Human Brain (2957-6296) journal endorses peer-reviewed cutting-edge research on the entire genre of neurological science and clinical neurology. This journal publishes preferably original data derived from post-mortem brains, surgically resected brain samples, living human subjects and in vitro models) using various approaches (e.g., histological, neuropathological, biochemical, molecular, informatics, brain imaging). Clinical studies involving brain autopsy examination as the end measurement is much appreciated. Article formats include original research, case reports and systematic reviews, as well as technological innovations such as novel brain tissue processing for molecular localization, brain imaging analyses, proteomics, genomics and epigenomics studies.
Attribution-No-Derivatives 4.0 International (CC BY-ND 4.0): https://creativecommons.org/licenses/by-nd/4.0/
Molecular Mechanisms and Advances of Photobiomodulation for Alzheimer's Disease
Alzheimer’s disease (AD) is a complex neurodegenerative disorder. Current pharmacological interventions face challenges, including limited blood-brain barrier penetration and adverse effects. Red/near-infrared photobiomodulation (PBM) emerges as a promising non-invasive strategy targeting multiple AD pathologies simultaneously. Key molecular mechanisms include PBM-mediated activation of mitochondrial cytochrome c oxidase, enhancing ATP synthesis and reducing oxidative stress. Crucially, specific wavelengths such as 630 nm directly disassemble formaldehyde-crosslinked Aβ fibrils and restore formaldehyde dehydrogenase activity, breaking a pathogenic Aβ-formaldehyde cycle. PBM further reprograms microglial metabolism toward an anti-inflammatory phenotype, enhancing Aβ phagocytosis and suppressing pro-inflammatory cytokines. It also improves cerebrovascular function, augments glymphatic/meningeal lymphatic Aβ clearance, and restores synaptic plasticity and neural oscillations, correlating with cognitive improvements. Pilot clinical studies demonstrate enhanced cognitive function and functional connectivity following transcranial/intranasal PBM, with favorable safety. However, significant heterogeneity in treatment protocols (wavelength, fluence, pulsing) and questions regarding long-term efficacy necessitate rigorous standardization. Emerging combinatorial strategies integrating PBM with light-triggered nanomedicines offer enhanced BBB penetration and targeted Aβ disaggregation. Future directions emphasize interdisciplinary collaboration, biomarker-driven personalized dosing, and large-scale randomized controlled trials to realize PBM’s therapeutic potential for early AD intervention.
Copyright (c) 2025 Xuechao Fei https://creativecommons.org/licenses/by-nd/4.0
Recommendations for the clinical use of anti-amyloid-β monoclonal antibody for Alzheimer's disease (2024)
Several anti-amyloid-β monoclonal antibodies have been approved for clinical use in China and some other countries recently. To facilitate the safe and effective treatment of anti-amyloid-β monoclonal antibodies for Alzheimer's disease (AD) in China, we present recommendations for the clinical use of anti-amyloid-β monoclonal antibodies based on existing clinical trials and the clinical practice of AD treatment with Aducanumab at Ruijin Hospital Hainan Branch, Shanghai Jiaotong University School of Medicine. The recommendations include clinical indications, pre-medication assessment and preparation, medication instructions and precautions, as well as post-medication clinical monitoring, which is aimed at furnishing clinicians with comprehensive medication guidance.
Copyright (c) 2025 Gang Wang, Binyin Li , Rujing Ren, Jinwen Xiao, Shengdi Chen, Xiaochun Chen https://creativecommons.org/licenses/by-nd/4.0
A Fast Screen System for Dementia Based on EEG Signals
We proposed a set of quantitative, inexpensive, and non-invasive methods for screening dementia based on resting EEG. The methods used here included ensemble Holo spectrum (eHolo), ensemble intrinsic Probability Density function (eiPDF), and ensemble intrinsic Multiscale Entropy (eiMSE). These methods were developed originally for physical sciences, specifically to study the wave-turbulence interaction phenomena. Applications, however, were found in neuroscience and bioengineering. Tested on mostly retrospective open-source EEG data, the results measured by receiver operating characteristic (ROC) curves and area under the curve (AUC) values based on micro- and macro-average methods all passed the clinically acceptable threshold of 70%. Specifically, the AUC scores are these: eHolo above 0.89, eiPDF at 0.82, and eiMSE above 0.87, respectively. If we use all three methods in combination, the AUC score is above 0.91. Emulating the bone-density measurement, we have also established a quantitative Z-score to measure the relative standing of each subject. Encouragingly, the Z-score shows a moderate correlation with the widely scattered CDR score, with RHO values between 0.26 and 0.46. We strongly suggest that large-scale clinical trials be organized so that the method can be validated and ready for the WHO and Chinese calls for screening of the general population by 2030.
Copyright (c) 2025 Norden E. Huang, Wei-Shuai Yuan, Fang Yuan, Xiao-Min Guo, Albert CC Yang , Terry BJ Kuo , TieMei Zhang, Jian-Ping Cai, Helen Kang, Ying-Qiang Zhang , Wei-Kuang Liang https://creativecommons.org/licenses/by-nd/4.0
Advances of chronic pain: better insights, better treatment
Pain is often referred to as the fifth vital sign. It profoundly impacts both physical and psychological well-being, either as a primary condition or in conjunction with other systemic diseases. Pain typically results from complex neurophysiological processes, including peripheral and central sensitization, altered pain pathways, and maladaptive neuroplasticity, which can lead to persistent or chronic pain. Current pharmaceutical treatments, such as non-steroidal anti-inflammatory drugs (NSAIDs) and tricyclic antidepressants, often fall short of desired therapeutic outcomes. To improve efficacy, advanced drug delivery systems (DDS) with extended-release formulations and multimodal analgesia have shown promise. Surgical interventions are increasingly recognized for chronic pain resistant to conservative treatments, while exercise, psychological counseling, and strong social support have proven benefits. This review examines the mechanisms of chronic pain, current management approaches, and explores potential future advancements in analgesic strategies.
