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Polyethylene glycol fusion repair of severed rat sciatic nerves reestablishes axonal continuity and reorganizes sensory terminal fields in the spinal cord

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Neural Regeneration Research 2025年第7期20卷 2095-2107页

作者： Emily A.Hibbard Liwen Zhou Cathy Z.Yang Karthik Venkudusamy Yessenia Montoya Alexa Olivarez George D.Bittner Dale R.Sengelaub Program in neuroscience Indiana UniversityBloomingtonINUSA department of neuroscience University of Texas at AustinAustinTXUSA

Peripheral nerve injuries result in the rapid degeneration of distal nerve segments and immediate loss of motor and sensory functions;behavioral recovery is typically *** used a plasmalemmal fusogen,polyethylene glycol(PEG),to immediately fuse closely apposed open ends of severed proximal and distal axons in rat sciatic *** have previously reported that sciatic nerve axons repaired by PEG-fusion do not undergo Wallerian degeneration,and PEG-fused animals exhibit rapid(within 2–6 weeks)and extensive locomotor ***,our previous report showed that PEG-fusion of severed sciatic motor axons was non-specific,i.e.,spinal motoneurons in PEG-fused animals were found to project to appropriate as well as inappropriate target *** this study,we examined the consequences of PEG-fusion for sensory axons of the sciatic *** adult male and female rats(Sprague–Dawley)received either a unilateral single cut or ablation injury to the sciatic nerve and subsequent repair with or without(Negative Control)the application of *** action potentials recorded immediately after PEG-fusion repair confirmed conduction across the injury *** success of PEG-fusion was confirmed through Sciatic Functional Index testing with PEG-fused animals showing improvement in locomotor function beginning at 35 days *** 2–42 days postoperatively,we anterogradely labeled sensory afferents from the dorsal aspect of the hindpaw following bilateral intradermal injection of wheat germ agglutinin conjugated horseradish ***-fusion repair reestablished axonal *** to unoperated animals,labeled sensory afferents ipsilateral to the injury in PEG-fused animals were found in the appropriate area of the dorsal horn,as well as inappropriate mediolateral and rostrocaudal ***,despite having intact peripheral nerves,similar reorganizations of labeled sensory afferents were also observed contralateral to the injury and repa

关键词： axotomy dorsal horn peripheral nerve injury plasticity polyethylene glycol(PEG) sciatic nerve sensory terminals wheat germ agglutinin horseradish peroxidase

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New complex physiological findings evolve hypothesized mechanisms of Dravet syndrome

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Neural Regeneration Research 2024年第9期19卷 1867-1868页

作者： MacKenzie A.Howard department of Neurology Dell Medical SchoolAustinTXUSA Center for Learning and Memory and department of neuroscience University of Texas at AustinAustinTXUSA

Developmental and epileptic encephalopathies(DEEs)are neurological disorders generally involving medically intractable seizures and a diverse array of comorbid neuropsychiatric delays and deficits that may severely affect cognition,mood,sleep,social behavior,movement control,learning,and/or *** syndrome(DS),also known as Severe Myoclonic Epilepsy of Infancy.

关键词： sized finding seizures

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Translating Pathological Brain Activity Primers in Parkinson’s Disease Research

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Research 2024年第1期2023卷 735-752页

作者： Daniela Mirzac Svenja L.Kreis Heiko J.Luhmann Gabriel Gonzalez-Escamilla Sergiu Groppa Movement Disorders and Neurostimulation Department of NeurologyFocus Program Translational NeuroscienceRhine Main Neuroscience NetworkUniversity Medical Center of the Johannes Gutenberg University Mainz55131 MainzGermany Institute of Physiology University Medical Center of the Johannes Gutenberg University Mainz55131 MainzGermany

Translational experimental approaches that help us better trace Parkinson’s disease(PD)pathophysiological mechanisms leading to new therapeutic targets are urgently *** this article,we review recent experimental and clinical studies addressing abnormal neuronal activity and pathological network oscillations,as well as their underlying mechanisms and *** aim is to enhance our knowledge about the progression of Parkinson's disease pathology and the timing of its symptom’s ***,we present mechanistic insights relevant for the generation of aberrant oscillatory activity within the cortico-basal ganglia *** summarize recent achievements extrapolated from available PD animal models,discuss their advantages and limitations,debate on their differential applicability,and suggest approaches for transferring knowledge on disease pathology into future research and clinical applications.

