Neural Regeneration Research最新文献

{"title":"Generation, interrogation, and future applications of microglia-containing brain organoids.","authors":"Julia Di Stefano, Federica Di Marco, Ilaria Cicalini, Una FitzGerald, Damiana Pieragostino, Marleen Verhoye, Peter Ponsaerts, Elise Van Breedam","doi":"10.4103/NRR.NRR-D-24-00921","DOIUrl":"10.4103/NRR.NRR-D-24-00921","url":null,"abstract":"<p><p>Brain organoids encompass a large collection of in vitro stem cell-derived 3D culture systems that aim to recapitulate multiple aspects of in vivo brain development and function. First, this review provides a brief introduction to the current state-of-the-art for neuro-ectoderm brain organoid development, emphasizing their biggest advantages in comparison with classical two-dimensional cell cultures and animal models. However, despite their usefulness for developmental studies, a major limitation for most brain organoid models is the absence of contributing cell types from endodermal and mesodermal origin. As such, current research is highly investing towards the incorporation of a functional vasculature and the microglial immune component. In this review, we will specifically focus on the development of immune-competent brain organoids. By summarizing the different approaches applied to incorporate microglia, it is highlighted that immune-competent brain organoids are not only important for studying neuronal network formation, but also offer a clear future as a new tool to study inflammatory responses in vitro in 3D in a brain-like environment. Therefore, our main focus here is to provide a comprehensive overview of assays to measure microglial phenotype and function within brain organoids, with an outlook on how these findings could better understand neuronal network development or restoration, as well as the influence of physical stress on microglia-containing brain organoids. Finally, we would like to stress that even though the development of immune-competent brain organoids has largely evolved over the past decade, their full potential as a pre-clinical tool to study novel therapeutic approaches to halt or reduce inflammation-mediated neurodegeneration still needs to be explored and validated.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"3448-3460"},"PeriodicalIF":5.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma circulating cell-free DNA integrity and relative telomere length as diagnostic biomarkers for Parkinson's disease and multiple system atrophy: a cross-sectional study.","authors":"Chao Ying, Chao Han, Yuan Li, Mingkai Zhang, Shuying Xiao, Lifang Zhao, Hui Zhang, Qian Yu, Jing An, Wei Mao, Yanning Cai","doi":"10.4103/NRR.NRR-D-24-00599","DOIUrl":"10.4103/NRR.NRR-D-24-00599","url":null,"abstract":"&lt;p&gt;&lt;p&gt;JOURNAL/nrgr/04.03/01300535-202512000-00025/figure1/v/2025-01-31T122243Z/r/image-tiff In clinical specialties focusing on neurological disorders, there is a need for comprehensive and integrated non-invasive, sensitive, and specific testing methods. Both Parkinson's disease and multiple system atrophy are classified as α-synucleinopathies, characterized by abnormal accumulation of α-synuclein protein, which provides a shared pathological background for their comparative study. In addition, both Parkinson's disease and multiple system atrophy involve neuronal death, a process that may release circulating cell-free DNA (cfDNA) into the bloodstream, leading to specific alterations. This premise formed the basis for investigating cell-free DNA as a potential biomarker. Cell-free DNA has garnered attention for its potential pathological significance, yet its characteristics in the context of Parkinson's disease and multiple system atrophy are not fully understood. This study investigated the total concentration, nonapoptotic level, integrity, and cell-free DNA relative telomere length of cell-free DNA in the peripheral blood of 171 participants, comprising 76 normal controls, 62 patients with Parkinson's disease, and 33 patients with multiple system atrophy. In our cohort, 75.8% of patients with Parkinson's disease (stage 1-2 of Hoehn & Yahr) and 60.6% of patients with multiple system atrophy (disease duration less than 3 years) were in the early stages. The diagnostic potential of the cell-free DNA parameters was evaluated using receiver operating characteristic (ROC) analysis, and their association with disease prevalence was examined through logistic regression models, adjusting for confounders such as age, sex, body mass index, and education level. The results showed that cell-free DNA integrity was significantly elevated in both Parkinson's disease and multiple system atrophy patients compared with normal controls ( P &lt; 0.001 for both groups), whereas cell-free DNA relative telomere length was markedly shorter ( P = 0.003 for Parkinson's disease and P = 0.010 for multiple system atrophy). Receiver operating characteristic analysis indicated that both cell-free DNA integrity and cell-free DNA relative telomere length possessed good diagnostic