{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T10:19:11Z","timestamp":1760955551620,"version":"3.37.3"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,4,8]],"date-time":"2015-04-08T00:00:00Z","timestamp":1428451200000},"content-version":"vor","delay-in-days":38,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["30870669"],"award-info":[{"award-number":["30870669"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IUBMB Life"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Emerging evidence indicates that the water channel protein aquaporin 4 (AQP4) plays an essential role in water homeostasis and is implicated in the pathogenesis of brain edema. This study aimed to understand the physiological role of AQP4 in hypoxia\u2013ischemia\u2010mediated cytotoxic brain edema. We specifically knocked down AQP4 expression by intracerebral injection of a plasmid containing AQP4 siRNA into a neonatal piglet model. The success of the hypoxia\u2013ischemia\u2010induced piglet model was confirmed by conventional <jats:bold>magnetic resonance imaging<\/jats:bold> and diffusion\u2010weighted imaging. AQP4 knockdown led to reduced brain edema accompanied by a higher apparent diffusion coefficient value, compared to the control group injected with a plasmid containing scrambled siRNA. Real\u2010time polymerase chain reaction and immunohistochemical analysis confirmed that AQP4 siRNA significantly reduced AQP4 mRNA and protein expression. Finally, neurological function analysis revealed that AQP4 knockdown significantly improved neurobehavioral manifestation of the piglets after exposure to hypoxia\u2010ischemia. Taken together, these results indicate that AQP4 plays an important role in mediating brain edema in hypoxic\u2010ischemic encephalopathy. Therefore, AQP4 could be a therapeutic target to ameliorate early\u2010stage brain edema. \u00a9 2015 IUBMB Life, 67(3):182\u2013190, 2015<\/jats:p>","DOI":"10.1002\/iub.1356","type":"journal-article","created":{"date-parts":[[2015,4,8]],"date-time":"2015-04-08T07:48:00Z","timestamp":1428479280000},"page":"182-190","source":"Crossref","is-referenced-by-count":23,"title":["Aquaporin\u20104 knockdown ameliorates hypoxic\u2010ischemic cerebral edema in newborn piglets"],"prefix":"10.1002","volume":"67","author":[{"given":"Chao","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Radiology The Second Affiliated Hospital of Dalian Medical University Dalian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhengjuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The Second Affiliated Hospital of Dalian Medical University Dalian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongjie","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Radiology Dalian Friendship Hospital Dalian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fangbing","family":"Zhai","sequence":"additional","affiliation":[{"name":"Department of Radiology The Second Affiliated Hospital of Dalian Medical University Dalian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Nursing Dalian Medical University Dalian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Bian","sequence":"additional","affiliation":[{"name":"Department of Radiology The Second Affiliated Hospital of Dalian Medical University Dalian China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,4,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/siny.2000.0011"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)12658-X"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.102.2.323"},{"volume-title":"MRI of the Neonatal Brain","year":"2002","author":"Rutherford M. 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