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However, factors that induce the upregulation of HIF-1\u03b1 expression remain unclear. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase played a critical role in reperfusion-induced BBB damage after stroke. However, the role of NADPH oxidase in BBB injury during the acute ischemia stage remains unclear. This study is aimed at investigating the role of NADPH oxidase in BBB injury and the expression of HIF-1\u03b1 after acute ischemic stroke. A sutured middle cerebral artery occlusion (MCAO) model was used to mimic ischemic stroke in rats. Our results show that the inhibition of NADPH oxidase by apocynin can significantly reduce the BBB damage caused by 2\u2009h ischemic stroke accompanied by reducing the degradation of tight junction protein occludin. In addition, treatment with apocynin significantly decreased the upregulation of HIF-1\u03b1 induced by 2\u2009h MCAO. More importantly, apocynin could also inhibit the MMP-2 upregulation. Of note, HIF-1\u03b1 was not colocalized with a bigger blood vessel. Taken together, our results showed that inhibition of NADPH oxidase-mediated HIF-1\u03b1 upregulation reduced BBB damage accompanied by downregulating MMP-2 expression and occludin degradation after 2\u2009h ischemia stroke. These results explored the mechanism of BBB damage after acute ischemic stroke and may help reduce the associated cerebral hemorrhage transformation after thrombolysis and endovascular treatment after ischemic stroke.<\/jats:p>","DOI":"10.1155\/2021\/9928232","type":"journal-article","created":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T22:50:12Z","timestamp":1629154212000},"page":"1-8","source":"Crossref","is-referenced-by-count":12,"title":["Role of NADPH Oxidase-Induced Hypoxia-Induced Factor-1\u03b1 Increase in Blood-Brain Barrier Disruption after 2-Hour Focal Ischemic Stroke in Rat"],"prefix":"10.1155","volume":"2021","author":[{"given":"Yanping","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurology, The Second Hospital of Jiaxing City, Jiaxing, 314000 Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufei","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Hospital of Jiaxing City, Jiaxing, 314000 Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Yu","sequence":"additional","affiliation":[{"name":"Bengbu Medical College (Department of Neurology, The Second Hospital of Jiaxing City), China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingxia","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Hospital of Jiaxing City, Jiaxing, 314000 Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Hospital of Jiaxing City, Jiaxing, 314000 Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beiqun","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Hospital of Jiaxing City, Jiaxing, 314000 Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyun","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Soochow University, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5430-4315","authenticated-orcid":true,"given":"Congying","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Hospital of Jiaxing City, Jiaxing, 314000 Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5785-3029","authenticated-orcid":true,"given":"Shuxia","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Hospital of Jiaxing City, Jiaxing, 314000 Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.104769"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2018.06.033"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00050.2017"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.2174\/1567202611666140530145643"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-015-9504-8"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.114.005249"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002862"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(07)70055-8"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-014-0336-z"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-016-0447-9"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0804656"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2017.00257"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2018.00288"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2009.01.008"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-014-8952-x"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.107.489765"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2009.47"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000037063.90643.0B"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-016-9932-0"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2012.07.007"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.15570"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12572"},{"issue":"2","key":"23","first-page":"668","article-title":"Combination of hypoxia\/aglycemia compromises in vitro blood-brain barrier integrity","volume":"289","author":"T. 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