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High mobility group box 1 in the central nervous system:regeneration hidden beneath inflammation

Neural Regeneration Research 2025年第1期20卷 107-115页

作者： Hanki Kim Bum Jun Kim Seungyon Koh Hyo Jin Cho Xuelian Jin Byung Gon Kim Jun Young Choi Department of Brain Science Ajou University School of MedicineSuwonSouth Korea Department of Biomedical Sciences Ajou University Graduate School of MedicineSuwonSouth Korea Department of Neurology Ajou University School of MedicineSuwonSouth Korea Department of Geriatrics The Affiliated Suqian First People’s Hospital of Nanjing Medical UniversitySuqianJiangsu ProvinceChina

High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and ***-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain *** drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system *** it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system *** this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory *** targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.

关键词： central nervous system damage-associated molecular pattern ethyl pyruvate glycyrhizzin high mobility group box 1 inflammation neural stem cells neurodevelopment oligodendrocyte progenitor cells redox status regeneration

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Liposomes as versatile agents for the management of traumatic and nontraumatic central nervous system disorders:drug stability,targeting efficiency,and safety

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Neural Regeneration Research 2025年第7期20卷 1883-1899页

作者： Mingyu Zhang Chunyu Xiang Renrui Niu Xiaodong He Wenqi Luo Wanguo Liu Rui Gu Department of Orthopedic Surgery China-Japan Union Hospital of Jilin UniversityChangchunJilin ProvinceChina

Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely ***,their inability to cross the blood–brain barrier hampers the clinical translation of these therapeutic *** are nanoparticles composed of lipid bilayers,which can effectively encapsulate drugs and improve drug delivery across the blood–brain barrier and into brain tissue through their targeting and ***,they can potentially treat traumatic and nontraumatic central nervous system *** this review,we outlined the common properties and preparation methods of liposomes,including thin-film hydration,reverse-phase evaporation,solvent injection techniques,detergent removal methods,and microfluidics ***,we comprehensively discussed the current applications of liposomes in central nervous system diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,traumatic brain injury,spinal cord injury,and brain *** studies related to liposomes are still in the laboratory stage and have not yet entered clinical ***,their application as drug delivery systems in clinical practice faces challenges such as drug stability,targeting efficiency,and ***,we proposed development strategies related to liposomes to further promote their development in neurological disease research.

关键词： Alzheimer's disease amyotrophic lateral sclerosis brain tumors central nervous system Huntington's disease liposome drug delivery neurological disorders Parkinson's disease spinal cord injury traumatic brain injury

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Role of copper in central nervous system physiology and pathology

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Neural Regeneration Research 2025年第4期20卷 1058-1068页

作者： Martina Locatelli Cinthia Farina Institute of Experimental Neurology Division of NeuroscienceIstituto di Ricovero e Cura a Carattere Scientifico(IRCCS)San Raffaele Scientific InstituteMilanItaly Vita-Salute San Raffaele University MilanItaly

Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central nervous *** copper dysregulations have been evidenced in two genetic disorders characterized by mutations in the copper-ATPases ATP7A and ATP7B,Menkes disease and Wilson’s disease,respectively,and also in multifactorial neurological disorders such as Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,and multiple *** review summarizes current knowledge about the role of copper in central nervous system physiology and pathology,reports about unbalances in copper levels and/or distribution under disease,describes relevant animal models for human disorders where copper metabolism genes are dysregulated,and discusses relevant therapeutic approaches modulating copper ***,alterations in copper metabolism may contribute to the etiology of central nervous system disorders and represent relevant therapeutic targets to restore tissue homeostasis.

关键词： astrocytes central nervous system copper cuprizone multiple sclerosis myelin neurodegenerative disorders

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Microglia lactylation in relation to central nervous system diseases

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Neural Regeneration Research 2025年第1期20卷 29-40页

作者： Hui Yang Nan Mo Le Tong Jianhong Dong Ziwei Fan Mengxian Jia Juanqing Yue Ying Wang School of Pharmacy Hangzhou Normal UniversityHangzhouZhejiang ProvinceChina Department of Clinical Laboratory The Fourth Clinical Medical College of Zhejiang University of Traditional Chinese Medicine(Hangzhou First People’s Hospital)HangzhouZhejiang ProvinceChina College of Medical Veterinary and Life SciencesUniversity of GlasgowGlasgowUK Department of Orthopedics(Spine Surgery) the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina Department of Pathology Affiliated Hangzhou First People’s HospitalWestlake University School of MedicineHangzhouZhejiang ProvinceChina Department of Clinical Research Center Affiliated Hangzhou First People’s HospitalWestlake University School of MedicineHangzhouZhejiang ProvinceChina

The development of neurodegenerative diseases is closely related to the disruption of central nervous system ***,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative *** has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of *** is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various *** review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting ***,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.