accuracy for differentiating Parkinson's disease and multiple system atrophy from normal controls. Specifically, higher cell-free DNA integrity was associated with increased risk of Parkinson's disease (odds ratio [OR]: 5.72; 95% confidence interval [CI]: 1.54-24.19) and multiple system atrophy (OR: 10.10; 95% CI: 1.55-122.98). Conversely, longer cell-free DNA relative telomere length was linked to reduced risk of Parkinson's disease (OR: 0.16; 95% CI: 0.04-0.54) and multiple system atrophy (OR: 0.10; 95% CI: 0.01-0.57). These findings suggest that cell-free DNA integrity and cell-free DNA relative telomere length may serve as promising biomarkers for the early diagnosis of Parkinson's disease and multi","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"3553-3563"},"PeriodicalIF":5.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of astrocytes and microglia in hepatic encephalopathy associated with advanced chronic liver disease: lessons from animal studies.","authors":"Wouter Claeys, Anja Geerts, Lien Van Hoecke, Christophe Van Steenkiste, Roosmarijn E Vandenbroucke","doi":"10.4103/NRR.NRR-D-24-00600","DOIUrl":"10.4103/NRR.NRR-D-24-00600","url":null,"abstract":"<p><p>Hepatic encephalopathy, defined as neuropsychiatric dysfunction secondary to liver disease, is a frequent decompensating event in cirrhosis. Its clinical impact is highlighted by a notable increase in patient mortality rates and a concomitant reduction in overall quality of life. Systemically, liver disease, liver function failure, portosystemic shunting, and associated multi-organ dysfunction result in the increase of disease-causing neurotoxins in the circulation, which impairs cerebral homeostasis. Key circulating neurotoxins are ammonia and inflammatory mediators. In the brain, pathophysiology is less well understood, but is thought to be driven by glial cell dysfunction. Astrocytes are the only brain resident cells that have ammonia-metabolizing machinery and are therefore putatively most susceptible to ammonia elevation. Based on a large body of mostly in vitro evidence, ammonia-induced cellular and molecular disturbances include astrocyte swelling and oxidative stress. Microglia, the brain resident macrophages, have been linked to the translation of systemic inflammation to the brain microenvironment. Recent evidence from animal studies has provided novel insights into old and new downstream effects of astrocyte and microglial dysfunction such as toxin clearance disruption and myeloid cell attraction to the central nervous system parenchyma. Furthermore, state of the art research increasingly implicates neuronal dysfunction and possibly even irreversible neuronal cell death. Cell-type specific investigation in animal models highlights the need for critical revision of the contribution of astrocytes and microglia to well-established and novel cellular and molecular alterations in hepatic encephalopathy. In this review, we therefore give a current and comprehensive overview of causes, features, and consequences of astrocyte and microglial dysfunction in hepatic encephalopathy, including areas of interest for future investigation.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"3461-3475"},"PeriodicalIF":5.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142838366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional abnormalities of the glymphatic system in cognitive disorders.","authors":"Wuyue Shentu, Qi Kong, Yier Zhang, Wenyao Li, Qiulu Chen, Sicheng Yan, Junjun Wang, Qilun Lai, Qi Xu, Song Qiao","doi":"10.4103/NRR.NRR-D-24-01049","DOIUrl":"10.4103/NRR.NRR-D-24-01049","url":null,"abstract":"<p><p>Various pathological mechanisms represent distinct therapeutic targets for cognitive disorders, but a balance between clearance and production is essential for maintaining the stability of the brain's internal environment. Thus, the glymphatic system may represent a common pathway by which to address cognitive disorders. Using the established model of the glymphatic system as our foundation, this review disentangles and analyzes the components of its clearance mechanism, including the initial inflow of cerebrospinal fluid, the mixing of cerebrospinal fluid with interstitial fluid, and the outflow of the mixed fluid and the clearance. Each section summarizes evidence from experimental animal models and human studies, highlighting the normal physiological properties of key structures alongside their pathological manifestations in cognitive disorders. The same pathologic manifestations of different cognitive disorders appearing in the glymphatic system and the same upstream influences are main points of interest of this review. We conclude this article by discussing new findings and outlining the limitations identified in current research progress.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"3430-3447"},"PeriodicalIF":5.