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Neutrophil extracellular traps mediate neuro-immunothrombosis

neural regeneration Research 2024年第8期19卷 1734-1740页

作者： Jianbo Lou Jianning Zhang Quanjun Deng Xin Chen Department of Neurosurgery Tianjin Medical University General HospitalTianjinChina Tianjin Neurological Institute Key Laboratory of Post-Trauma Neuro-Repair and Regeneration in Central Nervous SystemMinistry of EducationTianjin Key Laboratory of InjuriesVariations and Regeneration of Nervous SystemTianjinChina

Neutrophil extracellular traps are primarily composed of DNA and histones and are released by neutrophils to promote inflammation and thrombosis when stimulated by various inflammato ry *** extracellular trap formation occurs through lytic and non-lytic pathways that can be further classified by formation ***,von Willebrand factor,fibrin,and many other factors participate in the interplay between inflammation and *** summarizes the intricate interplay between inflammation and thrombosis during neural development and the pathogenesis of neurological diseases,providing cutting-edge insights into post-neurotrauma thrombotic *** blood-brain barrier defends the brain and spinal cord against external assaults,and neutrophil extracellular trap involvement in blood-brain barrier disruption and immunothrombosis contributes substantially to secondary injuries in neurological *** research is needed to understand how neutrophil extracellular traps promote blood-brain barrier disruption and immunothrombosis,but recent studies have demonstrated that neutrophil extracellular traps play a crucial role in immunothrombosis,and identified modulators of ***,these neurological diseases occur in blood vessels,and the mechanisms are unclear by which neutrophil extracellular traps penetrate the blood-brain barrier to participate in immunothrombosis in traumatic brain *** review discusses the role of neutrophil extracellular traps in neuro-immunothrombosis and explores potential therapeutic interventions to modulate neutrophil extracellular traps that may reduce immunothrombosis and improve traumatic brain injury outcomes.

关键词： inflammation neuro-immunothrombosis neurologic diseases neurotrauma neutrophil extracellular traps platelet thrombosis traumatic brain injury

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Brain circuits for retching-like behavior

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National Science Review 2024年第1期11卷 145-160页

作者： Lifang Huo Zhimin Ye Meiling Liu Ziqing He Meizhu Huang Dapeng Li Qian Wu Qian Wang Xiaoqun Wang Peng Cao Ji Dong Congping Shang School of Basic Medical Sciences Guangzhou National Laboratory The Fifth Afflliated Hospital Guangzhou Medical University Bioland laboratory (Guangzhou Regenerative Medicine and Health Guangdong laboratory) Department of Neurobiology School of Basic Medical Sciences Beijing Key Laboratory of Neural Regeneration and Repair Advanced Innovation Center for Human Brain Protection Capital Medical University State key laboratory of Cognitive Neuroscience and Learning IDG/McGovern Institute for Brain Research Beijing Normal University Changping Life Science laboratory National Institute of Biological Sciences

Nausea and vomiting are important defensive responses to cope with pathogens and toxins that invade the body. The nucleus of the solitary tract(NTS) is important for initiating these responses. However, the molecular heterogeneities and cellular diversities of the NTS occlude a better understanding of these defensive responses. Here, we constructed the single-nucleus transcriptomic atlas of NTS cells and found multiple populations of NTS neurons that may be involved in these defensive responses. Among these, we identified Calbindin1-positive(Calb1+) NTS neurons that are molecularly distinct from Tac1+*** Calb1+neurons are critical for nausea and retching induced by cereulide; an emetic toxin secreted by Bacillus Cereus. Strikingly, we found that cereulide can directly modulate vagal sensory neurons that innervate Calb1+NTS neurons, a novel mechanism distinct from that for nausea and retching induced by Staphylococcal enterotoxin A. Together, our transcriptomic atlas of NTS neurons and the functional analyses revealed the neural mechanism for cereulide-induced retching-like behavior. These results demonstrate the molecular and cellular complexities in the brain that underlie defensive responses to the diversities of pathogens and toxins.

关键词： vomiting nausea nucleus of the solitary tract Calbindin1 neural circuits

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Cortico-striatal gamma oscillations are modulated by dopamine D3 receptors in dyskinetic rats

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neural regeneration Research 2025年第4期20卷 1164-1177页

作者： Pengfei Wang Yuewei Bi Min Li Jiazhi Chen Zhuyong Wang Huantao Wen Ming Zhou Minjie Luo Wangming Zhang Neurosurgery Center Department of Pediatric NeurosurgeryGuangdong Provincial Key Laboratory on Brain Function Repair and RegenerationZhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina

Long-term levodopa administration can lead to the development of levodopa-induced *** oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced ***,studies have reported increased oscillation power in cases of levodopa-induced ***,little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced ***,the role of the dopamine D3 receptor,which is implicated in levodopa-induced dyskinesia,in movement disorder-related changes in neural oscillations is *** found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s ***,levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components,as well as bidirectional primary motor cortex(M1)↔dorsolateral striatum gamma *** of PD128907(a selective dopamine D3 receptor agonist)induced dyskinesia and excessive gamma oscillations with a bidirectional M1↔dorsolateral striatum ***,administration of PG01037(a selective dopamine D3 receptor antagonist)attenuated dyskinesia,suppressed gamma oscillations and cortical gamma aperiodic components,and decreased gamma causality in the M1→dorsolateral striatum *** findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity,and that it has potential as a therapeutic target for levodopa-induced dyskinesia.

