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Polyethylene glycol fusion repair of severed sciatic nerves accelerates recovery of nociceptive sensory perceptions in male and female rats of different strains

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Neural Regeneration Research 2025年第9期20卷 2667-2681页

作者： Liwen Zhou Karthik Venkudusamy Emily A.Hibbard Yessenia Montoya Alexa Olivarez Cathy Z.Yang Adelaide Leung Varun Gokhale Guhan Periyasamy Zeal Pathak Dale R.Sengelaub George D.Bittner department of Neuroscience University of TexasAustinTXUSA Program in Neuroscience Indiana UniversityBloomingtonINUSA department of molecular biosciences University of TexasAustinTXUSA

Successful polyethylene glycol fusion(PEG-fusion)of severed axons following peripheral nerve injuries for PEG-fused axons has been reported to:(1)rapidly restore electrophysiological continuity;(2)prevent distal Wallerian Degeneration and maintain their myelin sheaths;(3)promote primarily motor,voluntary behavioral recoveries as assessed by the Sciatic Functional Index;and,(4)rapidly produce correct and incorrect connections in many possible combinations that produce rapid and extensive recovery of functional peripheral nervous system/central nervous system connections and reflex(e.g.,toe twitch)or voluntary *** preceding companion paper describes sensory terminal field reo rganization following PEG-fusion repair of sciatic nerve transections or ablations;howeve r,sensory behavioral recovery has not been explicitly explored following PEG-fusion *** the current study,we confirmed the success of PEG-fusion surgeries according to criteria(1-3)above and more extensively investigated whether PEG-fusion enhanced mechanical nociceptive recovery following sciatic transection in male and female outbred Sprague-Dawley and inbred Lewis *** nociceptive responses were assessed by measuring withdrawal thresholds using von Frey filaments on the dorsal and midplantar regions of the *** von Frey filament tests were a more reliable method than plantar von Frey filament tests to assess mechanical nociceptive sensitivity following sciatic nerve *** withdrawal thresholds of the sciatic-mediated lateral dorsal region differed significantly across strain but not *** thresholds did not change significantly from baseline in chronic Unoperated and Sham-operated *** sciatic transection,all rats exhibited severe hyposensitivity to stimuli at the lateral dorsal region of the hindpaw ipsilateral to the ***,PEG-fused rats exhibited significantly earlier return to baseline withdrawal thresholds than Negative

关键词： autophagia axotomy collateral sprouting neuropathic pain peripheral nerve repair polyethylene glycol fusion(PEG-fusion) saphenous nerve sensory neurons sex and strain Wallerian degeneration

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Polyethylene glycol has immunoprotective effects on sciatic allografts, but behavioral recovery and graft tolerance require neurorrhaphy and axonal fusion

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Neural Regeneration Research 2025年第4期20卷 1192-1206页

作者： Tyler A.Smith Liwen Zhou Cameron L.Ghergherehchi Michelle Mikesh Cathy Z.Yang Haley O.Tucker JuliAnne Allgood Jared S.Bushman George D.Bittner department of molecular biosciences University of Texas at AustinAustinTXUSA department of Neuroscience University of Texas at AustinAustinTXUSA Division of Pharmaceutical Sciences University of WyomingLaramieWYUSA

Behavioral recovery using(viable)peripheral nerve allografts to repair ablation-type(segmental-loss)peripheral nerve injuries is delayed or poor due to slow and inaccurate axonal ***,such peripheral nerve allografts undergo immunological rejection by the host immune *** contrast,peripheral nerve injuries repaired by polyethylene glycol fusion of peripheral nerve allografts exhibit excellent behavioral recovery within weeks,reduced immune responses,and many axons do not undergo Wallerian *** relative contribution of neurorrhaphy and polyethylene glycol-fusion of axons versus the effects of polyethylene glycol per se was unknown prior to this *** hypothesized that polyethylene glycol might have some immune-protective effects,but polyethylene glycol-fusion was necessary to prevent Wallerian degeneration and functional/behavioral *** examined how polyethylene glycol solutions per se affect functional and behavioral recovery and peripheral nerve allograft morphological and immunological responses in the absence of polyethylene glycol-induced axonal ***-type sciatic nerve injuries in outbred Sprague–Dawley rats were repaired according to a modified protocol using the same solutions as polyethylene glycol-fused peripheral nerve allografts,but peripheral nerve allografts were loose-sutured(loose-sutured polyethylene glycol)with an intentional gap of 1–2 mm to prevent fusion by polyethylene glycol of peripheral nerve allograft axons with host *** to negative control peripheral nerve allografts not treated by polyethylene glycol and in contrast to polyethylene glycol-fused peripheral nerve allografts,animals with loose-sutured polyethylene glycol peripheral nerve allografts exhibited Wallerian degeneration for all axons and myelin degeneration by 7 days postoperatively and did not recover sciatic-mediated behavioral functions by 42 days *** morphological signs of rejection,such as col