Copyright (c) 2025 Fengrun Sun, Ning Yu, Tao Wang https://creativecommons.org/licenses/by-nd/4.0
Biomarkers of Cerebral Amyloid Angiopathy and Neuropathological Relationship with Alzheimer's Disease
Cerebral amyloid angiopathy (CAA), characterized by beta-amyloid (Aβ) deposits within small- to medium-sized blood vessels of the brain and leptomeninges, is known to be associated with an elevated risk of lobar intracerebral hemorrhage. Clinical diagnosis of CAA is complicated due to the limited diagnosis methods and lack of biomarkers for this disease. It was found that CAA has a significantly high probability of comorbidity with Alzheimer's disease (AD) due to the similar neuropathological characteristics known as amyloid-related imaging abnormalities (ARIA). Anti-Aβ monoclonal antibody therapy has been extensively investigated in the treatment of AD patients and applied in several clinical trials worldwide. However, common side effects such as hemorrhage and edema may occur for patients with preclinical or asymptomatic CAA when using antibody therapy. Therefore, it is crucial to identify CAA comorbidity in AD patients before starting anti-Aβ monoclonal antibody therapy. This review summarizes the clinical diagnostic methods and related biomarkers for AD and CAA. Further investigation of CAA for its neuropathological relationship with AD and the discovery of novel biomarkers may pave the way for a more accurate diagnosis and effective prevention of harmful side effects during treatment. It is of great importance to avoid adverse outcomes such as cerebral hemorrhage and edema caused by CAA in the treatment of AD and CAA comorbid patients.
Copyright (c) 2025 Ting Jiang, Wenying Qiu, Jun Ni, Yuhui Sha, Xiangsha Yin, Xiaojing Qian https://creativecommons.org/licenses/by-nd/4.0
Neural mechanisms underlying painful diabetic neuropathy
Painful diabetic neuropathy (PDN), a prevalent complication of diabetes, has become a significant public health concern. It is characterized by nerve damage induced by chronic hyperglycemia, leading to pain, tingling, and numbness, predominantly in the hands and feet. This review comprehensively explores the neural mechanisms underlying PDN, emphasizing the dorsal root ganglion (DRG) as a central hub for pain initiation and transmission. In the periphery, dysregulated pathways in the DRG, including ion channel dysfunction, mitochondrial abnormalities, impaired glucose metabolism, and inflammatory disturbances, contribute to the hyperexcitability of nociceptors and the amplification of pain signals. In the central nervous system, PDN is characterized by structural and functional changes in the spinal dorsal horn and higher brain centers, leading to central sensitization and altered pain processing. The review also highlights the role of epigenetic regulation and emerging insights from single-cell RNA sequencing in understanding PDN. By integrating these peripheral and central mechanisms, future research can focus on developing targeted therapies and multimodal treatment strategies to improve patient outcomes.
Copyright (c) 2025 Peng Liu, Yan Chen, Xu Zhang, Chao Ma https://creativecommons.org/licenses/by-nd/4.0
Reconstructing Structure and Function Post Spinal Cord Injury by Facilitating Novel Integration Therapy and Neuromodulation
Spinal cord injury (SCI) has been a research hotspot for its poor prognosis and limited effects in current treatment methods. Consistent hostile responses in damaged regions and functional incapabilities can lead to major complications. Most approaches focus on either structural or functional reconstruction. For restoring function, facilitating innate neuroplasticity and neuromodulation showed promising potentials, including rehabilitation therapy and various forms of electrical stimulation, examples include epidural electrical stimulation (EES), functional electrical stimulation (FES), transcutaneous electrical neural stimulation (TENS), and deep brain stimulation (DBS). Recent advances in treatments for SCI include integrating conventional methods and installing interfaces, such as brain-computer interface (BCI) and brain-spine interface (BSI).
Copyright (c) 2025 Qiqi Yang, Chenyuan Ding, Fengzeng Jian, Zan Chen, Zhuofan Xu, Wanru Duan https://creativecommons.org/licenses/by-nd/4.0
Bow Hunter's Syndrome: Illustrative Teaching Case with Insights and Lessons
A 63-year-old woman with a history of left basal ganglia and paraventricular infarcts, type II diabetes, and hypertension presented with recurrent dizziness when turning her head to the right. These episodes, lasting for eight months, were often accompanied by nausea and vision disturbances but resolved spontaneously. Dynamic digital subtraction angiography (DSA) revealed significant blood flow slowdown in the left vertebral artery (VA) with a 90° right neck turn, showing narrowing in the V3 segment of the left VA. The patient was diagnosed with Bow Hunter's Syndrome (BHS) and underwent atlantoaxial fusion surgery. On day three post-surgery, she developed sudden weakness in the left upper limb, visual field hemianopia, impaired sensation, and slurred speech. Emergency CT and MRI revealed acute infarcts in the basal ganglia and periventricular area. Following antiplatelet therapy and volume expansion, her symptoms improved, and by day seven, her speech and left upper limb strength had partially recovered, though residual symptoms persisted at discharge. One year post-surgery, the dizziness had resolved, but residual symptoms from the infarction remained. Cervical fusion effectively treated the symptoms of BHS; however, surgery should be considered with caution in patients with thromboembolic risk factors.
