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Maintaining moderate levels of hypochlorous acid promotes neural stem cell proliferation and differentiation in the recovery phase of stroke

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neural Regeneration Research 2025年第3期20卷 845-857页

作者： Lin-Yan Huang Yi-De Zhang Jie Chen Hai-Di Fan Wan Wang Bin Wang Ju-Yun Ma Peng-Peng Li Hai-Wei Pu Xin-Yian Guo Jian-Gang Shen Su-Hua Qi School of Medical Technology Xuzhou Key Laboratory of Laboratory DiagnosticsXuzhou Medical UniversityXuzhouJiangsu ProvinceChina School of Pharmacy Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina Department of Laboratory Medicine Branch Hospital of Huai’an First People’s HospitalHuai’anJiangsu ProvinceChina Department of Laboratory Medicine the Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina School of Chinese Medicine The University of Hong KongHong Kong Special Administrative RegionChina

It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late ***,previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain *** previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke,but its specific role and mechanism are currently *** simulate stroke in vivo,a middle cerebral artery occlusion rat model was established,with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic *** found that in the early stage(within 24 hours)of ischemic stroke,neutrophils produced a large amount of hypochlorous acid,while in the recovery phase(10 days after stroke),microglia were activated and produced a small amount of hypochlorous ***,in acute stroke in rats,hypochlorous acid production was prevented using a hypochlorous acid scavenger,taurine,or myeloperoxidase inhibitor,4-aminobenzoic acid *** results showed that high levels of hypochlorous acid(200μM)induced neuronal apoptosis after oxygen/glucose deprivation/***,in the recovery phase of the middle cerebral artery occlusion model,a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and *** suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion *** levels of hypochlorous acid(5 and 100μM)promoted nuclear translocation ofβ-*** transfection of single-site mutation plasmids,we found that hypochlorous acid induced chlorination of theβ-catenin tyrosine 30 residue,which promoted nuclear ***,our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.

关键词： cell differentiation cerebral ischemia/reperfusion injury chlorination hypochlorous acid microglia neural stem cell neurogenesis nuclear translocation stroke β-catenin

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neural stem cell-derived exosome as a nano-sized carrier for BDNF delivery to a rat model of ischemic stroke

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neural Regeneration Research 2023年第2期18卷 404-409页

作者： Zhi-Han Zhu Feng Jia Waqas Ahmed Gui-Long Zhang Hong Wang Chao-Qun Lin Wang-Hao Chen Lu-Kui Chen Department of Neurosurgery School of MedicineSoutheast UniversityNanjingJiangsu ProvinceChina Department of Neurosurgery Neuroscience CenterCancer CenterIntegrated Hospital of Traditional Chinese MedicineSouthern Medical UniversityGuangzhouGuangdong ProvinceChina Department of Neurosurgery The Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Department of Neurosurgery Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

Our previo us study demonstrated the potential therapeutic role of human neural stem cell-derived exosomes(hNSC-Exo)in ischemic ***,we loaded brain-derived neurotrophic factor(BDNF)into exosomes derived from NSCs to construct engineered exosomes(BDNF-hNSC-Exo)and compared their effects with those of hNSC-Exo on ischemic stroke both in vitro and in *** a model of H_(2)O_(2)-induced oxidative stress in NSCs,BDNF-hNSC-Exo markedly enhanced cell *** a rat middle cerebral arte ry occlusion model,BDNF-hNSC-Exo not only inhibited the activation of microglia,but also promoted the differentiation of endogenous NSCs into *** results suggest that BDNF can improve the function of NSC-derived exosomes in the treatment of ischemic stro *** research may support the clinical use of other neurotrophic factors for central nervous system diseases.

