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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

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Multiple sclerosis is at a checkpoint: advancing the program

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neural Regeneration Research 2025年第3期20卷 811-812页

作者： brandon c.Smith jessica l.Williams department of neurosciences Lerner Research InstituteCleveland ClinicClevelandOHUSA department of biological Geologicaland Environmental SciencesCleveland State UniversityClevelandOHUSA

Multiple sclerosis(MS) is a chronic inflammatory and demyelinating disease of the central nervous system(cnS). Patients with MS experience sensory and motor function loss due to myelin and/or axon damage perpetuated b... 详细信息

关键词： Hauser sclerosis damage

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Generation of brain vascular heterogeneity:recent advances from the perspective of angiogenesis

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neural Regeneration Research 2025年第7期20卷 2013-2014页

作者： nathanael j.lee Ryota l.Matsuoka department of neurosciences Lerner Research InstituteCleveland ClinicClevelandOHUSA department of Molecular Medicine Cleveland Clinic Lerner College of MedicineCase Western Reserve UniversityClevelandOHUSA

Heterogeneous proper t i es of vascular endothelial cells in the brain:The brain displays large energy dynamics and consumption,and this high level of metabolic demands is fulfilled by a continuous supply of glucose and oxygen through its vascular *** vasculature consists of highly divergent blood vessel branches,giving rise to a dense network of capillaries that supply blood to all cells across the *** elaborated vascular network is thought to develop via angiogenesis,a process in which new blood vessels grow from pre-existing *** capillaries exhibit organotypic features distinct from other tissues and are formed primarily by two major endothelial cell(Ec)types:those that form the semi-permeable blood-brain barrier(bbb)and those that develop highly permeable pores known as fenestrae(Matsuoka et al.,2022).The structural and functional differences between bbb and fenestrated vascular Ecs represent a fundamental feature of brain vasculature and form the foundation for both brain function and homeostasis.

关键词： angiogenesis homeostasis network

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Anti-amyloid antibodies in Alzheimer’s disease: what did clinical trials teach us?

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neural Regeneration Research 2025年第4期20卷 1092-1093页

作者： danko jeremic lydia jiménez-díaz juan d.navarro-lópez neuroPhysiology&behavior lab University of Castilla-La ManchaBiomedical Research Center(CRIB)School of Medicine of Ciudad RealCiudad RealSpain

Although many causes of Alzheimer’s disease(Ad)may exist,both the original amyloid cascade and tau hypotheses posit that abnormal misfolding and accumulation of amyloid-β(Aβ)and tau protein is the central event causing the ***,that conclusion could be only partly true,and there is conflicting evidence about the role of both proteins in Ad,being able to precede and influence one *** researchers argue that these proteins are mere executors rather than primary causes of ***,there have been continuing refinements of both hypotheses,with alternative explanations proposed.Aβand tau proteins may be independently involved in specific neurotoxic pathways;yet there may be other crucial processes going on in early ***,accumulating evidence suggests that Aβand tau act synergistically,rather than additively in disease onset(jeremic et al.,2021,2023a).

关键词： amyloid Alzheimer additive

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nucleoside modified mRnA-lipid nanoparticles as a new delivery platform for the repair of the injured spinal cord

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neural Regeneration Research 2025年第8期20卷 2311-2312页

作者： Krisztián Pajer Tamás bellák Antal nógrádi department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary

Spinal cord injury and treatment opportunities:The adult mammalian spinal cord has a very limited capacity for spontaneous regeneration due to various intrinsic molecular and cellular *** the spinal cord neurons have the capacity to regenerate their axons,the expression of growth inhibitory factors,lack or suppression of proper guidance cues,and profound inflammatory responses do not permit successful regeneration(Khyeam et al.,2021).

