Neural Regeneration Research最新文献

{"title":"An integrated single-nucleus ribonucleic acid sequencing and spatial transcriptomic atlas reveals stage-specific neuronal and glial trajectories in a mouse model of amyotrophic lateral sclerosis.","authors":"Qi Zhou, Tian Gong, Jiahao Liu, Junpeng Ma, Minxiu Zheng, Ziwei Zhong, Haitao Deng, Haiyan Lin, Nan Feng, Xiao Lei, Chengsheng Zhang","doi":"10.4103/NRR.NRR-D-25-00859","DOIUrl":"10.4103/NRR.NRR-D-25-00859","url":null,"abstract":"","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"5649-5661"},"PeriodicalIF":8.5,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148033528","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":"Electroacupuncture improves spatial learning and memory functions in triple-transgenic Alzheimer's disease model mice by enhancing glutamatergic synapse plasticity in the entorhinal cortex-hippocampal CA1 circuit.","authors":"Bingbing Lin, Linsong Chai, Shuang Zuo, Yaling Dai, Lidian Chen, Jia Huang","doi":"10.4103/NRR.NRR-D-25-00606","DOIUrl":"10.4103/NRR.NRR-D-25-00606","url":null,"abstract":"","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"5594-5603"},"PeriodicalIF":8.5,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147355741","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":"Dendritic mesoporous silica nanoparticle-based nasal delivery carriers for passive immunotherapy of Alzheimer's disease.","authors":"Kai Cao, Jun Xie, Xiaohan Liang, Yanqing Li, Hui Gong, Haiming Luo","doi":"10.4103/NRR.NRR-D-25-00917","DOIUrl":"10.4103/NRR.NRR-D-25-00917","url":null,"abstract":"","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"5404-5414"},"PeriodicalIF":8.5,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147675485","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":"Corrigendum: Inhibitory gamma-aminobutyric acidergic neurons in the anterior cingulate cortex participate in the comorbidity of pain and emotion.","authors":"","doi":"10.4103/NRR.NRR-D-26-00540","DOIUrl":"10.4103/NRR.NRR-D-26-00540","url":null,"abstract":"","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":"21 11","pages":"5105"},"PeriodicalIF":8.5,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874949","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}

{"title":"Mechanisms of auditory cortex injury and the protective effects of reoxygenation in a rat model of intermittent hypoxia.","authors":"Yue Wu, Tao Li, Mengqin Li, Furong Ma, Yan Yan","doi":"10.4103/NRR.NRRONLINE-D-26-00775","DOIUrl":"https://doi.org/10.4103/NRR.NRRONLINE-D-26-00775","url":null,"abstract":"<p><strong>Abstract: </strong>Intermittent hypoxia associated with obstructive sleep apnea can impair auditory function, but the early mechanisms underlying auditory cortical injury and the extent to which these changes recover after the restoration of normoxia remain unclear. This study investigated the mechanisms underlying auditory cortical injury in a rat model of intermittent hypoxia and evaluated the protective effects of reoxygenation. Adult male Sprague-Dawley rats were assigned to control, intermittent hypoxia, intermittent hypoxia followed by 1 week of normoxic recovery, or control followed by normoxic recovery groups. Short-term intermittent hypoxia caused high-frequency hearing loss and increased spontaneous firing in the primary auditory cortex. After 1 week of normoxic recovery, auditory thresholds and cortical firing rates returned to levels comparable to those in the control group. Glutamate levels did not differ significantly among the groups, whereas γ-aminobutyric acid and 5-hydroxytryptamine levels were elevated in the intermittent hypoxia followed by normoxic recovery group. Intermittent hypoxia increased superoxide dismutase activity, reduced catalase activity, and elevated the levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6. Normoxic recovery normalized catalase activity and reduced tumor necrosis factor-α and interleukin-6 levels, whereas superoxide dismutase activity and interleukin- 1β levels remained elevated. Metabolomic analysis identified alterations in unsaturated fatty acid biosynthesis, branched-chain amino acid metabolism, ferroptosis-related pathways, redox-related metabolism, and amino acid and protein turnover, several of which persisted after recovery. These findings indicate that acute intermittent hypoxia-induced auditory dysfunction and cortical hyperexcitability are reversible, whereas redox, inflammatory, and metabolic abnormalities recover asynchronously. Persistent molecular disturbances after functional recovery may provide potential targets for further investigation of obstructive sleep apnea-associated central auditory injury.