Copyright (c) 2025 Tianyu Jin, Yanfei Chen, Zan Chen, Wanru Duan https://creativecommons.org/licenses/by-nd/4.0
Clinical Practice Guideline for Adolescent and Adult Patients with Spinal Muscular Atrophy – Part 3
In recent years, the field of spinal muscular atrophy (SMA) has made progress in multidisciplinary care and disease-modifying therapies. Survival and the quality of life of patients have significantly improved. However, no clinical practice guidelines exist for the management of SMA in adult and adolescent patients. Multidisciplinary experts from a number of tertiary medical centers in China, specializing in the diagnosis and treatment of SMA, came together to remedy this using evidence-based medicine. This guideline serves as an instrumental reference for the standardized care of Chinese SMA patients.
Copyright (c) 2024 Yi Dai, Liying Cui https://creativecommons.org/licenses/by-nd/4.0
Clinical Practice Guideline for Adolescent and Adult Patients with Spinal Muscular Atrophy – Part 2
Clinical Practice Guideline for Adolescent and Adult Patients with Spinal Muscular Atrophy – Part 1
In recent years, the field of spinal muscular atrophy (SMA) has made progress in multidisciplinary care and disease-modifying therapies (DMTs). Survival and the quality of life of patients have significantly improved. However, no clinical practice guidelines exist for the management of SMA in adult and adolescent patients. Multidisciplinary experts from a number of tertiary medical centers in China, specializing in the diagnosis and treatment of SMA, came together to remedy this using evidence-based medicine. This guideline serves as an instrumental reference for the standardized care of Chinese SMA patients.
To Probe, Protect & Promote the Human Brain
“Human Brain, the future has arrived.” Following the remark sentence at the end of the promotional trailer, the Human Brain Forum 2024 was successfully launched in Beijing on August 24, 2024. Hosted by the Chinese Society for Anatomical Science and organized by the National Human Brain Bank for Development and Function (Institute of Basic Medical Science, Chinese Academy of Medical Sciences-CAMS) and the Institute for Neuroscience (CAMS), co-organized by Peking Union Medical College Hospital (PUMCH), the Chinese Human Brain Consortium, and HUMAN BRAIN Journal, the forum attracted nearly 300 participants, including scholars, clinicians, and graduate students from domestic and international medical schools and institutions, research institutes, and related industries. Opening Remarks and Keynotes The event commenced with an opening address by Vice President Bin Peng of PUMCH, followed by keynote speeches from Deputy Director Fan Lu (National Science and Technology Infrastructure, Ministry of Science and Technology of China), and Director Shan Lu (China National Center for Biotechnology Development). Professor Chao Ma (Vice President and Secretary-General of the Chinese Society for Anatomy Science, Director of the National Human Brain Bank for Development and Function, Institute for Neuroscience, CAMS), delivered a welcome speech and highlighted the progress of the human brain database released since the inaugural forum in 2023. Groundbreaking Study on Normative Neurological Data and Launch of NeuroFunctionDataset-CN Prof. Yicheng Zhu (Director of the Department of Neurology of PUMCH), presided over the opening ceremony and jointly held the release ceremony of the NeuroFunctionDataset-CN with Vice President Bin Peng (PUMCH), Prof. Liying Cui (PUMCH), Prof. Jun Ni (PUMCH), Researcher Feng Tian (Institute of Software, Chinese Academy of Sciences-CAS), and Researcher Xiangmin Fan (Beijing Zhongke Ruiyi Information Technology Co., Ltd). The study on the Normative Data for Chinese General Population Quantitative Neurological Function was led by PUMCH and involved 13 hospitals across 12 provinces and cities in China. Initiated in 2021, the study enrolled over 1,800 adults with normal cognitive and motor functions, using the ReadyGo™ balance test system and the BrainFit™ digital cognitive function evaluation system to comprehensively assess their motor and cognitive abilities. The release of the database has filled a critical gap in China's clinical normative data for quantitative neurological function. It serves as a reference for determining normal ranges in clinical evaluations, offering a baseline for comparison in future neurological research. Additionally, the database is accessible to the global scientific community, allowing researchers to submit data use applications through the National Human Brain DataBank Platform (http://neurofunction.humanbrainbank.cn/). These studies were funded by the Science and Technology Innovation 2030 (STI2030)- Brain Science and Brain-Inspired Intelligence Technology Major Project, and the CAMS Innovation Fund for Medical Sciences (CIFMS). Thematic Reports and Sub-forums Following the opening ceremony, the forum transitioned into the theme report stage, hosted by Prof. Liying Cui and Prof. Xiaoping Wang. Several prominent experts delivered insightful presentations that captivated the audience: Prof. Shumin Duan, an academician of the CAS, presented on "A Brain Circuit Underlying Sexually Dimorphic Aggression". Prof. Shimin Hu, an academician of the CAS, discussed "Innovation and Medical Application of Deep Learning Framework". Prof. Xunming Ji, an academician of the Chinese Academy of Engineering, focused on "Clinical and Translational Research Driven by New Findings in Patients". Researcher Qi Xu from the Institute of Basic Medicine, CAMS, gave a talk on "A Pivotal Role of Human Brain in Neuropsychiatric Research and Strategies for Validation and Drug Discovery”. These reports sparked considerable interest and discussion among the attendees. In the afternoon, six sub-forums were organized, covering themes like Human Brain Banking, Neuropsychiatric Disorders, Neurodegenerative Diseases, Neuro-Imaging, Brain Aging Cohorts, and Multidisciplinary Innovations. A total of 24 domestic and foreign scholars delivered reports in these sub-forums, which were novel and rich in content. The Human Brain Banking sub-forum was hosted by Prof. Aimin Bao and Prof. Xinjie Bao. Prof. Inge Huitinga(Director of the Netherlands Brain Bank and the Netherlands Institute for Neuroscience in Amsterdam), gave a report titled "The Netherlands Neurogenetics Database." Prof. Jing Zhang(The First Affiliated Hospital of Zhejiang University) discussed the progress in the study of co-morbidities in the Chinese human brain bank. Prof. Jiangning Zhou (School of Life Sciences, University of Science and Technology of China) presented "The Molecular Regulation and Single-Cell Dissection of Stress Circuits." Lastly, Prof. Maurice Curtis of Neuroscience at the University of Auckland spoke on preparing the Neurological Foundation Human Brain Bank for the future of neuroscience. The Neuropsychiatric Disorders sub-forum was hosted by Prof. Chao Ma and Prof. Naihong Chen. The following reports were given during the forum: Prof. Zhang Yan (Vice President of The Second Xiangya Hospital of Central South University) presented on "Stress and the Brain." Prof. Chao Chen (Central South University) delivered a report on "Investigating the Etiology of Schizophrenia Based on Human Brain Samples." Prof. Aimin Bao (Zhejiang University) discussed "The Role of Oxytocin in Bipolar Disorder: From Animal Model to Postmortem Human Brain Study." Prof. Yizheng Wang (an academician of the CAS, Fudan University) spoke on "TRPC6 and the Diagnosis of Alzheimer's Disease." At the Neurodegenerative Disorders sub-forum hosted by Prof. Gang Wang and Dr. Fei Han (Associate Chief Physician), several reports were presented: Prof. Jianzhi Wang (Tongji Medical College, Huazhong University of Science and Technology) discussed the key role of abnormal tau accumulation in neurodegeneration and its targeting strategy. Assistant Prof. Xiaoying Chen (School of Medicine, University of Washington) presented on brain-immune interaction in health and disease. Researcher Jianxiong Zeng (Shanghai Jiaotong University) spoke about infection and immune modulation of Alzheimer's disease. Prof. Zhentao Zhang (Department of Neurology, Renmin Hospital of Wuhan University) discussed the role of pathologic protein aggregation in neurodegenerative diseases. The Neuro-Imaging sub-forum, hosted by Prof. Feng Feng and Dr. Ming Yao (Associate Chief Physician), featured the following reports: Prof. Jiahong Gao (Magnetic Resonance Imaging Research Center, Peking University) shared advances in neuroimaging technologies. Prof. Yufeng Zang (The Affiliated Hospital of Hangzhou Normal University) presented the localization and precise modulation of abnormal brain activity by rs-fMRI reference normals. Prof. Yong He (Beijing Normal University) discussed the developmental mapping and computational modeling of the human brain connectome. Shi Feng, a distinguished researcher at Shanghai Tech University, talked about how artificial intelligence enables brain image analysis. The Brain Aging Cohort sub-forum was chaired by Prof. Yicheng Zhu and Prof. Jun Ni. During the forum, several reports were presented: Prof. Ni Zhen (National Institute of Neurological Disorders and Stroke, National Institutes of Health) delivered a report on the application of brain stimulation in neurological diseases. Prof. Guangliang Shan (Institute of Basic Medicine, CAMS) presented a report on modern cohort study concepts and models in practice. Prof. Lu Shen (Department of Neurology, Xiangya Hospital, Central South University) discussed the development of clinical cohort studies and precision diagnostics for neurodegenerative diseases. Director Lei Cao (The General Office of Stroke Prevention Project Committee, National Health Commission) provided insights on the National Stroke Screening and Intervention Program for People at High Risk of Stroke. The Multidisciplinary Innovations sub-forum was chaired by Prof. Deling Li and Prof. Haiteng Deng and included the following presentations: Prof. Luping Shi (Tsinghua University) spoke about brain-inspired computing and perception. Assistant researcher Xiaolan Peng (Institute of Software, CAS) discussed the key intelligent interaction technology in the ancillary diagnosis of nervous system diseases. Associate researcher Youning Lin (Shenzhen BGI Life Sciences Research Institute) explained spatiotemporal omics approaches to understanding brain development and disease. Associate Prof. Junxia Zhang (Department of Neurosurgery, Jiangsu Provincial People's Hospital) presented on precision surgery for Glioma - The intraoperative application of precision cell-level imaging technology. Young Scholars Forum A roundtable forum for young scholars was held in the evening, co-chaired by Prof. Linya You, Associate Researcher Fan Liu, and Assistant Prof. Xiaoying Chen. Eight young scholars presented their research, including Prof. Qiong Liu (Department of Anatomy and Histoembryology, School of Basic Medical Sciences, Fudan University) spoke about the mechanism of cognitive impairment and depressive disorder based on the molecular dynamic of human hippocampus aging. Dr.Fei Han (associate chief physician of the Department of Neurology, PUMCH) reported on key points in the clinical trial design for cerebral small vessel disease. Prof. Yan Li (School of Basic Medicine, Shanghai Jiao Tong University) presented a draft human brain spatial proteome atlas for understanding the molecular basis of brain function. Associate researcher Xia Wang (the Institute of Basic Medicine, CAMS) shared insights on the ALDH2 rs671 G>A enhances Alzheimer’s disease pathology. Prof. Zhiyong Chen (School of Basic Medicine, Harbin Medical University) highlighted the application experiences of neuroelectrophysiology and imaging technologies in neuroscience research. Assistant researcher Yuting Hu (National Health and Disease Human Brain Tissue Resource Center, Zhejiang University) discussed the downregulation of peripheral luteinizing hormone rescues ovariectomy-associated cognitive deficits in APP/PS1 mice. Prof. Linya You (Department of Human Anatomy and Histoembryology, School of Basic Medicine, Fudan University) spoke about neuronal excitotoxicity in aging and mental illness. Lastly, Dr. Jiuyang Ding (School of Forensic Medicine, Guizhou Medical University) shared insights on APOE4 couples AS and AD-like tau pathology. Starting in 2023, the Human Brain Forum is dedicated to the aims of "Probe, Protect & Promote the Human Brain". Planned to be held annually, this forum convenes leading experts in both basic and clinical brain science to share the latest advancements in the establishment of human brain banks and research on human brain science worldwide. The forum organizers wish to pave the way to promote scientific and technological innovation in neuroscience, particularly related to human brain health and diseases, by facilitating an opportunity to integrate basic, clinical research and translational research, including industrial transformation of academic results. Conflict of interest All members declare no conflict of interest. List of abbreviations CAMS Chinese Academy of Medical Sciences; PUMCH Peking Union Medical College Hospital; CAS Chinese Academy of Sciences.
