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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 Reg.neration Research 2025年第4期20卷 1031-1041页

作者： Ramón Pérez-Núñez maría Fernanda g.nzález 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 g.ial cell in the central nervous *** injury and inflammation,astrocytes become reactive and underg. morpholog.cal 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 g.ne expression profiles,which emphasizes the heterog.neous nature of their *** actively participate in reg.lating.central nervous system inflammation by interacting.with microg.ia and other cell types,releasing.cytokines,and influencing.the immune *** phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)sig.aling.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 trig.er a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory ***,we review the heterog.neity of reactive astrocytes and the molecular mechanisms underlying.their *** hig.lig.t the involvement of various sig.aling.pathways that reg.late astrocyte reactivity,including.the PI3K/AKT/mammalian targ.t of rapamycin(mTOR),αvβ3 integ.in/PI3K/AKT/connexin 43,and Notch/PI3K/AKT *** targ.ting.the inactivation of the PI3K/AKT cellular sig.aling.pathway to control reactive astrocytes and prevent central nervous system damag.,evidence sug.ests 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 integ.ins neuroprotective neurotoxic phosphatidylinositol 3-kinase reactive astrocytes sig.al transduction Thy-1(CD90)

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Astrocytes, reactive astrog.iosis, and g.ial scar formation in traumatic brain injury

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Neural Reg.neration Research 2025年第4期20卷 973-989页

作者： maría Belén Cieri Alberto Javier Ramos Laboratorio de Neuropatolog.a Molecular IBCN UBA-CONICETFacultad de MedicinaUniversidad de Buenos AiresBuenos AiresArgentina

Traumatic brain injury is a g.obal health crisis,causing.sig.ificant death and disability *** that follows traumatic brain injury has serious consequences for neuronal survival and cog.itive impairments,with astrocytes involved in this *** traumatic brain injury,astrocytes rapidly become reactive,and astrog.iosis propag.tes from the injury core to distant brain *** astrog.ial proteins are downreg.lated near the traumatic brain injury core,while pro-inflammatory astrog.ial g.nes are *** altered g.ne expression is considered a patholog.cal remodeling.of astrocytes that produces serious consequences for neuronal survival and cog.itive *** addition,g.ial scar formed by reactive astrocytes is initially necessary to limit immune cell infiltration,but in the long.term impedes axonal reconnection and functional *** therapeutic strateg.es for traumatic brain injury are focused on preventing.acute ***,cannabinoids,prog.sterone,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 sig.aling.pathways activated in reactive astrocytes following.traumatic brain injury and we discuss some of the potential new strateg.es aimed to modulate astrog.ial responses in traumatic brain injury,especially using.cell-targ.ted strateg.es with miRNAs or lncRNA,viral vectors,and repurposed drug..

关键词： astrocyte g.ial scar innate immunity neuroinflammation stab injury Toll-like receptors

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Differential response of injured and healthy retinas to syng.neic and allog.neic transplantation of a clonal cell line of immortalized olfactory ensheathing.g.ia:a double-edg.d sword

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Neural Reg.neration Research 2025年第8期20卷 2395-2407页

作者： maría Norte-Muñoz maría Portela-Lomba Paloma sobrado-Calvo Diana Simón Johnny Di Pierdomenico Alejandro g.lleg.-Orteg. mar Pérez JoséMCabrera-Maqueda Javier Sierra Manuel Vidal-Sanz maría Teresa Moreno-Flores marta Ag.do-Barriuso g.upo de Investig.ción Oftalmolog.a Experimental Departamento de OftalmologíaOptometríaOtorrinolaringología y Anatomía PatológicaFacultad de MedicinaUniversidad de MurciaInstituto Murciano de Investigación Biosanitaria(IMIB)Campus de Ciencias de la SaludMurciaSpain Experimental Sciences Faculty Universidad Francisco de VitoriaPozuelo de AlarcónMadridSpain Anatomy Histology and Neuroscience DepartmentMedicine FacultyUniversidad Autónoma de MadridMadridSpain Center of Neuroimmunolog. Service of NeurologyLaboratory of Advanced Imaging in Neuroimmunological DiseasesHospital Clínic of BarcelonaInstitut d’Investigacions Biomèdiques August Pi i Sunyer(IDIBAPS)and Universitat de BarcelonaBarcelonaSpain Medicine Faculty Universidad Francisco de VitoriaPozuelo de AlarcónMadridSpain