关键词： brain central nervous system glycolysis immune response inflammation lactate metabolism lactate lactylation microglia neurodegenerative diseases

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Meningeal lymphatic vessel crosstalk with central nervous system immune cells in aging and neurodegenerative diseases

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Neural Regeneration Research 2025年第3期20卷 763-778页

作者： Minghuang Gao Xinyue Wang Shijie Su Weicheng Feng Yaona Lai Kongli Huang Dandan Cao Qi Wang Science and Technology Innovation Center Guangzhou University of Chinese MedicineGuangzhouGuangdong ProvinceChina Institute of Clinical Pharmacology Guangzhou University of Chinese MedicineGuangzhouGuangdong ProvinceChina The Sixth Affiliated Hospital Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina

Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.

关键词： central nervous system meningeal lymphatic vessels immunity myeloid cells lymphatic cells neurodegenerative disease

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central nervous system vasculitis and polyneuropathy as first manifestations of hepatitis C

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World Journal of Gastroenterology 2012年第2期18卷 188-191页

作者： Roberto J Carvalho-Filho Janaína Luz Narciso-Schiavon Luciano HL Tolentino Leonardo L Schiavon Maria Lucia G Ferraz Antonio Eduardo B Silva Division of Gastroenterology Hepatitis SectionFederal University of Sao Paulo04037-003 Sao PauloBrazil

Sensory or motor peripheral neuropathy may be observed in a significant proportion of hepatitis C virus (HCV)-infected ***,central nervous system (CNS) involvement is uncommon,especially in cryoglobulin-negative *** describe a case of peripheral neuropathy combined with an ischemic CNS event as primary manifestations of chronic HCV infection without *** improvement was observed after antiviral *** discuss the spectrum of neurological manifestations of HCV infection and review the literature.

关键词： Hepatitis C central nervous system Poly-neuropathy Interferon-α

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central nervous system Toxicity of Sodium Nitroprusside in Treatment of Patients with Aortic Dissection

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2012年第6期32卷 927-930页

作者：黄雪渊侯凌波唐家荣张艳梅陈复琼汪道文 Department of Cardiology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

This study examined the sodium nitroprusside (SNP) toxicity to central nervous system (CNS) in treatment of patients with aortic dissection (AD). The medical records of 191 AD patients who were admitted to Tongji Hospital, China, from Jan. 1998 to Feb. 2009 were retrospectively analyzed. There were 140 cases of hypertension (73.3%) and 13 cases of Marfan syndrome (6.8%) among the 191 AD patients. A total of 157 patients were given SNP treatment. The toxic reactions of CNS occurred in 18 subjects (11.5%). Most of the adverse reactions occurred on the fifth day following SNP injection. SNP infusion rate was significantly higher in patients who developed CNS toxicity. It was suggested that systemic hypertension is the most common predisposing factor for AD. The combination of SNP with a β-receptor blocker is a medical therapy commonly used in patients with AD. Cyanide and thio-cyanate toxicity from SNP treatment is always the consequence of prolonged drug infusion or relatively high dose administration.

