{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T15:44:18Z","timestamp":1768319058531,"version":"3.49.0"},"reference-count":48,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,10,18]],"date-time":"2016-10-18T00:00:00Z","timestamp":1476748800000},"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":["81171782"],"award-info":[{"award-number":["81171782"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Hypoxic\u2010ischemic brain injury (HIBI) in neonates can lead to lifelong cognitive and memory impairment, but protective strategies are lacking at present. It has been demonstrated that autophagy plays a critical role in HIBI, while the function of autophagy in cognitive and memory impairment induced by HIBI in neonates has not been tested. In this study, we tested the impact of autophagy on the impairment of cognitive function and memory in HIBI neonatal rats by using a Morris water maze and investigated its possible mechanisms, which were established as HIBI model by ligating the left common carotid artery in neonatal rats, followed by 2\u2010h hypoxia. The expression of microtubule\u2010associated protein 1 light chain 3 (LC3)\u2010II increased in HI group 24\u00a0h after HI in neonatal rats, while Sequestosome 1 (P62\/SQSTM1), phosphorylated cAMP\u2010response element\u2010binding protein (p\u2010CREB) decreased (compared with the sham group, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05), which were shown in the same left hippocampus CA3 region by immunofluorescence analysis. Brain injury of neonatal rats was aggravated significantly at 7\u00a0day after HI, coinciding with the results of Morris water maze. An autophagy inhibitor, 3\u2010methyladenine (3\u2010MA) pretreatment significantly attenuated the increase of LC3II and the loss of P62\/SQSTM1 and p\u2010CREB, ameliorated neuronal death, and improved the results of Morris water maze. Our results demonstrate that HIBI in neonatal rats induced excessive autophagy flux, which aggravated brain injury and induced cognitive and memory impairment during adolescence. Inhibition of autophagy reversed the results partly and improved the function of spatial learning and memory by attenuating the reduction of p\u2010CREB. The use of autophagy modulators in the immature brain would create new opportunities for protective strategies clinically in the future.<\/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\/jnc13851-fig-0007-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13851","type":"journal-article","created":{"date-parts":[[2016,9,23]],"date-time":"2016-09-23T07:59:22Z","timestamp":1474617562000},"page":"795-805","source":"Crossref","is-referenced-by-count":65,"title":["Autophagy activation involved in hypoxic\u2010ischemic brain injury induces cognitive and memory impairment in neonatal rats"],"prefix":"10.1111","volume":"139","author":[{"given":"Ying","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Shengjing Hospital China Medical University Shenyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ye","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of orthopedics Shengjing Hospital China Medical University Shenyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Shengjing Hospital China Medical University Shenyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingyue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Shengjing Hospital China Medical University Shenyang 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