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

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

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Treadmill exercise improves hippocampal neural plasticity and relieves cognitive deficits in a mouse model of epilepsy

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Neural Regeneration Research 2024年第3期19卷 657-662页

作者： Hang Yu Mingting Shao Xi Luo Chaoqin Pang kwok-fai so Jiandong Yu Li Zhang Key Laboratory of CNS Regeneration(Ministry of Education) Guangdong-Hong Kong-Macao Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong ProvinceChina State Key Laboratory of Brain and Cognitive Science Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina Neuroscience and Neurorehabilitation Institute University of Health and Rehabilitation SciencesQingdaoShandong ProvinceChina Department of Neurosurgery The First Affiliated Hospital of Bengbu Medical CollegeBengbuShandong ProvinceChina School of Psychology Shanghai University of SportShanghaiChina

Epilepsy frequently leads to cognitive dysfunction and approaches to treatment remain *** regular exercise effectively improves learning and memory functions across multiple neurological diseases,its application in patients with epilepsy remains ***,we adopted a 14-day treadmill-exercise paradigm in a pilocarpine injection-induced mouse model of *** assays confirmed the improvement of object and spatial memory after endurance training,and electrophysiological studies revealed the maintenance of hippocampal plasticity as a result of physical *** of the mechanisms underlying this effect revealed that exercise protected parvalbumin interneurons,probably via the suppression of neuroinflammation and improved integrity of blood-brain *** summary,this work identified a previously unknown mechanism through which exercise improves cognitive rehabilitation in epilepsy.

关键词： blood-brain barrier cognition hippocampus interneurons long-term potentiation microglial cell neuroinflammation spatial memory temporal epilepsy treadmill exercise

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Multiple factors to assist human-derived induced pluripotent stem cells to efficiently differentiate into midbrain dopaminergic neurons

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Neural Regeneration Research 2024年第4期19卷 908-914页

作者： Yalan Chen Junxin Kuang Yimei Niu Hongyao Zhu Xiaoxia Chen kwok-fai so Anding Xu Lingling Shi Guangdong-Hong Kong-Macao Institute of CNS Regeneration Ministry of Education CNS Regeneration Collaborative Joint LaboratoryJinan University Department of Neurology and Stroke Center The First Affiliated HospitalJinan University Department of Psychiatry The First Affiliated HospitalJinan University Co-innovation Center of Neuroregeneration Nantong University

Midbrain dopaminergic neurons play an important role in the etiology of neurodevelopmental and neurodegenerative *** also represent a potential source of transplanted cells for therapeutic *** vitro differentiation of functional midbrain dopaminergic neurons provides an accessible platform to study midbrain neuronal dysfunction and can be used to examine obstacles to dopaminergic neuronal *** evidence and impressive advances in human induced pluripotent stem cells,with tuned neural induction and differentiation protocols,makes the production of induced pluripotent stem cell-derived dopaminergic neurons *** SB431542 and dorsomorphin dual inhibitor in an induced pluripotent stem cell-derived neural induction protocol,we obtained multiple subtypes of neurons,including 20%tyrosine hydroxylase-positive dopaminergic *** obtain more dopaminergic neurons,we next added sonic hedgehog(SHH)and fibroblast growth factor 8(FGF8)on day 8 of *** increased the proportion of dopaminergic neurons,up to 75%tyrosine hydroxylase-positive neurons,with 15%tyrosine hydroxylase and forkhead box protein A2(FOXA2)co-expressing *** further optimized the induction protocol by applying the small molecule inhibitor,CHIR99021(CHIR).This helped facilitate the generation of midbrain dopaminergic neurons,and we obtained 31-74%midbrain dopaminergic neurons based on tyrosine hydroxylase and FOXA2 ***,we have established three induction protocols for dopaminergic *** on tyrosine hydroxylase and FOXA2 immunostaining analysis,the CHIR,SHH,and FGF8 combined protocol produces a much higher proportion of midbrain dopaminergic neurons,which could be an ideal resource for tackling midbrain-related diseases.

