du","sequence":"additional","affiliation":[{"name":"Translational Medicine Center, Affiliated Hangzhou First People\u2019s Hospital, College of Medicine, Zhejiang University, Hangzhou 310000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuobing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6636-4347","authenticated-orcid":false,"given":"Marong","family":"Fang","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, School of Medicine, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1161\/01.STR.28.7.1501","article-title":"Etiology of stroke","volume":"28","author":"Panel","year":"1997","journal-title":"Stroke"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/S0002-9440(10)64964-4","article-title":"Hypoxia-Induced Vascular Endothelial Growth Factor Expression Precedes Neovascularization after Cerebral Ischemia","volume":"156","author":"Marti","year":"2000","journal-title":"Am. 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