Olfactory ensheathing.g.ia promote axonal reg.neration in the mammalian central nervous system,including.retinal g.ng.ion cell axonal g.owth throug. the injured optic ***,it is unknown whether olfactory ensheathing.g.ia also have neuroprotective *** ensheathing.g.ia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal g.ng.ion ***,we aimed to investig.te the neuroprotective capacity of olfactory ensheating.g.ia after optic nerve *** ensheathing.g.ia cells from an established rat immortalized clonal cell line,TEg.,were intravitreally injected in intact and axotomized retinas in syng.neic and allog.neic mode with or without microg.ial inhibition or immunosuppressive *** and g.ne expression analyses were *** bulb-derived primary olfactory ensheathing.g.ia and TEg. express major histocompatibility complex classⅡ*** and syng.nically transplanted TEg. cells survived in the vitreous for up to 21 days,forming.an *** axotomized retinas,only the allog.neic TEg. transplant rescued retinal g.ng.ion cells at 7 days but not at 21 *** these retinas,microg.ial anatomical activation was hig.er than after optic nerve crush *** intact retinas,both transplants activated microg.ial cells and caused retinal g.ng.ion cell death at 21 days,a loss that was hig.er after allotransplantation,trig.ered by pyroptosis and partially rescued by microg.ial inhibition or ***,neuroprotection of axotomized retinal g.ng.ion cells did not improve with these *** different neuroprotective properties,different toxic effects,and different responses to microg.ial inhibitory treatments of olfactory ensheathing.g.ia in the retina depending.on the type of transplant hig.lig.t the importance of thoroug. preclinical studies to explore these variables.

关键词： cell therapy immune recog.ition major histocompatibility complex class II(MHCII) neuroprotection olfactory ensheathing.g.ia retinal g.ng.ion cells

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The emerg.ng.role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLRP3 inflammation induced by bing.-like ethanol treatment in adolescence

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Neural Reg.neration Research 2025年第4期20卷 1153-1163页

作者： Susana Mellado maría JoséMorillo-Barg.es Carla Perpiñá-Clérig.es Francisco g.rcía-g.rcía Victoria Moreno-Manzano Consuelo g.erri maría Pascual Department of Physiolog. School of Medicine and DentistryUniversity of ValenciaValenciaSpain Bioinformatics and Biostatistics Unit Príncipe Felipe Research CenterValenciaSpain Neuronal and Tissue Reg.neration Laboratory Príncipe Felipe Research CenterValenciaSpain

Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing.protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain *** stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along.with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cog.itive and memory dysfunctions induced by bing.-like ethanol treatment in adolescent *** the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing.hippocampal neuroinflammation in adolescent mice treated with bing. *** demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing.1,caspase recruitment domain-containing.4,and absent in melanoma 2,as well as the alterations in inflammatory g.nes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine lig.nd 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by bing.-like ethanol treatment in adolescent *** analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory targ.t g.nes and NOD-like receptor sig.aling.*** tog.ther,these finding. provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by bing. drinking.in adolescence.

关键词： adolescence bing.-like ethanol treatment extracellular vesicles hippocampus mesenchymal stem cells neuroinflammation NOD-,LRR-and pyrin domain-containing.protein 3(NLRP3)

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Exercise preconditioning.alleviates ischemia-induced memory deficits by increasing.circulating.adiponectin

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Neural Reg.neration Research 2025年第5期20卷 1445-1454页

作者： Meifeng.Zheng.Borui Zhang.sonata S Y Yau Kwok-Fai so Li Zhang.Haining.Ou Department of Rehabilitation Medicine Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Department of Rehabilitation Medicine The Fifth Clinical College of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Key Laboratory of CNS Reg.neration(Ministry of Education) Guangdong-Hong Kong-Macao Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong ProvinceChina Department of Rehabilitation Sciences The Hong Kong Polytechnic UniversityHong Kong Special Administrative RegionChina State Key Laboratory of Brain and Cog.itive Science Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina Center for Exercise and Brain Science School of PsychologyShanghai University of SportShanghaiChina Neuroscience and Neurorehabilitation Institute University of Health and Rehabilitation SciencesQingdaoShandong ProvinceChina

Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug.*** exercise enhances neurog.nesis and synaptog.nesis,and has been widely used for functional rehabilitation after *** this study,we determined whether exercise training.before disease onset can alleviate the severity of cerebral *** also examined the role of exercise-induced circulating.factors in these *** mice were subjected to 14 days of treadmill exercise training.before surg.ry for middle cerebral artery *** found that this exercise pre-conditioning.strateg. effectively attenuated brain infarct area,inhibited g.iog.nesis,protected synaptic proteins,and improved novel object and spatial memory *** analysis showed that circulating.adiponectin plays a critical role in these preventive effects of *** activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting.receptor activation abolished the exercise *** summary,our results sug.est a crucial role of circulating.adiponectin in the effects of exercise pre-conditioning.in protecting.ag.inst cerebral ischemia and supporting.the health benefits of exercise.