关键词： clinical knowledge insight

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Dysfunction of synaptic endocytic trafficking in Parkinson's disease

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Neural Regeneration Research 2024年第12期19卷 2649-2660页

作者： Xin Yi Ng Mian Cao Programme in neuroscience and Behavioural Disorders Duke-NUS Medical SchoolSingaporeSingapore department of Physiology National University of SingaporeSingaporeSingapore

Parkinson's disease is characterized by the selective degeneration of dopamine neurons in the nigrostriatal pathway and dopamine deficiency in the *** precise reasons behind the specific degeneration of these dopamine neurons remain largely *** investigations have identified over 20 causative PARK genes and 90 genomic risk loci associated with both familial and sporadic Parkinson's ***,several of these genes are linked to the synaptic vesicle recycling process,particularly the clathrinmediated endocytosis *** suggests that impaired synaptic vesicle recycling might represent an early feature of Parkinson's disease,followed by axonal degeneration and the eventual loss of dopamine cell bodies in the midbrain via a"dying back"***,several new animal and cellular models with Parkinson's disease-linked mutations affecting the endocytic pathway have been created and extensively *** models faithfully recapitulate certain Parkinson's disease-like features at the animal,circuit,and cellular levels,and exhibit defects in synaptic membrane trafficking,further supporting the findings from human genetics and clinical *** this review,we will first summarize the cellular and molecular findings from the models of two Parkinson's disease-linked clathrin uncoating proteins:auxilin(DNAJC6/PARK19)and synaptojanin 1(SYNJ1/PARK20).The mouse models carrying these two PARK gene mutations phenocopy each other with specific dopamine terminal pathology and display a potent synergistic ***,we will delve into the involvement of several clathrin-mediated endocytosis-related proteins(GAK,endophilin A1,SAC2/INPP5 F,synaptotagmin-11),identified as Parkinson's disease risk factors through genome-wide association studies,in Parkinson's disease *** will also explore the direct or indirect roles of some common Parkinson's disease-linked proteins(alpha-synuclein(PARK1/4),Parkin(PARK2),and LRRK2(PARK

关键词： autophagy auxilin/PARK19 clathrin-mediated endocytosis dopamine neurons neurodegeneration nigrostriatal pathway Parkinson's disease synaptic vesicle recycling synaptojanin1/PARK20

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K^(+) channel-mediated retarded maturation of interneurons and its role in neurodevelopmental disorders

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Neural Regeneration Research 2024年第7期19卷 1403-1404页

作者： Kaizhen Li Daria Savitska Olga Garaschuk Laboratory of Systems neuroscience Department of PhysiologyUniversity of BernBernSwitzerland Institute of Physiology Department of NeurophysiologyEberhard Karls University of TübingenTübingenGermany

De novo mutations in genes encoding K^(+)channels are implicated in many severe neurodevelopmental ***,mutations in KCNA2,encoding the Shaker-type voltage-gated K^(+)channel Kv1.2,and KCNJ2,encoding the inwardly rectifying K^(+)channel Kir2.1,associate with focal and generalized epilepsies,brain atrophy,autism,ataxia and hereditary spastic paraplegia(Syrbe et al.,2015;Masnada et al.,2017;Cheng et al.,2021).

