{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T21:41:00Z","timestamp":1790199660488,"version":"4.1.0"},"reference-count":57,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2014,5,28]],"date-time":"2014-05-28T00:00:00Z","timestamp":1401235200000},"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":[[2014,9]]},"abstract":"<jats:p>Increased blood level of homocysteine (Hcy), called hyperhomocysteinemia (HHcy) accompanies many cognitive disorders including Alzheimer's disease. We hypothesized that HHcy-enhanced cerebrovascular permeability occurs via activation of matrix metalloproteinase-9 (MMP9) and leads to an increased formation of fibrinogen- \u03b2-amyloid (Fg-A \u03b2) complex. Cerebrovascular permeability changes were assessed in C57BL\/6J (wild type, WT), cystathionine- \u03b2-synthase heterozygote (Cbs+\/\u2212, a genetic model of HHcy), MMP9 gene knockout (Mmp9\u2212\/\u2212), and Cbs and Mmp9 double knockout (Cbs+\/\u2212\/Mmp9\u2212\/\u2212) mice using a dual-tracer probing method. Expression of vascular endothelial cadherin (VE-cadherin) and Fg-A \u03b2 complex formation was assessed in mouse brain cryosections by immunohistochemistry. Short-term memory of mice was assessed with a novel object recognition test. The cerebrovascular permeability in Cbs +\/\u2212- mice was increased via mainly the paracellular transport pathway. VE-cadherin expression was the lowest and Fg-A \u03b2 complex formation was the highest along with the diminished short-term memory in Cbs +\/\u2212 mice. These effects of HHcy were ameliorated in Cbs+\/\u2212\/Mmp9\u2212\/\u2212 mice. Thus, HHcy causes activation of MMP9 increasing cerebrovascular permeability by downregulation of VE-cadherin resulting in an enhanced formation of Fg-A \u03b2 complex that can be associated with loss of memory. These data may lead to the identification of new targets for therapeutic intervention that can modulate HHcy-induced cerebrovascular permeability and resultant pathologies.<\/jats:p>","DOI":"10.1038\/jcbfm.2014.102","type":"journal-article","created":{"date-parts":[[2014,5,28]],"date-time":"2014-05-28T03:59:04Z","timestamp":1401249544000},"page":"1472-1482","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":44,"title":["Ablation of\n                    <i>MMP9<\/i>\n                    Gene Ameliorates Paracellular Permeability and Fibrinogen\u2013Amyloid Beta Complex Formation during Hyperhomocysteinemia"],"prefix":"10.1177","volume":"34","author":[{"given":"Nino","family":"Muradashvili","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, University of Louisville, School of Medicine, Louisville, Kentucky, 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