关键词： brain-derived neurotrophic factor exosome inflammation ischemic stroke neural stem cell neurogenesis neurological recovery transplantation

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neural stem cell therapy for brain disease

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World Journal of stem cells 2021年第9期13卷 1278-1292页

作者： Lan Zhao Jian-Wei Liu Hui-Yan Shi Ya-Min Ma First Teaching Hospital of Tianjin University of Traditional Chinese Medicine Tianjin 300381China National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion Tianjin 300381China Tianjin University of Traditional Chinese Medicine Tianjin 301617China

Brain diseases, including brain tumors, neurodegenerative disorders, cerebrovasculardiseases, and traumatic brain injuries, are among the major disordersinfluencing human health, currently with no effective therapy. Due to the lowregeneration capacity of neurons, insufficient secretion of neurotrophic factors,and the aggravation of ischemia and hypoxia after nerve injury, irreversible lossof functional neurons and nerve tissue damage occurs. This damage is difficult torepair and regenerate the central nervous system after injury. neural stem cells(NSCs) are pluripotent stem cells that only exist in the central nervous *** have good self-renewal potential and ability to differentiate into neurons,astrocytes, and oligodendrocytes and improve the cellular *** transplantation approaches have been made for various neurodegenerativedisorders based on their regenerative potential. This review summarizes anddiscusses the characteristics of NSCs, and the advantages and effects of NSCs inthe treatment of brain diseases and limitations of NSC transplantation that need tobe addressed for the treatment of brain diseases in the future.

关键词： neural stem cell Brain disease Therapy Animal experiment Clinical trial cellular therapy

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Total Ginsenoside Extract from Panax ginseng Enhances neural stem cell Proliferation and Neuronal Differentiation by Inactivating GSK-3β

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Chinese Journal of Integrative Medicine 2022年第3期28卷 229-235页

作者： LIN Kai-li ZHANG Ji CHUNG Hau-lam WU Xin-yi LIU Bin ZHAO Bo-xin SZE Stephen Cho-wing ZHOU Ping-zheng YUNG Ken Kin-lam ZHANG Shi-qing School of Public Health Guangzhou Medical UniversityGuangzhou(511436)China Department of Biology Hong Kong Baptist University(HKBU)Hong Kong Special Administrative Region(999077)China HKBU Shenzhen Research Institute and Continuing Education ShenzhenGuangdong Provinee(518057)China Department of Plastic Surgery Zhujiang HospitalSouthern Medical UniversityGuangzhou(510515)China Guangzhou Institute of Cardiovascular Disease the Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhou(510260)China Department of Pharmacy Nan fang HospitalSouther n Medical Un iversityGuan gzhou(510515)China Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou(510515)China

Objective:To study the effects of total ginsenosides(TG)extract from Panax ginseng on neural stem cell(NSC)proliferation and differentiation and their underlying ***:The migration of NSCs after treatment with various concentrations of TG extract(50,100,or 200μg/mL)were *** proliferation of NSCs was examined by a combination of cell counting kit-8 and neurosphere *** differentiation mediated by TG extract was evaluated by Western blotting and immunofluorescence staining to monitor the expression of nestin and microtubule associated protein 2(MAP2).The GSK-3β/β-catenin pathway in TG-treated NSCs was examined by Western blot *** NSCs with constitutively active GSK-3βmutant were made by adenovirus-mediated gene transfection,then the proliferation and differentiation of NSCs mediated by TG were further ***:TG treatment significantly enhanced NSC migration(P<0.01 or P<0.05)and increased the proliferation of NSCs(P<0.01 or P<0.05).TG mediation also significantly upregulated MAP2 expression but downregulated nestin expression(P<0.01 or P<0.05).TG extract also significantly induced GSK-3βphosphorylation at Ser9,leading to GSK-3βinactivation and,consequently,the activation of the GSK-3β/β-catenin pathway(P<0.01 or P<0.05).In addition,constitutive activation of GSK-3βin NSCs by the transfection of GSK-3βS9 A mutant was found to significantly suppress TG-mediated NSC proliferation and differentiation(P<0.01 or P<0.05).Conclusion:TG promoted NSC proliferation and neuronal differentiation by inactivating GSK-3β.

