Neural Regeneration Research最新文献

{"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}

{"title":"Peripheral nerve regeneration: Sensory and motor neurons and tissue engineering repair strategies.","authors":"Chengcheng Luan, Dong Ming, Panjian Lu, Xiaosong Gu","doi":"10.4103/NRR.NRRONLINE-D-26-00896","DOIUrl":"https://doi.org/10.4103/NRR.NRRONLINE-D-26-00896","url":null,"abstract":"<p><strong>Abstract: </strong>The functional reconstruction bottleneck induced by peripheral nerve injury essentially arises from a spatiotemporal mismatch between the regenerative dynamics of injured neurons and tissue remodeling. Longsegment nerve defects represent the most intractable clinical scenario, where the approximately 1 mm daily axonal regeneration rate cannot counteract rapid, irreversible skeletal muscle denervation atrophy, frequently resulting in permanent motor deficits even after anatomical nerve reconnection. Autologous nerve transplantation, regarded as the clinical gold standard for longgap repair, is limited by donor tissue scarcity and donorsite morbidity, which further drives the development of alternative tissueengineering strategies. Although tissue-engineered nerve grafts have advanced from simple physical bridging in animal models to the reconstruction of biomimetic microenvironments, their clinical performance in motor function restoration remains suboptimal. This review systematically elaborates the distinct response patterns of sensory neurons and motor neurons throughout the entire process of nerve injury and regeneration, with in-depth analysis of their asymmetric regulatory characteristics within the central-peripheral neural network. Sensory neurons exhibit robust cellautonomous regenerative competence, whereas motor neuron regeneration strongly depends on retrograde trophic feedback from skeletal muscle and suffers progressive regenerative decay under prolonged denervation. Notably, considerable knowledge gaps still exist regarding subtypespecific transcriptional reprogramming of motor neurons, restricting precise motorfunction repair. Furthermore, we summarize state-of-the-art tissue-engineered nerve graft strategies, contrasting microenvironmental remodeling with subtype-targeted therapies. Finally, we propose an innovative framework for next-generation tissue-engineered nerve grafts: evolving from physical bridges into central-peripheral signal relay stations capable of remotely modulating somatic transcriptional programs to achieve synchronized sensory and motor functional recovery. Collectively, this work provides solid theoretical support and a biomimetic design paradigm for the synchronized and efficient reconstruction of both sensory and motor functions following peripheral nerve 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":"149271315","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":"Constructing functional neural circuits to model amyotrophic lateral sclerosis with induced pluripotent stem cell-derived brain organoids.","authors":"Yuhu Niu, Dong Zhang, Tao Gong, Guoying Guo, Hao Zhang, Chong Gao, Jiangli Yang","doi":"10.4103/NRR.NRRONLINE-D-26-00781","DOIUrl":"https://doi.org/10.4103/NRR.NRRONLINE-D-26-00781","url":null,"abstract":"<p><strong>Abstract: </strong>Amyotrophic lateral sclerosis is a progressive neurodegenerative disease characterized by the degeneration of both upper and lower motor neurons. Recent advances in human-induced pluripotent stem cell-derived brain organoids offer an innovative platform to model amyotrophic lateral sclerosis in a human-specific context. These three-dimensional organoid systems allow for the study of neuronal circuit-level dysfunction, which is central to amyotrophic lateral sclerosis pathogenesis, by incorporating multiple neuronal subtypes and supporting glial populations. In particular, the integration of region-specific brain organoids into assembloid models has enabled the reconstruction of functional long-range projections and cortico-motor circuits, closely resembling human neural connectivity. This review summarizes the generation and application of human induced pluripotent stem cell-derived brain organoids for amyotrophic lateral sclerosis research, with a focus on the reconstruction of neural circuits, multi-omics profiling, and functional assays. We also discuss how organoid systems can be leveraged for drug discovery and personalized medicine in amyotrophic lateral sclerosis, highlighting their potential to unveil human-specific disease mechanisms. Lastly, we address the current challenges and future directions for improving the physiological relevance of organoid models in amyotrophic lateral sclerosis research.