{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T15:47:53Z","timestamp":1790351273977,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,1,6]],"date-time":"2017-01-06T00:00:00Z","timestamp":1483660800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81571804"],"award-info":[{"award-number":["81571804"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004945","name":"Nankai University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004945","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Vascular dementia is a neurodegenerative disorder caused by the reduction of cerebral blood flow. It shows a progressive cognitive impairment. In our previous study, we found that etidronate (<jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>) showed neuroprotective effects against glutamate\u2010injured <jats:styled-content style=\"fixed-case\">PC<\/jats:styled-content>12 cells. Thus, in this study, we aimed to observe the effects of <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content> on learning and memory impairment and the related mechanism in 2\u2010vessel occlusion (2<jats:styled-content style=\"fixed-case\">VO<\/jats:styled-content>) model rats. Rats were administered a permanent bilateral common carotid artery occlusion to induce vascular dementia model. Two weeks later, 2<jats:styled-content style=\"fixed-case\">VO<\/jats:styled-content> model rats were treated with <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content> (20\u00a0mg\/kg\/day i.p.) for 1\u00a0week. Results showed that <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content> improved the spatial learning and memory function in 2<jats:styled-content style=\"fixed-case\">VO<\/jats:styled-content> rats detected by Morris water maze experiment. A reduced long\u2010term potentiation was also rescued by <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content> treatment in 2<jats:styled-content style=\"fixed-case\">VO<\/jats:styled-content> rats. Moreover, the long\u2010term potentiation\u2010related proteins, calcium\/calmodulin\u2010dependent protein kinase <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> (Ca<jats:styled-content style=\"fixed-case\">MKII<\/jats:styled-content>), <jats:styled-content style=\"fixed-case\">NMDAR<\/jats:styled-content> 2B and <jats:styled-content style=\"fixed-case\">PSD<\/jats:styled-content>95 were up\u2010regulated after treatment with <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>. By testing the levels of malondialdehyde and superoxide dismutase in 2<jats:styled-content style=\"fixed-case\">VO<\/jats:styled-content> rats, we discovered that <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content> lowered oxidative stress. Furthermore, <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content> displayed a better anti\u2010apoptosis ability through detecting the levels of Bcl\u20102 and Bax protein and terminal deoxynucleotidyl transferase dUTP nick\u2010end labeling\u2010positive cells. In conclusion, <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content> shows neuroprotective effects on 2<jats:styled-content style=\"fixed-case\">VO<\/jats:styled-content> rats through rescuing spatial working memory deficits, and a possible mechanism may be related to the increased synaptic transmission and the inhibition of oxidative stress and apoptosis.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13904-fig-0008-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13904","type":"journal-article","created":{"date-parts":[[2016,11,22]],"date-time":"2016-11-22T17:15:00Z","timestamp":1479834900000},"page":"476-484","source":"Crossref","is-referenced-by-count":22,"title":["Etidronate rescues cognitive deficits through improving synaptic transmission and suppressing apoptosis in 2\u2010vessel occlusion model rats"],"prefix":"10.1111","volume":"140","author":[{"given":"Wen","family":"Li","sequence":"first","affiliation":[{"name":"School of Medicine State Key Laboratory of Medicinal Chemical Biology Key Laboratory of Bioactive Materials Ministry of Education Nankai University Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijuan","family":"Yuan","sequence":"additional","affiliation":[{"name":"School of Medicine State Key Laboratory of Medicinal Chemical 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