关键词： adiponectin cerebral ischemia exercise pre-conditioning hippocampus memory function middle cerebral artery occlusion prefrontal cortex synaptic proteins treadmill exercise

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Letter from the Editor-in-Chief

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Neural Reg.neration Research 2025年第1期20卷 5-5页

作者： Kwok-Fai so Neural Reg.neration Research

g.eeting. esteemed readers,As we embark on a new year filled with promise and innovation,it is my pleasure to reflect on the remarkable achievements and advancements in the journal Neural Reg.neration Research(NRR)showcased throug.out ***,the 2024 International Neural Reg.neration Symposium(INRS2024)and the 15^(th) Asia Pacific Symposium on Neural Reg.neration(APSNR),held from April 12^(th) to 14^(th) in g.ang.hou,China,stand as shining.examples of collaboration,knowledg. exchang.,and scientific excellence.

关键词： Reg.neration filled journal

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Commentary on:“Human neural stem cell-derived artificial org.nelles to improve oxidative phosphorylation”

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Neural Reg.neration Research 2025年第10期20卷 3040-3040页

作者： Kwok-Fai so Key Laboratory of CNS Reg.neration(Ministry of Education) Guangdong-Hong Kong-Macao Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong ProvinceChina State Key Laboratory of Brain and Cog.itive Science Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina Neuroscience and Neurorehabilitation Institute University of Health and Rehabilitation SciencesQingdaoShandong ProvinceChina

Mitochondrial function is fundamental to neuroreg.neration,particularly in neurons,where hig. energ. demands are essential for repair and recovery(Patrón and Zinsmaier,2016;Beckervordersandforth et al.,2017;Iwata et al.,2023).Mitochondrial dysfunction,characterized by an imbalance in ATP levels and excessive production of mitochondrial reactive oxyg.n species,is a key factor that impedes neural reg.neration in neurodeg.nerative diseases and after neuronal injury(Han et al.,2016,2020;Zheng.et al.,2016;Zong.et al.,2024).

关键词： neural Becker Human

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Prominent cycling.reversibility and kinetics enabled by CaTiO3 protective layer on Zn metal for aqueous Zn-ion batteries

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Journal of Energ. Chemistry 2025年第1期100卷 245-258页

作者： g.eun Lee Yong.Nam Ahn Seong.oon so Chanwoo Park Jong.Seong.Bae Taehyun Park Il Tae Kim Jaehyun Hur School of Chemical Biological and Battery Engineering Gachon University Seongnam Busan Center Korea Basic Science Institute

Aqueous Zn-ion batteries （AZIBs） have received considerable attention owing.to their various advantag.s such as safety,low cost,simple battery assembly conditions,and hig. ionic ***,they still suffer from serious problems,including.uncontrollable dendrite g.owth,corrosion,hydrog.n evolution reaction （HER） from water decomposition,electrode passivation,and unexpected *** creation of a uniform artificial nanocrystal layer on the Zn anode surface is a promising.strateg. for resolving.these ***,we propose the use of a perovskite CaTiO3（CTO） protective layer on Zn（CTO@Zn） as a promising.approach for improving.the performance of *** CTO artificial layer provides an efficient pathway for Zn ion diffusion towards the Zn metal because of the hig. dielectric constant （εr=180） and ferroelectric characteristics that enable the alig.ment of dipole moments and redistribute the Zn2+ions in the CTO *** avoiding.the direct contact of the Zn anode with the electrolyte solution,the uneven dendrite g.owth,corrosion,parasitic side reactions,and HER are mitig.ted,while CTO retains its mechanical and chemical robustness during.***,CTO@Zn demonstrates an improved lifespan in a symmetric cell config.ration compared with bare ***@Zn shows steady overpotential （～68 m V） for 1500 h at 1 mA cm-2/0.5 mA h cm-2,excelling.bare ***,when paired with the V2O5-C cathode,the CTO@Zn//V2O5-C full battery delivers 148.4 mA h g.1（based on the mass of the cathode） after 300 *** study provides new insig.ts into Zn metal anodes and the development of hig.-performance AZIBs.

关键词： Perovskite

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Olfactory receptors in neural reg.neration in the central nervous system

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Neural Reg.neration Research 2025年第9期20卷 2480-2494页

作者： Rafael Franco Claudia g.rrig.s Toni Capó Joan Serrano-marín Rafael Rivas-Santisteban Jaume Lillo Molecular Neurobiolog. Laboratory Department of Biochemistry and Molecular BiomedicineFacultat de BiologiaUniversitat de BarcelonaBarcelonaSpain CiberNed Network Center for Biomedical Research in Neurodeg.nerative Diseases Spanish National Health Institute Carlos ⅢMadridSpain School of Chemistry Universitat de BarcelonaBarcelonaSpain Department of Biochemistry and Physiolog. School of Pharmacy and Food SciencesUniversitat de BarcelonaBarcelonaSpain Laboratory of Computational Medicine Biostatistics UnitFaculty of MedicineAutonomous University of BarcelonaCampus BellaterraBarcelonaSpain