关键词： injured capacity modified

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Force and impulse multi-sensor based on flexible gate dielectric field effect transistor

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International journal of Minerals,Metallurgy and Materials 2025年第1期32卷 214-220页

作者： chao Tan junling lü chunchi Zhang dong liang lei yang Zegao Wang college of Materials Science and Engineering Sichuan UniversityChengdu 610065China The 54th Research Institute of china Electronics Technology Group corporation Shijiazhuang 050081China

nowadays,force sensors play an important role in industrial production,electronic information,medical health,and many other ***-dimensional material-based filed effect transistor(2d-FET)sensors are competitive with nano-level size,lower power consumption,and accurate ***,few of them has the capability of impulse detection which is a path function,expressing the cumulative effect of the force on the particle over a period of *** we fabricated the flexible polymethyl methacrylate(PMMA)gate dielectric MoS_(2)-FET for force and impulse sensor *** systematically investigated the responses of the sensor to constant force and varying forces,and achieved the conversion factors of the drain current signals(I_(ds))to the detected impulse(I).The applied force was detected and recorded by I_(ds)with a low power consumption of~30 *** sensitivity of the device can reach~8000%and the 4×1 sensor array is able to detect and locate the normal force applied on ***,there was almost no performance loss for the device as left in the air for two months.

关键词： flexible gate dielectric transistor force sensor impulse sensor force sensor array

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Viscosity and structure relationship with equimolar substitution of caO with MgO in the caO–MgO–Al_(2)O_(3)–SiO_(2)slag melts

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International journal of Minerals,Metallurgy and Materials 2025年第1期32卷 70-79页

作者： yong Hou Shuo Zhang jie dang jia Guo Hanghang Zhou xuewei lü college of Materials Science and Engineering Chongqing UniversityChongqing 400044China chongqing Key laboratory of Vanadium-Titanium Metallurgy and new Materials Chongqing UniversityChongqing 400044China

currently,the Al_(2)O_(3)content in the high-alumina slag systems within blast furnaces is generally limited to 16wt%–18.5wt%,making it challenging to overcome this *** most studies that concentrated on managing the MgO/Al_(2)O_(3)ratio or basicity,this paper explored the effect of equimolar substitution of MgO for caO on the viscosity and structure of a high-alumina caO-MgO-Al_(2)O_(3)-SiO_(2)slag system,providing theoretical guidance and data to facilitate the application of high-alumina *** results revealed that the viscosity first decreased and then increased with higher MgO substitution,reaching a minimum at 15mol%MgO *** transform infrared spectroscopy(FTIR)results found that the depths of the troughs representing[SiO_(4)]tetrahedra,[AlO_(4)]tetrahedra,and Si-O-Al bending became progressively deeper with increased MgO *** of the Raman spectra showed that the average number of bridging oxygens per Si atom and the x_(Q^(3))/x_(Q^(2))(x_(Q^(i))is the molar fraction of Q^(i) unit,and i is the number of bridging oxygens in a[SiO_(4)]tetrahedral unit)ratio increased from 2.30 and 1.02 to 2.52 and 2.14,respectively,indicating a progressive polymerization of the silicate structure.x-ray photoelectron spectroscopy(xPS)results highlighted that non-bridging oxygen content decreased from 77.97mol% to 63.41mol% with increasing MgO concentration,whereas bridging oxygen and free oxygen contents *** analysis demonstrated a gradual increase in the polymerization degree of the tetrahedral structure with the increase in MgO ***,bond strength is another important factor affecting the slag *** occurrence of a viscosity minimum can be attributed to the complex evolution of bond strengths of non-bridging oxygens generated during depolymerization of the[SiO_(4)]and[AlO_(4)]tetrahedral structures by caO and MgO.

