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Molecular dynamics study of interactions between edge dislocation and irradiation-induced defects in Fe–10Ni–20Cr alloy 被引量:1
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作者 熊涛文 陈小平 +5 位作者 林也平 贺新福 杨文 胡望宇 高飞 邓辉球 《Chinese Physics B》 SCIE EI CAS CSCD 2023年第2期80-86,共7页
Irradiation-induced defects frequently impede the slip of dislocations, resulting in a sharp decline in the performance of nuclear reactor structural materials, particularly core structural materials. In the present w... Irradiation-induced defects frequently impede the slip of dislocations, resulting in a sharp decline in the performance of nuclear reactor structural materials, particularly core structural materials. In the present work, molecular dynamics method is used to investigate the interactions between edge dislocations and three typical irradiation-induced defects(void,Frank loop, and stacking fault tetrahedron) with the sizes of 3 nm, 5 nm, and 7 nm at different temperatures in Fe–10Ni–20Cr alloy. The critical resolved shear stresses(CRSSs) are compared among different defect types after interacting with edge dislocations. The results show that the CRSS decreases with temperature increasing and defect size decreasing for each defect type during the interaction with edge dislocations, except for the case of 3-nm Frank loops at 900 K. According to a comparison, the CRSS in Frank loop is significantly higher than that of others of the same size, which is due to the occurrence of unfaulting and formation of superjog or stacking-fault complex during the interaction. The atomic evolution of irradiation-induced defects after interacting with dislocations can provide a novel insight into the design of new structural materials. 展开更多
关键词 molecular dynamics simulation edge dislocation irradiation-induced defects austenitic stainless steel
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Resident immune responses to spinal cord injury:role of astrocytes and microglia 被引量:3
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作者 Sydney Brockie Cindy Zhou Michael G.Fehlings 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第8期1678-1685,共8页
Spinal cord injury can be traumatic or non-traumatic in origin,with the latter rising in incidence and prevalence with the aging demographics of our society.Moreove r,as the global population ages,individuals with co-... Spinal cord injury can be traumatic or non-traumatic in origin,with the latter rising in incidence and prevalence with the aging demographics of our society.Moreove r,as the global population ages,individuals with co-existent degenerative spinal pathology comprise a growing number of traumatic spinal cord injury cases,especially involving the cervical spinal cord.This makes recovery and treatment approaches particula rly challenging as age and comorbidities may limit regenerative capacity.For these reasons,it is critical to better understand the complex milieu of spinal cord injury lesion pathobiology and the ensuing inflammatory response.This review discusses microglia-specific purinergic and cytokine signaling pathways,as well as microglial modulation of synaptic stability and plasticity after injury.Further,we evaluate the role of astrocytes in neurotransmission and calcium signaling,as well as their border-forming response to neural lesions.Both the inflammatory and reparative roles of these cells have eluded our complete understanding and remain key therapeutic targets due to their extensive structural and functional roles in the nervous system.Recent advances have shed light on the roles of glia in neurotransmission and reparative injury responses that will change how interventions are directed.Understanding key processes and existing knowledge gaps will allow future research to effectively target these cells and harness their regenerative potential. 展开更多
关键词 ASTROCYTES glial signaling MICROGLIA spinal cord injury synaptic transmission
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Connecting cellular mechanisms and extracellular vesicle cargo in traumatic brain injury 被引量:1
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作者 Nikita Ollen-Bittle Austyn D.Roseborough +2 位作者 Wenxuan Wang Jeng-liang D.Wu Shawn N.Whitehead 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第10期2119-2131,共13页
Traumatic brain injury is followed by a cascade of dynamic and complex events occurring at the cellular level. These events include: diffuse axonal injury, neuronal cell death, blood-brain barrier break down, glial ac... Traumatic brain injury is followed by a cascade of dynamic and complex events occurring at the cellular level. These events include: diffuse axonal injury, neuronal cell death, blood-brain barrier break down, glial activation and neuroinflammation, edema, ischemia, vascular injury, energy failure, and peripheral immune cell infiltration. The timing of these events post injury has been linked to injury severity and functional outcome. Extracellular vesicles are membrane bound secretory vesicles that contain markers and cargo pertaining to their cell of origin and can cross the blood-brain barrier. These qualities make extracellular vesicles intriguing candidates for a liquid biopsy into the pathophysiologic changes occurring at the cellular level post traumatic brain injury. Herein, we review the most commonly reported cargo changes in extracellular vesicles from clinical traumatic brain injury samples. We then use knowledge from animal and in vitro models to help infer what these changes may indicate regrading cellular responses post traumatic brain injury. Future research should prioritize labeling extracellular vesicles with markers for distinct cell types across a range of timepoints post traumatic brain injury. 展开更多
