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Frontiers of Medicine 2021年第6期15卷 887-902页

作者： Xin Wu Zongqi Wang Haiying Li Xueshun Xie Jiang Wu Haitao Shen Xiang Li Zhong Wang Gang Chen Department of Neurosurgery&Brain and Nerve Research Laboratory The First Affiliated Hospital of Soochow UniversitySuzhou215006China

Monocarboxylic acid transporter 1(MCT1)maintains axonal function by transferring lactic acid from oligodendrocytes to *** hemorrhage(SAH)induces white matter injury,but the involvement of MCT1 is *** this study,the SAH model of adult male Sprague-Dawley rats was used to explore the role of MCT1 in white matter injury after *** 48 h after SAH,oligodendrocyte MCT1 was significantly reduced,and the exogenous overexpression of MCT1 significantly improved white matter integrity and long-term cognitive *** training after SAH significantly increased the number of ITPR2+SOX10+oligodendrocytes and upregulated the level of MCT1,which was positively correlated with the behavioral ability of *** addition,miR-29b and miR-124 levels were significantly increased in SAH rats compared with non-SAH *** intervention experiments showed that miR-29b and miR-124 could negatively regulate the level of *** study confirmed that the loss of MCT1 may be one of the mechanisms of white matter damage after SAH and may be caused by the negative regulation of miR-29b and ***1 may be involved in the neurological improvement of rehabilitation training after SAH.

关键词： microRNAs monocarboxylate transporter 1 motor training subarachnoid hemorrhage white matter injury

Compound from Magnolia officinalis Ameliorates white matter injury by Promoting Oligodendrocyte Maturation in Chronic Cerebral Ischemia Models

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Neuroscience Bulletin 2023年第10期39卷 1497-1511页

作者： Zhi Zhang Xin Shu Qian Cao Lushan Xu Zibu Wang Chenggang Li Shengnan Xia Pengfei Shao Xinyu Bao Liang Sun Yuhao Xu Yun Xu Department of Neurology Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjing 210008China Department of Neurology Nanjing Drum Tower HospitalAfliated Hospital of Medical School and State Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical DiseasesNanjing UniversityNanjing 210008China Jiangsu Key Laboratory for Molecular Medicine Medical School of Nanjing UniversityNanjing 210008China Jiangsu Provincial Key Discipline of Neurology Nanjing 210008China Nanjing Neurology Medical Center Nanjing 210008China

Chronic cerebral hypoperfusion leads to white matter injury(WMI),which subsequently causes neurodegeneration and even cognitive ***,due to the lack of treatment specifically for WMI,novel recognized and effective therapeutic strategies are urgently *** this study,we found that honokiol and magnolol,two compounds derived from Magnolia officinalis,significantly facilitated the differentiation of primary oligodendrocyte precursor cells(OPCs)into mature oligodendrocytes,with a more prominent effect of the former ***,our results demonstrated that honokiol treatment improved myelin injury,induced mature oligodendrocyte protein expression,attenuated cognitive decline,promoted oligodendrocyte regeneration,and inhibited astrocytic activation in the bilateral carotid artery stenosis ***,honokiol increased the phosphorylation of serine/threonine kinase(Akt)and mammalian target of rapamycin(mTOR)by activating cannabinoid receptor 1 during OPC ***,our study indicates that honokiol might serve as a potential treatment for WMI in chronic cerebral ischemia.

关键词： Honokiol white matter injury Oligodendrocyte Vascular dementia

Lipocalin-2-Mediated Insufficient Oligodendrocyte Progenitor Cell Remyelination for white matter injury After Subarachnoid Hemorrhage via SCL22A17 Receptor/Early Growth Response Protein 1 Signaling

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Neuroscience Bulletin 2022年第12期38卷 1457-1475页

作者： Qiang Li Xufang Ru Yang Yang Hengli Zhao Jie Qu Weixiang Chen Pengyu Pan Huaizhen Ruan Chaojun Li Yujie Chen Hua Feng Department of Neurosurgery and State Key Laboratory of Trauma Burn and Combined InjurySouthwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China Department of Neurobiology College of Basic Medical SciencesThird Military Medical University(Army Medical University)Chongqing 400038China Model Animal Research Center Nanjing UniversityNanjing 210032China Chongqing Key Laboratory of Precision Neuromedicine and Neuroregenaration Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China Chongqing Clinical Research Center for Neurosurgery Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China

Insufficient remyelination due to impaired oligodendrocyte precursor cell(OPC)differentiation and maturation is strongly associated with irreversible white matter injury(WMI)and neurological *** analyzed whole transcriptome expression to elucidate the potential role and underlying mechanism of action of lipocalin-2(LCN2)in OPC differentiation and WMI and identified the receptor SCL22A17 and downstream transcription factor early growth response protein 1(EGR1)as the key signals contributing to LCN2-mediated insufficient OPC *** LCN-knockdown and OPC EGR1 conditional-knockout mice,we discovered enhanced OPC differentiation in developing and injured white matter(WM);consistent with this,the specific inactivation of LCN2/SCl22A17/EGR1 signaling promoted remyelination and neurological recovery in both atypical,acute WMI due to subarachnoid hemorrhage and typical,chronic WMI due to multiple *** potentially represents a novel strategy to enhance differentiation and remyelination in patients with white matter injury.

