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A core scientific problem in the treatment of central nervous system diseases:newborn neurons

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Neural Regeneration Research 2024年第12期19卷 2588-2601页

作者： Peng Hao Zhaoyang Yang Kwok-Fai So Xiaoguang Li department of neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina Guangdong-HongKong-Macao Institute of CNS Regeneration Ministry of Education CNS Regeneration Collaborative Joint LaboratoryJinan UniversityGuangzhouGuangdong ProvinceChina Bioland laboratory(Guangzhou Regenerative Medicine and Health Guangdong laboratory) GuangzhouGuangdong ProvinceChina department of Ophthalmology and state key laboratory of brain and Cognitive sciences The University of Hong KongHong Kong Special Administration RegionChina center for brain science and brain-Inspired Intelligence Guangdong-Hong Kong-Macao Greater Bay AreaGuangzhouGuangdong ProvinceChina Co-innovation center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina department of Biomedical Engineering School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina

It has long been asserted that failure to recover from central nervous system diseases is due to the system's intricate structure and the regenerative incapacity of adult *** over recent decades,numerous studies have established that endogenous neurogenesis occurs in the adult central nervous system,including humans'.This has challenged the long-held scientific consensus that the number of adult neurons remains constant,and that new central nervous system neurons cannot be created or ***,we present a comprehensive overview of the alterations and regulatory mechanisms of endogenous neurogenesis following central nervous system injury,and describe novel treatment strategies that to rget endogenous neurogenesis and newborn neurons in the treatment of central nervous system *** nervous system injury frequently results in alterations of endogenous neurogenesis,encompassing the activation,proliferation,ectopic migration,diffe rentiation,and functional integration of endogenous neural stem *** of the unfavorable local microenvironment,most activated neural stem cells diffe rentiate into glial cells rather than ***,the injury-induced endogenous neurogenesis response is inadequate for repairing impaired neural *** have attempted to enhance endogenous neurogenesis using various strategies,including using neurotrophic factors,bioactive materials,and cell reprogramming *** alone or in combination,these therapeutic strategies can promote targeted migration of neural stem cells to an injured area,ensure their survival and diffe rentiation into mature functional neurons,and facilitate their integration into the neural *** can integration re plenish lost neurons after central nervous system injury,by improving the local *** regulating each phase of endogenous neurogenesis,endogenous neural stem cells can be harnessed to promote effective regeneration of newborn ***

关键词： bioactive materials brain trauma endogenous neurogenesis hippocampal dentate gyrus neural stem cells neurotrophic factors newborn neurons spinal cord injury stroke subventricular zone

Chitosan-based thermosensitive hydrogel with long-term release of murine nerve growth factor for neurotrophic keratopathy

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Neural Regeneration Research 2024年第3期19卷 680-686页

作者： Jie Wu Yulei Huang Hanrui Yu Kaixiu Li Shifeng Zhang Guoqing Qiao Xiao Liu Hongmei Duan Yifei Huang Kwok-Fai So Zhaoyang Yang Xiaoguang Li Liqiang Wang department of Ophthalmology the Third Medical CenterChinese PLA General HospitalBeijingChina The PLA medical College Department of NephrologyChinese PLA Institute of NephrologyState Key Laboratory of Kidney DiseasesNational Clinical Research Center for Kidney DiseasesBeijingChina department of Ophthalmology Hainan Hospital of Chinese PLA General HospitalSanyaHainan ProvinceChina medical School of Chinese PLA BeijingChina department of neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina Guangdong-Hongkong-Macao Institute of CNS Regeneration Ministry of Education CNS Regeneration Collaborative Joint LaboratoryJinan UniversityGuangzhouGuangdong ProvinceChina Bioland laboratory(Guangzhou Regenerative Medicine and Health Guangdong laboratory) GuangzhouGuangdong ProvinceChina department of Ophthalmology and state key laboratory of brain and Cognitive sciences The University of Hong KongHong Kong Special Administrative RegionChina center for brain science and brain-Inspired Intelligence Guangdong-Hong Kong-Macao Greater Bay AreaGuangzhouGuangdong ProvinceChina Co-innovation center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina School of Engineering Medicine Beijing Key Laboratory for Biomaterials and Neural RegenerationBeihang UniversityBeijingChina Beijing International Cooperation Bases for science and Technology on Biomaterials and Neural Regeneration Beijing Advanced Innovation Center for Big Data-Based Precision MedicineBeihang UniversityBeijingChina