关键词： dopaminergic neurons FGF signal induced pluripotent stem cells midbrain neural differentiation SHH signal SMAD signal WNT signal

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Letter from the Editor-in-Chief

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Neural Regeneration Research 2024年第1期19卷 5-5页

作者： kwok-fai so Chinese Academy of Sciences GHM Institute of CNS Regeneration Jinan University the State Key Laboratory of Brain and Cognitive Sciences The University of Hong Kong Hong Kong Spinal Cord Injury Fund(HKSCIF) the Board of Director of the ChinaSCI Net

It is my great pleasure to introduce you the 19th volume of Neural Regeneration Research(NRR)and the first issue of *** new volume still features a large number of manuscripts reporting on neural regeneration,which we... 详细信息

关键词： Regeneration pleasure neural

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Effects of Lycium barbarum polysaccharide on cytokines in adolescents with subthreshold depression:a randomized controlled study

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Neural Regeneration Research 2024年第9期19卷 2036-2040页

作者： Xiaoyue Li Tao Liu Xuan Mo Runhua Wang Xueyan Kong Robin Shao Roger S.Mclntyre kwok-fai so Kangguang Lin Department of Affective Disorders The Affiliated Brain Hospital of Guangzhou Medical University(Guangzhou Huiai Hospital)GuangzhouGuangdong ProvinceChina Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Department of Psychiatry The Fifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Mood Disorders Psychopharmacology Unit Poul Hansen Family Centre for DepressionUniversity Health NetworkTorontoONCanada Department of Psychiatry University of TorontoTorontoONCanada Brain and Cognition Discovery Foundation TorontoCanada Ministry of Education Joint International Research Laboratory of CNS Regeneration Jinan UniversityGuangzhouGuangdong ProvinceChina Neuroscience and Neurorehabilitation Institute University of Health and Rehabilitation SciencesQingdaoShandong ProvinceChina

Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory ***,anti-inflammatory treatment has shown partial effectiveness in alleviating depression *** barbarum polysaccharide(LBP),derived from Goji berries,exhibits notable antioxidative and anti-inflammatory *** our recent double-blinded randomized placebo-controlled trial,we found that LBP significantly reduced depressive symptoms in adolescents with subthreshold *** is presumed that the antidepressant effect of LBP may be associated with its influence on inflammatory *** the double-blinded randomized controlled trial,we enrolled 29 adolescents with subthreshold depression and randomly divided them into an LBP group and a placebo *** the LBP group,adolescents were given 300 mg/d LBP.A 6-week follow up was completed by 24 adolescents,comprising 14 adolescents from the LBP group(15.36±2.06 years,3 men and 11 women)and 10 adolescents from the placebo group(14.9±1.6 years,2 men and 8 women).Our results showed that after 6 weeks of treatment,the interleukin-17A level in the LBP group was lower than that in the placebo *** analysis showed that LBP reduced the correlations and connectivity between inflammatory factors,which were associated with the improvement in depressive *** findings suggest that 6-week administration of LBP suppresses the immune response by reducing interleukin-17A level,thereby exerting an antidepressant effect.

关键词： adolescents cytokines efficacy Goji berry inflammatory responses interleukin-17A Lycium barbarum polysaccharide randomized controlled study subthreshold depression

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Lycium barbarum glycopeptide(wolfberry extract)slows N-methyl-N-nitrosourea-induced degradation of photoreceptors

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Neural Regeneration Research 2024年第10期19卷 2290-2298页

作者： Qihang Kong Xiu Han Haiyang Cheng Jiayu Liu Huijun Zhang Tangrong Dong Jiansu Chen kwok-fai so Xuesong Mi Ying Xu Shibo Tang Department of Ophthalmology Aier Eye HospitalJinan UniversityGuangzhouGuangdong ProvinceChina Department of Ophthalmology The First Affiliated Hospital of Jinan UniversityGuangzhouGuangdong ProvinceChina Guangdong-Hong Kong-Macao Institute of CNS Regeneration Key Laboratory of CNS Regeneration(Ministry of Education)Jinan UniversityGuangzhouGuangdong ProvinceChina Department of Ophthalmology Guangzhou Panyu Central HospitalGuangzhouGuangdong ProvinceChina School of Stomatology Jinan UniversityGuangzhouGuangdong ProvinceChina Aier Academician Station ChangshaHunan ProvinceChina Co-Innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina State Key Laboratory of Brain and Cognitive Sciences Hong Kong Special Administrative RegionChina