</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":"149271282","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":"Altered intersubject variability of functional connectivity in gray and white matter underlying neurocognition and genetic profiles in neuromyelitis optica spectrum disorder.","authors":"Chuxin Huang, Wei Lu, Jun Liu","doi":"10.4103/NRR.NRRONLINE-D-26-00776","DOIUrl":"https://doi.org/10.4103/NRR.NRRONLINE-D-26-00776","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Abstract: &lt;/strong&gt;Neuromyelitis optica spectrum disorder is an autoimmune disease that causes inflammatory damage to the central nervous system. While alterations in functional connectivity have been reported in neuromyelitis optica spectrum disorder, changes in intersubject variability of functional connectivity within gray matter and white matter are not yet understood. A total of 66 patients with neuromyelitis optica spectrum disorder and 71 healthy controls were recruited. We compared intersubject variability of functional connectivity between patients with neuromyelitis optica spectrum disorder and healthy controls and performed subgroup analyses comparing neuromyelitis optica spectrum disorder patients with and without a history of optic neuritis. We also examined the associations between intersubject variability of functional connectivity alterations and disease duration, clinical disability, and cognitive scores. We combined our imaging results with those of the Allen Human Brain Atlas to conduct transcriptome-neuroimaging association analyses, identified gene expression profiles linked to intersubject variability of functional connectivity alterations and characterized their potential biological functions. Compared with healthy controls, patients with neuromyelitis optica spectrum disorder showed widespread increases in intersubject variability of functional connectivity. Notable gray matter alterations included the precentral and postcentral gyri; extensive occipital areas; and the insula, putamen, and thalamus. The corresponding white matter changes involved the fornix, corticospinal tract, widespread corona radiata, cingulum, and uncinate fasciculus. Compared with patients without optic neuritis, the optic neuritis subgroup exhibited distinct intersubject variability of functional connectivity alterations in specific regions, such as the inferior parietal lobule, angular gyrus, thalamus, fornix, and internal capsule. Clinically, only white matter-intersubject variability of functional connectivity correlated significantly with physical disability and cognitive processing speed and was not significantly associated with disease duration. Transcriptomic analysis revealed that genes positively associated with white matter-intersubject variability of functional connectivity were enriched in synaptic plasticity and cognition, while negatively associated genes were enriched in oxidative stress. Additionally, genes positively associated with the gray matter-intersubject variability of functional connectivity were enriched in myelination and lipid biosynthesis, whereas genes negatively associated with the gray matter-intersubject variability of functional connectivity were involved in synapse organization. In conclusion, our study revealed alterations in gray matter- and white matter-intersubject variability of functional connectivity across neuromyelitis optica spectrum disorder and clinical subtypes. We demonstrate that changes i","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":"149271275","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":"Membrane targeted rabies virus labeling system: Brain-wide single-neuron mapping of target-specific and intersectionally defined neuronal circuits.","authors":"Xinyu Yuan, Jianchao Zhang, Yunmiao Liu, Lin Jin, Lin Song, Yuxing Lan, Chi Xiao, Hui Gong, Qingming Luo, Xiaojun Wang","doi":"10.4103/NRR.NRRONLINE-D-26-00903","DOIUrl":"https://doi.org/10.4103/NRR.NRRONLINE-D-26-00903","url":null,"abstract":"<p><strong>Abstract: </strong>Elucidating neural circuit organization at single-neuron resolution is a core goal of modern neuroscience. Brain-wide input connectivity maps underpin the mammalian connectome, but systematic and comprehensive whole-brain input mapping with resolved single-neuron anatomy for defined brain regions remains a formidable technical challenge. Here, we developed a membrane-targeted rabies virus labeling system using mClover3 as the fluorescent reporter, which features high compatibility with fluorescence micro-optical sectioning tomography imaging and enables complete visualization of fine neuronal morphology across the entire brain. Validation in the mouse primary somatosensory cortex barrel field confirms robust full-morphology labeling and faithful reconstruction of brain-wide input neurons, revealing diverse projection patterns with distinct axonal targets. We further generated a dual-recombinase dependent TVA reporter mouse line to enable anatomical interrogation of intersectionally defined neuron populations via EnvA-pseudotyped membrane-targeted rabies virus, allowing specific targeting and single-neuron reconstruction of PV+/vGlut2+ L5b pyramidal neurons in the primary somatosensory cortex barrel field. These neurons exhibited a pathway-conserved population-level projection profile likely representing a subset of pyramidal tract neuron projections, while showing pronounced cellto-cell diversity in axonal target specificity. Overall, this work delivers a robust, versatile toolkit for brain-wide single-neuron mapping of target-specific and intersectionally defined neuronal circuits, with strong potential to advance brain connectomics.