Neurotrophic keratopathy is a persistent defect of the corneal epithelium,with or without stromal ulceration,due to corneal nerve deficiency caused by a variety of *** treatment options for neurotrophic keratopathy are *** this study,an ophthalmic solution was constructed from a chitosan-based thermosensitive hydrogel with long-term release of murine nerve growth factor(CTH-mNGF).Its effectiveness was evaluated in corneal denervation(CD)mice and patients with neurotrophic *** the preclinical setting,CTH-mNGF was assessed in a murine corneal denervation ***-mNGF was transparent,thermosensitive,and ensured sustained release of mNGF for over 20 hours on the ocular surface,maintaining the local mNGF concentration around 1300 pg/mL in *** denervation mice treated with CTH-mNGF for 10 days showed a significant increase in corneal nerve area and total corneal nerve length compared with non-treated and CTH treated mice.A subsequent clinical trial of CTH-mNGF was conducted in patients with stage 2 or 3 neurotrophic *** received topical CTH-mNGF twice daily for 8 *** sodium images,Schirmer’s test,intraocular pressure,Cochet-Bonnet corneal perception test,and best corrected visual acuity were *** total,six patients(total of seven eyes)diagnosed with neurotrophic keratopathy were *** 8 weeks of CTH-mNGF treatment,all participants showed a decreased area of corneal epithelial defect,as stained by ***,six out of seven eyes had fluorescence staining scores<***,best corrected visual acuity,intraocular pressure,Schirmer’s test and Cochet-Bonnet corneal perception test results showed no significant *** increase in corneal nerve density was observed by in vivo confocal microscopy after 8 weeks of CTH-mNGF treatment in three out of seven *** study demonstrates that CTH-mNGF is transparent,thermosensitive,and has sustained-release *** effecti

关键词： chitosan corneal reinnervation murine nerve growth factor neurotrophic keratopathy thermosensitive hydrogel

Activation of endogenous neurogenesis and angiogenesis by basic fibroblast growth factor-chitosan gel in an adult rat model of ischemic stroke

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Neural Regeneration Research 2024年第2期19卷 409-415页

作者： Hongmei Duan Shulun Li Peng Hao Fei Hao Wen Zhao Yudan Gao Hui Qiao Yiming Gu Yang Lv Xinjie Bao Kin Chiu Kwok-Fai So Zhaoyang Yang Xiaoguang Li department of neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina Beijing key laboratory for Biomaterials and Neural Regeneration School of Engineering MedicineBeihang UniversityBeijingChina department of Epidemiology and Statistics School of Public Health and ManagementNingxia Medical UniversityYinchuanNingxia Hui Autonomous RegionChina department of Physical Education Capital University of Economics and BusinessmBeijingChina department of Neurosurgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina department of Psychology State Key Lab of Brain and Cognitive SciencesThe University of Hong KongHong Kong Special Administration RegionChina Guangdong-Hongkong-Macao Institute of CNS Regeneration Ministry of Education CNS Regeneration Collaborative Joint LaboratoryJinan UniversityGuangzhouGuangdong ProvinceChina Bioland laboratory(Guangzhou Regenerative Medicine and Health Guangdong laboratory) GuangzhouGuangdong ProvinceChina department of Ophthalmology and state key laboratory of brain and Cognitive sciences The University of Hong KongHong Kong Special Administration RegionChina center for brain science and brain-Inspired Intelligence Guangdong-Hong Kong-Macao Greater Bay AreaGuangzhouGuangdong ProvinceChina Co-innovation center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina department of Biomedical Engineering School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina

Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain ***,whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still *** this study,we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in *** gel slowly released basic fibroblast growth factor,which improved the local microenvironment,activated endogenous neural stem/progenitor cells,and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons,while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional *** study revealed the mechanism by which bioactive materials repair ischemic strokes,thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.