关键词： ginsenoside neural stem cell proliferation neuronal differentiation GSK-3β

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TAX1BP1 and FIP200 orchestrate non-canonical autophagy of p62 aggregates for mouse neural stem cell maintenance

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Zoological Research 2024年第4期45卷 937-950页

作者： Yi-Fu Zhu Rong-Hua Yu Shuai Zhou Pei-Pei Tang Rui Zhang Yu-Xin Wu Ran Xu Jia-Ming Wei Ying-Ying Wang Jia-Li Zhang Meng-Ke Li Xiao-Jing Shi Yu-Wei Zhang Guang-Zhi Liu Rick FThorne Xu Dong Zhang Mian Wu Song Chen School of Life Sciences Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230001China Translational Research Institute of Henan Provincial People’s Hospital and People'’s Hospital of Zhengzhou University Tianjian Laboratory of Advanced Biomedical SciencesAcademy of Medical SciencesZhengzhou UniversityZhengzhouHenan 450053China Institute of Medicinal Biotechnology Jiangsu College of NursingHuai’anJiangsu 223300China Laboratory Animal Center Academy of Medical ScienceZhengzhou UniversityZhengzhouHenan 450052China Henan Key Laboratory of stem cell Differentiation and Modification Henan Provincial People’s HospitalHenan UniversityZhengzhouHenan 450053China School of Biomedical Sciences and Pharmacy The University of NewcastleNSW 2308Australia

Autophagy plays a pivotal role in diverse biological processes,including the maintenance and differentiation of neural stem cells(NSCs).Interestingly,while complete deletion of Fip200 severely impairs NSC maintenance and differentiation,inhibiting canonical autophagy via deletion of core genes,such as Atg5,Atg16l1,and Atg7,or blockade of canonical interactions between FIP200 and ATG13(designated as FIP200-4A mutant or FIP200 KI)does not produce comparable detrimental *** highlights the likely critical involvement of the non-canonical functions of FIP200,the mechanisms of which have remained ***,utilizing genetic mouse models,we demonstrated that FIP200 mediates non-canonical autophagic degradation of p62/sequestome1,primarily via TAX1BP1 in *** deletion of Tax1bp1 in fip200hGFAP conditional knock-in(cKI)mice led to NSC deficiency,resembling the fip200hGFAP conditional knockout(cKO)mouse ***,reintroducing wild-type TAX1BP1 not only restored the maintenance of NSCs derived from tax1bp1-knockout fip200hGFAP cKI mice but also led to a marked reduction in p62 aggregate ***,a TAX1BP1 mutant incapable of binding to FIP200 or NBR1/p62 failed to achieve this ***,conditional deletion of Tax1bp1 in fip200hGFAP cKO mice exacerbated NSC deficiency and p62 aggregate accumulation compared to fip200hGFAP cKO ***,these findings illustrate the essential role of the FIP200-TAX1BP1 axis in mediating the non-canonical autophagic degradation of p62 aggregates towards NSC maintenance and function,presenting novel therapeutic targets for neurodegenerative diseases.

关键词： Non-canonical autophagy TAX1BP1 FIP200 p62 Aggregates neural stem cell

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System approaches reveal the molecular networks involved in neural stem cell differentiation

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Protein & cell 2012年第3期3卷 213-224页

作者： Kai Wang Haifeng Wang Jiao Wang Yuqiong Xie Jun Chen Huang Yan Zengrong Liu Tieqiao Wen Laboratory of Molecular Neurobiology School of Life SciencesShanghai UniversityShanghai 200444China School of Communication and Information Engineering Shanghai UniversityShanghai 200444China College of Life Science Wuhan UniversityWuhan 430072China College of Chemical Engineering and Technology Wuhan University of Science and TechnologyWuhan 430081China Institute of Systems Biology Shanghai UniversityShanghai 200444China􀀍

The self-renewal and multipotent potentials in neural stem cells(NSCs)maintain the normal physiological functions of central nervous system(CNS).The ab-normal differentiation of NSCs would lead to CNS ***,the mechanisms of how NSCs differentiate into astrocytes,oligodendrocytes(OLs)and neurons are still unclear,which is mainly due to the complexity of differentiation processes and the limita-tion of the cell separation *** this study,we modeled the dynamics of neural cell interactions in a systemic approach by mining the high-throughput genomic and proteomic data,and identified 8615 genes that are involved in various biological processes and functions with significant changes during the differentiation processes.A total of 1559 genes are specifically expressed in neural cells,in which 242 genes are NSC specific,215 are astrocyte specific,551 are OL specific,and 563 are neuron *** addition,we proposed 57 transcriptional regulators specifically expressed in NSCs may play essential roles in the development *** findings provide more comprehensive analysis for better understanding the endogenous mechanisms of NSC fate determination.

