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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

Pyroptosis,ferroptosis,and autophagy in spinal cord injury:regulatory mechanisms and therapeutic targets

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Neural Regeneration Research 2025年第10期20卷 2787-2806页

作者： Qingcong Zheng Du Wang Rongjie Lin Weihong Xu Department of Spinal Surgery the First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian ProvinceChina Arthritis Clinical and Research Center Peking University People’s HospitalBeijingChina Department of Orthopedic Surgery Fujian Medical University Union HospitalFuzhouFujian ProvinceChina

Regulated cell death is a form of cell death that is actively controlled by *** studies have shown that regulated cell death plays a key role after spinal cord *** and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal ***,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord *** injury triggers not only cell death but also cellular survival *** signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and ***,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord *** analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord ***,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.

关键词： autophagy cell death ferroptosis inflammation pathological mechanisms pyroptosis regulated cell death regulatory pathways spinal cord injury therapeutic targets

Neuroprotective potential for mitigating ischemia-reperfusion-induced damage

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Neural Regeneration Research 2025年第8期20卷 2199-2217页

作者： Zi Ye Runqing Liu Hangxing Wang Aizhen Zuo Cen Jin Nan Wang Huiqi Sun Luqian Feng Hua Yang The Clinical Medical College Guizhou Medical UniversityGuiyangGuizhou ProvinceChina Division of Infectious Diseases Department of Internal MedicinePeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina School of Medical Imaging Guizhou Medical UniversityGuiyangGuizhou ProvinceChina Division of Gastroenterology First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina The Second Clinical Medical College Lanzhou UniversityLanzhouGansu ProvinceChina Department of Neurosurgery Affiliated Hospital of Guizhou Medical UniversityGuiyangGuizhou ProvinceChina

Reperfusion following cerebral ischemia causes both structural and functional damage to brain tissue and could aggravate a patient's condition;this phenomenon is known as cerebral ischemia-reperfusion *** studies have elucidated the neuroprotective role of the sirtuin protein family(Sirtuins)in modulating cerebral ischemia-reperfusion ***,the potential of utilizing it as a novel intervention target to influence the prognosis of cerebral ischemia-reperfusion injury requires additional *** this review,the origin and research progress of Sirtuins are summarized,suggesting the involvement of Sirtuins in diverse mechanisms that affect cerebral ischemia-reperfusion injury,including inflammation,oxidative stress,blood-brain barrier damage,apoptosis,pyroptosis,and *** therapeutic avenues related to Sirtuins that may improve the prognosis of cerebral ischemia-reperfusion injury were also investigated by modulating Sirtuins expression and affecting representative pathways,such as nuclear factor-kappa B signaling,oxidative stress mediated by adenosine monophosphate-activated protein kinase,and the forkhead box *** review also summarizes the potential of endogenous substances,such as RNA and hormones,drugs,dietary supplements,and emerging therapies that regulate Sirtuins *** review also reveals that regulating Sirtuins mitigates cerebral ischemia-reperfusion injury when combined with other risk *** Sirtuins show promise as a potential target for the treatment of cerebral ischemiareperfusion injury,most recent studies are based on rodent models with circadian rhythms that are distinct from those of humans,potentially influencing the efficacy of Sirtuinstargeting drug ***,this review provides new insights into the role of Sirtuins in the pathology and treatment of cerebral ischemia-reperfusion injury.

关键词： apoptosis autophagy blood-brain barrier dietary supplements drug hormones inflammation neuroprotection oxidative stress prognosis pyroptosis reperfusion injury risk factors RNA therapeutics

FK506 contributes to peripheral nerve regeneration by inhibiting neuroinflammatory responses and promoting neuron survival

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Neural Regeneration Research 2025年第7期20卷 2108-2115页

作者： Yuhui Kou Zongxue Jin Yusong Yuan Bo Ma Wenyong Xie Na Han Department of Trauma and Orthopedics Peking University People’s HospitalBeijingChina National Center for Trauma Medicine Peking University People’s HospitalBeijingChina Key Laboratory of Trauma and Neural Regeneration(Peking University) Ministry of EducationBeijingChina Trauma Medicine Center Peking University People’s HospitalBeijingChina Department of Orthopedics China-Japan Friendship HospitalBeijingChina

FK506(Tacrolimus)is a systemic immunosuppressant approved by the *** and Drug ***506 has been shown to promote peripheral nerve regeneration,however,its precise mechanism of action and its pathways remain *** this study,we established a rat model of sciatic nerve injury and found that FK506 improved the morphology of the injured sciatic nerve,increased the numbers of motor and sensory neurons,reduced inflammatory responses,markedly improved the conduction function of the injured nerve,and promoted motor function *** findings suggest that FK506 promotes peripheral nerve structure recovery and functional regeneration by reducing the intensity of inflammation after neuronal injury and increasing the number of surviving neurons.

