{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T21:56:58Z","timestamp":1787003818718,"version":"build-2736575974"},"reference-count":41,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2006,4,1]],"date-time":"2006-04-01T00:00:00Z","timestamp":1143849600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2006,4]]},"abstract":"<jats:p>\n                    Glutamate is accumulated in abundance during the early period of experimental hematoma, and the activation of N-methyl-D-aspartate (NMDA) receptors by glutamate can result in an influx of calcium and neuronal death in cases of intracerebral hemorrhage (ICH). Memantine, which is known to be a moderate-affinity, uncompetitive, NMDA receptor antagonist, was investigated with regard to its ability to block the glutamate overstimulation and tissue plasminogen activator (tPA)\/urokinase plasminogen activator (uPA)\/matrix metalloproteinase (MMP)-9 modulation in experimental ICH. Intracerebral hemorrhage was induced via the infusion of collagenase into the left basal ganglia of adult rats. Either memantine (20 mg\/kg\/day) or PBS was intraperitoneally administered 30 min after the induction of ICH, and, at daily intervals afterwards, for either 3 or 14 days. Hemorrhage volume decreased by 47% in the memantine group, as compared with the ICH-only group. In the memantine group, the numbers of TUNEL\n                    <jats:sup>+<\/jats:sup>\n                    , myeloperoxidase (MPO)\n                    <jats:sup>+<\/jats:sup>\n                    , and OX42\n                    <jats:sup>+<\/jats:sup>\n                    cells decreased in the periphery of the hematoma. Memantine resulted in an upregulation of bcl-2 expression and an inhibition of caspase-3 activation. Memantine also exerted a profound inhibitory effect on the upregulation of tPA\/uPA mRNA, and finally decreased the MMP-9 level in the hemorrhagic brain. In modified limbplacing test, the memantine-treated rats exhibited lower scores initially, and recovered more quickly and thoroughly throughout the 35 days of the study. Here, we show that memantine causes a reduction of hematoma expansion, coupled with an inhibitory effect on the tPA\/uPA and MMP-9 level. Subsequently, memantine was found to reduce inflammatory infiltration and apoptosis, and was also determined to induce functional recovery after ICH.\n                  <\/jats:p>","DOI":"10.1038\/sj.jcbfm.9600213","type":"journal-article","created":{"date-parts":[[2005,8,17]],"date-time":"2005-08-17T11:32:03Z","timestamp":1124278323000},"page":"536-544","source":"Crossref","is-referenced-by-count":80,"title":["Memantine Reduces Hematoma Expansion in Experimental Intracerebral Hemorrhage, Resulting in Functional Improvement"],"prefix":"10.1177","volume":"26","author":[{"given":"Soon-Tae","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Neurology, Stroke and Neural Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Seoul National University Hospital, Seoul, South Korea"},{"name":"Program in Neuroscience, Neuroscience Research Institute of SNUMRC, Seoul National University, Seoul, South 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