Neural Regeneration Research最新文献

{"title":"Nodose ganglion vagal afferents promote electroacupuncture efficacy in the gut-brain axis via proteasome restoration and CXCL10 suppression.","authors":"Jianmei Li, Jiao Yang, Jingqi Wang, Guangxin Xie, Zhixiao Zheng, Yufan Huang, Hongchi Wang, Junmeng Wang, Shuangchun Ai, Qiaofeng Wu","doi":"10.4103/NRR.NRRONLINE-D-26-00868","DOIUrl":"https://doi.org/10.4103/NRR.NRRONLINE-D-26-00868","url":null,"abstract":"<p><strong>Abstract: </strong>Electroacupuncture is a potent neuromodulatory strategy for mitigating intestinal pathologies. Nevertheless, the role of primary visceral sensory apparatuses in transducing somatosensory acupuncture signals remains unclear. Here, we sought to delineate the neuroanatomical necessity and cell type-specific molecular reprogramming within the nodose ganglion, the primary sensory relay of vagal afferents, underlying electroacupuncture-mediated intestinal homeostasis. Retrograde tracing confirmed a direct neuroanatomical conduit between the distal colon and nodose ganglion sensory neurons. Under pathological conditions, the nodose ganglion dynamically sensed colonic inflammation, manifesting as profound transcriptomic shifts. Electroacupuncture at Zusanli (ST36) significantly attenuated UC severity, suppressed systemic inflammation, and restored both physical (zonula occludens-1 and claudin-1) and chemical (Muc2 and Tff3) mucosal barriers. Crucially, targeted ablation of nodose ganglion vagal afferents completely abolished these macroscopic and molecular protective effects, along with the blockade of electroacupuncture-evoked cervical vagal discharge and colonic motility reflexes. Multomic deconvolution revealed that colitis triggered severe proteasome dysregulation and aberrant Cxcl10-mediated satellite glia/macrophage-to-neuron crosstalk within the nodose ganglion. Remarkably, electroacupuncture precisely reversed this pathological reprogramming by upregulating the expression of core proteasome-associated hub genes (Psma2, Psmd14, and Eif2s1) and potently quenching Cxcl10-induced neuroimmune hypersensitivity. These findings suggest that vagal sensory afferents within the nodose ganglion function as indispensable anatomical bottlenecks and functional responders for electroacupuncture-mediated colitis remission. By expanding the classic \"acupoint-organ-center\" paradigm, these findings demonstrate that disease-state sensory ganglia actively gate neuromodulatory therapy, providing a high-resolution molecular foundation for the clinical translation of electroacupuncture in treating intestinal disease.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149299261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibroblast-immune crosstalk in central nervous system injury and repair: Spatiotemporal control of barrier restoration, inflammation resolution and fibrotic scarring.","authors":"Peiyu Li, Xian Zhang, Haifeng Zhang, Liang Liu, Yan Chai, Shu Zhang, Xin Chen","doi":"10.4103/NRR.NRRONLINE-D-26-00971","DOIUrl":"https://doi.org/10.4103/NRR.NRRONLINE-D-26-00971","url":null,"abstract":"<p><strong>Abstract: </strong>Central nervous system repair after injury is increasingly understood as a spatially and temporally organized process involving vascular disruption, immune-cell recruitment, extracellular matrix remodeling and reconstruction of glial-stromal borders. Within this process, central nervous system fibroblasts are not merely matrix-producing scar cells, but injury-responsive stromal organizers positioned at key neuroimmune interfaces, including the meninges, perivascular spaces and choroid plexus. Recent single-cell, spatial and lineage-resolved studies indicate that anatomically distinct fibroblast populations undergo phase-specific state transitions after traumatic brain injury, stroke, and spinal cord injury. During the acute phase, activated fibroblasts and myofibroblast-like states contribute to lesion containment, barrier restoration and protection of surrounding parenchyma. In the subacute and chronic phases, fibroblasts interact dynamically with neutrophils, microglia, macrophages, lymphocytes and innate lymphoid cells to shape immune-cell positioning, inflammatory resolution, vascular repair and, when unresolved, persistent fibrotic scarring. This review synthesizes emerging evidence on fibroblast-immune crosstalk in central nervous system injury, with particular