{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:32:39Z","timestamp":1791361959769,"version":"4.3.1"},"reference-count":38,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,7,20]],"date-time":"2022-07-20T00:00:00Z","timestamp":1658275200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018617","name":"Liaoning Revitalization Talents Program","doi-asserted-by":"publisher","award":["XLYC1907178"],"award-info":[{"award-number":["XLYC1907178"]}],"id":[{"id":"10.13039\/501100018617","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971231"],"award-info":[{"award-number":["81971231"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ischemic stroke is a serious cerebrovascular disease with high morbidity and disability. Zinc accumulation has been shown to play a vital role in neuronal death and blood\u2013brain barrier damage following ischemia in acute stage. However, almost nothing is known about whether zinc is involved in neurological recovery in ischemic prolonged period. This study investigates whether zinc promotes neurological recovery through astrocytes\u2010induced angiogenesis during ischemic repair phase.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Sprague\u2013Dawley rats were subjected to 2\u2009h ischemia\/14, 21, and 28\u2009days reperfusion by middle cerebral artery occlusion, then administered ZnCl\n                      <jats:sub>2<\/jats:sub>\n                      (10\u2009mg\/kg) via intraperitoneally daily from 7\u2009days to tissue collection to observe brain tissue morphology, neurological function recovery by cortical width index, Adhesive removal test, and Forelimb placing test. Angiogenesis, astrocyte activation, and HIF\u20101\u03b1\/VEGF pathway were assessed via Western blot, immunofluorescence, and BrdU method in vivo and in vitro.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The results showed that zinc significantly alleviated brain atrophy and improved neurological function recovery during the cerebral ischemia repair stage. Zinc significantly increased the protein levels of HIF\u20101\u03b1, VEGF\u2010A, and VEGF\u2010R2 in astrocytes, and promoted angiogenesis during cerebral ischemia repair. In vitro and in vivo studies confirmed that zinc promoted angiogenesis via the astrocyte\u2010mediated HIF\u20101\u03b1\/VEGF signaling pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Zinc significantly improves neurological function recovery during the cerebral ischemia repair stage, providing new evidence supporting zinc as a potential therapeutic target for ischemic stroke by promoting astrocyte induced angiogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.13918","type":"journal-article","created":{"date-parts":[[2022,7,20]],"date-time":"2022-07-20T03:10:09Z","timestamp":1658286609000},"page":"1790-1799","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Zinc improves neurological recovery by promoting angiogenesis via the astrocyte\u2010mediated HIF\u20101\u03b1\/VEGF signaling pathway in experimental stroke"],"prefix":"10.1111","volume":"28","author":[{"given":"Yang","family":"Li","sequence":"first","affiliation":[{"name":"Institution of Life Science Jinzhou Medical University  Jinzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Ma","sequence":"additional","affiliation":[{"name":"Institution of Life Science Jinzhou Medical University  Jinzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institution of Life Science Jinzhou Medical University  Jinzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingqi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institution of Life Science Jinzhou Medical University  Jinzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Pharmacy Jinzhou Medical University  Jinzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9660-0147","authenticated-orcid":false,"given":"Peng","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Neurodegenerative Diseases of Liaoning Province, Department of Neurobiology Jinzhou Medical University  Jinzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3868-1724","authenticated-orcid":false,"given":"Jia","family":"Liang","sequence":"additional","affiliation":[{"name":"Institution of Life Science Jinzhou Medical University  Jinzhou China"},{"name":"Key Laboratory of Neurodegenerative Diseases of Liaoning Province, Department of Neurobiology Jinzhou Medical University  Jinzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,7,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2018.10.001"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2009.07176.x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2005.08.030"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2015.04.005"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2016.07.003"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2018.12.018"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.117351"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-18497-5_35"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.0115-20.2020"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.0888-20.2020"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01732"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci17977"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23109"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871530315666150316121956"},{"issue":"2","key":"e_1_2_10_16_1","first-page":"455","article-title":"Vascular endothelial growth factor (VEGF)\u2014key factor in normal and pathological angiogenesis","volume":"59","author":"Melincovici CS","year":"2018","journal-title":"Rom J Morphol Embryol"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci126655"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.12098"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678x20943823"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharep.2017.01.010"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.27.12.2299"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2010.25.10.1499"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci20622"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1532-2149.2013.00416.x"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0925-4773(01)00471-3"},{"issue":"3","key":"e_1_2_10_26_1","first-page":"369","article-title":"The role of zinc in the pathogenesis and treatment of central nervous system (CNS) diseases. Implications of zinc homeostasis for proper CNS function","volume":"71","author":"Tyszka\u2010Czochara M","year":"2014","journal-title":"Acta Pol Pharm"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13460"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom10081164"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22084280"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2013.12.071"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-017-9562-9"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2018.02.006"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1161\/jaha.117.007589"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00404-018-4802-9"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2019.09.023"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00038.2010"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19041264"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.104924"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678x20926787"}],"container-title":["CNS Neuroscience &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cns.13918","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cns.13918","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cns.13918","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T16:27:57Z","timestamp":1692635277000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cns.13918"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,20]]},"references-count":38,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2022,11]]}},"alternative-id":["10.1111\/cns.13918"],"URL":"https:\/\/doi.org\/10.1111\/cns.13918","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"value":"1755-5930","type":"print"},{"value":"1755-5949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,20]]},"assertion":[{"value":"2022-03-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}