关键词： white matter injury Oligodendrocyte progenitor cell Remyelination Subarachnoid hemorrhage Multiple sclerosis Lipocalin-2 Early growth response protein 1

The pivotal role of microglia in injury and the prognosis of subarachnoid hemorrhage

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Neural Regeneration Research 2025年第7期20卷 1829-1848页

作者： Wenjing Ning Shi Lv Qian Wang Yuzhen Xu Department of Rehabilitation The Second Affiliated Hospital of Shandong First Medical UniversityTaianShandong ProvinceChina Department of Central Laboratory The Affiliated Taian City Central Hospital of Qingdao UniversityTaianShandong ProvinceChina

Subarachnoid hemorrhage leads to a series of pathological changes,including vascular spasm,cellular apoptosis,blood–brain barrier damage,cerebral edema,and white matter ***,which are the key immune cells in the central nervous system,maintain homeostasis in the neural environment,support neurons,mediate apoptosis,participate in immune regulation,and have neuroprotective *** evidence has shown that microglia play a pivotal role in the pathogenesis of subarachnoid hemorrhage and affect the process of injury and the prognosis of subarachnoid ***,microglia play certain neuroprotective roles in the recovery phase of subarachnoid *** approaches aimed at modulating microglia function are believed to attenuate subarachnoid hemorrhage *** provides new targets and ideas for the treatment of subarachnoid ***,an in-depth and comprehensive summary of the role of microglia after subarachnoid hemorrhage is still *** review describes the activation of microglia after subarachnoid hemorrhage and their roles in the pathological processes of vasospasm,neuroinflammation,neuronal apoptosis,blood–brain barrier disruption,cerebral edema,and cerebral white matter *** also discusses the neuroprotective roles of microglia during recovery from subarachnoid hemorrhage and therapeutic advances aimed at modulating microglial function after subarachnoid ***,microglia in subarachnoid hemorrhage are targeted with TLR inhibitors,nuclear factor-κB and STAT3 pathway inhibitors,glycine/tyrosine kinases,NLRP3 signaling pathway inhibitors,Gasdermin D inhibitors,vincristine receptorαreceptor agonists,ferroptosis inhibitors,genetic modification techniques,stem cell therapies,and traditional Chinese ***,most of these are still being evaluated at the laboratory *** clinical studies and data on subarachnoid hemorrhage are required to improve the treatment of subarachnoid hemor

关键词： apoptosis blood–brain barrier brain edema microglia neuroinflammation neuron neuroprotection subarachnoid hemorrhage vasoconstriction white matter injury

Decellularized optic nerve functional scaffold transplant facilitates directional axon regeneration and remyelination in the injured white matter of the rat spinal cord

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Neural Regeneration Research 2021年第11期16卷 2276-2283页

作者： Yu-Rong Bai Bi-Qin Lai Wei-Tao Han Jia-Hui Sun Ge Li Ying Ding Xiang Zeng Yuan-Huan Ma Yuan-Shan Zeng Key Laboratory for Stem Cells and Tissue Engineering Ministry of EducationSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Department of Histology and Embryology Zhongshan School of MedicineSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Co-innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina Institute of Spinal Cord injury Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Guangdong Provincial Key Laboratory of Brain Function and Disease Zhongshan School of MedicineSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina

Axon regeneration and remyelination of the damaged region is the most common repair strategy for spinal cord ***,achieving good outcome remains *** previous study showed that porcine decellularized optic nerve better mimics the extracellular matrix of the embryonic porcine optic nerve and promotes the directional growth of dorsal root ganglion ***,it has not been reported whether this material promotes axonal regeneration in *** the present study,a porcine decellularized optic nerve was seeded with neurotrophin-3-overexpressing Schwann *** functional scaffold promoted the directional growth and remyelination of regenerating *** vitro,the porcine decellularized optic nerve contained many straight,longitudinal channels with a uniform distribution,and microscopic pores were present in the channel *** spatial micro topological structure and extracellular matrix were conducive to the adhesion,survival and migration of neural stem *** scaffold promoted the directional growth of dorsal root ganglion neurites,and showed strong potential for myelin ***,we transplanted the porcine decellularized optic nerve containing neurotrophin-3-overexpressing Schwann cells in a rat model of T10 spinal cord defect in *** weeks later,the regenerating axons grew straight,the myelin sheath in the injured/transplanted area recovered its structure,and simultaneously,the number of inflammatory cells and the expression of chondroitin sulfate proteoglycans were ***,these findings suggest that porcine decellularized optic nerve loaded with Schwann cells overexpressing neurotrophin-3 promotes the directional growth of regenerating spinal cord axons as well as myelin *** procedures involving animals were conducted in accordance with the ethical standards of the Institutional Animal Care and Use Committee of Sun Yat-sen University(approval ***-IACUC-2019-B034)on February 28,2019.