关键词： disorders atrophy

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Emerging role of galectin 3 in neuroinflammation and neurodegeneration

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Neural Regeneration Research 2024年第9期19卷 2004-2009页

作者： Brian M.Lozinski Khanh Ta Yifei Dong department of Clinical neuroscience University of CalgaryCalgaryABCanada Deparment of Biochemistry Microbiology&ImmunologyUniversity of SaskatchewanSaskatoonSKCanada

Neuroinflammation and neurodegeneration are key processes that mediate the development and progression of neurological ***,the mechanisms modulating these processes in different diseases remain incompletely *** in single cell based multi-omic analyses have helped to identify distinct molecular signatures such as Lgals3 that is associated with neuroinflammation and neurodegeneration in the central nervous system(CNS).Lgals3 encodes galectin-3(Gal3),aβ-galactoside and glycan binding glycoprotein that is frequently upregulated by reactive microglia/macrophages in the CNS during various neurological *** Gal3 has previously been associated with non-CNS inflammatory and fibrotic diseases,recent studies highlight Gal3 as a prominent regulator of inflammation and neuroaxonal damage in the CNS during diseases such as multiple sclerosis,Alzheimer’s disease,and Parkinson’s *** this review,we summarize the pleiotropic functions of Gal3 and discuss evidence that demonstrates its detrimental role in neuroinflammation and neurodegeneration during different neurological *** also consider the challenges of translating preclinical observations into targeting Gal3 in the human CNS.

关键词： Alzheimer’s disease Galectin 3 microglia multiple sclerosis neurodegeneration neuroinflammation Parkinson’s disease therapeutics

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Pathology of pain and its implications for therapeutic interventions

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2851-2899页

作者： Bo Cao Qixuan Xu Yajiao Shi Ruiyang Zhao Hanghang Li Jie Zheng Fengyu Liu You Wan Bo Wei department of General Surgery First Medical CenterChinese PLA General HospitalBeijing 100853China Medical School of Chinese PLA Beijing 100853China neuroscience Research Institute and department of Neurobiology School of Basic Medical SciencesKey Laboratory for NeuroscienceMinistry of Education/National Health CommissionPeking UniversityBeijing 100191China

Pain is estimated to affect more than 20%of the global population,imposing incalculable health and economic *** pain management is crucial for individuals suffering from ***,the current methods for pain assessment and treatment fall short of clinical *** from advances in neuroscience and biotechnology,the neuronal circuits and molecular mechanisms critically involved in pain modulation have been *** research achievements have incited progress in identifying new diagnostic and therapeutic *** this review,we first introduce fundamental knowledge about pain,setting the stage for the subsequent *** review next delves into the molecular mechanisms underlying pain disorders,including gene mutation,epigenetic modification,posttranslational modification,inflammasome,signaling pathways and *** better present a comprehensive view of pain research,two prominent issues,sexual dimorphism and pain comorbidities,are discussed in detail based on current *** status quo of pain evaluation and manipulation is summarized.A series of improved and innovative pain management strategies,such as gene therapy,monoclonal antibody,brain-computer interface and microbial intervention,are making strides towards clinical *** highlight existing limitations and future directions for enhancing the quality of preclinical and clinical *** to decipher the complexities of pain pathology will be instrumental in translating scientific discoveries into clinical practice,thereby improving pain management from bench to bedside.

关键词： pain thereby summarized

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Astrocyte syncytium:from neonatal genesis to aging degeneration

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Neural Regeneration Research 2024年第2期19卷 395-396页

作者： Min Zhou Shiying Zhong Alexei Verkhratsky department of neuroscience Ohio State University Wexner Medical CenterColumbusOHUSA Faculty of Biology Medicine and HealthThe University of ManchesterManchesterUK Achücarro Basque Center for neuroscience IKERBASQUEBasque Foundation for ScienceBilbaoSpain department of neurosciences University of the Basque Country UPV/EHU and CIBERNEDLeioaSpain

Modern neuroscience began from all reaching and fierce conflict between“neuronismo and reticulismo”——between neuronal and reticular theories of the organization of the nervous system;the conflict culminated in December of 1906 in Stockholm where Santiago Ramon y Cajal(the proponent of the neuronal doctrine)and Camillo Golgi(who advocated the syncytial reticular organization of neural networks)delivered their Noble prize lectures(Verkhratsky,2009).

