{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T02:56:54Z","timestamp":1790996214162,"version":"4.1.0"},"reference-count":49,"publisher":"SAGE Publications","issue":"2_suppl","license":[{"start":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T00:00:00Z","timestamp":1677024000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:p>\n                    Nicotinamide adenine dinucleotide (NAD\n                    <jats:sup>+<\/jats:sup>\n                    ) is a redox cofactor critical for oxidative phosphorylation. Nicotinamide (NAM) and nicotinamide riboside (NR) are NAD\n                    <jats:sup>+<\/jats:sup>\n                    precursors widely used as nutritional supplements to augment oxidative phosphorylation. Indeed, NAD\n                    <jats:sup>+<\/jats:sup>\n                    precursors have been reported to improve outcomes in ischemic stroke when administered as a rescue therapy after stroke onset. However, we have also reported that enhanced reliance on oxidative phosphorylation before ischemia onset might worsen outcomes. To address the paradox, we examined how NAD\n                    <jats:sup>+<\/jats:sup>\n                    precursors modulate the outcome of middle cerebral artery occlusion in mice, when administered either 20 minutes after reperfusion or daily for three days before ischemia onset. A single post-ischemic dose of NAM or NR indeed improved tissue and neurologic outcomes examined at 72 hours. In contrast, pre-ischemic treatment for three days enlarged the infarcts and worsened neurological deficits. As a possible explanation for the diametric outcomes, a single dose of NAM or NR augmented tissue AMPK, PGC1\u03b1, SIRT1, and ATP in both na\u00efve and ischemic brains, while the multiple-dose paradigm failed to do so. Our data suggest that NAD\n                    <jats:sup>+<\/jats:sup>\n                    precursor supplements may sensitize the brain to subsequent ischemic events, despite their neuroprotective effect when administered after ischemia onset.\n                  <\/jats:p>","DOI":"10.1177\/0271678x231156500","type":"journal-article","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T06:13:48Z","timestamp":1677046428000},"page":"37-48","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":18,"title":["NAD\n                    <sup>\n                      <b>+<\/b>\n                    <\/sup>\n                    precursor nutritional supplements sensitize the brain to future ischemic events"],"prefix":"10.1177","volume":"43","author":[{"given":"Wensheng","family":"Qu","sequence":"first","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"},{"name":"Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth M","family":"Ralto","sequence":"additional","affiliation":[{"name":"Division of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA"},{"name":"Division of Nephrology and Department of Medicine, Center for Vascular Biology Research, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinhong","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weifeng","family":"Zong","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Perez-Pinzon","sequence":"additional","affiliation":[{"name":"Peritz Scheinberg Cerebral Vascular Disease Laboratories, Department of Neurology, The University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir M","family":"Parikh","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Department of Medicine, Center for Vascular Biology Research, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA"},{"name":"Division of Nephrology, Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cenk","family":"Ayata","sequence":"additional","affiliation":[{"name":"Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA"},{"name":"Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 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