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Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

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Neural Regeneration Research 2025年第4期20卷 1207-1216页

作者： pascal J.Goldschmidt-Clermont Aisha Khan George Jimsheleishvili patricia Graham Adriana Brooks Risset Silvera Alexander J.p.Goldschmidt damien d.pearse W.dalton dietrich Allan d.levi James d.Guest miller School of medicine University of MiamiMiamiFLUSA Stem Cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The miami project to Cure paralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International llC MiamiFLUSA Neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular *** amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be ***,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been *** case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such *** 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral *** initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and *** patient volunteered to participate in an FdA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron *** confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in *** a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 ml of dulbecco’s phosphate-buffered *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

Emerging role of A-kinase anchoring protein 5 signaling in reward circuit function

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Neural Regeneration Research 2025年第10期20卷 2913-2914页

作者： William J.Flerlage mark l.dell’Acqua Brian m.Cox Fereshteh S.Nugent Uniformed Services University of the Health Sciences Department of Pharmacology and Molecular TherapeuticsBethesdaMDUSA department of pharmacology University of Colorado School of MedicineAnschutz Medical CampusAuroraCOUSA

There is a strong evidence supporting the hypothesis of synaptic dysfunction as a major contributor to neural circuit and network disruption underlying emotional and mood dysregulation in psychiatric disorders(Simmons et al.,2024).diverse sets of distinct molecular signaling pathways converge on the synapse to regulate synaptogenesis,synaptic function,and synaptic plasticity in brain regions and circuits through complex interactions organized by numerous multivalent protein scaffolds,including the family of proteins known as A-kinase anchoring proteins(AKAps).

关键词： function supporting

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

Heterogeneity of mature oligodendrocytes in the central nervous system

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Neural Regeneration Research 2025年第5期20卷 1336-1349页

作者： Chao Weng Adam m.R.Groh moein Yaqubi Qiao-ling Cui Jo Anne Stratton G.R.Wayne moore Jack p.Antel Neuroimmunology Unit Montreal Neurological Institute-HospitalDepartment of Neurology and NeurosurgeryMcGill UniversityMontrealQCCanada department of Neurology Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina

mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous *** evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to *** the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is *** delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature ***,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination ***,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system *** and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric ***,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined *** studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte *** research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,

关键词： aging central nervous system diseases electron microscopy heterogeneity immunohistochemistry myelin sheath natural history neuroglia oligodendroglia single-cell gene expression analysis

Neurogenesis dynamics in the olfactory bulb:deciphering circuitry organization, function, and adaptive plasticity

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Neural Regeneration Research 2025年第6期20卷 1565-1581页

作者： moawiah m.Naffaa department of psychology and Neuroscience Duke UniversityDurhamNCUSA department of Cell Biology Duke University School of MedicineDurhamNCUSA

Adult neurogenesis persists after birth in the subventricular zone, with new neurons migrating to the granule cell layer and glomerular layers of the olfactory bulb, where they integrate into existing circuitry as inhibitory interneurons. The generation of these new neurons in the olfactory bulb supports both structural and functional plasticity, aiding in circuit remodeling triggered by memory and learning processes. However, the presence of these neurons, coupled with the cellular diversity within the olfactory bulb, presents an ongoing challenge in understanding its network organization and function. moreover,the continuous integration of new neurons in the olfactory bulb plays a pivotal role in regulating olfactory information processing. This adaptive process responds to changes in epithelial composition and contributes to the formation of olfactory memories by modulating cellular connectivity within the olfactory bulb and interacting intricately with higher-order brain regions. The role of adult neurogenesis in olfactory bulb functions remains a topic of debate. Nevertheless, the functionality of the olfactory bulb is intricately linked to the organization of granule cells around mitral and tufted cells. This organizational pattern significantly impacts output, network behavior, and synaptic plasticity, which are crucial for olfactory perception and memory. Additionally, this organization is further shaped by axon terminals originating from cortical and subcortical regions. despite the crucial role of olfactory bulb in brain functions and behaviors related to olfaction, these complex and highly interconnected processes have not been comprehensively studied as a whole. Therefore, this manuscript aims to discuss our current understanding and explore how neural plasticity and olfactory neurogenesis contribute to enhancing the adaptability of the olfactory system. These mechanisms are thought to support olfactory learning and memory, potentially through increased

关键词： network adaptability neurogenesis neuronal communication olfactory bulb olfactory learning olfactory memory synaptic plasticity

Additive neurorestorative effects of exercise and docosahexaenoic acid intake in a mouse model of parkinson’s disease

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Neural Regeneration Research 2025年第2期20卷 574-586页

作者： Olivier Kerdiles méryl-Farelle Oye mintsa mi-mba Katherine Coulombe Cyntia Tremblay VincentÉmond martine Saint-pierre Clémence Rouxel line Berthiaume pierre Julien Francesca Cicchetti Frédéric Calon Facultéde pharmacie UniversitéLaval1050 Avenue de la MédecineQuebecQCCanada Axe Neuroscience Centre de recherche du CHU de Québec-UniversitéLaval(Pavillon CHUL)2705 Boulevard LaurierQuebecQCCanada Institute of Nutrition and Functional Foods QuebecQCCanada Optinutribrain International Associated laboratory(NutriNeuro FranceINAFCanada)QuebecQCCanada Axe Endocrinologie et Néphrologie Centre de recherche du CHU de Québec-UniversitéLavalQuebecQCCanada département de médecine Facultéde MédecineUniversitéLavalQuebecQCCanada département de psychiatrie et Neurosciences Facultéde MédecineQuebecQCCanada

There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in parkinson’s disease after *** that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids,such as docosahexaenoic acid,and exercise in parkinson’s disease,we investigated whether both could synergistically interact to induce recovery of the dopaminergic ***,mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal *** weeks after lesion,animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 *** this period,the animals had access to a running wheel,which they could use or *** acid treatment,voluntary exercise,or the combination of both had no effect on(i)distance traveled in the open field test,(ii)the percentage of contraversive rotations in the apomorphine-induction test or(iii)the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars ***,the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned *** to docosahexaenoic acid treatment or exercise alone,the combination of docosahexaenoic acid and exercise(i)improved forelimb balance in the stepping test,(ii)decreased the striatal dOpAC/dopamine ratio and(iii)led to increased dopamine transporter levels in the lesioned *** present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of parkinson’s disease.