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A macro-transection model of brain trauma for neuromaterial testing with functional electrophysiological readouts.","authors":"Jessica Wiseman, Raja Haseeb Basit, Akihiro Suto, Sagnik Middya, Bushra Kabiri, Michael Evans, Vinoj George, Christopher Adams, George Malliaras, Divya Maitreyi Chari","doi":"10.4103/NRR.NRR-D-24-00422","DOIUrl":"10.4103/NRR.NRR-D-24-00422","url":null,"abstract":"<p><p>JOURNAL/nrgr/04.03/01300535-202512000-00024/figure1/v/2025-01-31T122243Z/r/image-tiff Functional recovery in penetrating neurological injury is hampered by a lack of clinical regenerative therapies. Biomaterial therapies show promise as medical materials for neural repair through immunomodulation, structural support, and delivery of therapeutic biomolecules. However, a lack of facile and pathology-mimetic models for therapeutic testing is a bottleneck in neural tissue engineering research. We have deployed a two-dimensional, high-density multicellular cortical brain sheet to develop a facile model of injury (macrotransection/scratch wound) in vitro . The model encompasses the major neural cell types involved in pathological responses post-injury. Critically, we observed hallmark pathological responses in injury foci including cell scarring, immune cell infiltration, precursor cell migration, and short-range axonal sprouting. Delivering test magnetic particles to evaluate the potential of the model for biomaterial screening shows a high uptake of introduced magnetic particles by injury-activated immune cells, mimicking in vivo findings. Finally, we proved it is feasible to create reproducible traumatic injuries in the brain sheet (in multielectrode array devices in situ ) characterized by focal loss of electrical spiking in injury sites, offering the potential for longer term, electrophysiology plus histology assays. To our knowledge, this is the first in vitro simulation of transecting injury in a two-dimensional multicellular cortical brain cell sheet, that allows for combined histological and electrophysiological readouts of damage/repair. The patho-mimicry and adaptability of this simplified model of brain injury could benefit the testing of biomaterial therapeutics in regenerative neurology, with the option for functional electrophysiological readouts.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"3539-3552"},"PeriodicalIF":5.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic development of microglia and macrophages after spinal cord injury.","authors":"Hu-Yao Zhou, Xia Wang, Yi Li, Duan Wang, Xuan-Zi Zhou, Nong Xiao, Guo-Xing Li, Gang Li","doi":"10.4103/NRR.NRR-D-24-00063","DOIUrl":"10.4103/NRR.NRR-D-24-00063","url":null,"abstract":"<p><p>JOURNAL/nrgr/04.03/01300535-202512000-00029/figure1/v/2025-01-31T122243Z/r/image-tiff Secondary injury following spinal cord injury is primarily characterized by a complex inflammatory response, with resident microglia and infiltrating macrophages playing pivotal roles. While previous studies have grouped these two cell types together based on similarities in structure and function, an increasing number of studies have demonstrated that microglia and macrophages exhibit differences in structure and function and have different effects on disease processes. In this study, we used single-cell RNA sequencing and spatial transcriptomics to identify the distinct evolutionary paths of microglia and macrophages following spinal cord injury. Our results showed that microglia were activated to a pro-inflammatory phenotype immediately after spinal cord injury, gradually transforming to an anti-inflammatory steady state phenotype as the disease progressed. Regarding macrophages, our findings highlighted abundant communication with other cells, including fibroblasts and neurons. Both pro-inflammatory and neuroprotective effects of macrophages were also identified; the pro-inflammatory effect may be related to integrin β2 ( Itgb2 ) and the neuroprotective effect may be related to the oncostatin M pathway. These findings were validated by in vivo experiments. This research underscores differences in the cellular dynamics of microglia and macrophages following spinal cord injury, and may offer new perspectives on inflammatory mechanisms and potential therapeutic targets.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"3606-3619"},"PeriodicalIF":5.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing non-invasive vagus nerve stimulation for treatment in stroke.","authors":"Sheharyar S Baig, Samantha Dorney, Mudasar Aziz, Simon M Bell, Ali N Ali, Li Su, Jessica N Redgrave, Arshad Majid","doi":"10.4103/NRR.NRR-D-24-00945","DOIUrl":"10.4103/NRR.NRR-D-24-00945","url":null,"abstract":"<p><p>Stroke remains a leading cause of long-term disability worldwide. There is an unmet need for neuromodulatory therapies that can mitigate against neurovascular injury and potentially promote neurological recovery. Transcutaneous vagus nerve stimulation has been demonstrated to show potential therapeutic effects in both acute and chronic stroke. However, previously published research has only investigated a narrow range of stimulation settings and indications. In this review, we detail the ongoing studies of transcutaneous vagus nerve stimulation in stroke through systematic searches of registered clinical trials. We summarize the upcoming clinical trials of transcutaneous vagus nerve stimulation in stroke, highlighting their indications, parameter settings, scope, and limitations. We further explore the challenges and barriers associated with the implementation of transcutaneous vagus nerve stimulation in acute stroke and stroke rehabilitation, focusing on critical aspects such as stimulation settings, target groups, biomarkers, and integration with rehabilitation interventions.