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Impacts of PI3K/protein.kin.se B pathway activation.in.reactive astrocytes: from detrimen.al effects to protective fun.tion.

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n.ural Regen.ration.Research 2025年第4期20卷 1031-1041页

作者： Ramón.Pérez-n.ñez María Fern.n.a Gon.ález An. María Avalos Lisette Leyton Cellular Commun.cation.Laboratory Programa de Biología Celular y MolecularCenter for Studies on ExerciseMetabolism and Cancer(CEMC)Instituto de Ciencias Biomédicas(ICBM)Facultad de MedicinaUniversidad de ChileSantiagoChile Advan.ed Cen.er for Chron.c Diseases(ACCDiS) Faculty of Chemical and Pharmaceutical Sciences&Faculty of MedicineUniversidad de ChileSantiagoChile In.tituto de Cien.ias Biomédicas Facultad de Ciencias de la SaludUniversidad Autónoma de ChileSantiagoChile

Astrocytes are the most abun.an. type of glial cell in.the cen.ral n.rvous *** in.ury an. in.lammation.astrocytes become reactive an. un.ergo morphological an. fun.tion.l *** on.their phen.typic classification.as A1 or A2,reactive astrocytes con.ribute to both n.urotoxic an. n.uroprotective respon.es,***,this bin.ry classification.does n.t fully capture the diversity of astrocyte respon.es observed across differen. diseases an. *** an.lysis has revealed that reactive astrocytes have a complex lan.scape of gen. expression.profiles,which emphasizes the heterogen.ous n.ture of their *** actively participate in.regulatin. cen.ral n.rvous system in.lammation.by in.eractin. with microglia an. other cell types,releasin. cytokin.s,an. in.luen.in. the immun. *** phosphoin.sitide 3-kin.se(PI3K)/protein.kin.se B(AKT)sign.lin. pathway is a cen.ral player in.astrocyte reactivity an. impacts various aspects of astrocyte behavior,as eviden.ed by in.silico,in.vitro,an. in.vivo *** astrocytes,in.lammatory cues trigger a cascade of molecular even.s,where n.clear factor-κB serves as a cen.ral mediator of the pro-in.lammatory ***,we review the heterogen.ity of reactive astrocytes an. the molecular mechan.sms un.erlyin. their *** highlight the in.olvemen. of various sign.lin. pathways that regulate astrocyte reactivity,in.ludin. the PI3K/AKT/mammalian.target of rapamycin.mTOR),αvβ3 in.egrin.PI3K/AKT/con.exin.43,an. n.tch/PI3K/AKT *** targetin. the in.ctivation.of the PI3K/AKT cellular sign.lin. pathway to con.rol reactive astrocytes an. preven. cen.ral n.rvous system damage,eviden.e suggests that activatin. this pathway could also yield ben.ficial *** dual fun.tion.of the PI3K/AKT pathway un.erscores its complexity in.astrocyte reactivity an. brain.fun.tion.*** review emphasizes the importan.e of employin. astrocyte-exclusive models to un.erst

关键词： in.lammation in.egrin. n.uroprotective n.urotoxic phosphatidylin.sitol 3-kin.se reactive astrocytes sign.l tran.duction Thy-1(CD90)

Astrocytes, reactive astrogliosis, an. glial scar formation.in.traumatic brain.in.ury

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n.ural Regen.ration.Research 2025年第4期20卷 973-989页

作者： María Belén.Cieri Alberto Javier Ramos Laboratorio de n.uropatología Molecular IBCN UBA-CONICETFacultad de MedicinaUniversidad de Buenos AiresBuenos AiresArgentina

Traumatic brain.in.ury is a global health crisis,causin. sign.fican. death an. disability *** that follows traumatic brain.in.ury has serious con.equen.es for n.uron.l survival an. cogn.tive impairmen.s,with astrocytes in.olved in.this *** traumatic brain.in.ury,astrocytes rapidly become reactive,an. astrogliosis propagates from the in.ury core to distan. brain.*** astroglial protein. are down.egulated n.ar the traumatic brain.in.ury core,while pro-in.lammatory astroglial gen.s are *** altered gen. expression.is con.idered a pathological remodelin. of astrocytes that produces serious con.equen.es for n.uron.l survival an. cogn.tive *** addition.glial scar formed by reactive astrocytes is in.tially n.cessary to limit immun. cell in.iltration.but in.the lon. term impedes axon.l recon.ection.an. fun.tion.l *** therapeutic strategies for traumatic brain.in.ury are focused on.preven.in. acute ***,can.abin.ids,progesteron.,beta-blockers,an. cerebrolysin.demon.trate n.uroprotective ben.fits but most of them have n.t been.studied in.the con.ext of *** this review,we discuss the cell sign.lin. pathways activated in.reactive astrocytes followin. traumatic brain.in.ury an. we discuss some of the poten.ial n.w strategies aimed to modulate astroglial respon.es in.traumatic brain.in.ury,especially usin. cell-targeted strategies with miRn.s or ln.Rn.,viral vectors,an. repurposed drugs.

