{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T09:05:41Z","timestamp":1790154341001,"version":"4.0.1"},"reference-count":51,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2015,6,24]],"date-time":"2015-06-24T00:00:00Z","timestamp":1435104000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:p>Endothelin-1 (ET-1) is synthesized by endothelial cells and astrocytes in stroke and in brains of Alzheimer's disease patients. Our transgenic mice with ET-1 overexpression in the endothelial cells (TET-1) showed more severe blood\u2013brain barrier (BBB) breakdown, neuronal apoptosis, and glial reactivity after 2-hour transient middle cerebral artery occlusion (tMCAO) with 22-hour reperfusion and more severe cognitive deficits after 30 minutes tMCAO with 5 months reperfusion. However, the role of astrocytic ET-1 in contributing to poststroke cognitive deficits after tMCAO is largely unknown. Therefore, GET-1 mice were challenged with tMCAO to determine its effect on neurologic and cognitive deficit. The GET-1 mice transiently displayed a sensorimotor deficit after reperfusion that recovered shortly, then more severe deficit in spatial learning and memory was observed at 3 months after ischemia compared with that of the controls. Upregulation of TNF- a, cleaved caspase-3, and Thioflavin-S-positive aggregates was observed in the ipsilateral hemispheres of the GET-1 brains as early as 3 days after ischemia. In an in vitro study, ET-1 overexpressing astrocytic cells showed amyloid secretion after hypoxia\/ischemia insult, which activated endothelin A (ETA) and endothelin B (ETB) receptors in a PI3K\/AKT-dependent manner, suggesting role of astrocytic ET-1 in dementia associated with stroke by astrocyte-derived amyloid production.<\/jats:p>","DOI":"10.1038\/jcbfm.2015.109","type":"journal-article","created":{"date-parts":[[2015,6,24]],"date-time":"2015-06-24T04:02:36Z","timestamp":1435118556000},"page":"1687-1696","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":43,"title":["Selective Astrocytic Endothelin-1 Overexpression Contributes to Dementia Associated with Ischemic Stroke by Exaggerating Astrocyte-Derived Amyloid Secretion"],"prefix":"10.1177","volume":"35","author":[{"given":"Victor KL","family":"Hung","sequence":"first","affiliation":[{"name":"Department of Anatomy, The University of Hong Kong, HKSAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick KK","family":"Yeung","sequence":"additional","affiliation":[{"name":"Department of Anatomy, The University of Hong Kong, HKSAR, China"},{"name":"School of Biomedical Sciences, The University of Hong Kong, HKSAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela KW","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Anatomy, The University of Hong Kong, HKSAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maggie CY","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Anatomy, The University of Hong Kong, HKSAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy CY","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Anatomy, The University of Hong Kong, HKSAR, China"},{"name":"Current address: Department of Ophthalmology, Eye Institute, The University of Hong Kong, HKSAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin C","family":"Chan","sequence":"additional","affiliation":[{"name":"University of Biomedical Imaging and Signal Processing, The University of Hong Kong, HKSAR, China"},{"name":"Current address: Department of Ophthalmology and Bioengineering, The University of Pittsburgh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ed XK","family":"Wu","sequence":"additional","affiliation":[{"name":"University of Biomedical Imaging and Signal Processing, The University of Hong Kong, HKSAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen SM","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Physiology, The University of Hong Kong, HKSAR, China"},{"name":"Current address: Division of Science and Technology, United International College, Zhuhai, Guandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi W","family":"Cheung","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, The University of Hong Kong, HKSAR, China"},{"name":"Research Center of Heart, Brain, Hormone and Healthy Aging, The University of Hong Kong, HKSAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sookja K","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Anatomy, The University of Hong Kong, HKSAR, China"},{"name":"School of Biomedical Sciences, The University of Hong Kong, HKSAR, China"},{"name":"Research Center of Heart, Brain, Hormone and Healthy Aging, The University of Hong Kong, HKSAR, China"},{"name":"The State Key Laboratory of Pharmaceutical Biotechnology, Zhuhai, Guandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2015,6,24]]},"reference":[{"key":"bibr1-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.42.6.1185"},{"key":"bibr2-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1997.03540340047031"},{"key":"bibr3-jcbfm.2015.109","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.4103\/1673-5374.121652","volume":"8","author":"Song