Copyright (c) 2024 Lijing Fang, Chao Ma, Yi-Cheng Zhu https://creativecommons.org/licenses/by-nd/4.0
DNA Methylation in Aging and Alzheimer's Disease
DNA methylation undergoes significant changes with age. These alterations play a pivotal role in the development of age-related diseases, including Alzheimer's disease (AD). Recent advancements in DNA methylome profiling have revealed global hypomethylation patterns, particularly within repetitive elements, as well as gene-specific changes that are associated with neurodegeneration. Age-related alterations in DNA methylation have been implicated in the disruption of key cellular processes, such as inflammation and proteostasis, both central to AD pathology. However, several challenges persist in this field. One major issue is the inconsistency of findings across different brain regions and tissue types, which complicates result interpretation. Furthermore, the limited understanding of cell-type specificity raises concerns about the generalizability of findings from bulk tissue analyses. Key questions remain in DNA methylation research related to aging and AD, including elucidating the precise mechanisms driving methylation changes, exploring cell-type specificity, determining the functional consequences of these alterations, and investigating cross-tissue correlations. A deeper understanding of the spatiotemporal dynamics of methylation changes, the underlying mechanisms, and their therapeutic implications is essential to the development of novel prevention and treatment strategies. This review will delve into these findings and challenges, offering insights into future research directions.
Copyright (c) 2024 Raymond Cheng, Jingmin Shu, Hai Chen, Ming Li, Xiaodong Cheng, Li Liu https://creativecommons.org/licenses/by-nd/4.0
Guidelines for the Multidisciplinary Diagnosis and Treatment of Neurofibromatosis Type 1 (2023 Version) Multidisciplinary Diagnosis and Treatment Collaboration Group for Neurofibromatosis Type 1 of China Alliance for Rare Diseases
Neurofibromatosis type 1 (NF1) is an autosomal dominant hereditary neoplastic disease caused by mutations in the NF1 gene. Features of the disorder typically appear in early childhood. The clinical phenotypes of the patients are diverse but neurofibroma is the main feature. Patients with NF1 also suffer from multi-system involvement and have high risk of malignant tumor. NF1 poses significant challenges for diagnosis, treatment, follow-up and patients management. Therefore, it is imperative to develop a multidisciplinary collaborative diagnosis and treatment protocol. Under the leadership of the China Alliance for Rare Diseases, a multidisciplinary diagnosis and treatment collaborative team for NF1 has been formed and has developed the guideline. This guideline intends to lift the diagnosis and treatment level for NF1 and to provide a standardized treatment protocol for NF1 patients in China.
Copyright (c) 2024 Yicheng Zhu https://creativecommons.org/licenses/by-nd/4.0
Roles and Mechanisms of Lactylation Modification in Hypoxia-exacerbated Neuroinflammation
Lactate is a product of cellular energy metabolism. In the brain, lactate shuttles between astrocytes, microglia, and neurons, playing an important role in coordinating cellular metabolism and signaling. Hypoxia causes a shift in cellular metabolism from oxidative phosphorylation to glycolysis, increasing lactate. In addition to being a metabolic substrate, lactate also acts as a signaling molecule. More interestingly, lactate accumulation can induce protein lactylation modification, a newly identified post-translational modification (PTM). Lactylation modifications occur on both histone and non-histone proteins and are involved in the regulation of numerous cellular processes, including tumorigenesis, immune inflammation, and embryonic development. In the context of neuroinflammation, our recently published report showed that hypoxia activates microglia and exacerbates neuroinflammation in the brain. This review summarizes the effects of hypoxia on lactate metabolism, as well as the process of lactylation and delactylation in microglia. The regulatory mechanisms of protein lactylation in hypoxia-exacerbated neuroinflammation are further discussed.
