{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T01:43:56Z","timestamp":1790214236055,"version":"4.1.0"},"reference-count":40,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2013,1,30]],"date-time":"2013-01-30T00:00:00Z","timestamp":1359504000000},"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":[[2013,5]]},"abstract":"<jats:p>Vascular dementia (VaD) is the second leading cause of dementia behind Alzheimer's disease (AD) and is a frequent comorbidity with AD, estimated to occur in as many as 40% of AD patients. The causes of VaD are varied and include chronic cerebral hypoperfusion, microhemorrhages, hemorrhagic infarcts, or ischemic infarcts. We have developed a model of VaD by inducing hyperhomocysteinemia (HHcy) in wild-type mice. By placing wild-type mice on a diet deficient in folate, B6, and B12 and supplemented with excess methionine, we induced a moderate HHcy (plasma level homocysteine 82.93 \u00b1 3.561 \u03bcmol). After 11 weeks on the diet, the hyperhomocysteinemic mice showed a spatial memory deficit as assessed by the 2-day radial-arm water maze. Also, magnetic resonance imaging and subsequent histology revealed significant microhemorrhage occurrence. We found neuroinflammation induced in the hyperhomocysteinemic mice as determined by elevated interleukin (IL)-1\u03b2, tumor necrosis factor (TNF)\u03b1, and IL-6 in brain tissue. Finally, we found increased expression and increased activity of the matrix metalloproteinase 2 (MMP2) and MMP9 systems that are heavily implicated in the pathogenesis of cerebral hemorrhage. Overall, we have developed a dietary model of VaD that will be valuable for studying the pathophysiology of VaD and also for studying the comorbidity of VaD with other dementias and other neurodegenerative disorders.<\/jats:p>","DOI":"10.1038\/jcbfm.2013.1","type":"journal-article","created":{"date-parts":[[2013,1,30]],"date-time":"2013-01-30T04:00:49Z","timestamp":1359518449000},"page":"708-715","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":133,"title":["Induction of Hyperhomocysteinemia Models Vascular Dementia by Induction of Cerebral Microhemorrhages and Neuroinflammation"],"prefix":"10.1177","volume":"33","author":[{"given":"Tiffany L","family":"Sudduth","sequence":"first","affiliation":[{"name":"Department of Physiology, Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David K","family":"Powell","sequence":"additional","affiliation":[{"name":"Magnetic Resonance Imaging and Spectroscopy Center, Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, USA"},{"name":"Department of Biomedical Engineering, Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles D","family":"Smith","sequence":"additional","affiliation":[{"name":"Magnetic Resonance Imaging and Spectroscopy Center, Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, USA"},{"name":"Department of Neurology, Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail","family":"Greenstein","sequence":"additional","affiliation":[{"name":"Department of Physiology, Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna M","family":"Wilcock","sequence":"additional","affiliation":[{"name":"Department of Physiology, Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2013,1,30]]},"reference":[{"key":"bibr1-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0025-7125(02)00008-1"},{"key":"bibr2-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1159\/000054785"},{"key":"bibr3-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0404.2000.00314.x"},{"key":"bibr4-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21706"},{"key":"bibr5-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1161\/STR.0b013e3182299496"},{"key":"bibr6-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1126\/science.143.3613.1443"},{"key":"bibr7-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0805350105"},{"key":"bibr8-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10588"},{"key":"bibr9-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2010.07434.x"},{"key":"bibr10-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.275"},{"key":"bibr11-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5066-07.2008"},{"key":"bibr12-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-1-24"},{"key":"bibr13-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0031993"},{"key":"bibr14-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1042\/AN20110018"},{"key":"bibr15-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"bibr16-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00199.2004"},{"key":"bibr17-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-8-115"},{"key":"bibr18-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2010.06958.x"},{"key":"bibr19-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-131-5-199909070-00008"},{"key":"bibr20-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-131-5-199909070-00006"},{"key":"bibr21-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archger.2008.03.009"},{"key":"bibr22-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.279.3.H970"},{"key":"bibr23-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.5.433"},{"key":"bibr24-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1017\/S1041610211002511"},{"key":"bibr25-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114511000407"},{"key":"bibr26-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2008.07.008"},{"key":"bibr27-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn097"},{"key":"bibr28-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2012.03.020"},{"key":"bibr29-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.110.172932"},{"key":"bibr30-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.05.2351"},{"key":"bibr31-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181e396ea"},{"key":"bibr32-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.108.516112"},{"key":"bibr33-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2448"},{"key":"bibr34-jcbfm.2013.1","first-page":"495243","volume":"2012","author":"Wilcock DMA","year":"2012","journal-title":"Int J Alzheimers Dis"},{"key":"bibr35-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1100620"},{"key":"bibr36-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005518"},{"key":"bibr37-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-9-23"},{"key":"bibr38-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-010-0689-x"},{"key":"bibr39-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.110.600825"},{"key":"bibr40-jcbfm.2013.1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2011.00512.x"}],"container-title":["Journal of Cerebral Blood Flow &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1038\/jcbfm.2013.1","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1038\/jcbfm.2013.1","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1038\/jcbfm.2013.1","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T20:10:52Z","timestamp":1777493452000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1038\/jcbfm.2013.1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,1,30]]},"references-count":40,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2013,5]]}},"alternative-id":["10.1038\/jcbfm.2013.1"],"URL":"https:\/\/doi.org\/10.1038\/jcbfm.2013.1","relation":{},"ISSN":["0271-678X","1559-7016"],"issn-type":[{"value":"0271-678X","type":"print"},{"value":"1559-7016","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,1,30]]}}}