关键词： neural stem cell cell differentiation mo-lecular networks

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neural stem cell proliferation and differentiation in a neonatal rat model of hypoxia/ischemia injury Acupuncture at Ren,Du,and urinary bladder meridians

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neural Regeneration Research 2010年第4期5卷 267-272页

作者： Minghua Zhuang Jianming Luo Ye Bai Mingfa Liu Department of Neurosurgery First Affiliated Hospital of Shantou University Medical College Shantou 515041 Guangdong Province China Department of Neurosurgery Second Affiliated Hospital of Shantou University Medical College Shantou 515041 Guangdong Province China Department of Acupuncture and Moxibustion Second Affiliated Hospital of Shantou University Medical College Shantou 515041 Guangdong Province China Department of Neurosurgery Shantou Central Hospital Shantou 515041 Guangdong Province China

BACKGROUND： Acupuncture improves the prognosis of neonatal hypoxic-ischemic encephalopathy （HIE）. However, the cytological mechanism of acupuncture therapy remains poorly understood. In situ neural stem cell （NSC） proliferation theory proposes that the proliferation and differentiation of NSCs plays an important role in HIE treatment with acupuncture. OBJECTIVE： To investigate NSC proliferation and differentiation in the brain of a rat model of HIE during acupuncture at Ren, Du, and urinary bladder meridians. DESIGN, TIME AND SEB＇ING： A randomized, controlled animal experiment was performed at the Central Laboratory of Shantou University Medical College from July 2005 to June 2009. MATERIALS： A 32# 1-cun stainless steel acupuncture needle was purchased from Suzhou Acupuncture Supplies Co. Ltd., ***： A total of 90 Sprague-Dawley rats, aged 7 days, were randomly assigned to acupuncture, model and normal groups, with 30 animals in each group. Animals in acupuncture and model groups were subjected to left common carotid artery ligation followed by hypoxia for 2 hours to establish neonatal HIE models. Acupuncture group rats underwent acupuncture at Ren, Du, and urinary bladder meridians, once a day. MAIN OUTCOME MEASURES： The number, appearance, and distribution of bromodeoxyuridine （BrdU）-positive cells in the cerebral cortex and hippocampus of each group were compared. In addition, NSC differentiation in the occipital cortex and hippocampal dentate gyrus 40 days following model establishment was ***： BrdU-positive cells were dispersed in the cerebral cortex and hippocampus. The number of BrdU-positive cells in occipital cortex and hippocampal dentate gyrus of HIE rats remained unchanged following 3 and 7 days of acupuncture, but a significant increase was detected on days 14 and 28 （P 〈 0.01 or P 〈 0.05）. At 40 days, immunofluorescence showed that a majority of BrdU-positive cells were co-lableled with the neuron marker, and neuron specific enola

关键词： acupuncture bromodeoxyuridine neural stem cell Chinese medicine neural regeneration

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neural stem cell activation and glial proliferation in the hippocampal CA3 region of posttraumatic epileptic rats

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neural Regeneration Research 2011年第16期6卷 1232-1237页

作者： Yuanxiang Lin Kun Lin Dezhi Kang Feng Wang Department of Neurosurgery First Affiliated Hospital of Fujian Medical University Fuzhou 350005 Fujian Province China

The present study observed the dynamic expression of CD133, nuclear factor-κB and glial fibrUlary acidic protein in the hippocampal CA3 area of the experimental posttraumatic epilepsy rats to investigate whether gliosis occurs after posttraumatic epilepsy. CD133 and nuclear factor-κB expression was increased at 1 day after posttraumatic epilepsy, peaked at 7 days, and gradually decreased up to 14 days, as seen by double-irnmunohistochemical staining. Glial fibrillary acidic protein/nuclear factor-EB double-labeled cells increased with time and peaked at 14 days after posttraumatic epilepsy. Results show that activation of hippocampal neural stem cells and glial proliferation after posttraumatic epilepsy-induced oxidative stress increases hippocampal glial cell density.