Copyright (c) 2024 Xuechao Fei, Ming Zhao, Lingling Zhu https://creativecommons.org/licenses/by-nd/4.0
The Potential Role of Intestinal Macrophages in the Gut-Brain Axis
Intestinal macrophages are crucial for maintaining gastrointestinal (GI) homeostasis and also contribute to various inflammatory disorders within the gut. As the most abundant immune cells in the GI tract, intestinal macrophages perform multifaceted functions. These include balancing immune responses to either innocuous antigens or harmful stimuli, supporting mucosal barrier integrity, and affecting gut secretion and motility through interactions with the enteric nervous system (ENS) and other nerves. A complex communication system, known as the “gut-brain axis” (GBA), exists between the intestine and the central nervous system (CNS). It integrates multilevel signals and modulates the functions of these two organs. A myriad of studies have revealed that alterations in the enteric microbiota are linked to various CNS disorders, such as Alzheimer’s disease, Parkinson’s disease, brain malignancies, multiple sclerosis, stroke, stress, anxiety, depression, autism, and schizophrenia. The mechanisms underlying the impact of gut dysbiosis on neuroinflammatory and neuropsychiatric diseases involve microbial metabolites and products, neurotransmitters and neuropeptides, immune regulation (including cytokines and chemokines), and neuroendocrine pathways. Notably, the functional status of intestinal macrophages is highly sensitive to the composition of the microbiota and thus can regulate the progression of CNS diseases via the GBA. Intestinal macrophages are found throughout the GI tract and may communicate with the brain through the nervous, circulatory, and immune systems. Thus far, there are relatively few studies that have explored the cellular and molecular mechanisms by which intestinal macrophages regulate CNS homeostasis and pathological conditions. The heterogeneity and niche-specific phenotypes of intestinal macrophages may have hindered a complete understanding of their specific roles in the context of homeostasis and disease. Here, we describe the progress made in understanding the distinct populations of intestinal macrophages and their roles in the GBA, providing an overview of their contributions to CNS homeostasis and dysfunction.
Copyright (c) 2024 Haowu Jiang, Rui Sun https://creativecommons.org/licenses/by-nd/4.0
Lipotoxicity, the role in the process of atherosclerosis
Background: Atherosclerosis (AS) is a growing problem in the elderly population causing a variety of diseases with high mortality and disability rates. Lipotoxicity plays an important role in the process of AS. Aim: This review aims to summarize the characteristics of glucose and lipid metabolism, local pathological changes of arteries and functional changes or death of perivascular cells in the process of lipotoxicity. Result: From the perspective of lipotoxicity and aging, we review the current understanding of the relationship between lipid metabolism and the development of atherosclerosis, and discuss the corresponding pharmacological treatment options. Conclusion: Various metabolic factors can lead to lipotoxicity, which in turn affects the vascular wall and various cells within the blood vessels, leading to the development of atherosclerosis. Clarifying the role of lipotoxicity in atherosclerosis provides a new perspective for the prevention and treatment of atherosclerosis.
Copyright (c) 2024 Jiayao Li , Wenjing Li, Liqun Jiao, Shuaiwei Guo, Xintao Lv, Shengyan Cui, Yixin Sun, Zixuan Xing, Xiao Zhang, Tao Wang https://creativecommons.org/licenses/by-nd/4.0
Long-Term Prognosis of Ischemic Stroke in Young Adults
In recent years, the prevalence of ischemic stroke in young adults has been rising, which is of great significance to public health. In young stroke patients, the long-term effects on neurological, psychological, and social functioning are incalculable. This article reviews the latest knowledge on the prognosis of young ischemic stroke, with a particular focus on the long-term prognosis and socio-economic issues of young individuals who have experienced an ischemic stroke. The review revealed that young patients with ischemic stroke have a significantly higher long-term mortality rate compared to the general population of the same age and gender. The majority of these deaths are caused by cardiovascular issues. The overall occurrence rate of subsequent stroke can reach up to 9.4%~11.5% over 5 years and up to 19.4%~21.6% within 10 years. Among young stroke patients with atherosclerosis, cardioembolism, and multiple vascular risk factors, the risk of mortality and recurrent vascular events increased, whereas cryptogenic stroke was associated with the lowest risk of recurrent cerebrovascular events. During extended periods of observation, young individuals who have experienced a stroke frequently encounter additional negative long-term effects, such as epilepsy, cognitive decline, depression, and difficulties in returning to work. Overall, the outlook for young individuals with ischemic stroke in the long term is generally unfavorable, with the specific outcome depending on the cause and risk factors of the stroke. Early detection and proactive management of risk factors, together with the improvement of primary and secondary prevention and treatment, are essential in minimizing the impact of stroke on young individuals in the future.
Copyright (c) 2024 Qiqi Wang, Lixin Zhou, Jun Nib https://creativecommons.org/licenses/by-nd/4.0
Anatomical distribution of histone H3 acetylation in human hippocampus
In recent years, the role of histone acetylation in the brain has been studied from different aspects. However, the anatomical distribution of histone H3 acetylation in the human hippocampus and its potential relevance to triple synaptic circuits are unknown. As one of epigenetic remodeling ways, the modification of histones is involved in multiple aspects of neuronal function and development and is a key process in the onset and development of Alzheimer’s disease (AD). In our study, we compared acetylation levels of histone H3 at different regions of the hippocampus in AD and non-AD patients. We found that histone H3 acetylation can be detected in the dentate gyrus (DG), CA4, CA3, CA2, CA1, and lower Toya regions of the human hippocampus. The highest degree of acetylation in the hippocampus is in DG, and the level of acetylation changes gradually and systematically along the triple synaptic circuit. Besides, there were no significant differences in histone acetylation between AD and non-AD groups.
Copyright (c) 2024 Bingyue Cao, Fengling Luo, Wenwen Zhang, Renwei Luo, Lile Cai, Yongchang Wei, Yanqing Wang, Pan Liu https://creativecommons.org/licenses/by-nd/4.0
The role of ALDH2 and its substrates in central nervous system disorders
Background: Aldehyde Dehydrogenase 2 (ALDH2) is a mitochondrial dehydrogenase enzyme primarily tasked with the detoxification of acetaldehyde produced from alcohol metabolism and endogenous aldehydes. These aldehyde compounds, such as 4-Hydroxynonenal (4-HNE) and 3,4-dihydroxyphenylacetaldehyde (DOPAL), are predominantly generated through lipid peroxidation and are known to form adducts with proteins, DNA, and lipids, thereby inducing neurotoxicity. Methods: This review examines the role of ALDH2 in central nervous system (CNS) diseases by analyzing epidemiological studies and disease models. The focus is on understanding the impact of the ALDH2 rs671 G>A polymorphism, which reduces or eliminates enzyme activity. Results: This genetic polymorphism of ALDH2 is closely associated with the onset of various central nervous system (CNS) diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, and stroke potentially linked to the accumulation of aldehyde compounds within the CNS. Conclusions: A deeper understanding of the mechanisms by which ALDH2 influences these diseases will enhance therapeutic strategies for patients carrying the ALDH2 rs671 polymorphism and also offer new insights for the prevention and diagnosis of these conditions.