</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":"149271318","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":"Mechanisms of Spns2 in regulating neuroinflammatory activation of microglia after cerebral ischemia in rats.","authors":"Sixuan He, Jiecheng Guo, Yunsheng Fang, Huijing Hu, Le Li","doi":"10.4103/NRR.NRRONLINE-D-26-00929","DOIUrl":"https://doi.org/10.4103/NRR.NRRONLINE-D-26-00929","url":null,"abstract":"<p><strong>Abstract: </strong>Microglia, the resident innate immune cells of the brain, maintain central nervous system homeostasis but can also mediate inflammatory injury after ischemic stroke. Following ischemia, microglia can adopt pro-inflammatory M1- or reparative M2-like state; thus, regulating the balance between these phenotypes may be therapeutically relevant. Sphingosine-1-phosphate signaling regulates immune responses, angiogenesis, and endothelial barrier integrity. Enhanced sphingosine-1-phosphate signaling in activated microglia after ischemic injury may amplify inflammatory cascades. However, strategies targeting sphingosine-1-phosphate signaling are constrained by the heterogeneous expression of sphingosine-1-phosphate receptors. Spinster homolog 2 (Spns2), a sphingosine-1-phosphate exporter, may provide an alternative target, although its role in ischemic stroke remains unclear. To investigate the role of Spns2 in post-ischemic neuroinflammation, middle cerebral artery occlusion/reperfusion was induced in Spns2-deficient (Spns2-/-) and wild-type rats. BV2 microglial cells exposed to oxygen-glucose deprivation/reoxygenation were used as an in vitro model. Spns2 mRNA expression in the peri-infarct penumbra increased after middle cerebral artery occlusion/reperfusion and peaked at 24 hours. Compared with wild-type rats, Spns2-/- rats showed lower neurological deficit scores, improved motor performance, and smaller infarct volumes. In the peri-infarct penumbra, Spns2 deficiency was associated with decreased expression of pro-inflammatory markers, increased expression of anti-inflammatory markers, and attenuated microglia-associated NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome signaling. In BV2 cells, Spns2 knockdown produced similar changes in inflammatory-marker expression and reduced oxygen-glucose deprivation/reoxygenation-induced NLRP3 inflammasome-associated signaling and oxidative stress. Spns2 knockdown reduced extracellular sphingosine-1-phosphate levels in BV2-cell culture supernatants, whereas exogenous sphingosine-1-phosphate supplementation increased the expression of inflammasome-associated inflammatory mediators in Spns2-knockdown BV2 cells. RNA sequencing identified Itga5 upregulation in Spns2-/- rats and showed that differentially expressed genes between Spns2-/- and wild-type rats were enriched in the phosphoinositide 3-kinase/protein kinase B (Akt) signaling pathway. Increased Akt phosphorylation in Spns2-/- rats was further confirmed by western blotting. These findings indicate that Spns2 deficiency limits sphingosine-1-phosphate export and attenuates microglia-associated neuroinflammation after ischemic stroke. Itga5 upregulation and increased Akt phosphorylation may be associated with this neuroprotective effect. Collectively, our results provide a basis for further investigation of the Spns2-sphingosine-1-phosphate axis in ischemic stroke.</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":"149271272","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":"Synchronization of the nucleus accumbens-ventral hippocampus reflects cooperative ability and predicts social dysfunction after training in mice.","authors":"Xianji Pan, Chan Li, Qingwei Huo, Xinru Zhang, Xiaoxiao Zhang, Ying Zheng, Afzal Misrani, Cheng Long, Li Yang","doi":"10.4103/NRR.NRRONLINE-D-26-00835","DOIUrl":"https://doi.org/10.4103/NRR.NRRONLINE-D-26-00835","url":null,"abstract":"<p><strong>Abstract: </strong>Cooperation is a fundamental form of social behavior that promotes collective benefits and group survival. Although considerable progress has been made in understanding cooperation from behavioral and theoretical perspectives, the neural activities underlying cooperative behavior remain incompletely understood. In the present study, we established a cooperative behavioral paradigm in pairs of mice using a Skinner box, with the protocol spanning 22 days. Mice were retrospectively classified into high-, middle-, and low-performance groups based on their performance in the cooperation task. In vivo local field potential recordings from the nucleus accumbens and ventral hippocampus were then conducted in the three groups. High-cooperation mice showed significantly increased delta and low-gamma power in the nucleus accumbens, as well as enhanced delta, theta, beta, and low-gamma power