关键词 axonal injury biomarkers blood-brain barrier chronic traumatic encephalopathy extracellular vesicles glial activation NEUROINFLAMMATION traumatic brain injury
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A comprehensive look at the psychoneuroimmunoendocrinology of spinal cord injury and its progression: mechanisms and clinical opportunities 被引量:1
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作者 Miguel A.Ortega Oscar Fraile-Martinez +9 位作者 Cielo García-Montero Sergio Haro Miguel Ángel Álvarez-Mon Diego De Leon-Oliva Ana M.Gomez-Lahoz Jorge Monserrat Mar Atienza-Pérez David Díaz Elisa Lopez-Dolado Melchor Álvarez-Mon 《Military Medical Research》 SCIE CAS CSCD 2024年第2期228-267,共40页
Spinal cord injury(SCI)is a devastating and disabling medical condition generally caused by a traumatic event(primary injury).This initial trauma is accompanied by a set of biological mechanisms directed to ameliorate... Spinal cord injury(SCI)is a devastating and disabling medical condition generally caused by a traumatic event(primary injury).This initial trauma is accompanied by a set of biological mechanisms directed to ameliorate neural damage but also exacerbate initial damage(secondary injury).The alterations that occur in the spinal cord have not only local but also systemic consequences and virtually all organs and tissues of the body incur important changes after SCI,explaining the progression and detrimental consequences related to this condition.Psychoneuroimmunoendocrinology(PNIE)is a growing area of research aiming to integrate and explore the interactions among the different systems that compose the human organism,considering the mind and the body as a whole.The initial traumatic event and the consequent neurological disruption trigger immune,endocrine,and multisystem dysfunction,which in turn affect the patient's psyche and well-being.In the present review,we will explore the most important local and systemic consequences of SCI from a PNIE perspective,defining the changes occurring in each system and how all these mechanisms are interconnected.Finally,potential clinical approaches derived from this knowledge will also be collectively presented with the aim to develop integrative therapies to maximize the clinical management of these patients. 展开更多
关键词 Spinal cord injury(SCI) Psychoneuroimmunoendocrinology(PNIE) Secondary injury Immunoinflammatory dysfunction Gut microbiota Translational opportunities
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Lupenone improves motor dysfunction in spinal cord injury mice through inhibiting the inflammasome activation and pyroptosis in microglia via the nuclear factor kappa B pathway 被引量:1
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作者 Fudong Li Xiaofei Sun +3 位作者 Kaiqiang Sun Fanqi Kong Xin Jiang Qingjie Kong 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第8期1802-1811,共10页
Spinal cord injury-induced motor dysfunction is associated with neuroinflammation.Studies have shown that the triterpenoid lupenone,a natural product found in various plants,has a remarkable anti-inflammatory effect i... Spinal cord injury-induced motor dysfunction is associated with neuroinflammation.Studies have shown that the triterpenoid lupenone,a natural product found in various plants,has a remarkable anti-inflammatory effect in the context of chronic inflammation.However,the effects of lupenone on acute inflammation induced by spinal cord injury remain unknown.In this study,we established an impact-induced mouse model of spinal cord injury,and then treated the injured mice with lupenone(8 mg/kg,twice a day)by intrape ritoneal injection.We also treated BV2 cells with lipopolysaccharide and adenosine5’-triphosphate to simulate the inflammatory response after spinal cord injury.Our res ults showed that lupenone reduced IKBa activation and p65 nuclear translocation,inhibited NLRP3 inflammasome function by modulating nuclear factor kappa B,and enhanced the conve rsion of proinflammatory M1 mic roglial cells into anti-inflammatory M2 microglial cells.Furthermore,lupenone decreased NLRP3 inflammasome activation,NLRP3-induced mic roglial cell polarization,and microglia pyroptosis by inhibiting the nuclear factor kappa B pathway.These findings suggest that lupenone protects against spinal cord injury by inhibiting inflammasomes. 展开更多
关键词 INFLAMMASOME inflammation lupenone MICROGLIA polarization PYROPTOSIS spinal cord injury
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Epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China:a hospital-based retrospective study 被引量:3
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作者 Hengxing Zhou Yongfu Lou +32 位作者 Lingxiao Chen Yi Kang Lu Liu Zhiwei Cai David BAnderson Wei Wang Chi Zhang Jinghua Wang Guangzhi Ning Yanzheng Gao Baorong He Wenyuan Ding Yisheng Wang Wei Mei Yueming Song Yue Zhou Maosheng Xia Huan Wang Jie Zhao Guoyong Yin Tao Zhang Feng Jing Rusen Zhu Bin Meng Li Duan Zhongmin Zhang Desheng Wu Zhengdong Cai Lin Huang Zhanhai Yin Kainan Li Shibao Lu Shiqing Feng 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第5期1126-1132,共7页
Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic ... Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic spinal cord injury in China have mostly been regional in scope;national-level studies have been rare.To the best of our knowledge,no national-level study of treatment status and economic burden has been performed.This retrospective study aimed to examine the epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China at the national level.We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China.Patient epidemiological and clinical features,treatment status,and total and daily costs were recorded.Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program.The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall(annual percentage change,-0.5%and 2.1%,respectively).A total of 10,053(74.7%)patients underwent surgery.Only 2.8%of patients who underwent surgery did so within 24 hours of injury.A total of 2005(14.9%)patients were treated with high-dose(≥500 mg)methylprednisolone sodium succinate/methylprednisolone(MPSS/MP);615(4.6%)received it within 8 hours.The total cost for acute traumatic spinal cord injury decreased over the study period(-4.7%),while daily cost did not significantly change(1.0%increase).Our findings indicate that public health initiatives should aim at improving hospitals’ability to complete early surgery within 24 hours,which is associated with improved sensorimotor recovery,increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence. 展开更多
关键词 China clinical features COSTS EPIDEMIOLOGY methylprednisolone sodium succinate METHYLPREDNISOLONE retrospective study traumatic spinal cord injury TREATMENT
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Gut microbial regulation of innate and adaptive immunity after traumatic brain injury 被引量:4
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作者 Marta Celorrio Kirill Shumilov Stuart H.Friess 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第2期272-276,共5页
Acute care management of traumatic brain injury is focused on the prevention and reduction of secondary insults such as hypotension,hypoxia,intracranial hypertension,and detrimental inflammation.However,the imperative... Acute care management of traumatic brain injury is focused on the prevention and reduction of secondary insults such as hypotension,hypoxia,intracranial hypertension,and detrimental inflammation.However,the imperative to balance multiple clinical concerns simultaneously often results in therapeutic strategies targeted to address one clinical concern causing unintended effects in other remote organ systems.Recently the bidirectional communication between the gastrointestinal tract and the brain has been shown to influence both the central nervous system and gastrointestinal tract homeostasis in health and disease.A critical component of this axis is the microorganisms of the gut known as the gut microbiome.Changes in gut microbial populations in the setting of central nervous system disease,including traumatic brain injury,have been reported in both humans and experimental animal models and can be further disrupted by off-target effects of patient care.In this review article,we will explore the important role gut microbial populations play in regulating brain-resident and peripheral immune cell responses after traumatic brain injury.We will discuss the role of bacterial metabolites in gut microbial regulation of neuroinflammation and their potential as an avenue for therapeutic intervention in the setting of traumatic brain injury. 展开更多
关键词 gut microbiome gut microbiota gut-brain axis macrophage MICROGLIA MONOCYTE NEUROINFLAMMATION short-chain fatty acids T cell traumatic brain injury
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Biomaterials and tissue engineering in traumatic brain injury:novel perspectives on promoting neural regeneration 被引量:2
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作者 Shihong Zhu Xiaoyin Liu +7 位作者 Xiyue Lu Qiang Liao Huiyang Luo Yuan Tian Xu Cheng Yaxin Jiang Guangdi Liu Jing Chen 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第10期2157-2174,共18页
Traumatic brain injury is a serious medical condition that can be attributed to falls, motor vehicle accidents, sports injuries and acts of violence, causing a series of neural injuries and neuropsychiatric symptoms. ... Traumatic brain injury is a serious medical condition that can be attributed to falls, motor vehicle accidents, sports injuries and acts of violence, causing a series of neural injuries and neuropsychiatric symptoms. However, limited accessibility to the injury sites, complicated histological and anatomical structure, intricate cellular and extracellular milieu, lack of regenerative capacity in the native cells, vast variety of damage routes, and the insufficient time available for treatment have restricted the widespread application of several therapeutic methods in cases of central nervous system injury. Tissue engineering and regenerative medicine have emerged as innovative approaches in the field of nerve regeneration. By combining biomaterials, stem cells, and growth factors, these approaches have provided a platform for developing effective treatments for neural injuries, which can offer the potential to restore neural function, improve patient outcomes, and reduce the need for drugs and invasive surgical procedures. Biomaterials have shown advantages in promoting neural development, inhibiting glial scar formation, and providing a suitable biomimetic neural microenvironment, which makes their application promising in the field of neural regeneration. For instance, bioactive scaffolds loaded with stem cells can provide a biocompatible and biodegradable milieu. Furthermore, stem cells-derived exosomes combine the advantages of stem cells, avoid the risk of immune rejection, cooperate with biomaterials to enhance their biological functions, and exert stable functions, thereby inducing angiogenesis and neural regeneration in patients with traumatic brain injury and promoting the recovery of brain function. Unfortunately, biomaterials have shown positive effects in the laboratory, but when similar materials are used in clinical studies of human central nervous system regeneration, their efficacy is unsatisfactory. Here, we review the characteristics and properties of various bioactive materials, followed by the introduction of applications based on biochemistry and cell molecules, and discuss the emerging role of biomaterials in promoting neural regeneration. Further, we summarize the adaptive biomaterials infused with exosomes produced from stem cells and stem cells themselves for the treatment of traumatic brain injury. Finally, we present the main limitations of biomaterials for the treatment of traumatic brain injury and offer insights into their future potential. 展开更多