Copyright (c) 2024 Yashuang Chen , Fengyuan Tian, Shu Meng, Jiayu Wang https://creativecommons.org/licenses/by-nd/4.0
Direct mechanical thrombectomy with or without thrombolysis for acute ischemic stroke
The efficacy of direct mechanical thrombectomy (MT) and thrombectomy combined with intravenous thrombolysis (MT+IVT) in patients with acute ischemic stroke is still unclear. To comprehensively analyze the two strategies, we conducted a meta-analysis of randomized controlled trials (RCTs). Six RCTs were recruited from Ovid Medline, Embase, and Cochrane Central Register of Controlled Trials and published from 2020 to 2023, including 1164 in the MT group and 1170 in the MT + IVT group. There was no significant difference between the MT group and MT+IVT group in 90-day favorable outcome (OR 0.93, 95% CI 0.79-1.09, P=0.37, I2=0%,) and excellent outcome (OR 0.98, 95% CI 0.82-1.18, P=0.82, I2=0%). Similarly, there was no significant difference in 90-day mortality (OR 1.08, 95% CI 0.86-1.35, P=0.52, I2=0%) and symptomatic intracranial hemorrhage (OR 0.82, 95% CI 0.57-1.19, P=0.30, I2=0%). However, the successful recanalization rate of the MT group was significantly lower than that of the MT+IVT group (OR 0.73, 95% CI 0.57-0.94, P=0.01, I2=0%). There was no significant difference in functional outcome and safety endpoints between direct MT and MT+IVT, but the successful recanalization rate of MT+IVT was higher.
Copyright (c) 2024 Xuebing Feng, Yunying Feng, Jie Wang, Xin Xu, Yueqiao Xu https://creativecommons.org/licenses/by-nd/4.0
Potential applications of nanomedicine in the treatment of Parkinson's disease
Parkinson's disease (PD) is the second most common neurodegenerative disease and leads to severe disability and even death in patients, causing a heavy social burden worldwide. Among the therapeutics for PD, pharmacotherapy is usually the first-line therapy and is typically the basic treatment for other therapeutics, such as surgery, exercise therapy and psychological intervention. Unfortunately, the existing PD therapeutic agents fail to cure the disease due to their low efficacy, cytotoxicity, severe side effects and poor cell targeting. With the development of nanotechnology and the emergence of nanomedicine, the application of nanomaterials has helped improve the efficacy of pharmacotherapy for PD. In the following review, the current pharmacotherapy for PD and its pros and cons are described. A summary of the nanomaterial types commonly used in nanomedicine and their applications in PD treatment is provided. Additionally, challenges related to using nanomaterials for PD pharmacotherapy are discussed.
Copyright (c) 2024 Qi Xu, Jiawei Liu, Haiyan Liua https://creativecommons.org/licenses/by-nd/4.0
Roles of microglial calcium channels in neurodegenerative diseases
Microglia are crucial for neurodevelopment, and the maintenance of central nervous system functions. Calcium signals in microglia regulate the neuronal plasticity critical for learning, memory, and neuron survival. Growing evidence highlights the pivotal function of calcium channels in microglia, along with their cognate proteins, in modulating oxidative stress, neuroinflammation, and multiple neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. In this review, we summarized the important role and regulatory mechanism of these critical calcium channels and their associated proteins, highlighting their potential as novel therapeutic targets for neurodegenerative diseases.
