{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T02:31:08Z","timestamp":1790735468465,"version":"4.1.0"},"reference-count":22,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2016,2,23]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Existing rodent models of vascular cognitive impairment (VCI) show abrupt changes in cerebral blood flow (CBF) and do not reliably replicate the clinical pathogenesis of VCI. We therefore aimed to develop a mouse model of VCI where CBF is gradually reduced, followed by subsequent progressive motor and cognitive impairment, after surgical intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">Adult C57BL\/6J male mice were subjected to gradual common carotid artery stenosis (GCAS) surgery by using an ameroid constrictor vessel\u2010constricting device with an inner diameter of 0.75\u00a0mm. The common carotid arteries narrowed gradually after gradual constriction of ameroid constrictors over 28\u00a0days after GCAS, with subsequent 79.3% area stenosis as a result of smooth muscle cell proliferation and macrophage infiltration in the tunica intima. The 28\u2010day survival rate was 91%. Arterial spin labeling demonstrated gradual and continuous reduction of cortical and subcortical CBF (ratio to the preoperative value) to 54.6% and 51.5%, respectively, over 28\u00a0days. However, magnetic resonance angiography showed increment of collateral flow signals in the leptomeningeal artery. Rarefaction and proliferation of astrocytes and microglia, with loss of oligodendrocytes, were found in the white matter at 32\u00a0days. Hippocampal neuronal loss was observed in only 25% of GCAS mice, consistent with lack of abnormalities in the Morris water maze test. The rotarod test showed motor impairment, and the Y\u2010maze test showed working memory deficits.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">The GCAS model successfully generated gradual and continuous CBF reduction over 28\u00a0days, with replication of key histological, radiological, and behavioral features associated with cerebral hypoperfusion leading to VCI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.115.002757","type":"journal-article","created":{"date-parts":[[2016,2,22]],"date-time":"2016-02-22T22:34:44Z","timestamp":1456180484000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":71,"title":["Gradual Carotid Artery Stenosis in Mice Closely Replicates Hypoperfusive Vascular Dementia in Humans"],"prefix":"10.1161","volume":"5","author":[{"given":"Yorito","family":"Hattori","sequence":"first","affiliation":[{"name":"Department of Stroke and Cerebrovascular Diseases, National Cerebral and Cardiovascular Center, Suita, Japan"},{"name":"Department of Neurology, National Hospital Organization Minami Kyoto Hospital, Joyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun\u2010ichiro","family":"Enmi","sequence":"additional","affiliation":[{"name":"Department of Investigative Radiology, National Cerebral and Cardiovascular Center, Suita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Iguchi","sequence":"additional","affiliation":[{"name":"Department of Investigative Radiology, National Cerebral and Cardiovascular Center, Suita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine, National Cerebral and Cardiovascular Center, Suita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumi","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine, National Cerebral and Cardiovascular Center, Suita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Tsuji","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine, National Cerebral and Cardiovascular Center, Suita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyuki","family":"Nagatsuka","sequence":"additional","affiliation":[{"name":"Department of Stroke and Cerebrovascular Diseases, National Cerebral and Cardiovascular Center, Suita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh N.","family":"Kalaria","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Newcastle University Campus for Ageing &amp; 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The early phenomena of restenosis following percutaneous transluminal coronary angioplasty. Eur Heart J. 1991;12:937\u2013945.","journal-title":"Eur Heart J"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(02)00190-4"}],"updated-by":[{"DOI":"10.1161\/jaha.116.002022","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2016,3,15]],"date-time":"2016-03-15T00:00:00Z","timestamp":1458000000000}}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.115.002757","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T06:26:08Z","timestamp":1715581568000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.115.002757"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,23]]},"references-count":22,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2016,2,23]]}},"alternative-id":["10.1161\/JAHA.115.002757"],"URL":"https:\/\/doi.org\/10.1161\/jaha.115.002757","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,23]]},"assertion":[{"value":"2015-10-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-01-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-02-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e002757"}}