关键词： aperiodic components dopamine D3 receptor dorsolateral striatum functional connectivity gamma oscillations levodopa-induced-dyskinesia local field potentials neuromodulation Parkinson’s disease primary motor cortex

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Timp1 Deletion Induces Anxiety-like Behavior in Mice

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Neuroscience Bulletin 2024年第6期40卷 732-742页

作者： Xiaotong Wang Wei Zheng Ziyi Zhu Biyu Xing Weijie Yan Ke Zhu Lingli Xiao Chaojuan Yang Mengping Wei Lei Yang Zi-Bing Jin Xueyun Bi Chen Zhang State key laboratory of Neurology and Oncology Drug Development Nanjing210000China School of Basic Medical Sciences Wenzhou Medical UniversityWenzhou325035China School of Basic Medical Sciences Beijing Key Laboratory of Neural Regeneration and RepairAdvanced Innovation Center for Human Brain ProtectionBeijing Laboratory of Oral HealthCapital Medical UniversityBeijing100069China Beijing Institute of Ophthalmology Beijing Tongren Eye CenterBeijing Tongren HospitalCapital Medical UniversityBeijing100005China Chinese Institute for Brain Research Beijing102206China key laboratory for Biomechanics and Mechanobiology of the Ministry of Education Beijing Advanced Innovation Center for Biomedical EngineeringSchool of Engineering MedicineBeihang UniversityBeijing100191China

The hippocampus is essential for learning and memory,but it also plays an important role in regulating emotional behavior,as hippocampal excitability and plasticity affect anxiety and *** synaptic plasticity may be regulated by tissue inhibitor of matrix metalloproteinase 1(TIMP1),a known protein inhibitor of extracellular matrix(ECM),and the expression of TIMP1 in the hippocampus can be induced by neuronal excitation and various ***,the involvement of Timp1 in fear learning,anxiety,and hippocampal synaptic function remains to be *** study of Timp1 function in vivo revealed that Timp1 knockout mice exhibit anxiety-like behavior but normal fear *** results suggested that Timp1 knockout mice showed hyperactivity in the ventral CA1 region,but the basic synaptic transmission and plasticity were normal in the Schaffer collateral *** together,our results suggest that deletion of Timp1 in vivo leads to the occurrence of anxiety behaviors,but that Timp1 is not crucial for fear learning.

关键词： Timp1 Anxiety Fear Synaptic transmission Synaptic plasticity

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Development of Chinese herbal medicine for sensorineural hearing loss

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Acta Pharmaceutica Sinica B 2024年第2期14卷 455-467页

作者： Yunhao Wu Jingwen Zhang Qiuping Liu Zhuang Miao Renjie Chai Wenyong Chen State key laboratory of Bioelectronics Department of Otolaryngology Head and Neck SurgeryZhongda HospitalSchool of Life Sciences and TechnologyAdvanced Institute for Life and HealthJiangsu Province HighTech Key Laboratory for Bio-Medical ResearchSoutheast UniversityNanjing 210096China Department of Otolaryngology-Head and Neck the Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510120China Department of Otolaryngology-Head and Neck Surgery Affiliated Hospital of Jiangnan UniversityWuxi 214000China Department of Otolaryngology Head and Neck Surgery Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengdu 610000China Co-Innovation Center of Neuroregeneration Nantong UniversityNantong 226001China Institute for Stem Cell and regeneration Chinese Academy of ScienceBeijing 100085China Beijing key laboratory of neural regeneration and repair Capital Medical UniversityBeijing 100069China

According to the World Health Organization’s world report on hearing,nearly 2.5 billion people worldwide will suffer from hearing loss by 2050,which may contribute to a severe impact on individual life quality and national *** hearing loss(SNHL)occurs commonly as a result of noise exposure,aging,and ototoxic drugs,and is pathologically characterized by the impairment of mechanosensory hair cells of the inner ear,which is mainly triggered by reactive oxygen species accumulation,inflammation,and mitochondrial *** recent advances have been made in understanding the ability of cochlear repair and regeneration,there are still no effective therapeutic drugs for *** herbal medicine which is widely distributed and easily accessible in China has demonstrated a unique curative effect against SNHL with higher safety and lower cost compared with Western *** we present trends in research for Chinese herbal medicine for the treatment of SNHL,and elucidate their molecular mechanisms of action,to pave the way for further research and development of novel effective drugs in this field.