emphasis on the unresolved origins of injury-responsive stromal cells, lesion-topology-dependent fibroblast recruitment, C-X-C motif chemokine ligand 12-mediated lymphocyte organization, choroid plexus fibroblast-group 2 innate lymphoid cell niches, and fibroblast contributions to blood-brain barrier and vascular repair. Rather than framing fibrotic scars as uniformly detrimental, we propose that central nervous system fibrosis reflects context-dependent fibroblast states that can be either reparative or maladaptive depending on timing, anatomical niche and immune milieu. Therapeutic strategies should therefore avoid indiscriminate fibroblast depletion and instead aim to preserve early protective functions while selectively modulating chronic fibroblast-immune circuits that sustain inflammation and inhibit regeneration.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149299070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lung-derived proteinopathy: A new framework for peripheral contributions to neurodegeneration.","authors":"Tatiana Barichello, Khiany Mathias, Victoria Linden de Rezende, Josiane Budni, Felipe Dal-Pizzol, Fabricia Petronilho","doi":"10.4103/NRR.NRRONLINE-D-26-00893","DOIUrl":"https://doi.org/10.4103/NRR.NRRONLINE-D-26-00893","url":null,"abstract":"<p><strong>Abstract: </strong>Neurodegenerative diseases are characterized by the abnormal aggregation of amyloid-β, tau, and α-synuclein and have traditionally been viewed as disorders driven primarily by cell-autonomous processes within the central nervous system. Emerging evidence from in vitro, animal, and epidemiological studies suggests that neurodegeneration occurs within a systemic context in which peripheral organs, particularly the lung, serve as sources and modulators of central proteinopathy. The lung continuously encounters airborne pollutants, infectious agents, and inflammatory stimuli that perturb pulmonary proteostasis, trigger amyloid-like conformations of endogenous proteins, including surfactant protein C, and release cytotoxic, prion-like tau and amyloid-β from the pulmonary endothelium. This narrative review synthesizes evidence on pulmonary sources of misfolded proteins (bacterial and viral infections, fine particulate matter, ozone, diesel exhaust, surfactant protein mutations, and oxidative stress), molecular mechanisms driving misfolding and proteostatic collapse, candidate routes by which lung-derived aggregates reach the central nervous system (hematogenous transport with blood-brain barrier disruption, extracellular vesicle trafficking, vagal transmission, and peripheral immune cell trafficking), and proposed neurodegenerative consequences including tauopathy, amyloid-β deposition, microglial priming, synaptic loss, and cognitive decline. Emerging therapeutic strategies include immunomodulation, extracellular vesicle-targeted interventions, blood-brain barrier stabilization, and aggregation inhibitors. Current evidence distinguishes causal mechanistic data from epidemiological associations and hypothesis-generating observations. To date, no direct causal evidence in humans has demonstrated that lung-derived aggregates seed brain pathology; this framework is hypothesis-generating and intended to guide targeted experimental testing.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149299087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hippocampus-biased proteomic remodeling after multiple cerebral infarction: Mechanism of Rehmannia glutinosa extract.","authors":"Zishan Huang, Lan Miao, Feng Li, Miao Zhang, Mingjiang Yao, Jianxun Liu","doi":"10.4103/NRR.NRRONLINE-D-26-00884","DOIUrl":"https://doi.org/10.4103/NRR.NRRONLINE-D-26-00884","url":null,"abstract":"<p><strong>Abstract: </strong>Rehmannia glutinosa extract has been widely used in the treatment of multiple cerebral infarction, but its neurorepair effects and associated molecular responses remain incompletely characterized. In this study, a rat multiple cerebral infarction model was established by microsphere-induced cerebral ischemia, followed by treatment with Rehmannia glutinosa extract. Neurological function, brain atrophy, neuronal integrity, and hippocampal neurogenic responses were evaluated. Label-free quantitative proteomics was performed separately in the ipsilateral cortex and hippocampus to characterize region-specific molecular responses to Rehmannia glutinosa extract, and