关键词： astrocyte glial scar in.ate immun.ty n.uroin.lammation stab in.ury Toll-like receptors

Sex differen.es in.agin. an. in.ured brain

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n.ural Regen.ration.Research 2025年第10期20卷 2901-2902页

作者： Jordan.n.Williamson.Yuan.Yan. Un.versity of Illin.is Urban.-Champaign Grainger College of EngineeringDepartment of BioengineeringUrbanaILUSA Carle Foun.ation.Hospital Stephenson Family Clinical Research InstituteClinical Imaging Research CenterUrbanaILUSA Un.versity of Illin.is Urban.-Champaign Beckman Institute for Advanced Science and TechnologyUrbanaILUSA n.rthwestern.Un.versity Department of Physical Therapy and Human Movement SciencesChicagoILUSA

Backgroun.:The prevalen.e,age of on.et,an. symptomatology of traumatic brain.in.ury,stroke,an. n.urodegen.rative diseases(such as Alzheimer’s disease(AD),Parkin.on.s disease,amyotrophic lateral sclerosis,an. Hun.in.ton.s disease)differ substan.ially between.males an. *** higher prevalen.e of these brain.disorders has been.attributed to females havin. a greater lon.evity compared with *** on. of the greatest risk factors of acquired brain.in.ury(such as stroke,traumatic brain.in.ury caused by fall)an. n.urodegen.rative disease is age.

关键词： Hun.in.ton prevalen.e traumatic

Makin. bridges between.preclin.cal an. clin.cal in.ights in.o age-related cogn.tive declin.

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n.ural Regen.ration.Research 2025年第8期20卷 2321-2322页

作者： David VC Brito Clévio n.brega Algarve Biomedical Cen.er-Research In.titute(ABC-RI) Campus GambelasFaroPortugal Algarve Biomedical Cen.er-(ABC) Campus GambelasFaroPortugal Faculty of Medicin. an. Biomedical Scien.es(FMCB) University of AlgarveGambelas CampusFaroPortugal

With people livin. lon.er,the societal impact of age-related cogn.tive declin. is becomin. more pron.un.ed(Crimmin.,2015).Thus,it is in.reasin.ly importan. to comprehen. the cogn.tive shifts lin.ed to agin.-whether th... 详细信息

关键词： bridges becomin. in.ight

Amyloid-beta pathology-in.uced n.n.scale syn.ptic disruption.the case of the GABA_B-GIRK assembly

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n.ural Regen.ration.Research 2025年第5期20卷 1409-1410页

作者： Rafael Lujan.Alejan.ro Martín.Belmon.e Sergi Ferré Fran.isco Ciruela Syn.ptic 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 In.egrative n.urobiology Section National Institute on Drug AbuseIntramural Research ProgramNational Institutes of HealthBaltimoreMDUSA Pharmacology Un.t 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.imbalan.e between.excitatory an. in.ibitory brain.n.tworks,leadin. to aberran. homeostatic syn.ptic *** has progressively been.recogn.zed as syn. ptopathy an. syn. ptic dysfun.tion.has been.iden.ified as a key compon.n. of its pathogen.sis (Schirin.i et al.,2020).Syn. ptic dysfun.tion.is believed to precede syn.pse loss,a primary biological correlate of cogn.tive declin. in.AD,in.vita bly associated with n.uron.l death.

关键词： Alzheimer pathology

Data-driven.drug reposition.n. usin. olfactory omics profiles:challen.es an. perspectives in.n.urodegen.ration

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n.ural Regen.ration.Research 2025年第7期20卷 1997-1998页

作者： Paz Cartas-Cejudo Adrian. Cortés Mercedes Lachén.Mon.es Elen. An.ya-Cubero Joaquín.Fern.n.ez-Irigoyen.En.ique San.amaría Clin.cal n.uroproteomics Un.t Proteomics PlatformNavarrabiomedHospitalario Universitario de Navarra(HUN)Universidad Pública de Navarra(UPNA)IdiSNANavarra Institute for Health ResearchPamplonaSpain

Data-driven.drug reposition.n. usin. olfactory omics profiles-challen.es an. perspectives in.n.urodegen.ration.n.urodegen.rative diseases are characterized by progressive degen.ration.an. loss of n.uron.l fun.tion.in.the cen.ral n.rvous *** diseases are often.characterized as protein.pathies,which are disorders primarily driven.by the aggregation.or misfoldin. of specific amyloid protein. within.cells,leadin. to their dysfun.tion.an. even.ual *** the gain.of-fun.tion.hypothesis related to the aggregation.of these protein.,recen.ly,an.altern.tive hypothesis regardin. the loss-of-fun.tion.of the soluble mon.meric protein. durin. the process of aggregation.in.o amyloids is gain.n. *** last even. is called protein.pen.a an. refers to con.ition. characterized by a deficien.y or decrease in.the levels of specific soluble protein. in.the body(Ezzat et al.,2023).It has been.demon.trated that levels of soluble protein. in.olved in.n.urodegen.rative diseases are decreased.

关键词： diseases drug amyloid

n.urocircuit regen.ration.by extracellular matrix reprogrammin.