B","year":"2013","journal-title":"Neural Regen Res"},{"key":"bibr4-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033722"},{"key":"bibr5-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2007.04.025"},{"key":"bibr6-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2008.06151.x"},{"key":"bibr7-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.107.492660"},{"key":"bibr8-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.23.7.1014"},{"key":"bibr9-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.107.495044"},{"key":"bibr10-jcbfm.2015.109","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/BF02337614","volume":"12","author":"Agnati LF","year":"1991","journal-title":"Ital J Neurol Sci"},{"key":"bibr11-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(02)00043-X"},{"key":"bibr12-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1993.34"},{"key":"bibr13-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1161\/hs0901.94259"},{"key":"bibr14-jcbfm.2015.109","first-page":"71","volume":"60","author":"Stanimirovic DB","year":"1994","journal-title":"Acta Neurochir Suppl"},{"key":"bibr15-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2009.01.070"},{"key":"bibr16-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1016\/j.nlm.2013.01.002"},{"key":"bibr17-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2011.04.024"},{"key":"bibr18-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12149"},{"key":"bibr19-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19970315)47:6<590::AID-JNR4>3.0.CO;2-8"},{"key":"bibr20-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(94)90057-4"},{"key":"bibr21-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-004-0274-0"},{"key":"bibr22-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1038\/nm890"},{"key":"bibr23-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1007\/s007010170109"},{"key":"bibr24-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(89)90252-3"},{"key":"bibr25-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1995.80"},{"key":"bibr26-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2013.171"},{"key":"bibr27-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600108"},{"key":"bibr28-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1126\/science.7522345"},{"key":"bibr29-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-05-01858.2002"},{"key":"bibr30-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1096\/fj.99-1022com"},{"key":"bibr31-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.2174\/157016109787354178"},{"key":"bibr32-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.2010.01084.x"},{"key":"bibr33-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-130383"},{"key":"bibr34-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1038\/nn2003"},{"key":"bibr35-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1387"},{"key":"bibr36-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2005.02.001"},{"key":"bibr37-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2009.175"},{"key":"bibr38-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0270(84)90007-4"},{"key":"bibr39-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1002\/glia.10178"},{"key":"bibr40-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2002.tb04803.x"},{"key":"bibr41-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1038\/5715"},{"key":"bibr42-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.109.559641"},{"key":"bibr43-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1111\/apha.12250"},{"key":"bibr44-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2014.24"},{"key":"bibr45-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1111\/cns.12032"},{"key":"bibr46-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1038\/380168a0"},{"key":"bibr47-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(97)00383-1"},{"key":"bibr48-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2009.01.023"},{"key":"bibr49-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1966.29.4.788"},{"key":"bibr50-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000034791.52151.6B"},{"key":"bibr51-jcbfm.2015.109","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1996.3440"}],"container-title":["Journal of Cerebral Blood Flow &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1038\/jcbfm.2015.109","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1038\/jcbfm.2015.109","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1038\/jcbfm.2015.109","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T20:12:05Z","timestamp":1777493525000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1038\/jcbfm.2015.109"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,24]]},"references-count":51,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2015,10]]}},"alternative-id":["10.1038\/jcbfm.2015.109"],"URL":"https:\/\/doi.org\/10.1038\/jcbfm.2015.109","relation":{},"ISSN":["0271-678X","1559-7016"],"issn-type":[{"value":"0271-678X","type":"print"},{"value":"1559-7016","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,6,24]]}}}