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"3388-3399"},"PeriodicalIF":5.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut-brain axis and environmental factors in Parkinson's disease: bidirectional link between disease onset and progression.","authors":"Soo Jung Park, Kyung Won Kim, Eun Jeong Lee","doi":"10.4103/NRR.NRR-D-24-00994","DOIUrl":"10.4103/NRR.NRR-D-24-00994","url":null,"abstract":"<p><p>Parkinson's disease has long been considered a disorder that primarily affects the brain, as it is defined by the dopaminergic neurodegeneration in the substantia nigra and the brain accumulation of Lewy bodies containing α-synuclein protein. In recent decades, however, accumulating research has revealed that Parkinson's disease also involves the gut and uncovered an intimate and important bidirectional link between the brain and the gut, called the \"gut-brain axis.\" Numerous clinical studies demonstrate that gut dysfunction frequently precedes motor symptoms in Parkinson's disease patients, with findings including impaired intestinal permeability, heightened inflammation, and distinct gut microbiome profiles and metabolites. Furthermore, α-synuclein deposition has been consistently observed in the gut of Parkinson's disease patients, suggesting a potential role in disease initiation. Importantly, individuals with vagotomy have a reduced Parkinson's disease risk. From these observations, researchers have hypothesized that α-synuclein accumulation may initiate in the gut and subsequently propagate to the central dopaminergic neurons through the gut-brain axis, leading to Parkinson's disease. This review comprehensively examines the gut's involvement in Parkinson's disease, focusing on the concept of a gut-origin for the disease. We also examine the interplay between altered gut-related factors and the accumulation of pathological α-synuclein in the gut of Parkinson's disease patients. Given the accessibility of the gut to both dietary and pharmacological interventions, targeting gut-localized α-synuclein represents a promising avenue for developing effective Parkinson's disease therapies.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"3416-3429"},"PeriodicalIF":5.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142838091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aptamers as new promising entities for therapeutics: our experience from the neurological diseases.","authors":"Macarena Hernández-Jiménez, Fernando de Castro","doi":"10.4103/NRR.NRR-D-24-00667","DOIUrl":"10.4103/NRR.NRR-D-24-00667","url":null,"abstract":"","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":"20 12","pages":"3523-3524"},"PeriodicalIF":5.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bidirectional causality of physical exercise in retinal neuroprotection.","authors":"Stephen K Agadagba, Suk-Yu Yau, Ying Liang, Kristine Dalton, Benjamin Thompson","doi":"10.4103/NRR.NRR-D-24-00942","DOIUrl":"10.4103/NRR.NRR-D-24-00942","url":null,"abstract":"<p><p>Physical exercise is recognized as an effective intervention to improve mood, physical performance, and general well-being. It achieves these benefits through cellular and molecular mechanisms that promote the release of neuroprotective factors. Interestingly, reduced levels of physical exercise have been implicated in several central nervous system diseases, including ocular disorders. Emerging evidence has suggested that physical exercise levels are significantly lower in individuals with ocular diseases such as glaucoma, age-related macular degeneration, retinitis pigmentosa, and diabetic retinopathy. Physical exercise may have a neuroprotective effect on the retina. Therefore, the association between reduced physical exercise and ocular diseases may involve a bidirectional causal relationship whereby visual impairment leads to reduced physical exercise and decreased exercise exacerbates the development of ocular disease. In this review, we summarize the evidence linking physical exercise to eye disease and identify potential mediators of physical exercise-induced retinal neuroprotection. Finally, we discuss future directions for preclinical and clinical research in exercise and eye health.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"3400-3415"},"PeriodicalIF":5.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142838087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}