关键词： adult endogenous neurogenesis angiogenesis basic fibroblast growth factor-chitosan gel chitosan functional recovery ischemic stroke neural stem cell newborn neuron

Bioorthogonal microglia-inspired mesenchymal stem cell bioengineering system creates livable niches for enhancing ischemic stroke recovery via the hormesis

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1412-1427页

作者： Jianpei Xu Yinzhe Sun Yang You Yuwen Zhang Dan Huang Songlei Zhou Yipu Liu Shiqiang Tong Fenfen Ma Qingxiang Song Chengxiang Dai Suke Li Jigang Lei Zhihua Wang Xiaoling Gao Jun Chen Shanghai Pudong Hospital&department of Pharmaceutics School of PharmacyFudan UniversityShanghai 201203China key laboratory of Smart Drug Delivery Ministry of EducationSchool of PharmacyFudan UniversityShanghai 201203China department of pharmacology and Chemical Biology State Key Laboratory of Oncogenes and Related GenesShanghai Universities Collaborative Innovation Center for Translational MedicineShanghai Jiao Tong University School of MedicineShanghai 200025China department of Emergency Shanghai Pudong HospitalFudan University Pudong Medical CenterShanghai 201399China Institute of science and Technology for brain-Inspired Intelligence&department of Neurology Fudan UniversityShanghai 201203China department of Rehabilitation Medicine Huashan HospitalFudan UniversityShanghai 201203China Daxing Research Institute University of Science and Technology BeijingBiomedical Industry BaseZhongguancun Science and Technology ParkBeijing 102600China Cellular Biomedicine Group Inc. Shanghai 201210China

Mesenchymal stem cells(MSCs)experience substantial viability issues in the stroke infarct region,limiting their therapeutic efficacy and clinical *** levels of deadly reactive oxygen radicals(ROS)and proinflammatory cytokines(PC)in the infarct milieu kill transplanted MSCs,whereas low levels of beneficial ROS and PC stimulate and improve engrafted MSCs’*** on the intrinsic hormesis effects in cellular biology,we built a microglia-inspired MSC bioengineering system to transform detrimental high-level ROS and PC into vitality enhancers for strengthening MSC *** system is achieved by bioorthogonally arming metabolic glycoengineered MSCs with microglial membrane-coated nanoparticles and an antioxidative extracellular protective *** this system,extracellular ROSscavenging and PC-absorbing layers effectively buffer the deleterious effects and establish a microlivable niche at the level of a single MSC for ***,the infarct’s inanimate milieu is transformed at the tissue level into a new living niche to facilitate *** engineered MSCs achieved viability five times higher than natural MSCs at seven days after transplantation and exhibited a superior therapeutic effect for stroke recovery up to 28 *** vitality-augmented system demonstrates the potential to accelerate the clinical translation of MSC treatment and boost stroke recovery.

关键词： Ischemic stroke Mesenchymal stem cell Cell engineering Hormesis effect Bioorthogonal chemistry Microglia Reactive oxygen spices Proinflammatory cytokines

USH1C新杂合突变影响耳蜗毛细胞机械电转导功能并导致渐进性听力损伤（英文）

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science Bulletin 2024年第2期 167-172页

作者：贾岩岩贾高干郭荦宋楠王雨萌蒋罗颖舒易来陈岩竺淑佳李华伟李文妍 ENT Institute and Otorhinolaryngology department of Eye & ENT Hospital State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Fudan University Institutes of Biomedical sciences Fudan University NHC key laboratory of Hearing Medicine (Fudan University) The Institutes of brain science and the collaborative innovation center for brain science Fudan University Shanghai center for brain science and brain-Inspired Intelligence Technology Institute of Neuroscience State Key Laboratory of Neuroscience CAS Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of Sciences department of Cardiology and Institute for Developmental and Regenerative Cardiovascular Medicine Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine

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Study of tree shrew biology and models: A booming and prosperous field for biomedical research