proteins showing multiple cerebral infarction-associated alterations that changed in the opposite direction following Rehmannia glutinosa extract treatment were subjected to functional enrichment analysis. Catalpol, a representative constituent detected in Rehmannia glutinosa extract, was subsequently evaluated in oxygen-glucose deprivation/reoxygenation-injured PC12 cells, and the involvement of Hedgehog signaling was examined using cyclopamine, a smoothened inhibitor. Rehmannia glutinosa extract treatment improved neurological outcomes and reduced brain atrophy following multiple cerebral infarction, accompanied by preservation of neuronal integrity and enhanced early neurogenic responses in the hippocampal dentate gyrus. Proteomic profiling revealed distinct treatment-associated responses in the cortex and hippocampus. In the hippocampus, 102 multiple cerebral infarction-associated proteins exhibited opposite-direction changes following Rehmannia glutinosa extract treatment, with functional enrichment implicating injury and inflammatory responses, gliogenesis, cellular homeostasis, and synaptic-associated processes. In oxygen-glucose deprivation/reoxygenation-injured PC12 cells, catalpol improved cellular recovery and partially restored neuronal structural and repair-associated markers, including neurofilament light chain, whereas growth-associated protein 43 showed a non-significant recovery trend. Catalpol also modulated Hedgehog pathway-related proteins, and cyclopamine attenuated the catalpol-associated improvement in cell confluence, indicating an association between the cellular response to catalpol and Hedgehog pathway integrity. Collectively, these findings indicate that Rehmannia glutinosa extract promotes hippocampus-predominant proteomic remodeling after multiple cerebral infarction in model mice, accompanied by improved neurological function, attenuated brain atrophy, and enhanced hippocampal neurogenesis. Catalpol may participate in the remodeling-associated neural repair processes by modulating the Hedgehog pathway.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149299067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell and spatial transcriptomics reveal mesenchymal stem cell-associated neuroimmune and neuronal signaling patterns after ischemic stroke.","authors":"Qinfen Wu, Junhua Hu, Naibijiang Abuliezi, Yihan Sun, Yanyan Wu, Xiaoyi Dun","doi":"10.4103/NRR.NRRONLINE-D-26-00871","DOIUrl":"https://doi.org/10.4103/NRR.NRRONLINE-D-26-00871","url":null,"abstract":"<p><strong>Abstract: </strong>Ischemic stroke induces coordinated yet spatially heterogeneous neuroimmune and neuronal responses that shape secondary injury and tissue remodeling. However, how intranasal mesenchymal stem cell administration is associated with these cell type-specific responses remains incompletely understood. Here, we integrated single-cell RNA sequencing of the ipsilateral cerebrum on days 1, 7, and 14 after middle cerebral artery occlusion/reperfusion with spatial transcriptomic profiling on day 7. A total of 55,520 high-quality single-cell transcriptomes were obtained from control, middle cerebral artery occlusion/reperfusion, and mesenchymal stem cell-treated samples. In this exploratory dataset, the middle cerebral artery occlusion/reperfusion samples showed relatively greater representation of inflammatory and antigen-presenting microglial states and elevated expression of selected microglial state-associated genes, including Slfn4, Apoe, and Gpnmb. In the corresponding exploratory comparison, the mesenchymal stem cell-treated sample showed relatively greater representation of homeostatic-associated and Lgals3/Spp1-enriched microglial states and lower expression of several inflammatory-associated genes. Spatial mapping further revealed regionally restricted expression of microglial and neuronal markers within the injured tissue. Excitatory neurons displayed preliminary mesenchymal stem cell-associated transcriptional patterns involving mitochondrial transcripts, oxidative phosphorylation, synaptic signaling, calcium-related functions, and apoptosis/autophagy-associated pathways. CellChat analysis computationally predicted relatively high levels of tumor necrosis factor, C-X-C motif chemokine ligand, and complement signaling in the middle cerebral artery occlusion/reperfusion sample, whereas the mesenchymal stem cell-treated sample had relatively high levels of predicted activity of neuregulin, pleiotrophin and selected semaphorin. Together, these integrated datasets provide a hypothesis-generating framework linking microglial state remodeling, neuronal metabolic and synaptic programs, and predicted neuroimmune communication patterns after ischemic stroke. Because each omics condition or time point was represented by one biological sample, all the transcriptomic findings should be considered preliminary and exploratory and should be validated in independently replicated cohorts.