{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T19:09:01Z","timestamp":1790104141956,"version":"4.0.1"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:sec>\n            <jats:title>Background and Purpose\u2014<\/jats:title>\n            <jats:p>The harsh host brain microenvironment caused by production of reactive oxygen species after ischemic reperfusion injury offers a significant challenge to survival of transplanted neural stem cells (NSCs) after ischemic stroke. Copper\/zinc-superoxide dismutase (SOD1) is a specific antioxidant enzyme that counteracts superoxide anions. We have investigated whether genetic manipulation to overexpress SOD1 enhances survival of grafted stem cells and accelerates amelioration of ischemic stroke.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods\u2014<\/jats:title>\n            <jats:p>NSCs genetically modified to overexpress or downexpress SOD1 were administered intracerebrally 2 days after transient middle cerebral artery occlusion. Histological and behavioral tests were examined from Days 0 to 28 after stroke.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results\u2014<\/jats:title>\n            <jats:p>Overexpression of SOD1 suppressed production of superoxide anions after ischemic reperfusion injury and reduced NSC death after transplantation. In contrast, downexpression of SOD1 promoted superoxide generation and increased oxidative stress-mediated NSC death. Transplantation of SOD1-overexpressing NSCs enhanced angiogenesis in the ischemic border zone through upregulation of vascular endothelial growth factor. Moreover, grafted SOD1-overexpressing NSCs reduced infarct size and improved behavioral performance compared with NSCs that were not genetically modified.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Our findings reveal a strong involvement of SOD1 expression in NSC survival after ischemic reperfusion injury. We propose that conferring antioxidant properties on NSCs by genetic manipulation of SOD1 is a potential approach for enhancing the effectiveness of cell transplantation therapy in ischemic stroke.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.112.656900","type":"journal-article","created":{"date-parts":[[2012,6,20]],"date-time":"2012-06-20T04:57:51Z","timestamp":1340168271000},"page":"2423-2429","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":62,"title":["Neural Stem Cells Genetically Modified to Overexpress Cu\/Zn-Superoxide Dismutase Enhance Amelioration of Ischemic Stroke in Mice"],"prefix":"10.1161","volume":"43","author":[{"given":"Hiroyuki","family":"Sakata","sequence":"first","affiliation":[{"name":"From the Department of Neurosurgery, Department of Neurology and Neurological Sciences, and Program in Neurosciences, Stanford University School of Medicine, Stanford, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuniyasu","family":"Niizuma","sequence":"additional","affiliation":[{"name":"From the Department of Neurosurgery, Department of Neurology and Neurological Sciences, and Program in Neurosciences, Stanford University School of Medicine, Stanford, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuma","family":"Wakai","sequence":"additional","affiliation":[{"name":"From the Department of Neurosurgery, Department of Neurology and Neurological Sciences, and Program in Neurosciences, Stanford University School of Medicine, Stanford, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Purnima","family":"Narasimhan","sequence":"additional","affiliation":[{"name":"From the Department of Neurosurgery, Department of Neurology and Neurological Sciences, and Program in Neurosciences, Stanford University School of Medicine, Stanford, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina M.","family":"Maier","sequence":"additional","affiliation":[{"name":"From the Department of Neurosurgery, Department of Neurology and Neurological Sciences, and Program in Neurosciences, Stanford University School of Medicine, Stanford, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pak H.","family":"Chan","sequence":"additional","affiliation":[{"name":"From the Department of Neurosurgery, Department of Neurology and Neurological Sciences, and Program in Neurosciences, Stanford University School of Medicine, Stanford, 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