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Zoological Research 2024年第4期45卷 877-909页

作者： Yong-Gang Yao Li Lu Rong-Jun Ni Rui Bi Ceshi Chen Jia-Qi Chen Eberhard Fuchs Marina Gorbatyuk Hao Lei Hongli Li Chunyu Liu Long-Bao Lv Kyoko Tsukiyama-Kohara Michinori Kohara Claudia Perez-Cruz Gregor Rainer Bao-Ci Shan Fang Shen An-Zhou Tang Jing Wang Wei Xia Xueshan Xia Ling Xu Dandan Yu Feng Zhang Ping Zheng Yong-Tang Zheng Jumin Zhou Jiang-Ning Zhou key laboratory of Genetic Evolution and Animal Models Yunnan Key Laboratory of Animal Models and Human Disease MechanismsKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650204China National Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility) and National Resource Center for Non-Human PrimatesKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650107China KIZ-CUHK Joint laboratory of Bioresources and Molecular Research in Common Diseases Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650204China Kunming College of Life science University of Chinese Academy of SciencesKunmingYunnan 650204China Mental Health center and Psychiatric laboratory West China HospitalSichuan UniversityChengduSichuan 610041China Sichuan Clinical medical Research center for Mental Disorders ChengduSichuan 610044China German Primate center Leibniz Institute of Primate ResearchGöttingen 37077Germany department of Optometry and Vision science School of OptometryUniversity of Alabama at BirminghamBirminghamAL 35294USA state key laboratory of Magnetic Resonance and Atomic and Molecular Physics Innovation Academy for Precision Measurement Science and TechnologyChinese Academy of SciencesWuhanHubei 430071China Wuhan National laboratory for Optoelectronics Huazhong University of Science and TechnologyWuhanHubei 430074China Soong Ching Ling Institute of Maternity and Child Health International Peace Maternity and Child Health HospitalShanghai Jiao Tong University School of MedicineShanghai 200030China Transboundary Animal Diseases center Joint Faculty of Veterinary MedicineKagoshima UniversityKagoshima-cityKagoshima 890-8580Japan department of Microbiology and Cell Biology Tokyo Metropolitan Institute of Medical ScienceTokyo 156-8506Japan pharmacology department CinvestavMexico City 07360Mexico department of Medicine University of FribourgFribourg CH-1700Switzerland Beijing Engineering Research center of Radiog

The tree shrew(Tupaia belangeri)has long been proposed as a suitable alternative to non-human primates(NHPs)in biomedical and laboratory research due to its close evolutionary relationship with *** recent years,significant advances have facilitated tree shrew studies,including the determination of the tree shrew genome,genetic manipulation using spermatogonial stem cells,viral vector-mediated gene delivery,and mapping of the tree shrew brain ***,the limited availability of tree shrews globally remains a substantial challenge in the ***,determining the key questions best answered using tree shrews constitutes another *** shrew models have historically been used to study hepatitis B virus(HBV)and hepatitis C virus(HCV)infection,myopia,and psychosocial stress-induced depression,with more recent studies focusing on developing animal models for infectious and neurodegenerative *** these efforts,the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical *** review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this *** emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew *** use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models,meeting the increasing demands of life science and biomedical research.

关键词： Tree shrew Animal model Neurodegenerative diseases Infectious diseases Neuroscience Phenome

Characteristic Features of Deep brain Lymphatic Vessels and Their Regulation by Chronic Stress

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Research 2023年第4期2023卷 657-670页

作者： Junzhuang Chang Bingqing Guo Yan Gao Wei Li Xiaoyu Tong Yi Feng Nashat Abumaria state key laboratory of medical neurobiology and MOE Frontiers center for brain science Institutes of Brain ScienceFudan UniversityShanghai 200032China department of Integrative Medicine and neurobiology School of Basic Medical SciencesInstitutes of Brain ScienceBrain Science Collaborative Innovation CenterState Key Laboratory of Medical NeurobiologyInstitute of Acupuncture and MoxibustionFudan Institutes of Integrative MedicineFudan UniversityShanghai 200032China

