Raquel Coronel, Rosa González-Sastre, Patricia Mateos-Martínez, Laura Maeso, Elena Llorente-Beneyto, Sabela Martín-Benito, Viviana S Costa Gagosian, Leonardo Foti, Ma Carmen González-Caballero, Victoria López-Alonso, Isabel Liste
{"title":"Human cerebral organoids: Complex, versatile, and human-relevant models of neural development and brain diseases.","authors":"Raquel Coronel, Rosa González-Sastre, Patricia Mateos-Martínez, Laura Maeso, Elena Llorente-Beneyto, Sabela Martín-Benito, Viviana S Costa Gagosian, Leonardo Foti, Ma Carmen González-Caballero, Victoria López-Alonso, Isabel Liste","doi":"10.4103/NRR.NRR-D-24-01639","DOIUrl":"10.4103/NRR.NRR-D-24-01639","url":null,"abstract":"<p><p>The brain is the most complex human organ, and commonly used models, such as two-dimensional-cell cultures and animal brains, often lack the sophistication needed to accurately use in research. In this context, human cerebral organoids have emerged as valuable tools offering a more complex, versatile, and human-relevant system than traditional animal models, which are often unable to replicate the intricate architecture and functionality of the human brain. Since human cerebral organoids are a state-of-the-art model for the study of neurodevelopment and different pathologies affecting the brain, this field is currently under constant development, and work in this area is abundant. In this review, we give a complete overview of human cerebral organoids technology, starting from the different types of protocols that exist to generate different human cerebral organoids. We continue with the use of brain organoids for the study of brain pathologies, highlighting neurodevelopmental, psychiatric, neurodegenerative, brain tumor, and infectious diseases. Because of the potential value of human cerebral organoids, we describe their use in transplantation, drug screening, and toxicology assays. We also discuss the technologies available to study cell diversity and physiological characteristics of organoids. Finally, we summarize the limitations that currently exist in the field, such as the development of vasculature and microglia, and highlight some of the novel approaches being pursued through bioengineering.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"837-854"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020784","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}
Debbie Xiu En Lim, Shi Yun Yeo, Zhen You Ashley Chia, Aaron Zefrin Fernandis, Jimmy Lee, John Jia En Chua
{"title":"Schizophrenia: Genetics, neurological mechanisms, and therapeutic approaches.","authors":"Debbie Xiu En Lim, Shi Yun Yeo, Zhen You Ashley Chia, Aaron Zefrin Fernandis, Jimmy Lee, John Jia En Chua","doi":"10.4103/NRR.NRR-D-24-01375","DOIUrl":"10.4103/NRR.NRR-D-24-01375","url":null,"abstract":"<p><p>Schizophrenia is a complex psychiatric disorder marked by positive and negative symptoms, leading to mood disturbances, cognitive impairments, and social withdrawal. While anti-psychotic medications remain the cornerstone of treatment, they often fail to fully address certain symptoms. Additionally, treatment-resistant schizophrenia, affecting 30%-40% of patients, remains a substantial clinical challenge. Positive, negative symptoms and cognitive impairments have been linked to disruptions in the glutamatergic, serotonin, GABAergic, and muscarinic pathways in the brain. Recent advances using genome-wide association study and other approaches have uncovered a significant number of new schizophrenia risk genes that uncovered new, and reinforced prior, concepts on the genetic and neurological underpinnings of schizophrenia, including abnormalities in synaptic function, immune processes, and lipid metabolism. Concurrently, new therapeutics targeting different modalities, which are expected to address some of the limitations of anti-psychotic drugs currently being offered to patients, are currently being evaluated. Collectively, these efforts provide new momentum for the next phase of schizophrenia research and treatment.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"1089-1103"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036518","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":"Regulation of dendrite and axon growth and arborization by CD40L-reverse signaling: Interrelationships among JNK, PKC, and ERK1/2 signaling pathways.","authors":"Paulina Carriba","doi":"10.4103/NRR.NRR-D-24-01171","DOIUrl":"https://doi.org/10.4103/NRR.NRR-D-24-01171","url":null,"abstract":"","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":"21 3","pages":"1116-1117"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310177","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}
Marcus Elo Rytter, Cecilie Amalie Brøgger Svane, Joachim Størling, Wenqiang Chen
