{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T17:45:15Z","timestamp":1788371115039,"version":"build-2803163510"},"reference-count":45,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,6,29]],"date-time":"2020-06-29T00:00:00Z","timestamp":1593388800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31530091, 81870912, 81801221, and 81901253"],"award-info":[{"award-number":["31530091, 81870912, 81801221, and 81901253"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Environmental enrichment (EE) is a generally accepted strategy to promote stroke recovery and its beneficial effect is positively correlated with neuroplasticity. However, the mechanisms underlying it remain elusive. Histone deacetylase 2 (HDAC2), a negative regulator of neuroplasticity, is up\u2010regulated after stroke. Thus, we hypothesized that HDAC2 may participate in EE\u2010mediated stroke recovery. In this study, focal stroke was induced by photothrombosis in male mice exposing to EE or standard housing (SH) conditions. Recombinant virus vectors, including Ad\u2010HDAC2\u2010Flag, AAV\u2010CAG\u2010EGFP\u2010Cre, LV\u2010shHDAC2, or their controls were microinjected into the motor cortex at 3\u00a0days before stroke. Grid\u2010walking and cylinder tasks were conducted to assess motor function. Western blot and immunostaining were used to uncover the mechanisms underlying EE\u2010mediated stroke recovery. We found that EE exposure reversed stroke\u2010induced HDAC2 up\u2010regulation, implicating HDAC2 in EE\u2010mediated functional recovery. Importantly, EE\u2010dependent stroke recovery was counteracted by over\u2010expressing HDAC2, and HDAC2 knockdown promoted functional recovery from stroke to the similar extent as EE exposure. Moreover, the knockdown of HDAC2 epigenetically enhanced expressions of neurotrophins and neuroplasticity\u2010related proteins, with similar effects as EE, and consequently, whole brain and corticospinal tract (CST) rewiring. Together, our findings indicate that HDAC2 is critical for EE\u2010dependent functional restoration. Precisely targeting HDAC2 may mimic EE and serve as a novel therapeutic strategy for stroke recovery.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15043-fig-0008-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.15043","type":"journal-article","created":{"date-parts":[[2020,5,16]],"date-time":"2020-05-16T20:45:00Z","timestamp":1589661900000},"page":"679-696","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["HDAC2 (Histone deacetylase 2): A critical factor in environmental enrichment\u2010mediated stroke recovery"],"prefix":"10.1111","volume":"155","author":[{"given":"Yu\u2010Hui","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Pharmacology School of Pharmacy Nanjing Medical University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng\u2010Cheng","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Pharmacy Nanjing Medical University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai\u2010Yin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Pharmacy Nanjing Medical University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Pharmacy Nanjing Medical University Nanjing 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