关键词 bioactive materials BIOMATERIALS EXOSOMES neural regeneration scaffolds stem cells tissue engineering traumatic brain injury
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Transplantation of fibrin-thrombin encapsulated human induced neural stem cells promotes functional recovery of spinal cord injury rats through modulation of the microenvironment 被引量:2
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作者 Sumei Liu Baoguo Liu +4 位作者 Qian Li Tianqi Zheng Bochao Liu Mo Li Zhiguo Chen 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第2期440-446,共7页
Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells a... Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury model.Basso,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion core.Examination of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the microenvironment.Altogether,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion site.Graft-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats. 展开更多
关键词 biomaterial FIBRINOGEN functional recovery induced neural stem cell transplantation MICROENVIRONMENT MICROGLIA spinal cord injury THROMBIN
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Screening biomarkers for spinal cord injury using weighted gene co-expression network analysis and machine learning 被引量:5
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作者 Xiaolu Li Ye Yang +3 位作者 Senming Xu Yuchang Gui Jianmin Chen Jianwen Xu 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第12期2723-2734,共12页
Immune changes and inflammatory responses have been identified as central events in the pathological process of spinal co rd injury.They can greatly affect nerve regeneration and functional recovery.However,there is s... Immune changes and inflammatory responses have been identified as central events in the pathological process of spinal co rd injury.They can greatly affect nerve regeneration and functional recovery.However,there is still limited understanding of the peripheral immune inflammato ry response in spinal cord inju ry.In this study.we obtained microRNA expression profiles from the peripheral blood of patients with spinal co rd injury using high-throughput sequencing.We also obtained the mRNA expression profile of spinal cord injury patients from the Gene Expression Omnibus(GEO)database(GSE151371).We identified 54 differentially expressed microRNAs and 1656 diffe rentially expressed genes using bioinformatics approaches.Functional enrichment analysis revealed that various common immune and inflammation-related signaling pathways,such as neutrophil extracellular trap formation pathway,T cell receptor signaling pathway,and nuclear factor-κB signal pathway,we re abnormally activated or inhibited in spinal cord inju ry patient samples.We applied an integrated strategy that combines weighted gene co-expression network analysis,LASSO logistic regression,and SVM-RFE algorithm and identified three biomarke rs associated with spinal cord injury:ANO10,BST1,and ZFP36L2.We verified the expression levels and diagnostic perfo rmance of these three genes in the original training dataset and clinical samples through the receiver operating characteristic curve.Quantitative polymerase chain reaction results showed that ANO20 and BST1 mRNA levels were increased and ZFP36L2 mRNA was decreased in the peripheral blood of spinal cord injury patients.We also constructed a small RNA-mRNA interaction network using Cytoscape.Additionally,we evaluated the proportion of 22 types of immune cells in the peripheral blood of spinal co rd injury patients using the CIBERSORT tool.The proportions of naive B cells,plasma cells,monocytes,and neutrophils were increased while the proportions of memory B cells,CD8^(+)T cells,resting natural killer cells,resting dendritic cells,and eosinophils were markedly decreased in spinal cord injury patients increased compared with healthy subjects,and ANO10,BST1 and ZFP26L2we re closely related to the proportion of certain immune cell types.The findings from this study provide new directions for the development of treatment strategies related to immune inflammation in spinal co rd inju ry and suggest that ANO10,BST2,and ZFP36L2 are potential biomarkers for spinal cord injury.The study was registe red in the Chinese Clinical Trial Registry(registration No.ChiCTR2200066985,December 12,2022). 展开更多
关键词 bioinformatics analysis BIOMARKER CIBERSORT GEO dataset LASSO miRNA-mRNA network RNA sequencing spinal cord injury SVM-RFE weighted gene co-expression network analysis
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P7C3-A20 treats traumatic brain injury in rats by inhibiting excessive autophagy and apoptosis 被引量:2
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作者 Zhiqing Yang Zhenchao Wang +4 位作者 Xiaoqi Deng Lingxin Zhu Zhaomeng Song Changyu Cao Xinran Li 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第5期1078-1083,共6页
