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Silk-based nerve guidance conduits with macroscopic holes modulate the vascularization of regenerating rat sciatic nerve

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neural Regeneration Research 2025年第6期20卷 1789-1800页

作者： Carina hromada Patrick heimel markus Kerbl LászlóGál Sylvia nürnberger Barbara Schaedl James Ferguson nicole Swiadek Xavier monforte Johannes C.heinzel Antal nógrádi Andreas h.Teuschl-Woller David hercher Department Life Science Engineering University of Applied Sciences Technikum WienViennaAustria Austrian Cluster for Tissue Regeneration ViennaAustria Ludwig Boltzmann Institute for Traumatology The Research Center in Cooperation with AUVAViennaAustria University Clinic of Dentistry Medical University of ViennaViennaAustria Department of Plastic Reconstructive and Aesthetic SurgeryLandesklinikum Wiener Neustadt2700 Wiener NeustadtAustria Department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary medical University of Vienna Department of Orthopedics and Trauma SurgeryDevision of Trauma SurgeryViennaAustria Department of hand- PlasticReconstructive and Burn SurgeryBG Unfallklinik TuebingenUniversity of TuebingenTuebingenGermany

Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tnGCs). however, the use of tnGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tnGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tnGCs and compared the various features of these improved silk^(+) tnGCs with the tubes without holes(silk^(–) tnGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tnGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tnGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tnGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tnGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimizatio

关键词： axon regeneration blood vessel functional recovery macroporous nerve lesion peripheral nerve repair sciatic nerve silk-based nerve guidance conduit vascularization

The sexually dimorphic expression of glutamate transporters and their implication in pain after spinal cord injury

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neural Regeneration Research 2025年第11期20卷 3317-3329页

作者： Jennifer m.Colón-mercado Aranza I.Torrado-Tapias Iris K.Salgado Jose m.Santiago Samuel E.Ocasio Rivera Dina P.Bracho-Rincon Luis h.Pagan Rivera Jorge D.miranda Department of Physiology University of Puerto RicoMedical Sciences CampusSan JuanPRUSA national Institutes of health National Human Genome Research InstituteBethesdaMDUSA Universidad Central del Caribe School of MedicineBayamónPRUSA University of Puerto Rico Carolina CampusCarolinaPRUSA Institute of neurobiology San JuanPRUSA

In addition to the loss of motor function,~60% of patients develop pain after spinal cord *** cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epicenter,and caudal penumbra of the injury site initiates a cellularmolecular interplay that acts as a rewiring mechanism leading to central neuropathic *** can lead to the formation of new connections triggering abnormal sensory *** excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and *** previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator *** this study,we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord *** hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters,leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant *** and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control(placebo).We used von Frey monofilaments and the“up-down method”to evaluate mechanical *** treatment decreased allodynia only in female rats with spinal cord injury revealing a sexdependent *** expression profile of glutamatergic transporters(excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1)revealed a sexual dimorphism in the rostral,epicenter,and caudal areas of the spinal cord with a pattern of expression primarily on *** rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased

关键词： allodynia central neuropathic pain EAAT-1/GLAST EAAT-2/GLT-1 glutamate transporters selective estrogen receptor modulator sexual dimorphism spinal cord injury trauma

Regulator of G protein signaling 6 mediates exercise-induced recovery of hippocampal neurogenesis,learning,and memory in a mouse model of Alzheimer’s disease

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neural Regeneration Research 2025年第10期20卷 2969-2981页

作者： mackenzie m.Spicer Jianqi Yang Daniel Fu Alison n.DeVore marisol Lauffer nilufer S.Atasoy Deniz Atasoy Rory A.Fisher Department of neuroscience and Pharmacology University of Iowa Carver College of MedicineIowa CityIAUSA Iowa neuroscience Institute University of Iowa Carver College of MedicineIowa CityIAUSA Interdisciplinary Graduate Program in molecular medicine University of Iowa Carver College of MedicineIowa CityIAUSA neural Circuits and Behavior Core University of Iowa Carver College of MedicineIowa CityIAUSA

hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s *** hippocampal neurogenesis is reduced in patients with Alzheimer’s *** stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s ***,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly ***,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in ***,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse *** found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control *** cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal *** hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor ***6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing ***,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.

