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Vagus nerve stimulation in intracerebral hemorrhage:the need for further research

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Neural Regeneration Research 2025年第11期20卷 3213-3214页

作者： Sheharyar S.Baig Ali N.Ali Arshad Majid Sheffield Institute for Translational neuroscience Division of NeuroscienceThe University of SheffieldSheffieldUK

Vagus nerve stimulation(VNS)and stroke:Stroke is the second leading cause of death and the third leading cause of disability worldwide(Baig et al.,2023).There have been significant paradigm shifts in the management of acute ischemic stroke through mechanical *** chronic ischemic stroke,invasive VNS paired with rehabilitation is associated with a significant increase in upper limb motor recovery and is FDA-approved(Baig et al.,2023).There are no treatments of similar efficacy in acute intracerebral hemorrhage(ICH)where several promising trials,e.g.,TICH-2,STOP-AUST,and TRAIGE did not show improvements in functional outcomes(Puy et al.,2023).

关键词： stimulation acute

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

The complex role of protocadherin-19 in brain function:a focus on the oxytocin system

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Neural Regeneration Research 2025年第11期20卷 3211-3212页

作者： Sara Mazzoleni Marta Busnelli Silvia Bassani CNR Institute of neuroscience Vedano al LambroItaly NeuroMi Milan Center for neuroscience MilanItaly

Mutations in the protocadherin-19(PCDH19)gene(Xq22.1)cause the X-linked syndrome known as developmental and epileptic encephalopathy 9(DEE9,OMIM#300088)(Dibbens et al.,2008).DEE9 is characterized by early-onset clustering epilepsy associated with intellectual disability ranging from mild to profound,autism spectrum disorder,and other neuropsychiatric features including schizophrenia,anxiety,attentiondeficit/hyperactivity,and obsessive or aggressive *** seizures may become less frequent in adolescence,psychiatric comorbidities persist and often worsen with age(Dibbens et al.,2008;Kolc et al.,2020).

关键词： epilepsy function system

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

Human induced pluripotent stem cell-derived therapies for regeneration after central nervous system injury

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Neural Regeneration Research 2025年第11期20卷 3063-3075页

作者： Stephen Vidman Yee Hang Ethan Ma Nolan Fullenkamp Giles W.Plant Department of neuroscience Ohio State UniversityColumbusOHUSA

In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative *** the non-regenerative nature of the mature central nervous system,the concept that“blank”cells could be reprogrammed and functionally integrated into host neural networks remained *** work has also demonstrated the ability of such cells to stimulate intrinsic growth programs in post-mitotic cells,such as *** embryonic stem cells demonstrated great potential in treating central nervous system pathologies,ethical and technical concerns *** barriers,along with the clear necessity for this type of treatment,ultimately prompted the advent of induced pluripotent stem *** advantage of pluripotent cells in central nervous system regeneration is multifaceted,permitting differentiation into neural stem cells,neural progenitor cells,glia,and various neuronal *** precise spatiotemporal application of extrinsic growth factors in vitro,in addition to microenvironmental signaling in vivo,influences the efficiency of this directed *** the pluri-or multipotency of these cells is appealing,it also poses the risk of unregulated differentiation and teratoma *** of the neuroectodermal lineage,such as neuronal subpopulations and glia,have been explored with varying degrees of *** the risk of cancer or teratoma formation is greatly reduced,each subpopulation varies in effectiveness and is influenced by a myriad of factors,such as the timing of the transplant,pathology type,and the ratio of accompanying progenitor ***,successful transplantation requires innovative approaches to develop delivery vectors that can mitigate cell death and support ***,host immune responses to allogeneic grafts must be thoroughly characterized and further developed to reduce the need for *** to a clinical setting wi

关键词： axon regeneration central nervous system regeneration induced pluripotent stem cells neurotrauma regenerative medicine spinal cord injury stem cell therapy

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

Optimizing non-invasive vagus nerve stimulation for treatment in stroke

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Neural Regeneration Research 2025年第12期20卷 3388-3399页

