Lingyun Cao, Siyun Chen, Shuping Wang, Ya Zheng, Dongsheng Xu
{"title":"Multi-target neural circuit reconstruction and enhancement in spinal cord injury.","authors":"Lingyun Cao, Siyun Chen, Shuping Wang, Ya Zheng, Dongsheng Xu","doi":"10.4103/NRR.NRR-D-24-00434","DOIUrl":"10.4103/NRR.NRR-D-24-00434","url":null,"abstract":"<p><p>After spinal cord injury, impairment of the sensorimotor circuit can lead to dysfunction in the motor, sensory, proprioceptive, and autonomic nervous systems. Functional recovery is often hindered by constraints on the timing of interventions, combined with the limitations of current methods. To address these challenges, various techniques have been developed to aid in the repair and reconstruction of neural circuits at different stages of injury. Notably, neuromodulation has garnered considerable attention for its potential to enhance nerve regeneration, provide neuroprotection, restore neurons, and regulate the neural reorganization of circuits within the cerebral cortex and corticospinal tract. To improve the effectiveness of these interventions, the implementation of multi-target early interventional neuromodulation strategies, such as electrical and magnetic stimulation, is recommended to enhance functional recovery across different phases of nerve injury. This review concisely outlines the challenges encountered following spinal cord injury, synthesizes existing neurostimulation techniques while emphasizing neuroprotection, repair, and regeneration of impaired connections, and advocates for multi-targeted, task-oriented, and timely interventions.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"957-971"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066869","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":"Polysialic acid-Siglec immune checkpoints of microglia and macrophages: Perspectives for therapeutic intervention.","authors":"Hauke Thiesler, Herbert Hildebrandt","doi":"10.4103/NRR.NRR-D-24-01195","DOIUrl":"10.4103/NRR.NRR-D-24-01195","url":null,"abstract":"","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"661-662"},"PeriodicalIF":5.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142838352","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}
Mei Liu, Yijing Meng, Siguang Ouyang, Meng'ai Zhai, Likun Yang, Yang Yang, Yuhai Wang
{"title":"Neuromodulation technologies improve functional recovery after brain injury: From bench to bedside.","authors":"Mei Liu, Yijing Meng, Siguang Ouyang, Meng'ai Zhai, Likun Yang, Yang Yang, Yuhai Wang","doi":"10.4103/NRR.NRR-D-24-00652","DOIUrl":"10.4103/NRR.NRR-D-24-00652","url":null,"abstract":"<p><p>Spontaneous recovery frequently proves maladaptive or insufficient because the plasticity of the injured adult mammalian central nervous system is limited. This limited plasticity serves as a primary barrier to functional recovery after brain injury. Neuromodulation technologies represent one of the fastest-growing fields in medicine. These techniques utilize electricity, magnetism, sound, and light to restore or optimize brain functions by promoting reorganization or long-term changes that support functional recovery in patients with brain injury. Therefore, this review aims to provide a comprehensive overview of the effects and underlying mechanisms of neuromodulation technologies in supporting motor function recovery after brain injury. Many of these technologies are widely used in clinical practice and show significant improvements in motor function across various types of brain injury. However, studies report negative findings, potentially due to variations in stimulation protocols, differences in observation periods, and the severity of functional impairments among participants across different clinical trials. Additionally, we observed that different neuromodulation techniques share remarkably similar mechanisms, including promoting neuroplasticity, enhancing neurotrophic factor release, improving cerebral blood flow, suppressing neuroinflammation, and providing neuroprotection. Finally, considering the advantages and disadvantages of various neuromodulation techniques, we propose that future development should focus on closed-loop neural circuit stimulation, personalized treatment, interdisciplinary collaboration, and precision stimulation.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"506-520"},"PeriodicalIF":5.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033761","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":"p21 as an essential regulator of neurogenic homeostasis in neuropathological conditions.","authors":"Valentina Mastrorilli, Stefano Farioli-Vecchioli","doi":"10.4103/NRR.NRR-D-24-01255","DOIUrl":"10.4103/NRR.NRR-D-24-01255","url":null,"abstract":"","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"675-676"},"PeriodicalIF":5.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009011","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":"Rapamycin as a preventive intervention for Alzheimer's disease in APOE4 carriers: Targeting brain metabolic and vascular restoration.","authors":"Ai-Ling Lin, Chetan Aware","doi":"10.4103/NRR.NRR-D-24-01006","DOIUrl":"10.4103/NRR.NRR-D-24-01006","url":null,"abstract":"","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":"21 2","pages":"685-686"},"PeriodicalIF":5.