Traumatic brain injury is a severe health problem leading to autophagy and apoptosis in the brain.3,6-Dibromo-beta-fluoro-N-(3-methoxyphenyl)-9H-carbazole-9-propanamine(P7C3-A20)can be neuroprotective in various disea... Traumatic brain injury is a severe health problem leading to autophagy and apoptosis in the brain.3,6-Dibromo-beta-fluoro-N-(3-methoxyphenyl)-9H-carbazole-9-propanamine(P7C3-A20)can be neuroprotective in various diseases,including ischemic stroke and neurodegenerative diseases.However,whether P7C3-A20 has a therapeutic effect on traumatic brain injury and its possible molecular mechanisms are unclear.Therefore,in the present study,we investigated the therapeutic effects of P7C3-A20 on traumatic brain injury and explored the putative underlying molecular mechanisms.We established a traumatic brain injury rat model using a modified weight drop method.P7C3-A20 or vehicle was injected intraperitoneally after traumatic brain injury.Severe neurological deficits were found in rats after traumatic brain injury,with deterioration in balance,walking function,and learning memory.Furthermore,hematoxylin and eosin staining showed significant neuronal cell damage,while terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining indicated a high rate of apoptosis.The presence of autolysosomes was observed using transmission electron microscope.P7C3-A20 treatment reversed these pathological features.Western blotting showed that P7C3-A20 treatment reduced microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)autophagy protein,apoptosis-related proteins(namely,Bcl-2/adenovirus E1B 19-kDa-interacting protein 3[BNIP3],and Bcl-2 associated x protein[Bax]),and elevated ubiquitin-binding protein p62(p62)autophagy protein expression.Thus,P7C3-A20 can treat traumatic brain injury in rats by inhibiting excessive autophagy and apoptosis. 展开更多
关键词 APOPTOSIS AUTOPHAGY CORTEX HIPPOCAMPUS motor function P7C3-A20 traumatic brain injury
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The secondary injury cascade after spinal cord injury:an analysis of local cytokine/chemokine regulation 被引量:1
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作者 Daniel J.Hellenbrand Charles M.Quinn +8 位作者 Zachariah J.Piper Ryan T.Elder Raveena R.Mishra Taylor L.Marti Phoebe M.Omuro Rylie M.Roddick Jae Sung Lee William L.Murphy Amgad S.Hanna 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第6期1308-1317,共10页
After spinal cord injury,there is an extensive infiltration of immune cells,which exacerbates the injury and leads to further neural degeneration.Therefore,a major aim of current research involves targeting the immune... After spinal cord injury,there is an extensive infiltration of immune cells,which exacerbates the injury and leads to further neural degeneration.Therefore,a major aim of current research involves targeting the immune response as a treatment for spinal cord injury.Although much research has been performed analyzing the complex inflammatory process following spinal cord injury,there remain major discrepancies within previous literature regarding the timeline of local cytokine regulation.The objectives of this study were to establish an overview of the timeline of cytokine regulation for 2 weeks after spinal cord injury,identify sexual dimorphisms in terms of cytokine levels,and determine local cytokines that significantly change based on the severity of spinal cord injury.Rats were inflicted with either a mild contusion,moderate contusion,severe contusion,or complete transection,7 mm of spinal cord centered on the injury was harvested at varying times post-injury,and tissue homogenates were analyzed with a Cytokine/Chemokine 27-Plex assay.Results demonstrated pro-inflammatory cytokines including tumor necrosis factorα,interleukin-1β,and interleukin-6 were all upregulated after spinal cord injury,but returned to uninjured levels within approximately 24 hours post-injury,while chemokines including monocyte chemoattractant protein-1 remained upregulated for days post-injury.In contrast,several anti-inflammatory cytokines and growth factors including interleukin-10 and vascular endothelial growth factor were downregulated by 7 days post-injury.After spinal cord injury,tissue inhibitor of metalloproteinase-1,which specifically affects astrocytes involved in glial scar development,increased more than all other cytokines tested,reaching 26.9-fold higher than uninjured rats.After a mild injury,11 cytokines demonstrated sexual dimorphisms;however,after a severe contusion only leptin levels were different between female and male rats.In conclusion,pro-inflammatory cytokines initiate the inflammatory process and return to baseline within hours post-injury,chemokines continue to recruit immune cells for days post-injury,while anti-inflammatory cytokines are downregulated by a week post-injury,and sexual dimorphisms observed after mild injury subsided with more severe injuries.Results from this work define critical chemokines that influence immune cell infiltration and important cytokines involved in glial scar development after spinal cord injury,which are essential for researchers developing treatments targeting secondary damage after spinal cord injury. 展开更多
关键词 ASTROCYTES CHEMOKINES cytokines inflammation macrophages MICROGLIA secondary damage spinal cord injury
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Mesenchymal stem cell-derived extracellular vesicles as a cell-free therapy for traumatic brain injury via neuroprotection and neurorestoration 被引量:2
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作者 Ye Xiong Asim Mahmood Michael Chopp 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第1期49-54,共6页