关键词： FK506 inflammation motor neurons nerve regeneration neuron peripheral nerve injury sensory neurons

Non-coding RNAs in acute ischemic stroke:from brain to periphery

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Neural Regeneration Research 2025年第1期20卷 116-129页

作者： Shuo Li Zhaohan Xu Shiyao Zhang Huiling Sun Xiaodan Qin Lin Zhu Teng Jiang Junshan Zhou Fuling Yan Qiwen Deng Department of Neurology Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu ProvinceChina Department of Neurology Zhongda HospitalSchool of MedicineSoutheast UniversityNanjingJiangsu ProvinceChina General Clinical Research Center Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu ProvinceChina

Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and *** predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain *** innovations in high-throughput gene sequencing analysis,many aberrantly expressed non-coding RNAs(ncRNAs)in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental *** expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes,leading to neuroprotection or deterioration,thus ncRNAs can serve as therapeutic targets in acute ischemic ***,distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction,diagnosis,and *** particular,ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic *** this review,we consolidate the latest progress of research into the roles of ncRNAs(microRNAs,long ncRNAs,and circular RNAs)in the pathological processes of acute ischemic stroke–induced brain damage,as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction,diagnosis,and *** from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.

关键词： acute ischemic stroke apoptosis blood–brain barrier damage circular RNAs excitatory toxicity long non-coding RNAs microRNAs neuroinflammation non-coding RNAs oxidative stress

The emerging role of nitric oxide in the synaptic dysfunction of vascular dementia

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Neural Regeneration Research 2025年第2期20卷 402-415页

作者： Xiaorong Zhang Zhiying Chen Yinyi Xiong Qin Zhou Ling-Qiang Zhu Dan Liu Department of Pathology Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina Jiujiang Clinical Precision Medicine Research Center JiujiangJiangxi ProvinceChina Center for Cognitive Science and Transdisciplinary Studies Jiujiang UniversityJiangxi ProvinceChina Department of Neurology Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina Department of Rehabilitation Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina Department of Pathophysiology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic ***,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia *** in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive *** oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous ***,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular *** review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular ***,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.

关键词： endoplasmic reticulum stress endothelial nitric oxide synthase gene therapy nitric oxide NO-sGC-cGMP pathway synaptic dysfunction vascular dementia

Mitophagy in acute central nervous system injuries:regulatory mechanisms and therapeutic potentials

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Neural Regeneration Research 2025年第9期20卷 2437-2453页

作者： Siyi Xu Junqiu Jia Rui Mao Xiang Cao Yun Xu Department of Neurology Nanjing Drum Tower HospitalClinical College of Jiangsu UniversityNanjingJiangsu ProvinceChina Department of Neurology Nanjing Drum Tower HospitalChinese Academy of Medical Science&Peking Union Medical CollegeNanjingJiangsu ProvinceChina Department of Neurology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsu ProvinceChina State Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical Diseases Nanjing UniversityNanjingJiangsu ProvinceChina Jiangsu Key Laboratory for Molecular Medicine Medical School of Nanjing UniversityNanjingJiangsu ProvinceChina Nanjing Neurology Medical Center NanjingJiangsu ProvinceChina

Acute central nervous system injuries,including ischemic stro ke,intracerebral hemorrhage,subarachnoid hemorrhage,traumatic brain injury,and spinal co rd injury,are a major global health *** optimal therapies and improving the long-term neurological functions of patients with acute central nervous system injuries are urgent *** are susceptible to damage after acute central nervous system injury,and this leads to the release of toxic levels of reactive oxygen species,which induce cell ***,a selective form of autophagy,is crucial in eliminating redundant or damaged mitochondria during these *** evidence has highlighted the significant role of mitophagy in acute central nervous system *** this review,we provide a comprehensive overview of the process,classification,and related mechanisms of *** also highlight the recent developments in research into the role of mitophagy in various acute central nervous system injuries and drug therapies that regulate *** the final section of this review,we emphasize the potential for treating these disorders by focusing on mitophagy and suggest future research paths in this area.

关键词： autophagy intracerebral hemorrhage ischemic stroke mitochondria mitochondrial biogenesis mitochondrial quality control mitophagy spinal cord injury subarachnoid hemorrhage traumatic brain injury

Nanomaterials-mediated lysosomal regulation:a robust protein-clearance approach for the treatment of Alzheimer’s disease

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Neural Regeneration Research 2025年第2期20卷 424-439页

作者： Mengqi Hao Jianjian Chu Tinglin Zhang Tong Yin Yuankai Gu Wendanqi Liang Wenbo Ji Jianhua Zhuang Yan Liu Jie Gao You Yin Department of Neurology Second Affiliated Hospital of Naval Medical University(Shanghai Changzheng Hospital)ShanghaiChina School of Health Science and Engineering University of Shanghai for Science and TechnologyShanghaiChina Changhai Clinical Research Unit Shanghai Changhai HospitalNaval Medical UniversityShanghaiChina Department of Clinical Pharmacy Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Neurology Shanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina

Alzheimer’s disease is a debilitating,progressive neurodegenerative disorder characterized by the progressive accumulation of abnormal proteins,including amyloid plaques and intracellular tau tangles,primarily within the ***,crucial intracellular organelles responsible for protein degradation,play a key role in maintaining cellular *** studies have suggested a link between the dysregulation of the lysosomal system and pathogenesis of neurodegenerative diseases,including Alzheimer’s *** the normal physiological function of lysosomes hold the potential to reduce the pathological burden and improve the symptoms of Alzheimer’s ***,the efficacy of drugs in treating Alzheimer’s disease is limited,with major challenges in drug delivery efficiency and ***,nanomaterials have gained widespread use in Alzheimer’s disease drug research owing to their favorable physical and chemical *** review aims to provide a comprehensive overview of recent advances in using nanomaterials(polymeric nanomaterials,nanoemulsions,and carbon-based nanomaterials)to enhance lysosomal function in treating Alzheimer’s *** review also explores new concepts and potential therapeutic strategies for Alzheimer’s disease through the integration of nanomaterials and modulation of lysosomal *** conclusion,this review emphasizes the potential of nanomaterials in modulating lysosomal function to improve the pathological features of Alzheimer’s *** application of nanotechnology to the development of Alzheimer’s disease drugs brings new ideas and approaches for future treatment of this disease.

关键词： Alzheimer’s disease autophagy dysfunction lysosomal acidification lysosomal system nanomaterials neurodegenerative diseases

The potential mechanism and clinical application value of remote ischemic conditioning in stroke

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Neural Regeneration Research 2025年第6期20卷 1613-1627页

作者： Yajun Zhu Xiaoguo Li Xingwei Lei Liuyang Tang Daochen Wen Bo Zeng Xiaofeng Zhang Zichao Huang Zongduo Guo The First Affiliated hospital of Chongqing Medical University ChongqingChina

Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may be related to neuroinflammation, cellular immunity, apoptosis, and autophagy, the exact underlying molecular mechanisms are unclear. This review summarizes the current status of different types of remote ischemic conditioning methods in animal and clinical studies and analyzes their commonalities and differences in neuroprotective mechanisms and signaling pathways. Remote ischemic conditioning has emerged as a potential therapeutic approach for improving stroke-induced brain injury owing to its simplicity, non-invasiveness, safety, and patient tolerability. Different forms of remote ischemic conditioning exhibit distinct intervention patterns, timing, and application range. Mechanistically, remote ischemic conditioning can exert neuroprotective effects by activating the Notch1/phosphatidylinositol 3-kinase/Akt signaling pathway, improving cerebral perfusion, suppressing neuroinflammation, inhibiting cell apoptosis, activating autophagy, and promoting neural regeneration. While remote ischemic conditioning has shown potential in improving stroke outcomes, its full clinical translation has not yet been achieved.

关键词： Akt apoptosis autophagy cerebral perfusion cerebral vascular stenosis clinical transformation hemorrhagic stroke ischemic stroke neuroinflammation neuroprotection Notch1 PI3K remote ischemic conditioning stroke

Cell polarization in ischemic stroke: molecular mechanisms and advances

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Neural Regeneration Research 2025年第3期20卷 632-645页

作者： Yuanwei Li Xiaoxiao Xu Xuan Wu Jiarui Li Shiling Chen Danyang Chen Gaigai Li Zhouping Tang Department of Neurology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

Ischemic stroke is a cerebrovascular disease associated with high mortality and disability rates. Since the inflammation and immune response play a central role in driving ischemic damage, it becomes essential to modulate excessive inflammatory reactions to promote cell survival and facilitate tissue repair around the injury site. Various cell types are involved in the inflammatory response, including microglia, astrocytes, and neutrophils, each exhibiting distinct phenotypic profiles upon stimulation. They display either proinflammatory or anti-inflammatory states, a phenomenon known as ‘cell polarization.’ There are two cell polarization therapy strategies. The first involves inducing cells into a neuroprotective phenotype in vitro, then reintroducing them autologously. The second approach utilizes small molecular substances to directly affect cells in vivo. In this review, we elucidate the polarization dynamics of the three reactive cell populations(microglia, astrocytes, and neutrophils) in the context of ischemic stroke, and provide a comprehensive summary of the molecular mechanisms involved in their phenotypic switching. By unraveling the complexity of cell polarization, we hope to offer insights for future research on neuroinflammation and novel therapeutic strategies for ischemic stroke.

关键词： astrocyte polarization immune regulation inflammation ischemic injury microglia polarization neutrophil polarization signaling pathways stroke