关键词： axonal regeneration decellularized optic nerve directional regeneration functional scaffold microenvironment neurotrophin-3 optic nerve remyelination Schwann cells tissue engineering white matter injury

Digoxin Ameliorates Glymphatic Transport and Cognitive Impairment in a Mouse Model of Chronic Cerebral Hypoperfusion

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Neuroscience Bulletin 2022年第2期38卷 181-199页

作者： Jie Cao Di Yao Rong Li Xuequn Guo Jiahuan Hao Minjie Xie Jia Li Dengji Pan Xiang Luo Zhiyuan Yu Minghuan Wang Wei Wang Department of Neurology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Pediatrics Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Respiratory Medicine Quanzhou First Hospital Affiliated to Fujian Medical UniversityQuanzhou 362000China Key Laboratory of Neurological Diseases of the Chinese Ministry of Education School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

The glymphatic system plays a pivotal role in maintaining cerebral *** cerebral hypoperfusion,arising from small vessel disease or carotid stenosis,results in cerebrometabolic disturbances ultimately manifesting in white matter injury and cognitive ***,whether the glymphatic system serves as a potential therapeutic target for white matter injury and cognitive decline during hypoperfusion remains ***,we established a mouse model of chronic cerebral hypoperfusion via bilateral common carotid artery *** found that the hypoperfusion model was associated with significant white matter injury and initial cognitive impairment in conjunction with impaired glym・phatic system *** glymphatic dysfunction was associated with altered cerebral perfusion and loss of aquaporin 4 *** of digoxin rescued changes in glymphatic transport,white matter structure,and cognitive *** of glymphatic functions by treatment with the AQP4 inhibitor TGN-020 abolished this protective effect of digoxin from hypoperfusion *** research yields new insight into the relationship between hemodynamics,glymphatic transport,white matter injury,and cognitive changes after chronic cerebral hypoperfusion.

关键词： Chronic cerebral hypoperfusion Cognitive impairment Digoxin Glymphatic system white matter injury

Bystanders or not?Microglia and lymphocytes in aging and stroke

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Neural Regeneration Research 2023年第7期18卷 1397-1403页

作者： Justin N.Nguyen Anjali Chauhan University of Texas McGovern Medical School at Houston HoustonTXUSA Department of Neurology University of Texas McGovern Medical School at HoustonHoustonTXUSA

As the average age of the world population increases,more people will face debilitating aging-associated conditions,including dementia and *** only does the incidence of these conditions increase with age,but the recovery afterward is often worse in older *** and health professionals must unveil and understand the factors behind age-associated diseases to develop a therapy for older *** causes profound changes in the immune system including the activation of microglia in the *** microglia promote T lymphocyte transmigration leading to an increase in neuroinflammation,white matter damage,and cognitive impairment in both older humans and *** presence of T and B lymphocytes is observed in the aged brain and correlates with worse stroke *** strategies in stroke target either microglia or the lymphocytes or the communications between them to promote functional recovery in aged *** this review,we examine the role of the microglia and T and B lymphocytes in aging and how they contribute to cognitive ***,we provide an important update on the contribution of these cells and their interactions in preclinical aged stroke.

关键词： age B lymphocytes brain central nervous system cognition inflammation microglia middle cerebral artery occlusion neuroinflammation stroke T lymphocytes white matter injury

MFG-E8 Alleviates Cognitive Impairments Induced by Chronic Cerebral Hypoperfusion by Phagocytosing Myelin Debris and Promoting Remyelination

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Neuroscience Bulletin 2024年第4期40卷 483-499页

作者： Xiaohong Dong Zhi Zhang Xin Shu Zi Zhuang Pinyi Liu Renyuan Liu Shengnan Xia Xinyu Bao Yun Xu Yan Chen Department of Neurology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing210008China Department of Neurology Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjing210008China Department of Neurology Drum Tower Hospital of Nanjing Medical UniversityNanjing210008China Jiangsu Key Laboratory for Molecular Medicine Medical School of Nanjing UniversityNanjing210008China Jiangsu Provincial Key Discipline of Neurology Nanjing210008China