关键词： adult hippocampal neurogenesis Alzheimer’s disease dentate gyrus exercise learning/memory neural precursor cells regulator of G protein signaling 6(RGS6)

Amyloid-beta pathology-induced nanoscale synaptic disruption:the case of the GABA_B-GIRK assembly

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neural Regeneration Research 2025年第5期20卷 1409-1410页

作者： Rafael Lujan Alejandro martín-Belmonte Sergi Ferré Francisco Ciruela Synaptic Structure Laboratory Instituto de Biomedicina de la UCLM(IB-UCLM)Departamento de Ciencias MédicasInstituto de Investigación en Salud de Castilla-La Mancha(IDISCAM)Facultad de MedicinaUniversidad Castilla-La ManchaCampus BiosanitarioC/AlmansaAlbaceteSpain Integrative neurobiology Section National Institute on Drug AbuseIntramural Research ProgramNational Institutes of HealthBaltimoreMDUSA Pharmacology Unit Department of Pathology and Experimental TherapeuticsSchool of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaNeuropharmacology&Pain GroupNeuroscience ProgramBellvitge Institute for Biomedical ResearchL’Hospitalet de LlobregatSpain

Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic *** has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.

关键词： Alzheimer pathology

Leveraging ROTI map derived from Indonesian GnSS receiver network for advancing study of Equatorial Plasma Bubble in Southeast/East Asia

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Earth and Planetary Physics 2025年第1期9卷 101-116页

作者： Prayitno Abadi Ihsan n.muafiry Teguh n.Pratama Angga Y.Putra Suraina Gatot h.Pramono Sidik T.Wibowo Febrylian F.Chabibi Umar A.Ahmad Wildan P.Tresna Asnawi Research Center for Climate and Atmosphere Indonesian National Research and Innovation Agency(BRIN)BandungIndonesia School of Electrical Engineering Telkom UniversityBandungIndonesia Directorate of Laboratory management Facilities and Science and Technology Park Indonesian National Research and Innovation Agency(BRIN)PontianakIndonesia Geophysics Laboratory Master Program in PhysicsUniversitas Gadjah Mada(UGM)YogyakartaIndonesia Research Center for Space Indonesian National Research and Innovation Agency(BRIN)BandungIndonesia Indonesian Geospatial Information Agency(BIG) JakartaIndonesia Research Center for Photonics Indonesian National Research and Innovation Agency(BRIN)Tangerang SelatanIndonesia Department of Earth and Planetary Sciences Hokkaido UniversitySapporoJapan

This paper highlights the crucial role of Indonesia’s GnSS receiver network in advancing Equatorial Plasma Bubble(EPB)studies in Southeast and East Asia,as ionospheric irregularities within EPB can disrupt GnSS signals and degrade positioning *** by the Indonesian Geospatial Information Agency(BIG),the Indonesia Continuously Operating Reference Station(Ina-CORS)network comprises over 300 GnSS receivers spanning equatorial to southern low-latitude ***-CORS is uniquely situated to monitor EPB generation,zonal drift,and dissipation across Southeast *** provide a practical tool for EPB research,by sharing two-dimensional rate of Total Electron Content(TEC)change index(ROTI)derived from this *** generate ROTI maps with a 10-minute resolution,and samples from may 2024 are publicly available for further scientific *** preliminary findings from the ROTI maps of Ina-CORS are ***,the Ina-CORS ROTI maps reveal that the irregularities within a broader EPB structure persist longer,increasing the potential for these irregularities to migrate farther ***,we demonstrate that combined ROTI maps from Ina-CORS and GnSS receivers in East Asia and Australia can be used to monitor the development of ionospheric irregularities in Southeast and East *** have demonstrated the combined ROTI maps to capture the development of ionospheric irregularities in the Southeast/East Asian sector during the G5 Geomagnetic Storm on may 11,*** observed simultaneous ionospheric irregularities in Japan and Australia,respectively propagating northwestward and southwestward,before midnight,whereas Southeast Asia’s equatorial and low-latitude regions exhibited irregularities *** sharing ROTI maps from Indonesia and integrating them with regional GnSS networks,researchers can conduct comprehensive EPB studies,enhancing the understanding of EPB behavior across Southeast and East Asia and contributing significantly to ionosphe