Traumatic brain injury is a serious and complex neurological condition that affects millions of people worldwide.Despite significant advancements in the field of medicine,effective treatments for traumatic brain injur... Traumatic brain injury is a serious and complex neurological condition that affects millions of people worldwide.Despite significant advancements in the field of medicine,effective treatments for traumatic brain injury remain limited.Recently,extracellular vesicles released from mesenchymal stem/stromal cells have emerged as a promising novel therapy for traumatic brain injury.Extracellular vesicles are small membrane-bound vesicles that are naturally released by cells,including those in the brain,and can be engineered to contain therapeutic cargo,such as anti-inflammatory molecules,growth factors,and microRNAs.When administered intravenously,extra cellular vesicles can cross the blood-brain barrier and deliver their cargos to the site of injury,where they can be taken up by recipient cells and modulate the inflammatory response,promote neuroregeneration,and improve functional outcomes.In preclinical studies,extracellular vesicle-based therapies have shown promising results in promoting recove ry after traumatic brain injury,including reducing neuronal damage,improving cognitive function,and enhancing motor recovery.While further research is needed to establish the safety and efficacy of extra cellular vesicle-based therapies in humans,extra cellular vesicles represent a promising novel approach for the treatment of traumatic brain injury.In this review,we summarize mesenchymal ste m/stromal cell-de rived extracellular vesicles as a cell-free therapy for traumatic brain injury via neuroprotection and neurorestoration and brainderived extracellular vesicles as potential biofluid biomarkers in small and large animal models of traumatic brain injury. 展开更多
关键词 biomarkers extracellular vesicles functional outcome mesenchymal stem/stromal cells NEUROINFLAMMATION NEUROPLASTICITY NEUROPROTECTION traumatic brain injury
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Application of artificial hibernation technology in acute brain injury 被引量:1
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作者 Xiaoni Wang Shulian Chen +5 位作者 Xiaoyu Wang Zhen Song Ziqi Wang Xiaofei Niu Xiaochu Chen Xuyi Chen 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第9期1940-1946,共7页
Controlling intracranial pressure,nerve cell regeneration,and microenvironment regulation are the key issues in reducing mortality and disability in acute brain injury.There is currently a lack of effective treatment ... Controlling intracranial pressure,nerve cell regeneration,and microenvironment regulation are the key issues in reducing mortality and disability in acute brain injury.There is currently a lack of effective treatment methods.Hibernation has the characteristics of low temperature,low metabolism,and hibernation rhythm,as well as protective effects on the nervous,cardiovascular,and motor systems.Artificial hibernation technology is a new technology that can effectively treat acute brain injury by altering the body’s metabolism,lowering the body’s core temperature,and allowing the body to enter a state similar to hibernation.This review introduces artificial hibernation technology,including mild hypothermia treatment technology,central nervous system regulation technology,and artificial hibernation-inducer technology.Upon summarizing the relevant research on artificial hibernation technology in acute brain injury,the research results show that artificial hibernation technology has neuroprotective,anti-inflammatory,and oxidative stress-resistance effects,indicating that it has therapeutic significance in acute brain injury.Furthermore,artificial hibernation technology can alleviate the damage of ischemic stroke,traumatic brain injury,cerebral hemorrhage,cerebral infarction,and other diseases,providing new strategies for treating acute brain injury.However,artificial hibernation technology is currently in its infancy and has some complications,such as electrolyte imbalance and coagulation disorders,which limit its use.Further research is needed for its clinical application. 展开更多
关键词 cute brain injury artificial hibernation HYPOTHERMIA low metabolism mild hypothermia
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Long non-coding RNA H19 regulates neurogenesis of induced neural stem cells in a mouse model of closed head injury 被引量:3
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作者 Mou Gao Qin Dong +4 位作者 Zhijun Yang Dan Zou Yajuan Han Zhanfeng Chen Ruxiang Xu 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第4期872-880,共9页
Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regen... Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regeneration via cell replacement.However,the neural regeneration efficiency of induced neural stem cells remains limited.In this study,we explored differentially expressed genes and long non-coding RNAs to clarify the mechanism underlying the neurogenesis of induced neural stem cells.We found that H19 was the most downregulated neurogenesis-associated lnc RNA in induced neural stem cells compared with induced pluripotent stem cells.Additionally,we demonstrated that H19 levels in induced neural stem cells were markedly lower than those in induced pluripotent stem cells and were substantially higher than those in induced neural stem cell-derived neurons.We predicted the target genes of H19 and discovered that H19 directly interacts with mi R-325-3p,which directly interacts with Ctbp2 in induced pluripotent stem cells and induced neural stem cells.Silencing H19 or Ctbp2 impaired induced neural stem cell proliferation,and mi R-325-3p suppression restored the effect of H19 inhibition but not the effect of Ctbp2 inhibition.Furthermore,H19 silencing substantially promoted the neural differentiation of induced neural stem cells and did not induce apoptosis of induced neural stem cells.Notably,silencing H19 in induced neural stem cell grafts markedly accelerated the neurological recovery of closed head injury mice.Our results reveal that H19 regulates the neurogenesis of induced neural stem cells.H19 inhibition may promote the neural differentiation of induced neural stem cells,which is closely associated with neurological recovery following closed head injury. 展开更多