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025652","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":"Topical administration of GLP-1 eyedrops improves retinal ganglion cell function by facilitating presynaptic GABA release in early experimental diabetes.","authors":"Yu-Qi Shao, Yong-Chen Wang, Lu Wang, Hang-Ze Ruan, Yun-Feng Liu, Ti-Hui Zhang, Shi-Jun Weng, Xiong-Li Yang, Yong-Mei Zhong","doi":"10.4103/NRR.NRR-D-24-00001","DOIUrl":"10.4103/NRR.NRR-D-24-00001","url":null,"abstract":"<p><p>JOURNAL/nrgr/04.03/01300535-202602000-00048/figure1/v/2025-05-05T160104Z/r/image-tiff Diabetic retinopathy is a prominent cause of blindness in adults, with early retinal ganglion cell loss contributing to visual dysfunction or blindness. In the brain, defects in γ-aminobutyric acid synaptic transmission are associated with pathophysiological and neurodegenerative disorders, whereas glucagon-like peptide-1 has demonstrated neuroprotective effects. However, it is not yet clear whether diabetes causes alterations in inhibitory input to retinal ganglion cells and whether and how glucagon-like peptide-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to retinal ganglion cells. In the present study, we used the patch-clamp technique to record γ-aminobutyric acid subtype A receptor-mediated miniature inhibitory postsynaptic currents in retinal ganglion cells from streptozotocin-induced diabetes model rats. We found that early diabetes (4 weeks of hyperglycemia) decreased the frequency of GABAergic miniature inhibitory postsynaptic currents in retinal ganglion cells without altering their amplitude, suggesting a reduction in the spontaneous release of γ-aminobutyric acid to retinal ganglion cells. Topical administration of glucagon-like peptide-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency, subsequently enhancing the survival of retinal ganglion cells. Concurrently, the protective effects of glucagon-like peptide-1 on retinal ganglion cells in diabetic rats were eliminated by topical administration of exendin-9-39, a specific glucagon-like peptide-1 receptor antagonist, or SR95531, a specific antagonist of the γ-aminobutyric acid subtype A receptor. Furthermore, extracellular perfusion of glucagon-like peptide-1 was found to elevate the frequencies of GABAergic miniature inhibitory postsynaptic currents in both ON- and OFF-type retinal ganglion cells. This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca 2+ /protein kinase C signaling pathway downstream of glucagon-like peptide-1 receptor activation. Moreover, multielectrode array recordings revealed that glucagon-like peptide-1 functionally augmented the photoresponses of ON-type retinal ganglion cells. Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of glucagon-like peptide-1. These results suggest that glucagon-like peptide-1 facilitates the release of γ-aminobutyric acid onto retinal ganglion cells through the activation of glucagon-like peptide-1 receptor, leading to the de-excitation of retinal ganglion cell circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy. Collectively, our findings indicate th","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"800-810"},"PeriodicalIF":5.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458330","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":"Specific dendritic spine modifications and dendritic transport: From in vitro to in vivo.","authors":"Albert H K Fok, Charlotte H M Lam, Cora S W Lai","doi":"10.4103/NRR.NRR-D-24-01159","DOIUrl":"10.4103/NRR.NRR-D-24-01159","url":null,"abstract":"","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"665-666"},"PeriodicalIF":5.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009015","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}
Hongli Chen, Na Li, Yuanhao Cai, Chunyan Ma, Yutong Ye, Xinyu Shi, Jun Guo, Zhibo Han, Yi Liu, Xunbin Wei
{"title":"Exosomes in neurodegenerative diseases: Therapeutic potential and modification methods.","authors":"Hongli Chen, Na Li, Yuanhao Cai, Chunyan Ma, Yutong Ye, Xinyu Shi, Jun Guo, Zhibo Han, Yi Liu, Xunbin Wei","doi":"10.4103/NRR.NRR-D-24-00720","DOIUrl":"10.4103/NRR.NRR-D-24-00720","url":null,"abstract":"<p><p>In recent years, exosomes have garnered extensive attention as therapeutic agents and early diagnostic markers in neurodegenerative disease research. Exosomes are small and can effectively cross the blood-brain barrier, allowing them to target deep brain lesions. Recent studies have demonstrated that exosomes derived from different cell types may exert therapeutic effects by regulating the expression of various inflammatory cytokines, mRNAs, and disease-related proteins, thereby halting the progression of neurodegenerative diseases and exhibiting beneficial effects. However, exosomes are composed of lipid bilayer membranes and lack the ability to recognize specific target cells. This limitation can lead to side effects and toxicity when they interact with non-specific cells. Growing evidence suggests that surface-modified exosomes have enhanced targeting capabilities and can be used as targeted drug-delivery vehicles that show promising results in the treatment of neurodegenerative