in the ventral hippocampus, compared to low-cooperation mice. Meanwhile, nucleus accumbens-ventral hippocampus coherence within the beta and low-gamma frequency bands was significantly reduced in high-cooperation animals. Behaviorally, high-cooperation mice exhibited social dysfunction as shown by reduced social interaction and more pronounced anxiety-like behaviors compared with low-cooperation mice after training. Collectively, these findings provide early evidence that individual differences in cooperative behavior are associated with distinct patterns of neural oscillatory activity within the nucleus accumbens-ventral hippocampus circuit. Moreover, enhanced cooperative performance was correlated with alterations in social and affective behavior, such as increased social avoidance and anxiety-like behavior. The results suggest that nucleus accumbens-ventral hippocampus oscillatory dynamics may represent a neural correlate of cooperative behavior, and that training-induced differences in cooperative performance are associated with subsequent changes in social and affective functioning.</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":"149271187","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 activation protein and Periostin in cerebrospinal fluid: Candidate biomarkers in chronic spinal cord injury.","authors":"Senyu Yao, Jun Kang, Xiaomin Ye, Ziqi Xie, Yaobang Lin, Xu Huang, Yangfan Yu, Jimin Guan, Zifeng Liu, Bin Liu, Mao Pang, Limin Rong","doi":"10.4103/NRR.NRRONLINE-D-26-00877","DOIUrl":"https://doi.org/10.4103/NRR.NRRONLINE-D-26-00877","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Abstract: &lt;/strong&gt;Chronic spinal cord injury is biologically heterogeneous, and biomarkers that distinguish injury severity from longitudinal biological response are lacking. We evaluated whether fibroblast activation protein and Periostin in cerebrospinal fluid provide complementary, chronicity-dependent information on neurological severity and recovery in chronic traumatic spinal cord injury. This secondary biomarker study analyzed prospectively collected data and cerebrospinal fluid samples from two clinical trials. Seventy-two participants treated with human umbilical cord-derived mesenchymal stromal cells were classified as early chronic (2-12 months after injury; n = 35) or late chronic (&gt; 12 months; n = 37); 18 early chronic participants received saline, and 14 non-spinal cord injury patients served as controls. Fibroblast activation protein and Periostin were measured before intervention and at month 3, with paired samples available for 62 human umbilical cord-derived mesenchymal stromal cell-treated participants. American Spinal Injury Association Impairment Scale (AIS) grade and motor, sensory, and mobility outcomes were assessed through month 15. At baseline, both biomarkers were inversely associated with AIS grade in the human umbilical cord-derived mesenchymal stromal cell cohort, with a stronger correlation for fibroblast activation protein (ρ = .0.5730, P &lt; 0.001) than Periostin (ρ = .0.3125, P = 0.0075). Fibroblast activation protein discriminated AIS A from AIS B-D with an area under the curve (AUC) of 0.8522 and AIS A-B from AIS C-D with an AUC of 0.7337; corresponding AUCs for Periostin were 0.7009 and 0.6144. Associations with 15-month AIS outcomes were broader in early than late chronic spinal cord injury. In the early chronic human umbilical cord-derived mesenchymal stromal cell cohort, baseline fibroblast activation protein separated motor, pinprick, and light-touch improvement groups (AUCs, 0.7454-0.7989), and lower baseline fibroblast activation protein was associated with a higher cumulative probability of first AIS-grade improvement (log-rank P = 0.045). Early 3-month biomarker changes were not associated with motor improvement. In late chronic spinal cord injury, larger decreases in fibroblast activation protein and Periostin were associated with greater motor improvement (P = 0.0218 and P = 0.0139), differentiated longitudinal motor, sensory, and mobility trajectories, and were associated with a higher cumulative probability of first AIS-grade improvement (both log-rank P = 0.035). Saline-cohort findings were heterogeneous and exploratory. Fibroblast activation protein and Periostin in cerebrospinal fluid showed complementary patterns across trial-defined chronicity strata in chronic spinal cord injury. Baseline fibroblast activation protein was consistently associated with injury severity and subsequent neurological status, particularly in early chronic spinal cord injury, whereas within-person changes in","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":"149271331","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}