关键词 closed head injury Ctbp2 induced neural stem cell lncRNA H19 miR-325-3p NEUROGENESIS
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Crosstalk among mitophagy,pyroptosis,ferroptosis,and necroptosis in central nervous system injuries 被引量:1
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作者 Li Zhang Zhigang Hu +1 位作者 Zhenxing Li Yixing Lin 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第8期1660-1670,共11页
Central nervous system injuries have a high rate of resulting in disability and mortality;however,at present,effective treatments are lacking.Programmed cell death,which is a genetically determined fo rm of active and... Central nervous system injuries have a high rate of resulting in disability and mortality;however,at present,effective treatments are lacking.Programmed cell death,which is a genetically determined fo rm of active and ordered cell death with many types,has recently attra cted increasing attention due to its functions in determining the fate of cell survival.A growing number of studies have suggested that programmed cell death is involved in central nervous system injuries and plays an important role in the progression of brain damage.In this review,we provide an ove rview of the role of programmed cell death in central nervous system injuries,including the pathways involved in mitophagy,pyroptosis,ferroptosis,and necroptosis,and the underlying mechanisms by which mitophagy regulates pyroptosis,ferroptosis,and necro ptosis.We also discuss the new direction of therapeutic strategies to rgeting mitophagy for the treatment of central nervous system injuries,with the aim to determine the connection between programmed cell death and central nervous system injuries and to identify new therapies to modulate programmed cell death following central nervous system injury.In conclusion,based on these properties and effects,interventions targeting programmed cell death could be developed as potential therapeutic agents for central nervous system injury patients. 展开更多
关键词 central nervous system injuries death pyroptosis ferroptosis inflammation MITOPHAGY NECROPTOSIS programmed cell
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Mesenchymal stem cells’“garbage bags”at work:Treating radial nerve injury with mesenchymal stem cell-derived exosomes 被引量:1
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作者 Mazhar Mushtaq Doaa Hussein Zineldeen +1 位作者 Muhammad Abdul Mateen Khawaja Husnain Haider 《World Journal of Stem Cells》 SCIE 2024年第5期467-478,共12页
Unlike central nervous system injuries,peripheral nerve injuries(PNIs)are often characterized by more or less successful axonal regeneration.However,structural and functional recovery is a senile process involving mul... Unlike central nervous system injuries,peripheral nerve injuries(PNIs)are often characterized by more or less successful axonal regeneration.However,structural and functional recovery is a senile process involving multifaceted cellular and molecular processes.The contemporary treatment options are limited,with surgical intervention as the gold-standard method;however,each treatment option has its associated limitations,especially when the injury is severe with a large gap.Recent advancements in cell-based therapy and cell-free therapy approaches using stem cell-derived soluble and insoluble components of the cell secretome are fast-emerging therapeutic approaches to treating acute and chronic PNI.The recent pilot study is a leap forward in the field,which is expected to pave the way for more enormous,systematic,and well-designed clinical trials to assess the therapeutic efficacy of mesenchymal stem cell-derived exosomes as a bio-drug either alone or as part of a combinatorial approach,in an attempt synergize the best of novel treatment approaches to address the complexity of the neural repair and regeneration. 展开更多
关键词 EXOSOME Mesenchymal stem cells Nerve injury Stem cells SECRETOME Regeneration
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Dual-directional regulation of spinal cord injury and the gut microbiota 被引量:1
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作者 Yinjie Cui Jingyi Liu +7 位作者 Xiao Lei Shuwen Liu Haixia Chen Zhijian Wei Hongru Li Yuan Yang Chenguang Zheng Zhongzheng Li 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第3期548-556,共9页