关键词： degeneration neonatal aging

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Calcium-sensitive protein MLC1 as a possible modulator of the astrocyte functional state

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Neural Regeneration Research 2025年第7期20卷 2008-2010页

作者： Elena Ambrosini Angela Lanciotti Maria Stefania Brignone department of neuroscience Istituto Superiore di SanitàRomeItaly

Astrocytes,the main population of glial cells in the central nervous system(CNS),exert essential tasks for the control of brain tissue homeostasis,supporting neuron and other glial cell activity from the developmental stage to adult *** maintain the optimal functionality of the brain,astroglial cells are particularly committed to reacting to every change in tissue homeostatic conditions,from mild modifications of the physiological environment,a process called astrocyte activation,to the more severe alterations occurring in pathological situations causing astrocyte reactivity or reactive astrogliosis(Escartin et al.,2021).During these reactive states,astrocytes mount an active,progressive response encompassing morphological,molecular,and interactional remodeling,leading to the acquisition of new functions and the loss of others,whose intensity,duration,and reversibility are dependent on the nature of the stimulus and regulated in a context-specific manner.

关键词： alterations modulator maintain

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Role of glioma stem cells in promoting tumor chemo- and radioresistance: A systematic review of potential targeted treatments

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World Journal of Stem Cells 2024年第5期16卷 604-614页

作者： Edoardo Agosti Marco Zeppieri Mattia Ghidoni Tamara Ius Alessandro Tel Marco Maria Fontanella Pier Paolo Panciani Division of Neurosurgery Department of Medical and Surgical SpecialtiesRadiological Sciences and Public HealthUniversity of BresciaBrescia 25123Italy department of Ophthalmology University Hospital of UdineUdine 33100Italy Neurosurgery Unit Department of Head-Neck and NeuroScienceUniversity Hospital of UdineUdine 33100Italy Clinic of Maxillofacial Surgery Department of Head-Neck and NeuroScienceUniversity Hospital of UdineUdine 33100Italy

BACKGROUND Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and *** stem cells(GSCs),a subset within tumors,contribute to resistance,tumor heterogeneity,and *** studies reveal GSCs’role in therapeutic resistance,driven by DNA repair mechanisms and dynamic transitions between cellular *** mechanisms can involve different cellular pathways,most of which have been recently reported in the *** progress,targeted therapeutic approaches lack consensus due to GSCs’high *** To analyze targeted therapies against GSC-mediated resistance to radio-and chemotherapy in gliomas,focusing on underlying *** A systematic search was conducted across major medical databases(PubMed,Embase,and Cochrane Library)up to September 30,*** search strategy utilized relevant Medical Subject Heading terms and keywords related to including“glioma stem cells”,“radiotherapy”,“chemotherapy”,“resistance”,and“targeted therapies”.Studies included in this review were publications focusing on targeted therapies against the molecular mechanism of GSC-mediated re-sistance to radiotherapy resistance(RTR).RESULTS In a comprehensive review of 66 studies on stem cell therapies for SCI,452 papers were initially identified,with 203 chosen for full-text *** them,201 were deemed eligible after excluding 168 for various *** temporal breakdown of studies illustrates this trend:2005-2010(33.3%),2011-2015(36.4%),and 2016-2022(30.3%).Key GSC models,particularly U87(33.3%),U251(15.2%),and T98G(15.2%),emerge as significant in research,reflecting their representativeness of glioma *** analysis indicates a focus on phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(mTOR)(27.3%)and Notch(12.1%)pathways,suggesting their crucial roles in resistance *** molecules with mTOR(18.2%),CHK1/2(15.2%),and ATP binding cassette

关键词： Glioma stem cells Chemoresistance Radioresistance Molecular pathways Targeted therapies Systematic review

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