</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":"149271312","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":"Corticomuscular coupling alterations during task-dependent bimanual coordination after stroke: A multimodal functional near-infrared spectroscopy-surface electromyography analysis.","authors":"Mingchao Liu, Nan Zheng, Quanlin Lin, Yurong Li, Bo Sheng, Xiaoling Wang, Qiurong Xie","doi":"10.4103/NRR.NRRONLINE-D-26-00785","DOIUrl":"https://doi.org/10.4103/NRR.NRRONLINE-D-26-00785","url":null,"abstract":"<p><strong>Abstract: </strong>Post-stroke bimanual coordination dysfunction severely impairs activities of daily living. However, the underlying neurophysiological mechanisms remain incompletely understood, particularly regarding central-peripheral coupling characteristics under different bimanual coordination tasks and their distinction from aging effects. This study included 32 chronic subcortical stroke patients and 29 healthy controls. Functional near-infrared spectroscopy and surface electromyography signals were synchronously acquired during the execution of symmetrical and asymmetrical bimanual coordination tasks. Analyzed indices included cortical activation patterns, functional connectivity, corticomuscular coupling characterized by transfer entropy, intermuscular coupling, and muscle synergies. Correlations between these indices and the Fugl-Meyer Assessment for Upper Extremity and Modified Barthel Index were also evaluated. The results showed that during the symmetrical task, the ascending muscle-to-cortex connectivity was significantly reduced in the patient group, and this index was significantly positively correlated with the Modified Barthel Index. Brain functional connectivity and cortical activation were significantly increased in the patient group, and the connectivity from the ipsilesional prefrontal cortex to the contralesional SAC was significantly negatively correlated with Fugl-Meyer Assessment for Upper Extremity scores. Additionally, intermuscular coupling was significantly weakened, and muscle synergy patterns were abnormal in the patient group. During the asymmetrical task, no significant group differences in corticomuscular coupling were found, but brain functional connectivity and cortical activation were both significantly increased, and the connectivity from the ipsilesional supplementary motor area to the contralesional supplementary motor area was significantly positively correlated with MBI. Intermuscular coupling was significantly weakened, and muscle synergy patterns were abnormal. Attribution analysis suggested that cortical hyperactivation patterns and abnormal muscle synergies mainly reflect stroke effects, while abnormal sensory cortex activation and altered corticomuscular coupling may be influenced by both stroke and aging. This study suggests that post-stroke bimanual coordination impairment is closely related to selective damage to sensory feedback pathways, manifested as task-dependent reductions in ascending (muscle-to-cortex) corticomuscular coupling and compensatory cortical reorganization. Multimodal neurophysiological indicators may serve as potential quantitative tools for assessing upper limb function after stroke, but age-matched control studies are essential to dissociate stroke effects from aging effects.</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":"149271306","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":"Development of a biomimetic manganese dioxide nanoreactor delivery system: Combination of biomimetic platelet/M2 microglia hybrid membrane with Astragaloside IV for the treatment of ischemic stroke.","authors":"Congying Wang, Jing Wang, Ying Zhang, Xianglong Ge, Deteng Zhang, Yang Zhao","doi":"10.4103/NRR.NRRONLINE-D-26-00912","DOIUrl":"https://doi.org/10.4103/NRR.NRRONLINE-D-26-00912","url":null,"abstract":"<p><strong>Abstract: </strong>Conventional nanotherapeutics suffer from rapid immune clearance and insufficient accumulation in ischemic lesions. To overcome these bottlenecks, a stimuli-responsive biomimetic immunomodulatory delivery system was engineered by fusing platelet and M2 microglial membranes onto hollow mesoporous manganese dioxide nanoparticles loaded with the neuroprotective drug Astragaloside IV. The results show that this integrated nanoplatform fully leverages the synergistic properties of its biomimetic shell. Tracing the nanoparticles with the fluorescent dye Did revealed that the integrated nanoplatform exhibited more pronounced fluorescent enrichment in ischemic brain tissue; both in vivo and ex vivo imaging supported its specific homing ability. In a mouse model of middle cerebral artery occlusion and reperfusion, the platform significantly reduced the extent of cerebral infarction, alleviated neuronal damage caused by ischemia-reperfusion, and improved neurovascular integrity and neurological function. Furthermore, the platform mitigated oxidative stress in ischemic brain tissue, curtailed the inflammatory response, and facilitated a transition in microglial phenotype toward an anti-inflammatory and reparative state. Bioinformatics results indicate that this platform significantly alters gene expression profiles following cerebral ischemia-reperfusion. Differential expression and functional enrichment analyses further point to biological processes related to inflammation and immune regulation. These findings demonstrate that this biomimetic targeted nanoplatform integrates biomimetic targeting, reactive oxygen species scavenging, and immune modulation capabilities, thereby providing a new therapeutic platform technology for the precise delivery of therapeutic agents and the remodeling of the pathological microenvironment 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":"149271321","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}