关键词： Sensorineural hearing loss Chinese herbal medicine Molecular mechanism Active ingredients Prescriptions Ototoxic drugs Noise Hair cells

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Advance and Application of Single‑cell Transcriptomics in Auditory Research

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Neuroscience Bulletin 2024年第7期40卷 963-980页

作者： Xiangyu Ma Jiamin Guo Mengyao Tian Yaoyang Fu Pei Jiang Yuan Zhang Renjie Chai State key laboratory of Digital Medical Engineering Department of Otolaryngology Head and Neck SurgeryZhongda HospitalSchool of Life Sciences and TechnologyAdvanced Institute for Life and HealthJiangsu Province High‑Tech Key Laboratory for Bio‑Medical ResearchSoutheast UniversityNanjing 210096China Department of Psychiatry Affiliated Hangzhou First People’s HospitalZhejiang University school of MedicineHangzhou 310030China Department of Otolaryngology Head and Neck Surgery Affiliated Drum Tower Hospital of Nanjing University Medical SchoolJiangsu Provincial Key Medical Discipline(Laboratory)NanjingChina Research Institute of Otolaryngology Nanjing 210008China Department of Otolaryngology Head and Neck Surgery Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengdu 610072China Co‑Innovation Center of Neuroregeneration Nantong UniversityNantong 226001China Institute for Stem Cell and regeneration Chinese Academy of ScienceBeijing 101408China Beijing key laboratory of neural regeneration and repair Capital Medical UniversityBeijing 100069China

Hearing loss and deafness,as a worldwide disability disease,have been troubling human ***,the auditory organ of the inner ear is highly heterogeneous and has a very limited number of cells,which are largely uncharacterized in ***,with the development and utilization of single-cell RNA sequencing(scRNA-seq),researchers have been able to unveil the complex and sophisticated biological mechanisms of various types of cells in the auditory organ at the single-cell level and address the challenges of cellular heterogeneity that are not resolved through by conventional bulk RNA sequencing(bulk RNAseq).Herein,we reviewed the application of scRNA-seq technology in auditory research,with the aim of providing a reference for the development of auditory organs,the pathogenesis of hearing loss,and regenerative *** about spatial transcriptomic scRNA-seq,single-cell based genome,and Live-seq technology will also be discussed.

关键词： Single-cell RNA sequencing Inner ear Cochlear Auditory sensory epithelium Spiral ganglion neuron

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Elevated peripheral levels of receptor-interacting protein kinase 1(RIPK1)and IL-8 as biomarkers of human amyotrophic lateral sclerosis

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Signal Transduction and Targeted Therapy 2024年第1期9卷 271-278页

作者： Jun Wei Min Li Zhi Ye Xinqian Hu Xiaoyan He Jia Wang Gaofeng Chen Chengyu Zou Daichao Xu Hongbing Zhang Junying Yuan Yunhong Zha Institute of neural regeneration and repair and Department of Neurology The First College of Clinical Medical ScienceYichang Central HospitalCollege of Basic Medical ScienceChina Three Gorges UniversityHubei Province Clinical Medical Research Center for Rare Diseases of Nervous SystemYichang 443000China Interdisciplinary Research Center on Biology and Chemistry Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai Key Laboratory of Aging StudiesShanghai 201210China State key laboratory of Common Mechanism Research for Major Diseases Haihe Laboratory of Cell EcosystemDepartment of PhysiologyInstitute of Basic Medical Sciences and School of Basic MedicineChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Amyotrophic lateral sclerosis(ALS)is a devastating fatal neurodegenerative disease with no ***-interacting protein kinase 1(RIPK1)has been proposed to mediate pathogenesis of *** has been identified as an old drug that can also inhibit RIPK1 *** conducted a drug-repurposing biomarker study of primidone as a RIPK1 inhibitor using SOD1G93A mice and ALS ***1G93A mice treated with primidone showed significant delay of symptomatic onset and improved motor ***-hundred-sixty-two ALS participants dosed daily with primidone(62.5 mg)completed 24-week follow-up.A significant reduction was showed in serum levels of RIPK1 and IL-8,which were significantly higher in ALS patients than that of healthy controls(P<0.0001).Serum RIPK1 levels were correlated positively with the severity of bulbar symptoms(P<0.05).Our study suggests that serum levels of RIPK1 and IL-8 in peripheral can be used as clinical biomarkers for the activation of RIPK1 in central nervous system in human ALS *** primidone may provide a promising therapeutic strategy for *** effect of primidone for the treatment of other inflammatory diseases may also be considered,since the activation of RIPK1 has been implicated in mediating a variety of inflammatory diseases including COVID-19-associated cytokine release syndrome(CRS).(ChiCTR2200060149).

