{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T01:50:44Z","timestamp":1784857844058,"version":"3.55.0"},"reference-count":63,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2020,2,18]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Hyperhomocysteinemia is a risk factor for ischemic stroke; however, a targeted treatment strategy is lacking partly because of limited understanding of the causal role of homocysteine in cerebrovascular pathogenesis.<\/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\">\n              In a genetic model of cystathionine beta synthase (\n              <jats:styled-content style=\"fixed-case\">CBS<\/jats:styled-content>\n              ) deficiency, we tested the hypothesis that elevation in plasma total homocysteine exacerbates cerebrovascular injury and that memantine, a N\u2010methyl\u2010D\u2010aspartate receptor antagonist, is protective. Mild or severe elevation in plasma total homocysteine was observed in\n              <jats:italic>Cbs+\/\u2212<\/jats:italic>\n              (6.1\u00b10.3\u00a0\u03bcmol\/L) or\n              <jats:italic>Cbs\u2212\/\u2212<\/jats:italic>\n              (309\u00b118\u00a0\u03bcmol\/L) mice versus\n              <jats:italic>Cbs+\/+<\/jats:italic>\n              (3.1\u00b10.6\u00a0\u03bcmol\/L) mice. Surprisingly,\n              <jats:italic>Cbs\u2212\/\u2212<\/jats:italic>\n              and\n              <jats:italic>Cbs+\/\u2212<\/jats:italic>\n              mice exhibited similar increases in cerebral infarct size following middle cerebral artery ischemia\/reperfusion injury, despite the much higher total homocysteine levels in\n              <jats:italic>Cbs\u2212\/\u2212<\/jats:italic>\n              mice. Likewise, disruption of the blood brain barrier was observed in both\n              <jats:italic>Cbs+\/\u2212<\/jats:italic>\n              and\n              <jats:italic>Cbs\u2212\/\u2212<\/jats:italic>\n              mice. Administration of the N\u2010methyl\u2010D\u2010aspartate receptor antagonist memantine protected\n              <jats:italic>Cbs+\/\u2212<\/jats:italic>\n              but not\n              <jats:italic>Cbs\u2212\/\u2212<\/jats:italic>\n              mice from cerebral infarction and blood brain barrier disruption. Our data suggest that the differential effect of memantine in\n              <jats:italic>Cbs+\/\u2212<\/jats:italic>\n              versus\n              <jats:italic>Cbs\u2212\/\u2212<\/jats:italic>\n              mice may be related to changes in expression of N\u2010methyl\u2010D\u2010aspartate receptor subunits.\n              <jats:italic>Cbs\u2212\/\u2212<\/jats:italic>\n              , but not\n              <jats:italic>Cbs+\/\u2212<\/jats:italic>\n              mice had increased expression of\n              <jats:styled-content style=\"fixed-case\">NR<\/jats:styled-content>\n              2B subunit, which is known to be relatively insensitive to homocysteine.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">These data provide experimental evidence that even a mild increase in plasma total homocysteine can exacerbate cerebrovascular injury and suggest that N\u2010methyl\u2010D\u2010aspartate receptor antagonism may represent a strategy to prevent reperfusion injury after acute ischemic stroke in patients with mild hyperhomocysteinemia.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.119.013368","type":"journal-article","created":{"date-parts":[[2020,2,13]],"date-time":"2020-02-13T10:00:38Z","timestamp":1581588038000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":20,"title":["Memantine Protects From Exacerbation of Ischemic Stroke and Blood Brain Barrier Disruption in Mild But Not Severe Hyperhomocysteinemia"],"prefix":"10.1161","volume":"9","author":[{"given":"Sean X.","family":"Gu","sequence":"first","affiliation":[{"name":"Department of Internal Medicine University of Iowa Carver College of Medicine Iowa City IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay K.","family":"Sonkar","sequence":"additional","affiliation":[{"name":"Department 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