Brain Extract of Subacute Traumatic Brain Injury Promotes the Neuronal Differentiation of Human Neural Stem Cells via Autophagy

Background: After a traumatic brain injury (TBI), the cell environment is dramatically changed, which has various influences on grafted neural stem cells (NSCs). At present, these influences on NSCs have not been fully elucidated, which hinders the finding of an optimal timepoint for NSC transplanta...

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Main Authors: Zhenghui He, Lijian Lang, Jiyuan Hui, Yuxiao Ma, Chun Yang, Weiji Weng, Jialin Huang, Xiongfei Zhao, Xiaoqi Zhang, Qian Liang, Jiyao Jiang, Junfeng Feng
Format: Article
Language:English
Published: MDPI AG 2022-05-01
Series:Journal of Clinical Medicine
Subjects:
Online Access:https://www.mdpi.com/2077-0383/11/10/2709
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author Zhenghui He
Lijian Lang
Jiyuan Hui
Yuxiao Ma
Chun Yang
Weiji Weng
Jialin Huang
Xiongfei Zhao
Xiaoqi Zhang
Qian Liang
Jiyao Jiang
Junfeng Feng
author_facet Zhenghui He
Lijian Lang
Jiyuan Hui
Yuxiao Ma
Chun Yang
Weiji Weng
Jialin Huang
Xiongfei Zhao
Xiaoqi Zhang
Qian Liang
Jiyao Jiang
Junfeng Feng
author_sort Zhenghui He
collection DOAJ
description Background: After a traumatic brain injury (TBI), the cell environment is dramatically changed, which has various influences on grafted neural stem cells (NSCs). At present, these influences on NSCs have not been fully elucidated, which hinders the finding of an optimal timepoint for NSC transplantation. Methods: Brain extracts of TBI mice were used in vitro to simulate the different phase TBI influences on the differentiation of human NSCs. Protein profiles of brain extracts were analyzed. Neuronal differentiation and the activation of autophagy and the WNT/CTNNB pathway were detected after brain extract treatment. Results: Under subacute TBI brain extract conditions, the neuronal differentiation of hNSCs was significantly higher than that under acute brain extract conditions. The autophagy flux and WNT/CTNNB pathway were activated more highly within the subacute brain extract than in the acute brain extract. Autophagy activation by rapamycin could rescue the neuronal differentiation of hNSCs within acute TBI brain extract. Conclusions: The subacute phase around 7 days after TBI in mice could be a candidate timepoint to encourage more neuronal differentiation after transplantation. The autophagy flux played a critical role in regulating neuronal differentiation of hNSCs and could serve as a potential target to improve the efficacy of transplantation in the early phase.
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spelling doaj.art-aba472f6ba5f4d42892367f447709b9b2023-11-23T11:33:34ZengMDPI AGJournal of Clinical Medicine2077-03832022-05-011110270910.3390/jcm11102709Brain Extract of Subacute Traumatic Brain Injury Promotes the Neuronal Differentiation of Human Neural Stem Cells via AutophagyZhenghui He0Lijian Lang1Jiyuan Hui2Yuxiao Ma3Chun Yang4Weiji Weng5Jialin Huang6Xiongfei Zhao7Xiaoqi Zhang8Qian Liang9Jiyao Jiang10Junfeng Feng11Brain Injury Center, Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, ChinaBrain Injury Center, Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, ChinaBrain Injury Center, Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, ChinaBrain Injury Center, Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, ChinaBrain Injury Center, Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, ChinaDepartment of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, ChinaShanghai Institute of Head Trauma, Shanghai 200127, ChinaShanghai Angecon Biotechnology Co., Ltd., Shanghai 201318, ChinaShanghai Angecon Biotechnology Co., Ltd., Shanghai 201318, ChinaDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USABrain Injury Center, Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, ChinaBrain Injury Center, Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, ChinaBackground: After a traumatic brain injury (TBI), the cell environment is dramatically changed, which has various influences on grafted neural stem cells (NSCs). At present, these influences on NSCs have not been fully elucidated, which hinders the finding of an optimal timepoint for NSC transplantation. Methods: Brain extracts of TBI mice were used in vitro to simulate the different phase TBI influences on the differentiation of human NSCs. Protein profiles of brain extracts were analyzed. Neuronal differentiation and the activation of autophagy and the WNT/CTNNB pathway were detected after brain extract treatment. Results: Under subacute TBI brain extract conditions, the neuronal differentiation of hNSCs was significantly higher than that under acute brain extract conditions. The autophagy flux and WNT/CTNNB pathway were activated more highly within the subacute brain extract than in the acute brain extract. Autophagy activation by rapamycin could rescue the neuronal differentiation of hNSCs within acute TBI brain extract. Conclusions: The subacute phase around 7 days after TBI in mice could be a candidate timepoint to encourage more neuronal differentiation after transplantation. The autophagy flux played a critical role in regulating neuronal differentiation of hNSCs and could serve as a potential target to improve the efficacy of transplantation in the early phase.https://www.mdpi.com/2077-0383/11/10/2709traumatic brain injuryneural stem cellsdifferentiationautophagy
spellingShingle Zhenghui He
Lijian Lang
Jiyuan Hui
Yuxiao Ma
Chun Yang
Weiji Weng
Jialin Huang
Xiongfei Zhao
Xiaoqi Zhang
Qian Liang
Jiyao Jiang
Junfeng Feng
Brain Extract of Subacute Traumatic Brain Injury Promotes the Neuronal Differentiation of Human Neural Stem Cells via Autophagy
Journal of Clinical Medicine
traumatic brain injury
neural stem cells
differentiation
autophagy
title Brain Extract of Subacute Traumatic Brain Injury Promotes the Neuronal Differentiation of Human Neural Stem Cells via Autophagy
title_full Brain Extract of Subacute Traumatic Brain Injury Promotes the Neuronal Differentiation of Human Neural Stem Cells via Autophagy
title_fullStr Brain Extract of Subacute Traumatic Brain Injury Promotes the Neuronal Differentiation of Human Neural Stem Cells via Autophagy
title_full_unstemmed Brain Extract of Subacute Traumatic Brain Injury Promotes the Neuronal Differentiation of Human Neural Stem Cells via Autophagy
title_short Brain Extract of Subacute Traumatic Brain Injury Promotes the Neuronal Differentiation of Human Neural Stem Cells via Autophagy
title_sort brain extract of subacute traumatic brain injury promotes the neuronal differentiation of human neural stem cells via autophagy
topic traumatic brain injury
neural stem cells
differentiation
autophagy
url https://www.mdpi.com/2077-0383/11/10/2709
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