{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:32:56Z","timestamp":1790911976988,"version":"4.1.0"},"reference-count":37,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T00:00:00Z","timestamp":1104537600000},"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":[[2005,1]]},"abstract":"<jats:p>\n                    We previously demonstrated that pharmacological inhibition of Na\n                    <jats:sup>+<\/jats:sup>\n                    \u2212K\n                    <jats:sup>+<\/jats:sup>\n                    \u2212Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    cotransporter isoform 1 (NKCC1) is neuroprotective in in vivo and in vitro ischemic models. In this study, we investigated whether genetic ablation of NKCC1 provides neuroprotection after ischemia. Focal ischemia was induced by 2 hours occlusion of the left middle cerebral artery (MCAO) followed by 10 or 24 hours reperfusion. Two hours MCAO and ten or twenty-four hours reperfusion caused infarction (\u02dc85 mm\n                    <jats:sup>3<\/jats:sup>\n                    ) in NKCC1 wild-type (NKCC1\n                    <jats:sup>+\/+<\/jats:sup>\n                    ) mice. Infarction volume in NKCC1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice was reduced by \u02dc30% to 46%. Heterozygous mutant (NKCC1\n                    <jats:sup>+\/\u2013<\/jats:sup>\n                    ) mice showed \u02dc28% reduction in infarction ( P&gt;0.05). Two hours MCAO and twenty-four hours reperfusion led to a significant increase in brain edema in NKCC1\n                    <jats:sup>+\/+<\/jats:sup>\n                    mice. In contrast, NKCC1\n                    <jats:sup>+\/\u2013<\/jats:sup>\n                    and NKCC1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice exhibited \u02dc50% less edema ( P&lt;0.05). Moreover, white matter damage was assessed by immunostaining of amyloid precursor protein (APP). An increase in APP was detected in NKCC1\n                    <jats:sup>+\/+<\/jats:sup>\n                    mice after 2 hours MCAO and 10 hours reperfusion. However, NKCC1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice exhibited significantly less APP accumulation ( P&lt;0.05). Oxygen-glucose deprivation (OGD) induced \u02dc67% cell death and a fourfold increase in Na\n                    <jats:sup>+<\/jats:sup>\n                    accumulation in cultured NKCC1\n                    <jats:sup>+\/+<\/jats:sup>\n                    cortical neurons. OGD-mediated cell death and Na\n                    <jats:sup>+<\/jats:sup>\n                    influx were significantly reduced in NKCC1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    neurons ( P&lt;0.05). In addition, inhibition of NKCC1 by bumetanide resulted in similar protection in NKCC1\n                    <jats:sup>+\/+<\/jats:sup>\n                    neurons and astrocytes ( P&lt;0.05). These results imply that stimulation of NKCC1 activity is important in ischemic neuronal damage.\n                  <\/jats:p>","DOI":"10.1038\/sj.jcbfm.9600006","type":"journal-article","created":{"date-parts":[[2005,1,27]],"date-time":"2005-01-27T11:32:31Z","timestamp":1106825551000},"page":"54-66","source":"Crossref","is-referenced-by-count":122,"title":["Na\n                    <sup>+<\/sup>\n                    -Dependent Chloride Transporter (NKCC1)-Null Mice Exhibit Less Gray and White Matter Damage after Focal Cerebral Ischemia"],"prefix":"10.1177","volume":"25","author":[{"given":"Hai","family":"Chen","sequence":"first","affiliation":[{"name":"Neuroscience Training Program, University of Wisconsin Medical School, Madison, Wisconsin, USA"},{"name":"Department of Neurosurgery, University of Wisconsin Medical School, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Wisconsin Medical School, Madison, Wisconsin, USA"},{"name":"Department of Physiology, University of Wisconsin Medical School, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas B","family":"Kintner","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Wisconsin Medical School, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary E","family":"Shull","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati, Cincinnati, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Wisconsin Medical School, Madison, Wisconsin, USA"},{"name":"Department of Physiology, University of Wisconsin Medical School, Madison, Wisconsin, 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