关键词： 6-hydroxydopamine dopamine dopamine transporter exercise neurorestoration parkinson’s disease polyunsaturated fatty acids omega-3

Tuning the particle size,physical properties,and photocatalytic activity of Ag_(3)pO_(4)materials by changing the Ag^(+)/pO_(4)^(3-)ratio

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Chinese physics B 2023年第3期32卷 561-568页

作者： Hung N m Oanh l T m Chung d p Thang d V mai V T Hang l T minh N V Center for Nano Science and Technology Hanoi National University of Education136 Xuan Thuy RoadCau Giay DistrictHanoi 100000Vietnam department of physics Hanoi National University of Education136 Xuan Thuy RoadCau Giay DistrictHanoi 100000Vietnam Hanoi University of mining and Geology Duc Thang WardNorth Tu Liem DistrictHanoi 100000Vietnam Institute of materials Science Vietnam Academy of Science and Technology18 Hoang Quoc VietHanoi 100000Vietnam Faculty of Basic Sciences Hanoi University of Natural Resources and Environment41 A Phu Dien RoadNorth Tu LiemHanoi 100000Vietnam

This study demonstrates the influence of the Ag^(+)/pO_(4)^(3-)ratio in precursor solution on the crystal structural formation,morphology,physical properties,and photocatalytic performance of a Ag_(3)pO_(4)photocatalyst that is fabricated,using a facile precipitation method,from AgNO_(3)and Na2HpO_(4)·12H_(2)*** material characterizations were carried out using x-ray diffraction(XRd),scanning electron microscopy(SEm),energy-dispersive x-ray spectroscopy(EdX),Brunauer–Emmett–Teller(BET)surface area,Fourier transform infrared(FTIR)absorption,Raman scattering,x-ray photoelectron spectroscopy(XpS),UV-vis absorption,and photoluminescence(pl).The results show that Ag_(3)pO_(4)crystallizes better when the excess pO_(4)^(3-)content increases,and the lattice parameters decrease slightly,while the crystal diameter and the particle size *** change is also observed in the Raman scattering and FTIR spectra with the increase in the vibration frequency of the[pO_(4)]*** compression of the[pO_(4)]unit was also confirmed in the XpS spectra with the shift of p 2p peaks toward higher binding *** photocatalytic results showed that the samples synthesized from excess pO_(4)^(3-)solution exhibited higher photocatalytic performance compared to the sample with a Ag^(+)/pO_(4)^(3-)ratio of 3:1.A sample prepared from the precursor solution with a Ag^(+)/pO_(4)^(3-)ratio of 3:1.5 was optimal for RhB decomposition under both visible light and natural sunlight,completely decomposing 10 ppm RhB after 15 minutes of xenon lamp irradiation and after 60 minutes under solar light *** is attributed to the high crystallinity,small particle size and low electron–hole recombination rate of the sample.

关键词： morphology photocatalytic Ag^(+)/pO_(4)^(3-)ratio visible light

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

Getting physical with medical education:Exercise based virtual anatomy review classes for medical students

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World Journal of methodology 2025年第1期15卷 20-25页

作者： Nadeesha R Samarasinghe Taniya S Nagpal michele l Barbeau Charys m martin division of General Surgery Faculty of MedicineUniversity of British ColumbiaVancouver V6T 1Z3BCCanada Faculty of Kinesiology Sport and RecreationUniversity of AlbertaEdmonton T6G 2R3ABCanada Anatomy and Cell Biology University of Western OntarioLondon N6A 3K7ONCanada department of Anatomy and Cell Biology Schulich School of Medicine and DentistryThe University of Western OntarioLondon N6A 3K7ONCanada

The benefits of regular physical activity are well ***,few studies have examined the effectiveness of integrating physical activity(pA)into curricula within a post-secondary *** investigate the incorporation of pA into medical curriculum,we developed a series of optional exercise-based review sessions designed to reinforce musculoskeletal(mSK)anatomy course *** synchronous sessions were co-taught by a group fitness instructor and an anatomy *** fitness instructor would lead students through both strength and yoga style exercises,while the anatomy instructor asked questions about relevant anatomical structures related to course material previously *** the sessions,participants were asked to evaluate the classes on their self-reported exam preparedness in improving mSK anatomy knowledge,pA levels,and mental *** participants completed surveys;a majority agreed that the classes increased understanding of mSK concepts(90.0%)and activity levels(97.7%).many(70.0%)felt that the classes helped reduce *** majority of respondents(90.0%)agreed that the classes contributed to increased feelings of social ***,medical students saw benefit in pA based interventions to supplement mSK course *** with increasing activity levels and promoting health behaviours,integrating pA into medical curriculum may improve comprehension of learning material,alleviate stress and foster social connectivity among medical students.

关键词： medical education musculoskeletal Anatomy Exercise Online learning