作者： Sheharyar S.Baig Samantha Dorney Mudasar Aziz Simon M.Bell Ali N.Ali Li Su Jessica N.Redgrave Arshad Majid Sheffield Institute for Translational neuroscience Department of NeuroscienceUniversity of SheffieldSheffieldUK Doncaster and Bassetlaw Teaching Hospitals NHS Foundation Trust DoncasterUK

Stroke remains a leading cause of long-term disability *** is an unmet need for neuromodulatory therapies that can mitigate against neurovascular injury and potentially promote neurological *** vagus nerve stimulation has been demonstrated to show potential therapeutic effects in both acute and chronic ***,previously published research has only investigated a narrow range of stimulation settings and *** this review,we detail the ongoing studies of transcutaneous vagus nerve stimulation in stroke through systematic searches of registered clinical *** summarize the upcoming clinical trials of transcutaneous vagus nerve stimulation in stroke,highlighting their indications,parameter settings,scope,and *** further explore the challenges and barriers associated with the implementation of transcutaneous vagus nerve stimulation in acute stroke and stroke rehabilitation,focusing on critical aspects such as stimulation settings,target groups,biomarkers,and integration with rehabilitation interventions.

关键词： neuromodulation neuroplasticity rehabilitation stroke vagal nerve stimulation vagus nerve stimulation

Insights from an academic endeavor into central nervous system drug discovery

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Neural Regeneration Research 2025年第6期20卷 1717-1718页

作者： Lieve van Veggel An M.Voets Tim Vanmierlo Rudy Schreiber BIOMED Biomedical Research Institute Faculty of Medicine and Life SciencesHasselt UniversityHasseltBelgium Department of Psychiatry and Neuropsychology Division of Translational NeuroscienceEuropean Graduate School of NeuroscienceSchool for Mental Health and NeuroscienceMaastricht UniversityMaastrichtThe Netherlands Section of Psychopharmacology Neuropsychology and PsychopharmacologyFaculty of Psychology and NeuroscienceMaastricht UniversityMaastrichtThe Netherlands University MS Center(UMSC) Hasselt-PeltBelgium

Historically,"big pharma"did most central nervous system drug discovery R&D ***,in modern times their"management reductionism"resulted in disappointing pipelines and pharma resided to(late)development,regulatory approval,and marketing(Thong,2015).This had significant consequences for financing and executing research,resulting in a larger role for funding by governments and patient-organizations and a shift of research to academia(Mazzucato,2013).

关键词： academic approval consequences

A systematic review of progenitor survival and maturation in Parkinsonian models

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Neural Regeneration Research 2025年第11期20卷 3172-3178页

作者： Giulia Comini Eilís Dowd Pharmacology&Therapeutics and Galway neuroscience Center University of GalwayGalwayIreland

Stem cell-based brain repair is a promising emergent therapy for Parkinson's disease based on years of foundational research using human fetal donors as a cell *** current therapeutic options for patients,this approach has the potential to provide longterm stem cell–derived reconstruction and restoration of the dopaminergic input to denervated regions of the brain allowing for restoration of certain functions to *** ultimate clinical success of stem cell–derived brain repair will depend on both the safety and efficacy of the approach and the latter is dependent on the ability of the transplanted cells to survive and differentiate into functional dopaminergic neurons in the Parkinsonian *** the pre-clinical literature suggests that there is considerable variability in survival and differentiation between studies,the aim of this systematic review was to assess these parameters in human stem cell-derived dopaminergic progenitor transplant studies in animal models of Parkinson's disease.A defined systematic search of the PubMed database was completed to identify relevant studies published up to March *** screening,76 articles were included in the analysis from which 178 separate transplant studies were *** these,graft survival could be assessed in 52 studies and differentiation in 129 ***,we found that graft survival ranged from<1% to 500% of cells transplanted,with a median of 51%of transplanted cells surviving in the brain;while dopaminergic differentiation of the cells ranged from 0% to 46% of cells transplanted with a median of 3%.This systematic review suggests that there is considerable scope for improvement in the differentiation of stem cell-derived dopaminergic progenitors to maximize the therapeutic potential of this approach for patients.

关键词： cell replacement therapy differentiation embryonic stem cells graft induced pluripotent stem cells Parkinson's disease survival transplant