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n.ural Regen.ration.Research 2025年第8期20卷 2300-2301页

作者： Shen.zhan. Su Ian.n.Levasseur Kimberly M.Alon.e Departmen. of Medicin.l Chemistry University of WashingtonSeattleWAUSA Departmen. of Chemistry University of WashingtonSeattleWAUSA Departmen. of Medicin. University of Washington Medicine Diabetes InstituteSeattleWAUSA

The brain.s extracellular matrix(ECM),which is comprised of protein.an. glycosamin.glycan.GAG)scaffolds,con.titutes 20%-40% of the human.brain.an. is con.idered on. of the largest in.luen.ers on.brain.cell fun.tion.n.(Soles et al.,2023).Syn.hesized by n.ural an. glial cells,the brain.s ECM regulates a myriad of homeostatic cellular processes,in.ludin. n.uron.l plasticity an. firin.(Miyata et al.,2012),cation.bufferin.(Moraws ki et al.,2015),an. glia-n.uron.in.eraction.(An.erson.et al.,2016).Con.iderin. the diversity of fun.tion.,dyn.mic remodelin. of the brain.s ECM in.icates that this un.erstudied medium is an.active participan. in.both n.rmal physiology an. n.urological diseases.

关键词： matrix programmin.

Vagus n.rve stimulation.in.in.racerebral hemorrhage:the n.ed for further research

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n.ural Regen.ration.Research 2025年第11期20卷 3213-3214页

作者： Sheharyar S.Baig Ali n.Ali Arshad Majid Sheffield In.titute for Tran.lation.l n.uroscien.e Division of NeuroscienceThe University of SheffieldSheffieldUK

Vagus n.rve stimulation.Vn.)an. stroke:Stroke is the secon. leadin. cause of death an. the third leadin. cause of disability worldwide(Baig et al.,2023).There have been.sign.fican. paradigm shifts in.the man.gemen. of acute ischemic stroke through mechan.cal *** chron.c ischemic stroke,in.asive Vn. paired with rehabilitation.is associated with a sign.fican. in.rease in.upper limb motor recovery an. is FDA-approved(Baig et al.,2023).There are n. treatmen.s of similar efficacy in.acute in.racerebral hemorrhage(ICH)where several promisin. trials,e.g.,TICH-2,STOP-AUST,an. TRAIGE did n.t show improvemen.s in.fun.tion.l outcomes(Puy et al.,2023).

关键词： stimulation acute

From sin.le to combin.torial therapies in.spin.l cord in.uries for structural an. fun.tion.l restoration

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n.ural Regen.ration.Research 2025年第3期20卷 660-670页

作者： Ern.sto Don.el-Pérez Gabriel Guízar-Sahagún.Israel Grijalva-Otero Hospital n.cion.l de Parapléjicos de Toledo Servicio de Salud de Castilla La Mancha(SESCAM)ToledoSpain Medical Research Un.t for n.urological Diseases UMAE Hospital de EspecialidadesCentro Médico Nacional Siglo XXIIMSSCiudad de MéxicoMéxico

Spin.l cord in.ury results in.paralysis, sen.ory disturban.es, sphin.ter dysfun.tion. an. multiple systemic secon.ary con.ition., most arisin. from auton.mic dysregulation. All this produces profoun. n.gative psychosocial implication. for affected people, their families, an. their commun.ties;the fin.n.ial costs can.be challen.in. for their families an. health in.titution.. Treatmen.s aimed at restorin. the spin.l cord after spin.l cord in.ury, which have been.tested in.an.mal models or clin.cal trials, gen.rally seek to coun.eract on. or more of the secon.ary mechan.sms of in.ury to limit the exten. of the in.tial damage. Most published works on.structural/fun.tion.l restoration.in.acute an. chron.c spin.l cord in.ury stages use a sin.le type of treatmen.: a drug or trophic factor, tran.plan. of a cell type, an. implan.ation.of a biomaterial. Despite the sign.fican. ben.fits reported in.an.mal models, when.tran.latin. these successful therapeutic strategies to human., the result in.clin.cal trials has been.con.idered of little relevan.e because the improvemen., when.presen., is usually in.ufficien.. Un.il n.w, most studies design.d to promote n.uroprotection.or regen.ration.at differen. stages after spin.l cord in.ury have used sin.le treatmen.s. Con.iderin. the occurren.e of various secon.ary mechan.sms of in.ury in.the acute an. sub-acute phases of spin.l cord in.ury, it is reason.ble to speculate that more than.on. therapeutic agen. could be required to promote structural an. fun.tion.l restoration.of the damaged spin.l cord. Treatmen.s that combin. several therapeutic agen.s, targetin. differen. mechan.sms of in.ury, which, when.used as a sin.le therapy, have shown.some ben.fits, allow us to assume that they will have syn.rgistic ben.ficial effects. Thus, this n.rrative review article aims to summarize curren. tren.s in.the use of strategies that combin. therapeutic agen.s admin.stered simultan.ously or sequen.ially, seekin. structural an. fun.tion.l restoratio

关键词： n.ural regen.ration n.uroprotection spin.l cord in.ury repair spin.l cord in.ury treatmen.s structural restoration.of spin.l cord in.ury