{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:27:14Z","timestamp":1790807234453,"version":"4.1.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T00:00:00Z","timestamp":1615766400000},"content-version":"vor","delay-in-days":73,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Traumatic brain edema (TBE) is caused by a specific water channel mediated by membrane aquaporins. Aquaporin-4 (AQP4) plays an especially important role in this process, but the relationship between AQP4 and TBE remains unclear. The purpose of this study was to explore expression of AQP4 in the hippocampus after traumatic brain injury (TBI), as well as the effect of brain edema on skeletal protein and its function in hippocampal neurons.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The adult male Wistar rats we divided into a sham group and a TBI group, the latter of which was further divided into 1, 3, 6, 12, 24 and 72\u00a0hours (h) and 15\u00a0days (d) post injury subgroups. A proper TBI model was established, and brain edema was assessed in each group by water content. We measured the abundance of various proteins, including hypoxia inducible factor-1\u03b1 (HIF-1\u03b1), AQP4, microtubule-associated protein 2 (MAP2), tau-5 protein, phosphorylated level of TAU, synaptophysin, cyclic adenosine monophosphate response element binding protein (CREB), phosphorylated CREB and general control nonrepressed 2, in each group. Hippocampal neurons and spatial memory test were analyzed in different time points.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Compared with that in the sham group, the level of AQP4 in hippocampal neurons began to significantly increase at 1\u00a0h post TBI and then decreased at 15 d post TBI. During this time frame, AQP4 level peaked at 12 and 72\u00a0h, and these peaks were closely correlated with high brain water content. HIF-1\u03b1 displayed a similar trend. Conversely, levels of MAP2 began to decrease at 1\u00a0h post TBI and then increase at 15 d post TBI. In addition, the most severe brain edema in rats was found at 24\u00a0h post TBI, with neuronal loss and hippocampal dendritic spine injury. Compared to those in the sham group, rats in the TBI groups had significantly prolonged latency and significantly shortened exploration time.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>AQP4 level was closely correlated with severity of brain edema, and abnormal levels thereof aggravated such severity after TBI.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/burnst\/tkaa050","type":"journal-article","created":{"date-parts":[[2021,1,5]],"date-time":"2021-01-05T15:44:14Z","timestamp":1609861454000},"source":"Crossref","is-referenced-by-count":30,"title":["Aquaporin-4 is a potential drug target for traumatic brain injury via aggravating the severity of brain edema"],"prefix":"10.1093","volume":"9","author":[{"given":"Ao","family":"Xiong","sequence":"first","affiliation":[{"name":"Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450042, China"},{"name":"State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing 400042, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renping","family":"Xiong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing 400042, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing 400042, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijia","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing 400042, China"},{"name":"School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan, 610031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing 400042, China"},{"name":"School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan, 610031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Basic Medical College of Zhengzhou University, Zhengzhou, Henan 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianzhong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450042, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4123-348X","authenticated-orcid":false,"given":"Jun","family":"Yan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing 400042, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,3,15]]},"reference":[{"key":"2021042310352464600_ref1","first-page":"1","article-title":"Estimating the global incidence of traumatic brain injury","volume":"1","author":"Dewan","year":"2018","journal-title":"J Neurosurg."},{"key":"2021042310352464600_ref2","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1080\/02699052.2019.1605622","article-title":"Location of traumatic brain injury-related deaths: epidemiological analysis of 11 European countries","volume":"33","author":"Zelinkova","year":"2019","journal-title":"Brain Inj"},{"key":"2021042310352464600_ref3","doi-asserted-by":"crossref","first-page":"e19","DOI":"10.1016\/S2468-2667(19)30188-4","article-title":"Traumatic brain injury in homeless and marginally housed individuals: a systematic review and meta-analysis","volume":"5","author":"Stubbs","year":"2020","journal-title":"Lancet Public 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