{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T08:47:34Z","timestamp":1790758054571,"version":"4.1.0"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:sec>\n            <jats:title>Background and Purpose\u2014<\/jats:title>\n            <jats:p>Nicotinamide adenine dinucleotide (NAD) is a ubiquitous fundamental metabolite. Nicotinamide phosphoribosyltransferase (Nampt) is the rate-limiting enzyme for mammalian NAD salvage synthesis and has been shown to protect against acute ischemic stroke. In this study, we investigated the role of Nampt\u2013NAD cascade in brain regeneration after ischemic stroke.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods\u2014<\/jats:title>\n            <jats:p>Nampt transgenic (Nampt-Tg) mice and H247A mutant enzymatic-dead Nampt transgenic (\u0394Nampt-Tg) mice were subjected with experimental cerebral ischemia by middle cerebral artery occlusion. Activation of neural stem cells, neurogenesis, and neurological function recovery were measured. Besides, nicotinamide mononucleotide and NAD, two chemical enzymatic product of Nampt, were administrated in vivo and in vitro.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results\u2014<\/jats:title>\n            <jats:p>\n              Compared with wild-type mice, Nampt-Tg mice showed enhanced number of neural stem cells, improved neural functional recovery, increased survival rate, and accelerated body weight gain after middle cerebral artery occlusion, which were not observed in \u0394Nampt-Tg mice. A delayed nicotinamide mononucleotide administration for 7 days with the first dose at 12 hours post middle cerebral artery occlusion did not protect acute brain infarction and neuronal deficit; however, it still improved postischemic regenerative neurogenesis. Nicotinamide mononucleotide and NAD\n              <jats:sup>+<\/jats:sup>\n              promoted proliferation and differentiation of neural stem cells in vitro. Knockdown of NAD-dependent deacetylase sirtuin 1 (SIRT1) and SIRT2 inhibited the progrowth action of Nampt\u2013NAD axis, whereas knockdown of SIRT1, SIRT2, and SIRT6 compromised the prodifferentiation effect of Nampt\u2013NAD axis.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Our data demonstrate that the Nampt\u2013NAD cascade may act as a centralizing switch in postischemic regeneration through controlling different sirtuins and therefore represent a promising therapeutic target for long-term recovery of ischemic stroke.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.115.009216","type":"journal-article","created":{"date-parts":[[2015,6,10]],"date-time":"2015-06-10T18:05:14Z","timestamp":1433959514000},"page":"1966-1974","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":86,"title":["Regenerative Neurogenesis After Ischemic Stroke Promoted by Nicotinamide Phosphoribosyltransferase\u2013Nicotinamide Adenine Dinucleotide Cascade"],"prefix":"10.1161","volume":"46","author":[{"given":"Yan","family":"Zhao","sequence":"first","affiliation":[{"name":"From the Department of Pharmacology, Second Military Medical University, Shanghai, China (Y.Z., Y.-F.G., G.-Q.L., Z.-Y.L., C.-C.Z., P.W., C.-Y.M.); Department of Science and Education, Shandong Provincial Hospital affiliated to Shandong University, Jinan, China (X.-M.Z); and Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China (C.-Y.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Feng","family":"Guan","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Second Military Medical University, Shanghai, China (Y.Z., Y.-F.G., G.-Q.L., Z.-Y.L., C.-C.Z., P.W., C.-Y.M.); Department of Science and Education, Shandong Provincial Hospital affiliated to Shandong University, Jinan, China (X.-M.Z); and Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China (C.-Y.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Ming","family":"Zhou","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Second Military Medical University, Shanghai, China (Y.Z., Y.-F.G., G.-Q.L., Z.-Y.L., C.-C.Z., P.W., C.-Y.M.); Department of Science and Education, Shandong Provincial Hospital affiliated to Shandong University, Jinan, China (X.-M.Z); and Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China (C.-Y.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo-Qiang","family":"Li","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Second Military Medical University, Shanghai, China (Y.Z., Y.-F.G., G.-Q.L., Z.-Y.L., C.-C.Z., P.W., C.-Y.M.); Department of Science and Education, Shandong Provincial Hospital affiliated to Shandong University, Jinan, China (X.-M.Z); and Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China (C.-Y.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Yong","family":"Li","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Second Military Medical University, Shanghai, China (Y.Z., Y.-F.G., G.-Q.L., Z.-Y.L., C.-C.Z., P.W., C.-Y.M.); Department of Science and Education, Shandong Provincial Hospital affiliated to Shandong University, Jinan, China (X.-M.Z); and Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China (C.-Y.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can-Can","family":"Zhou","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Second Military Medical University, Shanghai, China (Y.Z., Y.-F.G., G.-Q.L., Z.-Y.L., C.-C.Z., P.W., C.-Y.M.); Department of Science and Education, Shandong Provincial Hospital affiliated to Shandong University, Jinan, China (X.-M.Z); and Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China (C.-Y.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Wang","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Second Military Medical University, Shanghai, China (Y.Z., Y.-F.G., G.-Q.L., Z.-Y.L., C.-C.Z., P.W., C.-Y.M.); Department of Science and Education, Shandong Provincial Hospital affiliated to Shandong University, Jinan, China (X.-M.Z); and Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China (C.-Y.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-Yu","family":"Miao","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Second Military Medical University, Shanghai, China (Y.Z., Y.-F.G., G.-Q.L., Z.-Y.L., C.-C.Z., P.W., C.-Y.M.); Department of Science and Education, Shandong Provincial Hospital affiliated to Shandong University, Jinan, China (X.-M.Z); 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