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We identified an apoptosis-inducing humoral factor and named this novel post translationally modified secreted form of eukaryotic translation initiation factor 5A (eIF5A) \u201coxidative stress-responsive apoptosis inducing protein\u201d (ORAIP). The purpose of this study was to investigate the role of ORAIP in the mechanisms of cerebral I\/R injury. Hypoxia\/reoxygenation induced expression of ORAIP in cultured rat cerebral neurons, resulting in extensive apoptosis of these cells, which was largely suppressed by neutralizing anti-ORAIP monoclonal antibody (mAb) <jats:italic>in vitro<\/jats:italic>. Recombinant-ORAIP induced extensive apoptosis of cerebral neurons. Cerebral I\/R induced expression of ORAIP in many neurons in a rat tandem occlusion model <jats:italic>in vivo<\/jats:italic>. In addition, we analyzed the effects of intracerebroventricular administration of neutralizing anti-ORAIP mAb on the development of cerebral infarction. Cerebral I\/R significantly increased ORAIP levels in cerebrospinal fluid. Treatment with intracerebroventricular administration of neutralizing anti-ORAIP mAb reduced infarct volume by 72%, and by 55% even when started after reperfusion. These data strongly suggest that ORAIP plays a pivotal role and will offer a critical therapeutic target for cerebral I\/R injury induced by thrombolysis and thrombectomy for acute ischemic stroke.<\/jats:p>","DOI":"10.1038\/s41598-019-50073-8","type":"journal-article","created":{"date-parts":[[2019,9,18]],"date-time":"2019-09-18T10:02:37Z","timestamp":1568800957000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Oxidative stress-responsive apoptosis inducing protein (ORAIP) plays a critical role in cerebral ischemia\/reperfusion injury"],"prefix":"10.1038","volume":"9","author":[{"given":"Masao","family":"Kishimoto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Suenaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Takase","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kota","family":"Araki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takako","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Fujimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimie","family":"Murayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ko","family":"Okumura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryu","family":"Ueno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyuki","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobutaka","family":"Kawahara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6646-4743","authenticated-orcid":false,"given":"Yoshinori","family":"Seko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,9,18]]},"reference":[{"key":"50073_CR1","doi-asserted-by":"publisher","first-page":"1612","DOI":"10.1016\/S0140-6736(08)60694-7","volume":"371","author":"GA Donnan","year":"2008","unstructured":"Donnan, G. 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