Chronic cerebral hypoperfusion is one of the pathophysiological mechanisms contributing to cognitive decline by causing white matter *** phagocytosing myelin debris in a timely manner can promote remyelination and contribute to the repair of white ***,milk fat globule-epidermal growth factor-factor 8(MFG-E8),a microglial phagocytosis-related protein,has not been well studied in hypoperfusion-related cognitive *** found that the expression of MFG-E8 was significantly decreased in the brain of mice after bilateral carotid artery stenosis(BCAS).MFG-E8 knockout mice demonstrated more severe BCAS-induced cognitive impairments in the behavioral *** addition,we discovered that the deletion of MFG-E8 aggravated white matter damage and the destruction of myelin microstructure through fluorescent staining and electron ***,MFG-E8 overexpression by AAV improved white matter injury and increased the number of mature oligodendrocytes after ***,in vitro and in vivo experiments showed that MFG-E8 could enhance the phagocytic function of microglia via theαVβ3/αVβ5/Rac1 pathway and IGF-1 production to promote the differentiation of oligodendrocyte progenitor cells into mature ***,we found that MFG-E8 was mainly derived from astrocytes,not *** findings suggest that MFG-E8 is a potential therapeutic target for cognitive impairments following cerebral hypoperfusion.

关键词： white matter injury Cognitive dysfunction MFG-E8 Remyelination Microglial phagocytosis

Potential physiological and pathological roles for axonal ryanodine receptors

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Neural Regeneration Research 2023年第4期18卷 756-759页

作者： David P.Stirling Kentucky Spinal Cord injury Research Center and Departments of Neurological Surgery Anatomical Sciences and NeurobiologyMicrobiology and ImmunologyUniversity of LouisvilleSchool of MedicineLouisvilleKYUSA

Clinical disability following trauma or disease to the spinal cord often involves the loss of vital white matter elements including axons and *** excessive Cais an established driver of axonal degeneration,therapeutically targeting externally sourced Cato date has had limited success in both basic and clinical *** factors that may underlie this limited success include the complexity of the many potential sources of Caentry and the discovery that axons also contain substantial amounts of stored Cathat if inappropriately released could contribute to axonal *** Castorage is largely accomplished by the axoplasmic reticulum that is part of a continuous network of the endoplasmic reticulum that provides a major sink and source of intracellular Cafrom the tips of dendrites to axonal ***“neuron-within-a-neuron”is positioned to rapidly respond to diverse external and internal stimuli by amplifying cytosolic Calevels and generating short and long distance regenerative Cawaves through Cainduced *** review provides a glimpse into the molecular machinery that has been implicated in regulating ryanodine receptor mediated Carelease in axons and how dysregulation and/or overstimulation of these internodal axonal signaling nanocomplexes may directly contribute to Ca-dependent axonal *** ryanodine receptors expressed in dendrites,soma,and axonal terminals have been implicated in synaptic transmission and synaptic plasticity,but a physiological role for internodal localized ryanodine receptors remains largely *** physiological roles for internodal ryanodine receptors and such an elaborate internodal binary membrane signaling network in axons will also be discussed.

关键词： axomyelinic synapse axon axoplasmic reticulum calcium ryanodine receptor secondary axonal degeneration spinal cord injury voltage-gated calcium channel white matter injury

Roles of NG2 Glia in Cerebral Small Vessel Disease

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Neuroscience Bulletin 2023年第3期39卷 519-530页

作者： Yixi He Zhenghao Li Xiaoyu Shi Jing Ding Xin Wang Department of Neurology Zhongshan HospitalFudan UniversityShanghai 200032China State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Institutes of Brain ScienceFudan UniversityShanghai 200032China Institute of Neuroscience MOE Key Laboratory of Molecular NeurobiologyNMUShanghai 200433China

Cerebral small vessel disease(CSVD)is one of the most prevalent pathologic processes affecting 5%of people over 50 years of age and contributing to 45%of dementia *** evidence has demonstrated the pathological roles of chronic hypoperfusion,impaired cerebral vascular reactivity,and leakage of the blood–brain barrier in ***,the pathogenesis of CSVD remains elusive thus far,and no radical treatment has been ***2 glia,also known as oligodendrocyte precursor cells,are the fourth type of glial cell in addition to astrocytes,microglia,and oligodendrocytes in the mammalian central nervous *** novel functions for NG2 glia in physiological and pathological states have recently been *** this review,we discuss the role of NG2 glia in CSVD and the underlying mechanisms.

关键词： NG2 glia Oligodendrocyte precursor cell Cerebral small vessel disease white matter injury