Studies have demonstrated that a functional network of meningeal lymphatic vessels exists in the ***,it is unknown whether lymphatic vessels could also extend deep into the brain parenchyma and whether the vessels could be regulated by stressful life *** used tissue clearing techniques,immunostaining,light-sheet whole-brain imaging,confocal imaging in thick brain sections and flow cytometry to demonstrate the existence of lymphatic vessels deep in the brain *** unpredictable mild stress or chronic corticosterone treatment was used to examine the regulation of brain lymphatic vessels by stressful *** blotting and coimmunoprecipitation were used to provide mechanistic *** demonstrated the existence of lymphatic vessels deep in the brain parenchyma and characterized their features in the cortex,cerebellum,hippocampus,midbrain,and ***,we showed that deep brain lymphatic vessels can be regulated by stressful life *** stress reduced the length and areas of lymphatic vessels in the hippocampus and thalamus but increased the diameter of lymphatic vessels in the *** changes were observed in prefrontal cortex,lateral habenula,or dorsal raphe *** corticosterone treatment reduced lymphatic endothelial cell markers in the ***,chronic stress might reduce hippocampal lymphatic vessels by down-regulating vascular endothelial growth factor C receptors and up-regulating vascular endothelial growth factor C neutralization *** results provide new insights into the characteristic features of deep brain lymphatic vessels,as well as their regulation by stressful life events.

关键词： insight stress Deep

Physiological Roles of β-amyloid in Regulating Synaptic Function:Implications for AD Pathophysiology

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神经科学通报:英文版 2023年第8期39卷 1289-1308页

作者： Wenwen Cai Linxi Li Shaoming Sang Xiaoli Pan Chunjiu Zhong department of Neurology Zhongshan HospitalFudan UniversityShanghai 200032China Basic medical College Nanchang UniversityNanchang 330031China state key laboratory of medical neurobiology Institutes of Brain Science&Collaborative Innovation Center for Brain ScienceFudan UniversityShanghai 200032China

The physiological functions of endogenous amyloid-β(Aβ),which plays important role in the pathology of Alzheimer's disease(AD),have not been paid enough ***,we review the multiple physiological effects of Aβ,particularly in regulating synaptic transmission,and the possible mechanisms,in order to decipher the real characters of Aβunder both physiological and pathological *** worthy studies have shown that the deprivation of endogenous Aβgives rise to synaptic dysfunction and cognitive deficiency,while the moderate elevation of this peptide enhances long term potentiation and leads to neuronal *** this review,we provide a new view for understanding the role of Aβin AD pathophysiology from the perspective of physiological meaning.

关键词： Aβ Physiological role Synapse LTP Synaptic vesicle cycle Cognition AD

A visualization pipeline for in vivo two-photon volumetric astrocytic calcium imaging

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The Journal of Biomedical Research 2022年第5期36卷 358-367页

作者： Qian Sun Yusi Hu Saiyue Deng Yanyu Xiong Zhili Huang department of pharmacology School of Basic Medical ScienceFudan UniversityShanghai 200032China state key laboratory of medical neurobiology Institutes of Brain Science and Collaborative Innovation Center for Brain ScienceFudan UniversityShanghai 200032China department of Neurology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China

Astrocytes,the multi-functional glial cells with the most abundant population in the brain,integrate information across their territories to regulate neuronal synaptic and cerebrovascular *** calcium(Ca^(2+))signaling is the major readout of cellular functional state of *** conventional two-photon in vivo imaging usually focuses on a single horizontal focal plane to capture the astrocytic Ca^(2+)signals,which leaves>80%spatial information *** fully probe the Ca^(2+)activity across the whole astrocytic territory,we developed a pipeline for imaging and visualizing volumetric astrocytic Ca^(2+)time-lapse *** the pipeline,we discovered a new signal distribution pattern from three-dimensional(3D)astrocytic Ca^(2+)imaging data of mice under isoflurane anesthetic *** tools developed in this study enable a better understanding of the spatiotemporal patterns of astrocytic activity in 3D space.

关键词： astrocyte calcium imaging three-dimensional visualization