Photoreceptor cell degeneration leads to blindness, for which there is currently no effective treatment. Our previous studies have shown that Lycium barbarum(L. barbarum) polysaccharide(LBP) protects degenerated photoreceptors in rd1, a transgenic mouse model of retinitis pigmentosa. L. barbarum glycopeptide(Lb GP) is an immunoreactive glycoprotein extracted from LBP. In this study, we investigated the potential protective effect of Lb GP on a chemically induced photoreceptor-degenerative mouse model. Wild-type mice received the following: oral administration of Lb GP as a protective pre-treatment on days 1–7;intraperitoneal administration of 40 mg/kg N-methylN-nitrosourea to induce photoreceptor injury on day 7;and continuation of orally administered Lb GP on days 8–14. Treatment with Lb GP increased photoreceptor survival and improved the structure of photoreceptors, retinal photoresponse, and visual behaviors of mice with photoreceptor degeneration. Lb GP was also found to partially inhibit the activation of microglia in N-methyl-N-nitrosourea-injured retinas and significantly decreased the expression of two pro-inflammatory cytokines. In conclusion, Lb GP effectively slowed the rate of photoreceptor degeneration in N-methyl-N-nitrosourea-injured mice, possibly through an anti-inflammatory mechanism, and has potential as a candidate drug for the clinical treatment of photoreceptor degeneration.

关键词： anti-inflammation inherited retinal diseases Lycium barbarum glycopeptide N-methyl-N-nitrosourea opsin photoreceptor reactive gliosis retinal degeneration retinitis pigmentosa rhodopsin

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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

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Exercise preconditioning alleviates ischemia-induced memory deficits by increasing circulating adiponectin

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Neural Regeneration Research 2025年第5期20卷 1445-1454页

作者： Meifeng Zheng Borui Zhang sonata S Y Yau kwok-fai so Li Zhang Haining Ou Department of Rehabilitation Medicine Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Department of Rehabilitation Medicine The Fifth Clinical College of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Key Laboratory of CNS Regeneration(Ministry of Education) Guangdong-Hong Kong-Macao Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong ProvinceChina Department of Rehabilitation Sciences The Hong Kong Polytechnic UniversityHong Kong Special Administrative RegionChina State Key Laboratory of Brain and Cognitive Science Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina Center for Exercise and Brain Science School of PsychologyShanghai University of SportShanghaiChina Neuroscience and Neurorehabilitation Institute University of Health and Rehabilitation SciencesQingdaoShandong ProvinceChina

Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug *** exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitation after *** this study,we determined whether exercise training before disease onset can alleviate the severity of cerebral *** also examined the role of exercise-induced circulating factors in these *** mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery *** found that this exercise pre-conditioning strategy effectively attenuated brain infarct area,inhibited gliogenesis,protected synaptic proteins,and improved novel object and spatial memory *** analysis showed that circulating adiponectin plays a critical role in these preventive effects of *** activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting receptor activation abolished the exercise *** summary,our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.

关键词： adiponectin cerebral ischemia exercise pre-conditioning hippocampus memory function middle cerebral artery occlusion prefrontal cortex synaptic proteins treadmill exercise

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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

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Letter from the Editor-in-Chief

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Neural Regeneration Research 2025年第1期20卷 5-5页

作者： kwok-fai so Neural Regeneration Research

Greetings esteemed readers,As we embark on a new year filled with promise and innovation,it is my pleasure to reflect on the remarkable achievements and advancements in the journal Neural Regeneration Research(NRR)showcased throughout ***,the 2024 International Neural Regeneration Symposium(INRS2024)and the 15^(th) Asia Pacific Symposium on Neural Regeneration(APSNR),held from April 12^(th) to 14^(th) in Guangzhou,China,stand as shining examples of collaboration,knowledge exchange,and scientific excellence.

关键词： Regeneration filled journal

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