关键词： posttraumatic epilepsy neural stem cell glial cell CD133 nuclear factor-κB glialfibrillary acidic protein neural regeneration

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Single-cell transcriptomics reveals neural stem cell trans-differentiation and cell subpopulations in whole heart decellularized extracellular matrix

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Biophysics Reports 2024年第4期10卷 241-253页

作者： Xiaoning Yang Yuwei Zhao Wei Liu Zhongbao Gao Chunlan Wang Changyong Wang Siwei Li Xiao Zhang Beijing Institute of Basic Medical Sciences

The whole heart decellularized extracellular matrix(ECM) has become a promising scaffold material for cardiac tissue engineering. Our previous research has shown that the whole heart acellular matrix possesses the memory function regulating neural stem cells(NSCs) trans-differentiating to cardiac lineage cells. However, the cell subpopulations and phenotypes in the trans-differentiation of NSCs have not been clearly identified. Here, we performed single-cell RNA sequencing and identified 2,765 cells in the recellularized heart with NSCs revealing the cellular diversity of cardiac and neural lineage, confirming NSCs were capable of trans-differentiating into the cardiac lineage while maintaining the original ability to differentiate into the neural lineage. Notably, the trans-differentiated heart-like cells have dual signatures of neuroectoderm and cardiac mesoderm. This study unveils an in-depth mechanism underlying the trans-differentiation of NSCs and provides a new opportunity and theoretical basis for cardiac regeneration.

关键词： Single-cell transcriptomics neural stem cell Trans-differentiation Decellularized extracellular matrix Cardiac lineage cells

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GENETIC ENGINEERING neural stem cell MODIFIED BY LENTIVIRUS FOR REPAIR OF SPINAL CORD INJURY IN RATS

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Chinese Medical Sciences Journal 2006年第2期21卷 120-124页

作者： Xun Tang Pei-qiang Cai Yue-qiu Lin Martin Oudega Bas Blits Ling Xu Yun-kang Yang Tian-hua Zhou Department of Orthopaedics Kunming General Hospital of Chengdu Military Command Kunming 650032 The Miami Project to Cure Paralysis University of Miami School of Medicine Miami FL 33101 USA Graduate School for Neurosciences Amsterdam Netherlands Institute for Brain Research Amsterdam Postbus 7057 1007 MB the Netherlands Kunming Institute of Zoology Chinese Academy of Sciences Kunming 650000

Objective To explore the feasibility for therapy of spinal cord injury （SCI） by genetic engineering neural stem cell （NSC） modified by lentiviral vector. Methods Following the construction of the genetic engineering NSC modified by lentivirus to secrete both neurotrophic factor-3 （NT-3） and green fluorescence protein （GFP）, hemisection of spinal cord at the level of T10 was performed in 56 adult Wistar rats that were randomly divided into 4 groups （ n = 14 ）, namely 3 therapeutic groups and 1 control group. The therapeutic groups were dealed with NSC, genetic engineering NSC, and concentrated lentiviral supematant which carries both GFP and NT-3, respectively. Then used fluorescence microscope to detect the transgenic expression in vitro and in vivo, migration of the grafted cells in vivo, and used the Basso, Beattie, and Bresnahan （BBB） open-field locomotor test to assess the recovery of function. Results The transplanted cells could survive for long time in vivo and migrate for long distance. The stable transgenie expression could be detected in vivo. The hindlimb function of the injured rats in 3 therapeutic groups, especially those dealed with genetic engineering NSC, improved obviously. Concision It is feasible to combine NSC with lentivirus for the repair of SCI. NSC modified by lentivirus to deliver NT-3, acting as a source of neurotrophic factors and function cell in vivo, has the potential to participate in spinal cord repair.

关键词： lentivirus spinal cord injury neural stem cell neurotrophic factor-3

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