{"title":"Dysregulated insulin signaling and inflammation contribute to the pathogenesis of Alzheimer's disease: From animal models to human cells.","authors":"Marcus Elo Rytter, Cecilie Amalie Brøgger Svane, Joachim Størling, Wenqiang Chen","doi":"10.4103/NRR.NRR-D-24-01591","DOIUrl":"10.4103/NRR.NRR-D-24-01591","url":null,"abstract":"","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"1126-1127"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493005","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":"Crucial role of microglia-mediated myelin sheath damage in vascular dementia: Antecedents and consequences.","authors":"Qi Shao, Simin Chen, Yuxiao Zheng, Wenxiu Xu, Jiahui Chen, Wei Shao, Qingguo Wang, Changxiang Li, Xueqian Wang","doi":"10.4103/NRR.NRR-D-24-01109","DOIUrl":"10.4103/NRR.NRR-D-24-01109","url":null,"abstract":"<p><p>Chronic cerebral hypoperfusion can lead to neuronal necrosis, trigger inflammatory responses, promote white matter damage, and ultimately result in cognitive impairment. Consequently, chronic cerebral hypoperfusion is an important factor influencing the onset and progression of vascular dementia. The myelin sheath is a critical component of white matter, and damage and repair of the white matter are closely linked to myelin sheath integrity. This article reviews the role of microglia in vascular dementia, focusing on their effects on myelin sheaths and the potential therapeutic implications. The findings suggest that ischemia and hypoxia cause disruption of the blood-brain barrier and activate microglia, which may worsen blood-brain barrier damage through the release of matrix-degrading enzymes. Microglia-mediated metabolic reprogramming is recognized as an important driver of inflammation. Damage to the blood-brain barrier and subsequent inflammation can lead to myelin injury and accelerate the progression of vascular dementia. Early activation of microglia is a protective response that contributes to the maintenance of blood-brain barrier integrity through sensing, debris-clearing, and defensive mechanisms. However, prolonged activation can trigger a shift in microglia toward the pro-inflammatory M1 phenotype, resulting in myelin damage and cognitive impairment. Triggering receptor expressed on myeloid cells 2 and triggering receptor expressed on myeloid cells 1 have been identified as potential biomarkers for vascular dementia, as both are closely linked to cognitive decline. Although effective clinical treatments for myelin damage in the central nervous system are currently lacking, researchers are actively working to develop targeted therapies. Several drugs, including nimodipine, dopaminergic agents, simvastatin, biotin, and quetiapine, have been evaluated for clinical use in treating microglial and myelin damage. Future research will face challenges in developing targeted therapeutic strategies for vascular dementia, requiring further investigation into the timing, duration, and specific mechanisms of microglial activation, as well as the exploration of new drug combinations and additional therapeutic targets.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"1000-1012"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720788","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":"Molecular mechanisms after optic nerve injury: Neurorepair strategies from a transcriptomic perspective.","authors":"Xiaxue Chen, Muyang Wei, Guangyu Li","doi":"10.4103/NRR.NRR-D-24-00794","DOIUrl":"10.4103/NRR.NRR-D-24-00794","url":null,"abstract":"<p><p>Retinal ganglion cells, a crucial component of the central nervous system, are often affected by irreversible visual impairment due to various conditions, including trauma, tumors, ischemia, and glaucoma. Studies have shown that the optic nerve crush model and glaucoma model are commonly used to study retinal ganglion cell injury. While these models differ in their mechanisms, both ultimately result in retinal ganglion cell injury. With advancements in high-throughput technologies, techniques such as microarray analysis, RNA sequencing, and single-cell RNA sequencing have been widely applied to characterize the transcriptomic profiles of retinal ganglion cell injury, revealing underlying molecular mechanisms. This review focuses on optic nerve crush and glaucoma models, elucidating the mechanisms of optic nerve injury and neuron degeneration induced by glaucoma through single-cell transcriptomics, transcriptome analysis, and chip analysis. Research using the optic nerve crush model has shown that different retinal ganglion cell subtypes exhibit varying survival and regenerative capacities following injury. Single-cell RNA sequencing has identified multiple genes associated with retinal ganglion cell protection and regeneration, such as Gal , Ucn , and Anxa2 . In glaucoma models, high-throughput sequencing has revealed transcriptomic changes in retinal ganglion cells under elevated intraocular pressure, identifying genes related to immune response, oxidative stress, and apoptosis. These genes are significantly upregulated early after optic nerve injury and may play key roles in neuroprotection and axon regeneration. Additionally, CRISPR-Cas9 screening and ATAC-seq analysis have identified key transcription factors that regulate retinal ganglion cell survival and axon regeneration, offering new potential targets for neurorepair strategies in glaucoma. In summary, single-cell transcriptomic technologies provide unprecedented insights into the molecular mechanisms underlying optic nerve injury, aiding in the identification of novel therapeutic targets. Future researchers should integrate advanced single-cell sequencing with multi-omics approaches to investigate cell-specific responses in retinal ganglion cell injury and regeneration. Furthermore, computational models and systems biology methods could help predict molecular pathways interactions, providing valuable guidance for clinical research on optic nerve regeneration and repair.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"989-999"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002704","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}
