Protective mechanism of FoxO1 against early brain injury after subarachnoid hemorrhage by regulating autophagy

Abstract Introduction 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...

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Autores principales:	Haitao Hao, Yahui Bai, Yu Liu, Junxin Liang, Shichao Guo
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	after subarachnoid hemorrhage autophagy early brain injury FoxO1 Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/bd50f6fe4889468a974ce4590f11982f
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spelling	oai:doaj.org-article:bd50f6fe4889468a974ce4590f11982f2021-11-25T06:06:36ZProtective mechanism of FoxO1 against early brain injury after subarachnoid hemorrhage by regulating autophagy2162-327910.1002/brb3.2376https://doaj.org/article/bd50f6fe4889468a974ce4590f11982f2021-11-01T00:00:00Zhttps://doi.org/10.1002/brb3.2376https://doaj.org/toc/2162-3279Abstract Introduction 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‐inflammatory effects of FoxO1 on EBI after SAH by regulating autophagy. Methods In this study, we constructed the SAH model. In experiment I, low dose (50 μl of 1 × 108 IU/ml) or high dose (50 μl of 1 × 1010 IU/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‐SAH evaluation included neurological function score, brain water content, evans blue exosmosis, pathological changes, inflammatory response and apoptosis. Results The experiment I showed that either low or high dose of ad‐FoxO1 could significantly improve nerve function, reduce cerebral water content and reduce blood‐brain barrier (BBB) destruction in rats, indicating that ad‐FoxO1 had a protective effect on brain injury in rats EBI after SAH. In addition, ad‐FoxO1 promoted autophagy in rat hippocampal tissue, as evidenced by accumulation of LC3II/I and Beclin‐1 and degradation of p62. Furthermore, ad‐FoxO1 inhibited the inflammatory response and apoptosis of rat hippocampal neurons after SAH. The experiment II showed that both ad‐FoxO1 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. Conclusions The findings in this study was beneficial for identifying the novel therapeutic target for the treatment of SAH.Haitao HaoYahui BaiYu LiuJunxin LiangShichao GuoWileyarticleafter subarachnoid hemorrhageautophagyearly brain injuryFoxO1Neurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENBrain and Behavior, Vol 11, Iss 11, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	after subarachnoid hemorrhage autophagy early brain injury FoxO1 Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	after subarachnoid hemorrhage autophagy early brain injury FoxO1 Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Haitao Hao Yahui Bai Yu Liu Junxin Liang Shichao Guo Protective mechanism of FoxO1 against early brain injury after subarachnoid hemorrhage by regulating autophagy
description	Abstract Introduction 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‐inflammatory effects of FoxO1 on EBI after SAH by regulating autophagy. Methods In this study, we constructed the SAH model. In experiment I, low dose (50 μl of 1 × 108 IU/ml) or high dose (50 μl of 1 × 1010 IU/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‐SAH evaluation included neurological function score, brain water content, evans blue exosmosis, pathological changes, inflammatory response and apoptosis. Results The experiment I showed that either low or high dose of ad‐FoxO1 could significantly improve nerve function, reduce cerebral water content and reduce blood‐brain barrier (BBB) destruction in rats, indicating that ad‐FoxO1 had a protective effect on brain injury in rats EBI after SAH. In addition, ad‐FoxO1 promoted autophagy in rat hippocampal tissue, as evidenced by accumulation of LC3II/I and Beclin‐1 and degradation of p62. Furthermore, ad‐FoxO1 inhibited the inflammatory response and apoptosis of rat hippocampal neurons after SAH. The experiment II showed that both ad‐FoxO1 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. Conclusions The findings in this study was beneficial for identifying the novel therapeutic target for the treatment of SAH.
format	article
author	Haitao Hao Yahui Bai Yu Liu Junxin Liang Shichao Guo
author_facet	Haitao Hao Yahui Bai Yu Liu Junxin Liang Shichao Guo
author_sort	Haitao Hao
title	Protective mechanism of FoxO1 against early brain injury after subarachnoid hemorrhage by regulating autophagy
title_short	Protective mechanism of FoxO1 against early brain injury after subarachnoid hemorrhage by regulating autophagy
title_full	Protective mechanism of FoxO1 against early brain injury after subarachnoid hemorrhage by regulating autophagy
title_fullStr	Protective mechanism of FoxO1 against early brain injury after subarachnoid hemorrhage by regulating autophagy
title_full_unstemmed	Protective mechanism of FoxO1 against early brain injury after subarachnoid hemorrhage by regulating autophagy
title_sort	protective mechanism of foxo1 against early brain injury after subarachnoid hemorrhage by regulating autophagy
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/bd50f6fe4889468a974ce4590f11982f
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_version_	1718414187269455872

Protective mechanism of FoxO1 against early brain injury after subarachnoid hemorrhage by regulating autophagy

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