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149299203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuronal receptor remodeling in the aging periosteum: From single-cell atlases to regenerative targets.","authors":"Ziyu Liu, Jianguo Qi, Yong Liu, Hongshang Chu","doi":"10.4103/NRR.NRRONLINE-D-26-00902","DOIUrl":"https://doi.org/10.4103/NRR.NRRONLINE-D-26-00902","url":null,"abstract":"<p><strong>Abstract: </strong>The periosteum is the most densely innervated compartment of the skeleton and harbors periosteal stem cells expressing a broad repertoire of neuronal receptors traditionally associated with the nervous system. This narrative review aimed to map the neuronal receptor landscape of the periosteum and its age-dependent remodeling, and to evaluate the therapeutic implications of these receptors for age-related skeletal disorders. Literature was identified using a structured, PRISMA-informed search strategy across PubMed/MEDLINE, Web of Science, Scopus, and Embase from database inception. Eligible studies addressed neuronal receptor expression or signaling in periosteal tissue, periosteal stem and progenitor cells, or bone. Additionally, an exploratory reanalysis of the publicly available GSE297256 single-cell transcriptomic dataset was performed to contextualize the literature synthesis; no unpublished data were included. The literature synthesis delineated seven major neuronal receptor families in periosteal homeostasis: semaphorin-neuropilin, neurotrophin-Trk, Slit-Robo, adrenergic, cannabinoid, purinergic, and sensory neuropeptide systems. Restricting the analysis to bona fide neuronal receptors, 29 receptor genes were actively transcribed in periosteal stem cells, with neuropilin 2 (Nrp2) ranking highest by a composite score integrating expression magnitude, detection frequency, and cell-type specificity. In exploratory cell-level analysis, Nrp2 expression showed a progressive age-associated increase from young (log1p mean 1.35) to middle-aged (1.85) to old (2.70) mice, concomitant with a decline of Postn-expressing Osteo-X progenitors and activation of stress-response genes (Mt1, Mt2, Gadd45b, and Cebpd), and was associated with dysregulation of the axon guidance ligand Slit2, downregulation of osteocalcin-associated genes (Bglap and Bglap2), and predicted upstream regulation by the vitamin D receptor, implicating a vitamin D receptor-Nrp2 axis in periosteal aging. Age-related periosteal dysfunction, including cambium layer thinning, progenitor decline, and impaired progenitor-immune crosstalk, paralleled this receptor dysregulation. Neuronal receptor modulation, including Bdnf-TrkB, Sema3a-Nrp1, and Nrp2-targeted strategies, emerges as a promising multimodal approach for skeletal regeneration and aging intervention, warranting functional and clinical validation.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149299281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Divergent glial PANoptosis-related signatures and astrocyte-centered network remodeling in retinal ischemia-reperfusion injury: Single-cell RNAsequencing analysis.","authors":"Weitao Yan, Shuang Lu, Lewen Wang, Hao Wan, Yating Tan, Qi Zhang, Xinxing Wan, Yanxia Huang, Na Liu, Haifeng Wang, Ye He, Kun Xiong","doi":"10.4103/NRR.NRRONLINE-D-26-01034","DOIUrl":"https://doi.org/10.4103/NRR.NRRONLINE-D-26-01034","url":null,"abstract":"<p><strong>Abstract: </strong>Retinal ischemia-reperfusion injury is a major cause of irreversible vision loss. Although microglia, astrocytes, and Müller glia are key responders, how they coordinate their responses at single-cell resolution remains incompletely understood. Therefore, this study investigated differences in PANoptosis-related signatures among glial cells and astrocyte-centered network remodeling in retinal ischemia-reperfusion injury. In this study, we established a