{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:58:59Z","timestamp":1790618339881,"version":"4.1.0"},"reference-count":56,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82660281"],"award-info":[{"award-number":["82660281"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ischemic stroke (IS) is an acute cerebrovascular disease characterized by high morbidity and mortality, with limited current treatment options. Tumor protein p53\u2010inducible nuclear protein 2 (Tp53inp2) is known to be a positive regulator of autophagy under physiological conditions, but the mechanism of Tp53inp2 in IS remains unclear. In this study, we aimed to explore the mechanism of Tp53inp2 in IS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Primary neural stem cells (NSCs) were extracted and identified. An OGD\/R cell model was constructed. Tp53inp2 was knocked down and rapamycin was added. A middle cerebral artery occlusion (MCAO) animal model was constructed, and then 5\u2009\u03bcL of 5\u2009\u00d7\u200910\n                      <jats:sup>5<\/jats:sup>\n                      NSCs, either untreated or transfected with sh\u2010NC or sh\u2010Tp53inp2, were injected. Additionally, at the cellular level, Ptgs2 or Tp53inp2 was overexpressed, and METTL14 was knocked down.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Inhibition of Tp53inp2 mitigated OGD\/R\u2010induced mitophagy and ROS levels in\u00a0vitro. Moreover, inhibition of Tp53inp2 mediated neuronal differentiation of OGD\/R treated NSCs by suppressing mitophagy. At the animal level, the transplantation of NSCs with a knockdown of Tp53inp2 increased neuronal differentiation, thereby alleviating the effects of MCAO and mitigating cognitive impairments in MCAO model mice. Ptgs2 was further screened and validated as a downstream target mediating the effect of Tp53inp2 on NSCs. At the cellular level, Tp53inp2 alleviated OGD\/R\u2010induced mitophagy and ROS levels by regulating Ptgs2 expression. METTL14 could regulate Tp53inp2 expression by modulating the functional m6A modification sites on Tp53inp2 mRNA. Inhibition of METTL14 alleviated OGD\/R\u2010induced mitophagy and the rise of ROS levels in NSCs by inhibiting the Tp53inp2\/Ptgs2 axis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Inhibition of METTL14 alleviated OGD\/R\u2010induced neuronal differentiation injury in NSCs by inhibiting the Tp53inp2\/Ptgs2 axis. By elucidating the mechanisms involving Tp53inp2, Ptgs2, and METTL14, this research offers a foundation for developing new strategies to enhance neuronal differentiation and mitigate cognitive impairments in stroke patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71099","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T06:10:11Z","timestamp":1788329411000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inhibition of\n                    <scp>METTL14<\/scp>\n                    Alleviates\n                    <scp>OGD<\/scp>\n                    \/R\u2010Induced Neuronal Differentiation Injury in Neural Stem Cells Through Suppressing the Tp53inp2\/Ptgs2 Axis: Potential Benefits for the Mouse\n                    <scp>MCAO<\/scp>\n                    Model"],"prefix":"10.1002","volume":"32","author":[{"given":"Dan","family":"Hou","sequence":"first","affiliation":[{"name":"Department of Neurology, Haikou Research Institute of Xiangya School of Medicine Central South University  Haikou Hainan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Haikou Research Institute of Xiangya School of Medicine Central South University  Haikou Hainan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Yun","sequence":"additional","affiliation":[{"name":"Department of Neurology, Haikou Research Institute of Xiangya School of Medicine Central South University  Haikou Hainan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5575-2723","authenticated-orcid":false,"given":"Dan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of 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