There is increasing evidence that the gut microbiota affects the incidence and progression of central nervous system diseases via the brain-gut axis.The spinal cord is a vital important part of the central nervous sys... There is increasing evidence that the gut microbiota affects the incidence and progression of central nervous system diseases via the brain-gut axis.The spinal cord is a vital important part of the central nervous system;however,the underlying association between spinal cord injury and gut interactions remains unknown.Recent studies suggest that patients with spinal cord injury frequently experience intestinal dysfunction and gut dysbiosis.Alterations in the gut microbiota can cause disruption in the intestinal barrier and trigger neurogenic inflammatory responses which may impede recovery after spinal cord injury.This review summarizes existing clinical and basic research on the relationship between the gut microbiota and spinal cord injury.Our research identified three key points.First,the gut microbiota in patients with spinal cord injury presents a key characteristic and gut dysbiosis may profoundly influence multiple organs and systems in patients with spinal cord injury.Second,following spinal cord injury,weakened intestinal peristalsis,prolonged intestinal transport time,and immune dysfunction of the intestine caused by abnormal autonomic nerve function,as well as frequent antibiotic treatment,may induce gut dysbiosis.Third,the gut microbiota and associated metabolites may act on central neurons and affect recovery after spinal cord injury;cytokines and the Toll-like receptor ligand pathways have been identified as crucial mechanisms in the communication between the gut microbiota and central nervous system.Fecal microbiota transplantation,probiotics,dietary interventions,and other therapies have been shown to serve a neuroprotective role in spinal cord injury by modulating the gut microbiota.Therapies targeting the gut microbiota or associated metabolites are a promising approach to promote functional recovery and improve the complications of spinal cord injury. 展开更多
关键词 CHEMOKINES CYTOKINES gut microbiota NLRP3 spinal cord injury Toll-like receptor ligand TRYPTOPHAN
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Tumor necrosis factor-stimulated gene-6 ameliorates early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome-mediated astrocyte pyroptosis 被引量:2
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作者 Mingxiang Ding Lei Jin +4 位作者 Boyang Wei Wenping Cheng Wenchao Liu Xifeng Li Chuanzhi Duan 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第5期1064-1071,共8页
Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective treatment.Pyroptosis is a crucial mechanism underlying early brain injury after subarachnoid hemorrhage.Previous studies have... Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective treatment.Pyroptosis is a crucial mechanism underlying early brain injury after subarachnoid hemorrhage.Previous studies have confirmed that tumor necrosis factor-stimulated gene-6(TSG-6)can exert a neuroprotective effect by suppressing oxidative stress and apoptosis.However,no study to date has explored whether TSG-6 can alleviate pyroptosis in early brain injury after subarachnoid hemorrhage.In this study,a C57BL/6J mouse model of subarachnoid hemorrhage was established using the endovascular perforation method.Our results indicated that TSG-6 expression was predominantly detected in astrocytes,along with NLRC4 and gasdermin-D(GSDMD).The expression of NLRC4,GSDMD and its N-terminal domain(GSDMD-N),and cleaved caspase-1 was significantly enhanced after subarachnoid hemorrhage and accompanied by brain edema and neurological impairment.To explore how TSG-6 affects pyroptosis during early brain injury after subarachnoid hemorrhage,recombinant human TSG-6 or a siRNA targeting TSG-6 was injected into the cerebral ventricles.Exogenous TSG-6 administration downregulated the expression of NLRC4 and pyroptosis-associated proteins and alleviated brain edema and neurological deficits.Moreover,TSG-6 knockdown further increased the expression of NLRC4,which was accompanied by more severe astrocyte pyroptosis.In summary,our study revealed that TSG-6 provides neuroprotection against early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome activation-induced astrocyte pyroptosis. 展开更多
关键词 ASTROCYTE early brain injury INFLAMMASOME NLRC4 PYROPTOSIS subarachnoid hemorrhage tumor necrosis factor-stimulated gene-6(TSG-6)
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Neurophysiological, histological, and behavioral characterization of animal models of distraction spinal cord injury: a systematic review 被引量:1
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作者 Bo Han Weishi Liang +4 位作者 Yong Hai Duan Sun Hongtao Ding Yihan Yang Peng Yin 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第3期563-570,共8页
Distraction spinal cord injury is caused by some degree of distraction or longitudinal tension on the spinal cord and commonly occurs in patients who undergo corrective operation for severe spinal deformity.With the i... Distraction spinal cord injury is caused by some degree of distraction or longitudinal tension on the spinal cord and commonly occurs in patients who undergo corrective operation for severe spinal deformity.With the increased degree and duration of distraction,spinal cord injuries become more serious in terms of their neurophysiology,histology,and behavior.Very few studies have been published on the specific characteristics of distraction spinal cord injury.In this study,we systematically review 22 related studies involving animal models of distraction spinal cord injury,focusing particularly on the neurophysiological,histological,and behavioral characteristics of this disease.In addition,we summarize the mechanisms underlying primary and secondary injuries caused by distraction spinal cord injury and clarify the effects of different degrees and durations of distraction on the primary injuries associated with spinal cord injury.We provide new concepts for the establishment of a model of distraction spinal cord injury and related basic research,and provide reference guidelines for the clinical diagnosis and treatment of this disease. 展开更多
关键词 animal models behavior DISTRACTION heterogeneity HISTOLOGY mechanism NEUROPHYSIOLOGY spinal cord injury systematic review tension
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