关键词： allograft rejection axotomy macrophage myelin nerve repair polyethylene glycol(PEG) sciatic nerve T cell transplantation Wallerian degeneration

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Modulation of the Nogo signaling pathway to overcome amyloid-β-mediated neurite inhibition in human pluripotent stem cell-derived neurites

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Neural Regeneration Research 2025年第9期20卷 2645-2654页

作者： Kirsty Goncalves Stefan Przyborski department of biosciences Durham UniversityDurhamUK Reprocell Europe Ltd. GlasgowUK

Neuronal cell death and the loss of connectivity are two of the primary pathological mechanisms underlying Alzheimer's *** accumulation of amyloid-βpeptides,a key hallmark of Alzheimer's disease,is believed to induce neuritic abnormalities,including reduced growth,extension,and abnormal growth cone morphology,all of which contribute to decreased ***,the precise cellular and molecular mechanisms governing this response remain *** this study,we used an innovative approach to demonstrate the effect of amyloid-βon neurite dynamics in both two-dimensional and three-dimensional cultu re systems,in order to provide more physiologically relevant culture *** utilized various methodologies,including the addition of exogenous amyloid-βpeptides to the culture medium,growth substrate coating,and the utilization of human-induced pluripotent stem cell technology,to investigate the effect of endogenous amyloid-βsecretion on neurite outgrowth,thus paving the way for potential future applications in personalized ***,we also explore the involvement of the Nogo signaling cascade in amyloid-β-induced neurite *** demonstrate that inhibition of downstream ROCK and RhoA components of the Nogo signaling pathway,achieved through modulation with Y-27632(a ROCK inhibitor)and Ibuprofen(a Rho A inhibitor),respectively,can restore and even enhance neuronal connectivity in the presence of amyloid-β.In summary,this study not only presents a novel culture approach that offers insights into the biological process of neurite growth and inhibition,but also proposes a specific mechanism for reduced neural connectivity in the presence of amyloid-βpeptides,along with potential intervention points to restore neurite ***,we aim to establish a culture system that has the potential to serve as an assay for measuring preclinical,predictive outcomes of drugs and their ability to promote neurite outgrowth,both generally and in a patie

关键词： Alzheimer's disease induced pluripotent stem cell neurite outgrowth neuron Nogo Rho A ROCK stem cell three-dimensional culture

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Tilting homeostatic and dyshomeostatic microglial balance in health and disease:transforming growth factor-beta1 as a critical protagonist

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Neural Regeneration Research 2025年第10期20卷 2895-2897页

作者： Nicolas Hugues Yu Luo department of molecular and Cellular biosciences University of CincinnatiCincinnatiOHUSA Neuroscience Graduate Program University of CincinnatiCincinnatiOHUSA Division of Immunobiology Cincinnati Children’s Hospital Medical CenterUniversity of Cincinnati College of MedicineCincinnatiOHUSA

Adult microglia,by continuously sensing changes in their environment and communicating with nearly all brain cell types,are considered to be the immune sentinels of the *** the healthy central nervous system(CNS),microglia display a unique molecular homeostatic signature(i.e.,Tmem119,P2ry12,Sall1,Siglech,Gpr34,and Hexb)(Figure 1A).

关键词： Figure signature critical

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A-kinase anchoring protein-mediated compartmentalization of pro-survival signaling in the retina

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Neural Regeneration Research 2025年第2期20卷 479-480页

作者： Joanna Mackiewicz Tomasz Boczek department of molecular Neurochemistry Medical University of LodzLodzPoland

The retina plays a fundamental role in the process of vision,serving as the primary interface between external visual stimuli and the central nervous *** the retina is exposed to a variety of environmental stresses and deleterious insults,it is susceptible to a spectrum of pathological conditions that can detrimentally affect *** often leads to irreversible vision loss due to the injury of specific cell *** instance,inherited retinal degeneration and age-related macular degeneration can lead to the death of photoreceptors,while conditions like glaucoma and optic nerve injury can result in the loss of ganglion *** precise pathological mechanisms driving retinal degeneration remain largely elusive,although research utilizing mouse models suggests that disruptions in intracellular signal transduction pathways may play a pivotal *** pathways within the retina orchestrate various aspects of retinal physiology,including phototransduction,synaptic transmission,and neuronal survival.

关键词： degeneration utilizing irreversible

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Phosphodiesterase 9 localization in cytoplasm and nucleus:the gateway to selective targeting in neuroprotection?

