{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T21:43:19Z","timestamp":1788385399943,"version":"build-2803163510"},"reference-count":24,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T00:00:00Z","timestamp":1729641600000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Aquaporin\u20104 (AQP4), predominantly expressed in astrocytes, has been implicated in the development of brain edema following ischemic events. However, its role in post\u2010stroke neuroinflammation is not fully understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using a middle cerebral artery occlusion (MCAO) mouse model, we assessed AQP4's role in post\u2010stroke inflammation. Brain tissue slices from male C57BL\/6 mice were subjected to immunohistochemistry and western blot post\u2010MCAO. Additionally, primary astrocytes were isolated for quantitative real\u2010time PCR and immunofluorescence assays to evaluate the expression of inflammatory markers glial fibrillary acidic protein (GFAP) and AQP4. AQP4 modulation was achieved using viral knockdown and overexpression methods. Neuronal damage was assessed using flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) tests in co\u2010culture studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MCAO mice exhibited a significant upregulation in GFAP. This reactive astrogliosis corresponded with an elevation in inflammatory markers. AQP4 expression responded to this inflammatory trend, peaking at 6 h after OGD and returning to baseline levels at 24 and 48 h. Co\u2010culture experiments revealed that AQP4(+) astrocytes exacerbated injury in OGD\u2010treated neurons, as evidenced by increased TUNEL positivity and apoptotic events. Conversely, AQP4(\u2212) astrocytes appeared to have a protective effect. Knockdown of AQP4 resulted in reduced post\u2010OGD inflammatory response, whereas AQP4 overexpression intensified the injury to neurons post\u2010OGD. In vivo experiments also confirmed that AQP4 inhibitor TGN\u2010020 reduced and overexpression of AQP4 increased behavioral abnormalities and brain infarcts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings underscore AQP4's pivotal role in modulating post\u2010stroke neuroinflammation. Targeting AQP4 may present a novel therapeutic avenue for mitigating ischemia\u2010induced neuronal damage.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.70107","type":"journal-article","created":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T00:32:04Z","timestamp":1729729924000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Neuroprotective Role of AQP4 Knockdown in Astrocytes After Oxygen\u2013Glucose Deprivation"],"prefix":"10.1002","volume":"14","author":[{"given":"Xin","family":"Xing","sequence":"first","affiliation":[{"name":"Department of Neurology The Fourth Affiliated Hospital of Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3157-2818","authenticated-orcid":false,"given":"Shuyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology The Fourth Affiliated Hospital of Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.122.036946"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-021-01374-9"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.00579"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-022-02761-2"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11172728"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adc9020"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01973-4"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23010014"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-020-00182-8"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-023-03636-w"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-020-01756-x"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/4504363"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2021.113785"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-020-00635-0"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0888-20.2020"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.14780"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2019.106062"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.324858"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40779-022-00383-2"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.838990"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1159\/000517378"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2021.5070"},{"key":"e_1_2_9_24_1","first-page":"1031","article-title":"[Baicalin Treats Cerebral Ischemia Reperfusion\u2010Induced Brain Edema in Rats by Inhibiting TRPV4 and AQP4 of Astrocytes]","volume":"47","author":"Zheng X. Y.","year":"2022","journal-title":"Zhongguo Zhong Yao Za Zhi = Zhongguo Zhongyao Zazhi = China Journal of Chinese Materia Medica"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.714943"}],"container-title":["Brain and Behavior"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/brb3.70107","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T15:18:06Z","timestamp":1730128686000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/brb3.70107"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10]]},"references-count":24,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10.1002\/brb3.70107"],"URL":"https:\/\/doi.org\/10.1002\/brb3.70107","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/BRB3.70107\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.70107\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.70107\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.70107\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.70107\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.70107\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.70107\/v1\/decision1","asserted-by":"object"}]},"ISSN":["2162-3279","2162-3279"],"issn-type":[{"value":"2162-3279","type":"print"},{"value":"2162-3279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10]]},"assertion":[{"value":"2024-02-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70107"}}