high-intraocular-pressurerat model and performed single-cell RNA-sequencing on control and injured retinas. Subcluster analysis, cell death pathway profiling, and CellChat-based communication inference were integrated to resolve glial heterogeneity, death programs, and communication networks. The results suggested a trend toward compositional remodeling in microglia, astrocytes, and Müller glia, characterized by a trend toward reduction of homeostatic subcluster and a trend toward expansion of reactive subcluster. The three glial types displayed divergent PANoptosis-related transcriptional patterns. Microglia showed concurrent upregulation of pyroptotic, apoptotic, and necroptotic markers together with the upstream sensor transcripts Aim2, Pycard, and Nlrp12. Astrocytes exhibited selective upregulation of NLRC5transcripts but ASC remained unchanged. Müller glia displayed predominantly apoptotic features. CellChat analysis inferred an astrocyte-centered remodeling of the glial communication network, in which microglia lost their dominant position as senders of inflammatory and trophic signals, while astrocytes showed increased signaling associated with damage sensing, inflammatory output, neurotrophic support, and immune recruitment. These findings suggest that astrocyte-centered network remodeling may represent a potential target for further investigation in retinal ischemia-reperfusion injury.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149299120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuro-cutaneous interactions in inflammatory, neuropathic, and metabolic skin diseases.","authors":"Jiajun Zhao, Xiujun Cheng, Yue Li, Yanxi Chen, Hejia Yang, Ningwen Zhu, Linya You","doi":"10.4103/NRR.NRRONLINE-D-26-00911","DOIUrl":"https://doi.org/10.4103/NRR.NRRONLINE-D-26-00911","url":null,"abstract":"<p><strong>Abstract: </strong>The skin and nervous system engage in bidirectional communication. Disruption is implicated in inflammatory, neuropathic and metabolic disorders. To systematically review the structural and functional basis of skin-nerve interactions in health and disease, following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A systematic search of PubMed (inception to June 10, 2026) combined MeSH and free-text terms for skin innervation, sensory neurons, sympathetic nervous system, neuropeptides, neuroimmune regulation, and skin diseases. Manual supplementation via reference tracing and author searches improved recall. 86 original studies were ultimately included (45 from database search and 41 from manual supplementation). Key findings: (1) Keratinocytes, Merkel, Langerhans and melanocytes form synapse-like connections with nerve endings, establishing a \"sensory epithelium.\" (2) Substance P activates mast cells via neurokinin 1 receptor/mas-related G protein-coupled receptor X2 (neurogenic inflammation); while calcitonin gene-related peptide inhibits dendritic cells (immune tolerance). (3) In atopic dermatitis, stress recruits basophils/eosinophils via sympathetic-beta-2 adrenergic receptor axis; in psoriasis, TRPV1+ neurons activate the interleukin-23/interleukin-17 axis via calcitonin gene-related peptide. (4) Stress induces sensory neurons to release miR-let-7b, exacerbating psoriasis via macrophage Toll-like receptor 7. (5) Postherpetic neuralgia: intraepidermal nerve fiber density < 650 neurites/mm2 correlates with central hyperexcitability (\"phantom pain\"). (6) Neurofibromatosis type 1 (RAS) and guanine nucleotide-binding protein G(q) subunit alpha (ANGPT2) mutations reveal mechanisms for tumors or vascular malformations. (7) Heat stress induces skin kallikrein-related peptidase 14 to reprogram hypothalamic LRRC7+ astrocytes via blood, forming a \"heat memory\" that leads to metabolic disorders (reversed by vitamin A). Substance P/neurokinin 1 receptor, sensory nerve-calcitonin gene-related peptide-interleukin-23, sympathetic-beta-2 adrenergic receptor-basophil/eosinophil, and skin-hypothalamic circuits are key translational pathways. Targeting these (neurokinin 1 receptor antagonists, β-blockers, anti-calcitonin gene-related peptide antibodies, and vitamin A) offers therapeutic opportunities for inflammatory skin diseases, neuropathic itch/pain and stress-related metabolic disorders.