{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T14:46:45Z","timestamp":1788187605200,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,10,17]],"date-time":"2021-10-17T00:00:00Z","timestamp":1634428800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Early brain injury (EBI) plays a key role in the devastating outcomes after subarachnoid hemorrhage (SAH). Autophagy and apoptosis may share a common molecular inducer that regulates the process of cell death. FoxO1, as a key regulator of neuronal autophagy which is involved in apoptosis, has not been reported in SAH rats. This work was to investigate the protective and anti\u2010inflammatory effects of FoxO1 on EBI after SAH by regulating autophagy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this study, we constructed the SAH model. In experiment I, low dose (50\u00a0\u03bcl of 1 \u00d7 10\n                      <jats:sup>8<\/jats:sup>\n                      \u00a0IU\/ml) or high dose (50\u00a0\u03bcl of 1 \u00d7 10\n                      <jats:sup>10<\/jats:sup>\n                      \u00a0IU\/ml) of FoxO1 gene overexpressed adenovirus vector was injected into the lateral ventricle of rats before SAH. In experiment II, we reported the effect of FoxO1 overexpress on nerve function recovery, oedema, BBB leakage, neuronal death in rats after SAH through autophagy regulation. Post\u2010SAH evaluation included neurological function score, brain water content, evans blue exosmosis, pathological changes, inflammatory response and apoptosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The experiment I showed that either low or high dose of ad\u2010FoxO1 could significantly improve nerve function, reduce cerebral water content and reduce blood\u2010brain barrier (BBB) destruction in rats, indicating that ad\u2010FoxO1 had a protective effect on brain injury in rats EBI after SAH. In addition, ad\u2010FoxO1 promoted autophagy in rat hippocampal tissue, as evidenced by accumulation of LC3II\/I and Beclin\u20101 and degradation of p62. Furthermore, ad\u2010FoxO1 inhibited the inflammatory response and apoptosis of rat hippocampal neurons after SAH. The experiment II showed that both ad\u2010FoxO1 and rapamycin attenuated the injury of nerve function in rats after SAH, and this synergistic effect further reduced cerebral edema and evansblue extravasation, decreased hippocampus neuronal cell apoptosis, and declined inflammatory response. However, this was contrary to the results of chloroquine. These findings suggested that FoxO1 regulated the neural function of EBI after SAH through the autophagy pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The findings in this study was beneficial for identifying the novel therapeutic target for the treatment of SAH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.2376","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T00:48:03Z","timestamp":1634777283000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Protective mechanism of FoxO1 against early brain injury after subarachnoid hemorrhage by regulating autophagy"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8136-8293","authenticated-orcid":false,"given":"Haitao","family":"Hao","sequence":"first","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Zhengzhou University  Zhengzhou Henan P. 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