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Neural Regeneration Research 2025年第6期20卷 1701-1702页

作者： Giovanni Ribaudo Matteo Giannangeli Margrate Anyanwu Alessandra Gianoncelli department of molecular and Translational Medicine University of BresciaBresciaItaly

The umbrella term"neurodege ne rative disorders"(NDDs) refers to several conditions characterized by a progressive loss of structure and function of cells belonging to the nervous *** diseases affect more than 50million people *** disorders are characterized by sundry factors and pathophysiological mechanisms that a re challenging to be fully *** of these rely on cell signaling pathways to preserve homeostasis,involving second messengers such as cyclic adenosine monophosphate (cAMP)and cyclic guanosine 3',5'-monophosphate(cGMP).Their ability to control the duration and amplitude of the signaling cascade is given by the presence of several common and uncommon *** kinases A and G (PKA and PKG),phosphodiesterases (PDEs),and scaffold proteins are among them.

关键词： gateway homeostasis preserve

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Targeting cholesterol trafficking to mitigate axonal degeneration in hereditary spastic paraplegia

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Neural Regeneration Research 2025年第5期20卷 1397-1398页

作者： Zhenyu Chen Xue-Jun Li department of Biomedical Sciences University of Illinois College of Medicine RockfordRockfordILUSA department of bioengineering University of Illinois at ChicagoChicagoILUSA

Axonal degeneration underlies many debilitating diseases including hereditary spastic paraplegia(HSP),a genetically and clinically diverse group of disorders characterized by spasticity and weakness of the lower *** is one significant cause of chronic neurodisability due to the lack of effective treatments and a wide range of onset ages from early childhood to 70 years.

关键词： degeneration diseases hereditary

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A novel method for clustering cellular data to improve classification

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Neural Regeneration Research 2025年第9期20卷 2697-2705页

作者： Diek W.Wheeler Giorgio A.Ascoli Center for Neural Informatics Structures&PlasticityKrasnow Institute for Advanced Study bioengineering department Volgenau School of Engineering George Mason University FairfaxVAUSA

Many fields,such as neuroscience,are experiencing the vast prolife ration of cellular data,underscoring the need fo r organizing and interpreting large datasets.A popular approach partitions data into manageable subsets via hierarchical clustering,but objective methods to determine the appropriate classification granularity are *** recently introduced a technique to systematically identify when to stop subdividing clusters based on the fundamental principle that cells must differ more between than within *** we present the corresponding protocol to classify cellular datasets by combining datadriven unsupervised hierarchical clustering with statistical *** general-purpose functions are applicable to any cellular dataset that can be organized as two-dimensional matrices of numerical values,including molecula r,physiological,and anatomical *** demonstrate the protocol using cellular data from the Janelia MouseLight project to chara cterize morphological aspects of neurons.

关键词： cellular data clustering dendrogram data classification Levene's one-tailed statistical test unsupervised hierarchical clustering

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Adjusting Temperature and Salinity Effects on Single Capacitance Sensors

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Pedosphere 2009年第5期19卷 588-596页

作者： A.FARES M.SAFEEQ D.M.JENKINS department of Natural Resources and Environmental Management University of Hawaii at Manoa department of molecular biosciences and bioengineering University of Hawaii at Manoa

Several newly developed capacitance sensors have simplified real-time determination of soil water *** work has shown that salinity and temperature can affect these sensors,but relatively little has been done to correct these *** objectives of this study were to evaluate the effect of media temperature and salinity on the apparent water content measured with a single capacitance sensor(SCS),and to mitigate this effect using a temperature dependent scaled voltage technique under laboratory conditions.A column study was conducted containing two media:pure deionized water and quartz sand under varying water contents(0.05 to 0.30 cm3 cm-3) and salinity(0 to 80 mmol L-1).Media temperature was varied between 5 and 45℃ using an *** SCS probes and thermocouples were placed in the middle of the columns and were logged at an interval of 1 *** was strong negative correlation between sensor reading and temperature of deionized water with a rate of-0.779 mV ℃-*** of SCS apparent output were 0.454 and 0.535 mV ℃-1 for air in heating and cooling cycles,respectively.A similar positive correlation with temperature was observed in sand at different water *** SCS probe was less sensitive to temperature as salinity and water content *** a temperature-corrected voltage calibration model,the effect of temperature was reduced by 98%.An analytical model for salinity correction was able to minimize the error as low as ± 2% over the salinity level tested.

关键词： calibration ECH2O probes quartz sand water content

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Genistein:a possible solution for the treatment of Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2903-2905页

作者： Karolina Pierzynowska Bartosz Karaszewski Grzegorz Węgrzyn department of molecular Biology University of GdanskGdanskPoland Gdansk Polandand Department of Adult NeurologyFaculty of MedicineMedical University of GdanskGdanskPoland

Neurodegenerative diseases are defined as disorders resulting from the slow and progressive loss of function and eventual death of neural cells that result from the primary pathology of nervous *** can lead to severe nervous system dysfunction,eventually affecting multiple organs and *** hundred neurodegenerative diseases have been described,and owing to their prevalence,severity.

关键词： organs Alzheimer death

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