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149299196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic-epigenetic coupling links glycolysis to macrophage-mediated myelin clearance after peripheral nerve injury.","authors":"Yongxing Zhang, Lei Huang, Fanqi Kong, Qian Wu, Peng Yang, Chen Shan, Xiaosheng Xu, Zhuorun Song, Yunfei He, Xingdong Xiang, Guokang Mo, Cheng Zhang, Huilin Yang, Jian Zhang, Jiayi Wang, Dehua Meng, Shunyi Lu","doi":"10.4103/NRR.NRRONLINE-D-26-00965","DOIUrl":"https://doi.org/10.4103/NRR.NRRONLINE-D-26-00965","url":null,"abstract":"<p><strong>Abstract: </strong>Macrophages are essential for myelin clearance following peripheral nerve injury, yet the mechanisms linking their functional heterogeneity to metabolic regulation remain unclear. Single-cell RNA sequencing was combined with functional assays to characterize macrophage heterogeneity and investigate the relationship between metabolic reprogramming and myelin clearance after peripheral nerve injury. A distinct macrophage subset enriched was identified after injury that exhibited elevated expression of glycolysis-related and phagocytosis-associated genes. Functional analyses demonstrated that glycolytic activity was positively associated with macrophage-mediated myelin clearance. Among candidate regulators, solute carrier family 2 member 6 was highly expressed in this subset, and its knockdown impaired glycolysis, lactate production, histone lactylation and myelin clearance capacity, effects that were partially rescued by metabolic intervention or lactate supplementation. In vivo, lactate administration was associated with enhanced myelin clearance and improved nerve structural and functional recovery. These findings provide new insights into the interplay between metabolic reprogramming and immune function in nerve injury. These results provide a mechanistic foundation for the development of metabolism-targeted therapeutic strategies to enhance peripheral nerve regeneration.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149271297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oleanolic acid-hesperetin co-assembled nanoparticles alleviate neurological injury after ischemic stroke via the PI3K/AKT/GSK-3β axis.","authors":"Tianqing Xiong, Hong Zhu, Xingyi Wang, Ziying Wang, Yebin Zhou, Jingyan Liang, Yingge Wang","doi":"10.4103/NRR.NRRONLINE-D-26-00801","DOIUrl":"https://doi.org/10.4103/NRR.NRRONLINE-D-26-00801","url":null,"abstract":"<p><strong>Abstract: </strong>Ischemic stroke remains a leading cause of death and long-term disability, while the current clinically applicable adjunctive neuroprotective strategies face substantial limitations. Oleanolic acid and hesperetin exhibit synergistic antioxidant, anti-inflammatory, and anti-apoptotic activities; however, their poor aqueous solubility and limited bioavailability remain major limitations to their therapeutic development. Oleanolic acid and hesperetin were formulated as co-assembled nanoparticles using an emulsion-solvent evaporation method. A 5:2 mass ratio of oleanolic acid to hesperetin produced primarily spherical nanoparticles with a mean hydrodynamic diameter of approximately 282.6 nm, a polydispersity index of 0.197, and a zeta potential of -12.2 mV. Oleanolic acid-hesperetin nanoparticles displayed minimal hemolysis (0.199%) while maintaining a stable hydrodynamic diameter during 30 days of storage. Spectroscopic analyses and a 50 ns molecular dynamics simulation promoted co-assembly via multiple noncovalent-driven interactions. Oleanolic acid-hesperetin nanoparticles effectively reduced oxygen-glucose deprivation/reperfusion-induced viability loss and apoptosis in HT22 cells. In transient middle cerebral artery occlusion mice, Cy5.5-associated fluorescence was observed in brain tissue, whereas oleanolic acid-hesperetin nanoparticle treatment reduced infarct volume and ipsilesional brain water content, preserved neurons, resulting in improved sensorimotor and spatial cognitive outcomes through day 28. Treatment promoted PI3K and AKT phosphorylation, elevated inhibitory phosphorylation of glycogen synthase kinase 3β at Ser9 and BCL-2 expression, and reduced BAX expression. These findings suggest that oleanolic acid-hesperetin co-assembly offers a promising preclinical formulation approach for multifactorial neuroprotection after ischemic stroke and supports further pharmacokinetic, safety, and pathway-causality studies.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149271309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}