diseases. In this review, we provide an up-to-date overview of existing research aimed at devising approaches to modify exosomes and elucidating their therapeutic potential in neurodegenerative diseases. Our findings indicate that exosomes can efficiently cross the blood-brain barrier to facilitate drug delivery and can also serve as early diagnostic markers for neurodegenerative diseases. We introduce the strategies being used to enhance exosome targeting, including genetic engineering, chemical modifications (both covalent, such as click chemistry and metabolic engineering, and non-covalent, such as polyvalent electrostatic and hydrophobic interactions, ligand-receptor binding, aptamer-based modifications, and the incorporation of CP05-anchored peptides), and nanomaterial modifications. Research into these strategies has confirmed that exosomes have significant therapeutic potential for neurodegenerative diseases. However, several challenges remain in the clinical application of exosomes. Improvements are needed in preparation, characterization, and optimization methods, as well as in reducing the adverse reactions associated with their use. Additionally, the range of applications and the safety of exosomes require further research and evaluation.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":"21 2","pages":"478-490"},"PeriodicalIF":5.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982721","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":"Novel insights into non-coding RNAs and their role in hydrocephalus.","authors":"Zhiyue Cui, Jian He, An Li, Junqiang Wang, Yijian Yang, Kaiyue Wang, Zhikun Liu, Qian Ouyang, Zhangjie Su, Pingsheng Hu, Gelei Xiao","doi":"10.4103/NRR.NRR-D-24-00963","DOIUrl":"10.4103/NRR.NRR-D-24-00963","url":null,"abstract":"<p><p>A large body of evidence has highlighted the role of non-coding RNAs in neurodevelopment and neuroinflammation. This evidence has led to increasing speculation that non-coding RNAs may be involved in the pathophysiological mechanisms underlying hydrocephalus, one of the most common neurological conditions worldwide. In this review, we first outline the basic concepts and incidence of hydrocephalus along with the limitations of existing treatments for this condition. Then, we outline the definition, classification, and biological role of non-coding RNAs. Subsequently, we analyze the roles of non-coding RNAs in the formation of hydrocephalus in detail. Specifically, we have focused on the potential significance of non-coding RNAs in the pathophysiology of hydrocephalus, including glymphatic pathways, neuroinflammatory processes, and neurological dysplasia, on the basis of the existing evidence. Lastly, we review the potential of non-coding RNAs as biomarkers of hydrocephalus and for the creation of innovative treatments.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"636-647"},"PeriodicalIF":5.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142838246","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}
Qian Yue, Shang Li, Chon Lok Lei, Huaibin Wan, Zaijun Zhang, Maggie Pui Man Hoi
{"title":"Insights into the transcriptomic heterogeneity of brain endothelial cells in normal aging and Alzheimer's disease.","authors":"Qian Yue, Shang Li, Chon Lok Lei, Huaibin Wan, Zaijun Zhang, Maggie Pui Man Hoi","doi":"10.4103/NRR.NRR-D-24-00695","DOIUrl":"10.4103/NRR.NRR-D-24-00695","url":null,"abstract":"<p><p>Drug development for Alzheimer's disease is extremely challenging, as demonstrated by the repeated failures of amyloid-β-targeted therapeutics and the controversies surrounding the amyloid-β cascade hypothesis. More recently, advances in the development of Lecanemab, an anti-amyloid-β monoclonal antibody, have shown positive results in reducing brain A burden and slowing cognitive decline in patients with early-stage Alzheimer's disease in the Phase III clinical trial (Clarity Alzheimer's disease). Despite these promising results, side effects such as amyloid-related imaging abnormalities (ARIA) may limit its usage. ARIA can manifest as ARIA-E (cerebral edema or effusions) and ARIA-H (microhemorrhages or superficial siderosis) and is thought to be caused by increased vascular permeability due to inflammatory responses, leading to leakages of blood products and protein-rich fluid into brain parenchyma. Endothelial dysfunction is an early pathological feature of Alzheimer's disease, and the blood-brain barrier becomes increasingly leaky as the disease progresses. In addition, APOE4, the strongest genetic risk factor for Alzheimer's disease, is associated with higher vascular amyloid burden, increased ARIA incidence, and accelerated blood-brain barrier disruptions. These interconnected vascular abnormalities highlight the importance of vascular contributions to the pathophysiology of Alzheimer's disease. Here, we will closely examine recent research evaluating the heterogeneity of brain endothelial cells in the microvasculature of different brain regions and their relationships with Alzheimer's disease progression.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"569-576"},"PeriodicalIF":5.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142838254","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}