关键词： Equatorial Plasma Bubble(EPB) GnSS receivers’network Indonesia Continuously Operating Reference Station(Ina-CORS) ionospheric map Rate of TEC change index(ROTI)map

Brain-derived neurotrophic factor signaling in the neuromuscular junction during developmental axonal competition and synapse elimination

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neural Regeneration Research 2025年第2期20卷 394-401页

作者： Josep Tomàs Víctor Cilleros-mañé Laia Just-Borràs marta Balanyà-Segura Aleksandra Polishchuk Laura nadal marta Tomàs Carolina Silvera-Simón manel m.Santafé maria A.Lanuza Unitat d’histologia i neurobiologia(Uhneurob) Facultat de Medicina i Ciències de la SalutUniversitat Rovira i VirgiliReusSpain

During the development of the nervous system,there is an overproduction of neurons and *** competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or *** have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse *** purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this *** particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(PKA and PKC)and voltage-gated calcium channels,at different nerve endings in developmental *** dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific *** describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75nTR pathways that can influence the timing and fate of the competitive interactions between the different axon *** downstream displacement of the PKA/PKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary ***,calcium entry through L-and P/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the n-type channel in developing nerve terminals)contributes to red

关键词： acetylcholine release adenosine receptors axonal competition brain-derived neurotrophic factor calcium channels motor end-plate muscarinic acetylcholine receptors postnatal synapse elimination serine kinases tropomyosin-related kinase receptorB

From single to combinatorial therapies in spinal cord injuries for structural and functional restoration

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neural Regeneration Research 2025年第3期20卷 660-670页

作者： Ernesto Doncel-Pérez Gabriel Guízar-Sahagún Israel Grijalva-Otero hospital nacional de Parapléjicos de Toledo Servicio de Salud de Castilla La Mancha(SESCAM)ToledoSpain medical Research Unit for neurological Diseases UMAE Hospital de EspecialidadesCentro Médico Nacional Siglo XXIIMSSCiudad de MéxicoMéxico

Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoratio

关键词： neural regeneration neuroprotection spinal cord injury repair spinal cord injury treatments structural restoration of spinal cord injury

mitochondria–cGAS–STInG axis is a potential therapeutic target for senescence-dependent inflammaging-associated neurodegeneration

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neural Regeneration Research 2025年第3期20卷 805-807页

作者： Josém.Izquierdo Centro de Biología molecular Severo Ochoa(CBm) Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid(CSIC-UAM)MadridSpain

The word “senescence” comes from the Latin senescens, meaning “to begin to age”, and is characterized by a long-lasting but reversible block in proliferation, resulting from stress-induced cell cycle arrest of pre... 详细信息

关键词： Latin potential lasting

Three-dimensional free vibration analysis of multi-directional functionally graded piezoelectric annular plates on elastic foundations via state space based differential quadrature method

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Applied mathematics and mechanics(English Edition) 2015年第4期36卷 439-464页

作者： m.h.YAS n.mOLOUDI Department of mechanical Engineering Razi University

The three-dimensional free vibration analysis of a multi-directional func- tionally graded piezoelectric （FGP） annular plate resting on two parameter （Pasternak） elastic foundations is investigated under different boundary conditions. The material properties are assumed to vary continuously along the radial and thickness directions and have exponent-law distribution. A semi-analytical approach named the state space based differential quadrature method （SSDQm） is used to provide an analytical solution along the thickness using the state space method （SSm） and an approximate solution along the radial direction using the one-dimensional differential quadrature method （DQm）. The influence of the Winkler and shear stiffness of the foundation~ the material property graded variations, and the circumferential wave number on the nomdimensional natural frequency of multi-directional FGP annular plates is studied.

关键词： multi-directional functionally graded piezoelectric annular plate freevibration