Ze Liu, Teng Cheng, Hongtian Dong, Dingya Sun, Yan Wang, Jiayan Li, Zhongwang Yu, Li Cao
{"title":"Roles of central nervous system resident and recruited macrophages in the brain barrier system.","authors":"Ze Liu, Teng Cheng, Hongtian Dong, Dingya Sun, Yan Wang, Jiayan Li, Zhongwang Yu, Li Cao","doi":"10.4103/NRR.NRR-D-24-00986","DOIUrl":"10.4103/NRR.NRR-D-24-00986","url":null,"abstract":"<p><p>Macrophages in the brain barrier system include microglia in the brain parenchyma, border-associated macrophages at the brain's borders, and recruited macrophages. They are responsible for neural development, maintenance of homeostasis, and orchestrating immune responses. With the rapid exploitation and development of new technologies, there is a deeper understanding of macrophages in the brain barrier system. Here we review the origin, development, important molecules, and functions of macrophages, mainly focusing on microglia and border-associated macrophages. We also highlight some advances in single-cell sequencing and significant cell markers. We anticipate that more advanced methods will emerge to study resident and recruited macrophages in the future, opening new horizons for neuroimmunology and related peripheral immune fields.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"855-868"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066875","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}
Juan García-Revilla, Jose Luis Venero, José A Rodríguez-Gómez
{"title":"Galectin 3: A new player in the pathogenesis of Parkinson's disease.","authors":"Juan García-Revilla, Jose Luis Venero, José A Rodríguez-Gómez","doi":"10.4103/NRR.NRR-D-24-01410","DOIUrl":"10.4103/NRR.NRR-D-24-01410","url":null,"abstract":"","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"1132-1133"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720905","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}
Yujia Lu, Jie Jin, Huajing Zhang, Qianying Lu, Yingyi Zhang, Chuanchuan Liu, Yangfan Liang, Sijia Tian, Yanmei Zhao, Haojun Fan
{"title":"Traumatic brain injury: Bridging pathophysiological insights and precision treatment strategies.","authors":"Yujia Lu, Jie Jin, Huajing Zhang, Qianying Lu, Yingyi Zhang, Chuanchuan Liu, Yangfan Liang, Sijia Tian, Yanmei Zhao, Haojun Fan","doi":"10.4103/NRR.NRR-D-24-01398","DOIUrl":"10.4103/NRR.NRR-D-24-01398","url":null,"abstract":"<p><p>Blood-brain barrier disruption and the neuroinflammatory response are significant pathological features that critically influence disease progression and treatment outcomes. This review systematically analyzes the current understanding of the bidirectional relationship between blood-brain barrier disruption and neuroinflammation in traumatic brain injury, along with emerging combination therapeutic strategies. Literature review indicates that blood-brain barrier disruption and neuroinflammatory responses are key pathological features following traumatic brain injury. In the acute phase after traumatic brain injury, the pathological characteristics include primary blood-brain barrier disruption and the activation of inflammatory cascades. In the subacute phase, the pathological features are characterized by repair mechanisms and inflammatory modulation. In the chronic phase, the pathological features show persistent low-grade inflammation and incomplete recovery of the blood-brain barrier. Various physiological changes, such as structural alterations of the blood-brain barrier, inflammatory cascades, and extracellular matrix remodeling, interact with each other and are influenced by genetic, age, sex, and environmental factors. The dynamic balance between blood-brain barrier permeability and neuroinflammation is regulated by hormones, particularly sex hormones and stress-related hormones. Additionally, the role of gastrointestinal hormones is receiving increasing attention. Current treatment strategies for traumatic brain injury include various methods such as conventional drug combinations, multimodality neuromonitoring, hyperbaric oxygen therapy, and non-invasive brain stimulation. Artificial intelligence also shows potential in treatment decision-making and personalized therapy. Emerging sequential combination strategies and precision medicine approaches can help improve treatment outcomes; however, challenges remain, such as inadequate research on the mechanisms of the chronic phase traumatic brain injury and difficulties with technology integration. Future research on traumatic brain injury should focus on personalized treatment strategies, the standardization of techniques, cost-effectiveness evaluations, and addressing the needs of patients with comorbidities. A multidisciplinary approach should be used to enhance treatment and improve patient outcomes.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"887-907"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720764","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}