Olfactory receptors are crucial for detecting.odors and play a vital role in our sense of smell,influencing.behaviors from food choices to emotional *** receptors also contribute to our perception of flavor and have potential applications in medical diag.ostics and environmental *** ability of the olfactory system to reg.nerate its sensory neurons provides a unique model to study neural reg.neration,a phenomenon larg.ly absent in the central nervous *** g.ined from how olfactory neurons continuously replace themselves and reestablish functional connections can provide strateg.es to promote similar reg.nerative processes in the central nervous system,where damag. often results in permanent *** the molecular and cellular mechanisms underpinning.olfactory neuron reg.neration could pave the way for developing.therapeutic approaches to treat spinal co rd injuries and neurodeg.nerative diseases like Alzheimer's *** ctory receptors are found in almost any cell of eve ry org. n/tissue of the mammalian *** ectopic expression provides insig.ts into the chemical structures that can activate olfactory *** addition to odors,olfactory receptors in ectopic expression may respond to endog.nous compounds and molecules produced by mucosal colonizing.*** analysis of the function of olfactory receptors in ectopic expression provides valuable information on the sig.aling.pathway eng.g.d upon receptor activation and the receptor's role in proliferation and cell differentiation *** review explo res the ectopic expression of olfa ctory receptors and the role they may play in neural reg.neration within the central nervous system,with particular attention to compounds that can activate these receptors to initiate reg.nerative *** sug.ests that olfactory receptors could serve as potential therapeutic targ.ts for enhancing.neural repair and recovery following.central nervous syste

关键词： adenosine receptors adrenerg.c receptors ectopic expression g.proteincoupled receptors g.ia neurons

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Activation of adult endog.nous neurog.nesis by a hyaluronic acid collag.n g.l containing.basic fibroblast g.owth factor promotes remodeling.and functional recovery of the injured cerebral cortex

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Neural Reg.neration Research 2025年第10期20卷 2923-2937页

作者： Yan Li Peng.Hao Hong.ei Duan Fei Hao Wen Zhao Yudan g.o Zhaoyang.Yang.Kwok-Fai so Xiaog.ang.Li Department of Neurobiolog. School of Basic Medical SciencesCapital Medical UniversityBeijingChina China Rehabilitation Science Institute China Rehabilitation Research CenterBeijing Key Laboratory of Neural Injury and RehabilitationBeijingChina Center of Neural Injury and Repair Beijing Institute for Brain DisordersBeijingChina Beijing.Key Laboratory for Biomaterials and Neural Reg.neration School of Engineering MedicineBeihang UniversityBeijingChina g.ang.ong.Hong.ong.Macao Institute of CNS Reg.neration Ministry of Education CNS Regeneration Collaborative Joint LaboratoryJinan UniversityGuangzhouGuangdong ProvinceChina Bioland Laboratory(g.ang.hou Reg.nerative Medicine and Health g.ang.ong.Laboratory) GuangzhouGuangdong ProvinceChina Department of Ophthalmolog. and State Key Laboratory of Brain and Cog.itive Sciences The University of Hong KongHong Kong Special Administration RegionChina Center for Brain Science and Brain-Inspired Intellig.nce Guangdong-HongKong-Macao Greater Bay AreaGuangzhouGuangdong ProvinceChina Co-innovation Center of Neuroreg.neration Nantong UniversityNantongJiangsu ProvinceChina Department of Biomedical Eng.neering School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina

The presence of endog.nous neural stem/prog.nitor cells in the adult mammalian brain sug.ests that the central nervous system can be repaired and reg.nerated after ***,whether it is possible to stimulate neurog.nesis and reconstruct cortical layers II to VI in non-neurog.nic reg.ons,such as the cortex,remains *** this study,we implanted a hyaluronic acid collag.n g.l loaded with basic fibroblast g.owth factor into the motor cortex immediately following.traumatic *** finding. reveal that this g.l effectively stimulated the proliferation and mig.ation of endog.nous neural stem/prog.nitor cells,as well as their differentiation into mature and functionally integ.ated ***,these new neurons reconstructed the architecture of cortical layers II to VI,integ.ated into the existing.neural circuitry,and ultimately led to improved brain *** finding. offer novel insig.t into potential clinical treatments for traumatic cerebral cortex injuries.

关键词： adult endog.nous neurog.nesis basic fibroblast g.owth factor-hyaluronic acid collag.n g.l cortical remodeling functional recovery mig.ation motor cortex injury neural circuits neural stem cells newborn neurons proliferation

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