关键词： aluminosilicate viscosity structure spectroscopy

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Impacts of PI3K/protein kinase b pathway activation in reactive astrocytes: from detrimental effects to protective functions

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neural Regeneration Research 2025年第4期20卷 1031-1041页

作者： Ramón Pérez-núñez María Fernanda González Ana María Avalos lisette leyton cellular communication laboratory Programa de Biología Celular y MolecularCenter for Studies on ExerciseMetabolism and Cancer(CEMC)Instituto de Ciencias Biomédicas(ICBM)Facultad de MedicinaUniversidad de ChileSantiagoChile Advanced center for chronic diseases(AccdiS) Faculty of Chemical and Pharmaceutical Sciences&Faculty of MedicineUniversidad de ChileSantiagoChile Instituto de ciencias biomédicas Facultad de Ciencias de la SaludUniversidad Autónoma de ChileSantiagoChile

Astrocytes are the most abundant type of glial cell in the central nervous *** injury and inflammation,astrocytes become reactive and undergo morphological and functional *** on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,***,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and *** analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their *** actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune *** phosphoinositide 3-kinase(PI3K)/protein kinase b(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo *** astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κb serves as a central mediator of the pro-inflammatory ***,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their *** highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and notch/PI3K/AKT *** targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial *** dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function *** review emphasizes the importance of employing astrocyte-exclusive models to underst

关键词： inflammation integrins neuroprotective neurotoxic phosphatidylinositol 3-kinase reactive astrocytes signal transduction Thy-1(cd90)

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Sex differences in aging and injured brain

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neural Regeneration Research 2025年第10期20卷 2901-2902页

作者： jordan n.Williamson yuan yang university of Illinois urbana-champaign Grainger College of EngineeringDepartment of BioengineeringUrbanaILUSA carle Foundation Hospital Stephenson Family Clinical Research InstituteClinical Imaging Research CenterUrbanaILUSA university of Illinois urbana-champaign Beckman Institute for Advanced Science and TechnologyUrbanaILUSA northwestern university Department of Physical Therapy and Human Movement SciencesChicagoILUSA

background:The prevalence,age of onset,and symptomatology of traumatic brain injury,stroke,and neurodegenerative diseases(such as Alzheimer’s disease(Ad),Parkinson’s disease,amyotrophic lateral sclerosis,and Huntington’s disease)differ substantially between males and *** higher prevalence of these brain disorders has been attributed to females having a greater longevity compared with *** one of the greatest risk factors of acquired brain injury(such as stroke,traumatic brain injury caused by fall)and neurodegenerative disease is age.

关键词： Huntington prevalence traumatic

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Astrocytes, reactive astrogliosis, and glial scar formation in traumatic brain injury

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neural Regeneration Research 2025年第4期20卷 973-989页

作者： María belén cieri Alberto javier Ramos laboratorio de neuropatología Molecular IBCN UBA-CONICETFacultad de MedicinaUniversidad de Buenos AiresBuenos AiresArgentina

Traumatic brain injury is a global health crisis,causing significant death and disability *** that follows traumatic brain injury has serious consequences for neuronal survival and cognitive impairments,with astrocytes involved in this *** traumatic brain injury,astrocytes rapidly become reactive,and astrogliosis propagates from the injury core to distant brain *** astroglial proteins are downregulated near the traumatic brain injury core,while pro-inflammatory astroglial genes are *** altered gene expression is considered a pathological remodeling of astrocytes that produces serious consequences for neuronal survival and cognitive *** addition,glial scar formed by reactive astrocytes is initially necessary to limit immune cell infiltration,but in the long term impedes axonal reconnection and functional *** therapeutic strategies for traumatic brain injury are focused on preventing acute ***,cannabinoids,progesterone,beta-blockers,and cerebrolysin demonstrate neuroprotective benefits but most of them have not been studied in the context of *** this review,we discuss the cell signaling pathways activated in reactive astrocytes following traumatic brain injury and we discuss some of the potential new strategies aimed to modulate astroglial responses in traumatic brain injury,especially using cell-targeted strategies with miRnAs or lncRnA,viral vectors,and repurposed drugs.

关键词： astrocyte glial scar innate immunity neuroinflammation stab injury Toll-like receptors

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