关键词： sodium nitroprusside toxicity central nervous system aortic dissection

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3D genome organization in the central nervous system,implications for neuropsychological disorders

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Journal of Genetics and Genomics 2021年第12期48卷 1045-1056页

作者： Daijing Sun Jie Weng Yuhao Dong Yan Jiang Institutes of Brain Science State Key Laboratory of Medical NeurobiologyMOE Frontier Center for Brain ScienceFudan UniversityShanghai 200032China

Chromosomes in eukaryotic cell nuclei are highly compacted and finely organized into hierarchical threedimensional(3 D) configuration. In recent years, scientists have gained deeper understandings of 3 D genome structures and revealed novel evidence linking 3 D genome organization to various important cell events on the molecular level. Most importantly, alteration of 3 D genome architecture has emerged as an intriguing higher order mechanism that connects disease-related genetic variants in multiple heterogenous and polygenic neuropsychological disorders, delivering novel insights into the etiology. In this review, we provide a brief overview of the hierarchical structures of 3 D genome and two proposed regulatory models,loop extrusion and phase separation. We then focus on recent Hi-C data in the central nervous system and discuss 3 D genome alterations during normal brain development and in mature neurons. Most importantly,we make a comprehensive review on current knowledge and discuss the role of 3 D genome in multiple neuropsychological disorders, including schizophrenia, repeat expansion disorders, 22 q11 deletion syndrome, and others.

关键词： 3D genome Chromosome conformation Hi-C central nervous system Neuropsychological disorders

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Emerging Role of PD-1 in the central nervous system and Brain Diseases

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Neuroscience Bulletin 2021年第8期37卷 1188-1202页

作者： Junli Zhao Alexus Roberts Zilong Wang Justin Savage Ru-Rong Ji Department of Anesthesiology Duke University Medical CenterDurham27710USA Department of Biology Duke University Medical CenterDurham27710USA Department of Neurobiology Duke University Medical CenterDurham27710USA Department of Cell Biology Duke University Medical CenterDurham27710USA

Programmed cell death protein 1(PD-1)is an immune checkpoint modulator and a major target of immunotherapy as anti-PD-1 monoclonal antibodies have demonstrated remarkable efficacy in cancer *** evidence suggests an important role of PD-1 in the central nervous system(CNS).PD-1 has been implicated in CNS disorders such as brain tumors,Alzheimer’s disease,ischemic stroke,spinal cord injury,multiple sclerosis,cognitive function,and ***-1 signaling suppresses the CNS immune response via resident microglia and infiltrating peripheral immune ***,PD-1 is also widely expressed in neurons and suppresses neuronal activity via downstream Src homology 2 domain-containing protein tyrosine phosphatase 1 and modulation of ion channel *** improved understanding of PD-1 signaling in the cross-talk between glial cells,neurons,and peripheral immune cells in the CNS will shed light on immunomodulation,neuromodulation,and novel strategies for treating brain diseases.

关键词： PD-1 central nervous system Immune checkpoint Immunotherapy Neurotherapy

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CD93 and GIPC expression and localization during central nervous system inflammation

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Neural Regeneration Research 2014年第22期9卷 1995-2001页

作者： Chun Liu Zhichao Cui Shengjie Wang Dongmei Zhang Experimental Animal Center Key Laboratory of Inflammation and Molecular Drug Targets of Jiangsu ProvinceNantong University Department of Pathogen Biology Medical School of Nantong University

CD93 and GAIP-interacting protein, C termius （GIPC） have been shown to interactively alter phagocytic processes of immune cells. CD93 and GIPC expression and localization during cen-tral nervous system inflammation have not yet been reported. In this study, we established a rat model of brain inlfammation by lipopolysaccharide injection to the lateral ventricle. In the brain of rats with inlfammation, western blots showed increased CD93 expression that decreased over time. GIPC expression was unaltered. Immunohistochemistry demonstrated extensive distribution of CD93 expression mainly in cell membranes in the cerebral cortex. After lipopoly-saccharide stimulation, CD93 expression increased and then reduced, with distinct staining in the cytoplasm and nucleus. Double immunolfuorescence staining in cerebral cortex of normal rats showed that CD93 and GIPC widely expressed in resting microglia and neurons. CD93 was mainly expressed in microglial and neuronal cell membranes, while GIPC was expressed in both cell membrane and cytoplasm. In the cerebral cortex at 9 hours after model establishment, CD93-immunoreactive signal diminished in microglial membrane, with cytoplasmic transloca-tion and aggregation detected. GIPC localization was unaltered in neurons and microglia. These results are the ifrst to demonstrate CD93 participation in pathophysiological processes of central nervous system inlfammation.

关键词： nerve regeneration central nervous system brain inflammation model CD93 GIPC neurons microglia expression and localization lipopolysaccharide intracerebroventricular injection rats inducible nitric oxide synthase NSFC grants neural regeneration

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