关键词： RIPK1 diseases Serum

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Tumor necrosis factor-stimulated gene-6 ameliorates early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome-mediated astrocyte pyroptosis

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neural regeneration Research 2024年第5期19卷 1064-1071页

作者： Mingxiang Ding Lei Jin Boyang Wei Wenping Cheng Wenchao Liu Xifeng Li Chuanzhi Duan Neurosurgery Center Department of Cerebrovascular SurgeryThe National Key Clinical SpecialtyThe Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular DiseaseGuangdong Provincial Key Laboratory on Brain Function Repair and RegenerationThe Neurosurgery Institute of Guangdong ProvinceZhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina Department of Cerebrovascular Intervention Zhongshan City People’s HospitalZhongshanGuangdong ProvinceChina

Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective *** is a crucial mechanism underlying early brain injury after subarachnoid *** studies have confirmed that tumor necrosis factor-stimulated gene-6(TSG-6)can exert a neuroprotective effect by suppressing oxidative stress and ***,no study to date has explored whether TSG-6 can alleviate pyroptosis in early brain injury after subarachnoid *** this study,a C57BL/6J mouse model of subarachnoid hemorrhage was established using the endovascular perforation *** 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 *** 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 *** TSG-6 administration downregulated the expression of NLRC4 and pyroptosis-associated proteins and alleviated brain edema and neurological ***,TSG-6 knockdown further increased the expression of NLRC4,which was accompanied by more severe astrocyte *** summary,our study revealed that TSG-6 provides neuroprotection against early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome activation-induced astrocyte pyroptosis.

关键词： astrocyte early brain injury inflammasome NLRC4 pyroptosis subarachnoid hemorrhage tumor necrosis factor-stimulated gene-6(TSG-6)

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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

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neural regeneration Research 2024年第2期19卷 440-446页

作者： Sumei Liu Baoguo Liu Qian Li Tianqi Zheng Bochao Liu Mo Li Zhiguo Chen Cell Therapy Center Beijing Institute of GeriatricsXuanwu HospitalCapital Medical UniversityNational Clinical Research Center for Geriatric Diseasesand Key Laboratory of Neurodegenerative DiseasesMinistry of EducationBeijingChina Center of neural Injury and repair Beijing Institute for Brain DisordersBeijingChina Center of Parkinson’s Disease Beijing Institute for Brain DisordersBeijingChina

Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate *** a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury ***,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord *** 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 ***,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 *** 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 ***,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 ***-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.

关键词： biomaterial fibrinogen functional recovery induced neural stem cell transplantation microenvironment microglia spinal cord injury thrombin

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Chemokine platelet factor 4 accelerates peripheral nerve regeneration by regulating Schwann cell activation and axon elongation

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neural regeneration Research 2024年第1期19卷 190-195页

作者： Miao Gu Xiao Cheng Di Zhang Weiyan Wu Yi Cao Jianghong He key laboratory of Neuroregeneration of Jiangsu and Ministry of Education Co-innovation Center of NeuroregenerationNMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology ProductsNantong UniversityNantongJiangsu ProvinceChina School of Basic Medical Sciences Hebei Key Laboratory of Nerve Injury and RepairChengde Medical UniversityChengdeHebei ProvinceChina

Schwann cells in peripheral nerves react to traumatic nerve injury by attempting to grow and *** r,it is unclear what factors play a role in this *** this study,we searched a GEO database and found that expression of platelet factor 4 was markedly up-regulated after sciatic nerve *** factor is an important molecule in cell apoptosis,diffe rentiation,survival,and ***,polymerase chain reaction and immunohistochemical staining confirmed the change in platelet factor 4 in the sciatic nerve at different time points after ***-linked immunosorbent assay confirmed that platelet factor 4 was secreted by Schwann *** also found that silencing platelet factor 4 decreased the proliferation and migration of primary cultured Schwann cells,while exogenously applied platelet factor 4 stimulated Schwann cell prolife ration and migration and neuronal axon ***,knocking out platelet factor 4 inhibited the prolife ration of Schwann cells in injured rat sciatic *** findings suggest that Schwann cell-secreted platelet factor 4 may facilitate peripheral nerve repair and regeneration by regulating Schwann cell activation and axon ***,platelet factor 4 may be a potential therapeutic target for traumatic peripheral nerve injury.

关键词： axon elongation bioinformatic analysis cell migration cell proliferation dorsal root ganglia peripheral nerve regeneration peripheral nerve trauma platelet factor 4 rat sciatic nerve Schwann cells

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