{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T08:53:24Z","timestamp":1791017604907,"version":"4.1.0"},"reference-count":43,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100007015","name":"university of wisconsin-madison","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007015","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"national institutes of health","doi-asserted-by":"publisher","award":["R35 NS132184 and R01 NS140100"],"award-info":[{"award-number":["R35 NS132184 and R01 NS140100"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"u.s. department of veterans affairs","doi-asserted-by":"publisher","award":["IK6BX005690"],"award-info":[{"award-number":["IK6BX005690"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:p>\n                    N6-methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A) is the most pronounced epitranscriptomic modification of RNAs. Fat mass and obesity-associated (FTO) demethylates m\n                    <jats:sup>6<\/jats:sup>\n                    A-modified RNAs. Stroke reduces cerebral FTO expression, leading to increased abundance of m\n                    <jats:sup>6<\/jats:sup>\n                    A hypermethylated RNAs. FTO overexpression with a viral vector demethylates m\n                    <jats:sup>6<\/jats:sup>\n                    A-modified RNAs and improves post-stroke functional recovery. As NADPH activates FTO, we evaluated its therapeutic potential in a rodent stroke model. Adult and aged mice of both sexes were subjected to transient middle cerebral artery occlusion or photothrombotic ischemia, followed by intravenous administration of NADPH. FTO activity and m\n                    <jats:sup>6<\/jats:sup>\n                    A RNA methylation were measured enzymatically. NADPH efficacy and therapeutic window were assessed using sensorimotor and cognitive tests. Brain infarct volume, atrophy, and white matter damage were evaluated by MRI and histology analysis. Post-stroke administration of NADPH increased demethylase activity and reduced m\n                    <jats:sup>6<\/jats:sup>\n                    A-methylated RNA abundance, without altering FTO expression. NADPH treatment provided significant protection of gray and white matter, and better motor and cognitive recovery in both sexes, with a good therapeutic window and a low minimal efficacious dose. More importantly, FTO was also neuroprotective in aged mice subjected to stroke. These findings highlight NADPH as a promising post-stroke therapy that enhances FTO-mediated m\n                    <jats:sup>6<\/jats:sup>\n                    A RNA demethylation, leading to neuroprotection and functional recovery, irrespective of age and sex.\n                  <\/jats:p>","DOI":"10.1177\/0271678x261454259","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T09:17:41Z","timestamp":1780305461000},"page":"2548-2560","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["NADPH protects the post-stroke brain by activating the m\n                    <sup>6<\/sup>\n                    A demethylase FTO"],"prefix":"10.1177","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0101-0417","authenticated-orcid":false,"given":"Anil K","family":"Chokkalla","sequence":"first","affiliation":[{"name":"Department of Neurological Surgery, University of Wisconsin\u2013Madison, Madison, WI, USA"},{"name":"Cellular &amp; 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