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Immunol."],"abstract":"<jats:p>Ischemic stroke is caused by insufficient cerebrovascular blood and oxygen supply. It is a major contributor to death or disability worldwide and has become a heavy societal and clinical burden. To date, effective treatments for ischemic stroke are limited, and innovative therapeutic methods are urgently needed. Hypoxia inducible factor-1\u03b1 (HIF-1\u03b1) is a sensitive regulator of oxygen homeostasis, and its expression is rapidly induced after hypoxia\/ischemia. It plays an extensive role in the pathophysiology of stroke, including neuronal survival, neuroinflammation, angiogenesis, glucose metabolism, and blood brain barrier regulation. In addition, the spatiotemporal expression profile of HIF-1\u03b1 in the brain shifts with the progression of ischemic stroke; this has led to contradictory findings regarding its function in previous studies. Therefore, unveiling the Janus face of HIF-1\u03b1 and its target genes in different type of cells and exploring the role of HIF-1\u03b1 in inflammatory responses after ischemia is of great importance for revealing the pathogenesis and identifying new therapeutic targets for ischemic stroke. Herein, we provide a succinct overview of the current approaches targeting HIF-1\u03b1 and summarize novel findings concerning HIF-1\u03b1 regulation in different types of cells within neurovascular units, including neurons, endothelial cells, astrocytes, and microglia, during the different stages of ischemic stroke. The current representative translational approaches focused on neuroprotection by targeting HIF-1\u03b1 are also discussed.<\/jats:p>","DOI":"10.3389\/fimmu.2021.801985","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T04:28:13Z","timestamp":1639369693000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":141,"title":["Biological Functions and Regulatory Mechanisms of Hypoxia-Inducible Factor-1\u03b1 in Ischemic Stroke"],"prefix":"10.3389","volume":"12","author":[{"given":"Qianyan","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinzhong","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianhui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoyu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JunLei","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen-Ni","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.neuron.2015.05.041","article-title":"Novel Stroke Therapeutics: Unraveling Stroke Pathophysiology and Its Impact on Clinical Treatments","volume":"87","author":"George","year":"2015","journal-title":"Neuron"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-020-00806-z","article-title":"Cell Death Pathways in Ischemic Stroke and Targeted Pharmacotherapy","volume":"11","author":"Datta","year":"2020","journal-title":"Transl Stroke Res"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/7875396","article-title":"Mechanisms of Acupuncture in the Regulation of Oxidative Stress in Treating Ischemic Stroke","volume":"2020","author":"Su","year":"2020","journal-title":"Oxid Med Cell Longev"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/neuros\/nyx341","article-title":"Cerebral Ischemic Reperfusion Injury Following Recanalization of Large Vessel Occlusions","volume":"82","author":"Al-Mufti","year":"2018","journal-title":"Neurosurgery"},{"key":"B5","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.brainres.2017.05.016","article-title":"Protective Effect of Remote Limb Post Conditioning via Upregulation of Heme Oxygenase-1\/BDNF Pathway in Rat Model of Cerebral Ischemic Reperfusion Injury","volume":"1669","author":"Ramagiri","year":"2017","journal-title":"Brain Res"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.36.22642","article-title":"Hypoxia-Inducible Factor 1alpha (HIF-1alpha) Protein is Rapidly Degraded by the Ubiquitin-Proteasome System Under Normoxic Conditions. 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