Copyright (c) 2024 Shasha Wang, Jinyu Zhang, Jingdan Zhang, Ao li, Zengqiang Yuan, Jinbo Cheng https://creativecommons.org/licenses/by-nd/4.0
In 2023, our journal Human Brain maintained its original aims of integrating basic and clinical scientists in the study of human brain. The journal remains focusing on advancing our understanding of the human brain and brain disorders, the development of collaborative research platforms and databases related to the human brain. The following 10 manuscripts may be of particular interest to readers from a broad range of background and are presented in this editorial. The Brain Aging National Cohort (BANC)-PUMC, characterized by its large-scale samples, strict enrollment strategy, and scientific evaluation, represents a domestic breakthrough in the systematic study of the causes and consequences of age-related neurological diseases (Han et al., 2023). This examination addresses the data gap present in the Chinese demographic, fills an industrial void, and contributes to the advancement of our understanding of the origins of age-related neurodegenerative diseases. The ongoing follow-up program is expected to have a profound impact on the exploration of relevant pathological mechanisms. Given the lack of standardized operational protocol (SOP) for human brain banking in amyotrophic lateral sclerosis (ALS), research groups have provided a guideline for the construction and operation of an ALS brain bank, aligning with the SOP for the human brain banking in China. Chen et al. (2023) offer a detailed introduction to this guideline, which serves as a remarkable milestone for the research of ALS. With the gradual establishment and improvement of ALS brain bank, we anticipate increased attention and investment in ALS study, leading to a potential cure for this disease and ultimately benefiting patients. With the rapid growth in the incidence of Alzheimer’s disease (AD) and other types of dementia, China has become the country with the largest number of AD patients in the world. Understanding the facts is important to improve existing early-intervention strategies and treatment. Xiao et al. (2023) explored the major domestic challenges in the diagnosis and treatment of AD through a population-based study. This study provided us with a comprehensive view of the current states of AD care in China and laid a solid foundation for more comprehensive and effective approaches to AD control in the future. This article has made a significant impact among our readers and was viewed for over 1000 times in the month following its online publication on our journal’s website. Some studies demonstrate that the TrkB receptor and its pathway may serve as potential therapeutic targets for AD. He et al. (2023) discuss the role of primary TrkB-dependent signaling in the processes of AD pathogenesis. The article indicates that TrkB signaling activation can be effective in reducing Aß accumulation and Tau phosphorylation, which may open a new trial for AD treatment. To date, some preclinical small-molecule drugs targeting TrkB have shown promising positive effects. Aging is one of the pivotal factors causing neurodegenerative diseases and dementia, which is known not to affect individuals uniformly, even within the same person. Focusing on the variations from different brain regions and cell types, Chen et al. (2023) fully evaluate the impact of healthy aging on the human brain. With the advent of new imaging techniques that allow us to visualize cerebral venules more clearly than before, an increasing body of evidences shows that cerebral venules play an important role in many neurological disorders. Wang et al. (2023) summarize the latest research advances regarding cerebral venules alterations related to several neurological disorders. Immune checkpoint inhibitors, as a breakthrough discovery of the 21st century, have heralded a new era for biotechnology and remain a hotspot in cancer research. Currently, researchers are exploring the application of immune checkpoint modulators for the treatment of CNS diseases. Sun et al. (2023) focus on these related advances, especially the PD-1 and CTLA-4 inhibitors. Currently, great progress has been made in the field of nerve ultrasound, which aids conduct nerve studies for the diagnosis of peripheral neuropathies. Niu et al. (2023) have introduced the application of ultrasonics in various inflammatory neuropathies. This application has rendered CSA (cross-sectional area) enlargement and its distribution as useful and quantifiable parameters, thereby enabling the assessment of peripheral nerves. Deep brain stimulation (DBS) has been proven to be a promising strategy for enhancing the recovery of ischemic stroke. Geng et al. (2023) suggest that electrical stimulation of multiple deep brain nuclei as targets may have a variety of positive effects on both rodents and humans. Despite the rapid development and wide adoption of tissue transparency methodology in animal brains, high-resolution imaging and transparency in human brain tissues still face major challenges, such as high fat content, high density, and strong background fluorescence. Li et al. (2023) have successfully developed a new method for human brain transparency called dFC-Tesos, which involves steps including tissue electrophoresis degreasing, antibody labeling, decolorization, and three-dimensional high-resolution imaging. To demonstrate the concept, the authors clearly showed the spatial relationships and pathological changes between microglia and Aβ plaques in the brain cortex from patients with Alzheimer's disease. For the first time, the dFC-Tesos method provides a useful tool for studying the macroscopic and ultrastructural structures of human brain tissue with transparency. This manuscript is also in memory of the fist author, Ms. Di-Di Li, who is both a talent scientist and a diligent collaborator. In summary, the 2023 issue of Human Brain presented here attempts to reflect the latest research trends and developments, deepen our understanding of the brain, and improve the medical practice and quality of life for patients suffering from brain disorders. Furthermore, we typically hope that readers could leverage our sources as a platform to accelerate academic communication in the broad field of human brain science.
Copyright (c) 2024 Chao Ma, Yi-Cheng Zhub https://creativecommons.org/licenses/by-nd/4.0
RNA m6A Methylation and Alzheimer's Disease: Current Evidence and Future Perspectives
Background: Alzheimer’s disease (AD) is the most common neurodegenerative disease characterized by the pathological accumulation of b-amyloid and neurofibrillary tangles. Despite substantial progress in both basic and clinical research on AD, the detailed mechanism of AD pathogenesis is still elusive. RNA N6-methyladenosine methylation (m6A) is the most predominant post-transcriptional modification on eukaryotic mRNA, prominently enriched in the mammalian brain. Notably, m6A-modified RNA showed significant changes during the development of AD, indicating an important role of this modification in AD pathogenesis. Aim: In this study, we aim to provide a summary of recent advances highlighting the indispensable role of m6A in AD pathogenesis. Result: From the perspective of m6A modification, we review our current understanding of the association between RNA m6A machinery and the risk factors of AD, as well as its involvement in various pathophysiological hallmarks of AD. We also discuss the main obstacles in current studies about m6A in AD pathogenesis and the corresponding caveats and solutions to them. Conclusion: This review emphasizes the significance of investigating m6A in the context of AD and highlights the considerable potential for m6A to emerge as a novel therapeutic target for AD.
Copyright (c) 2024 Wenqi Pan, Yan Chen, Yuesi Xu, Wei-Min Tong, Yamei Niu https://creativecommons.org/licenses/by-nd/4.0
Brain metastasis from non-small cell lung cancer: management and prognosis of primary lung tumor resection
Brain metastases (BM) will develop in 30-50% of non-small cell lung cancer (NSCLC) patients in the course of their illness. Systemic treatment is recommended for most advanced-stage NSCLC patients with BM but the prognosis remains poor. The prognosis and management of primary lung tumor resection are still a debated topic in this complex clinical setting. The present study will gather and review related research evidence. The survival benefit, patient selection and proper surgical strategy of primary lung tumor resection will be summarized and discussed in the treatment for NSCLC patients with BM.
Copyright (c) 2023 Donghang Li, Hongfeng Tong, Yaoguang Sun, Qingjun Wu, Chao Ma, Wenxin Tian, Chuan Huang, Hanbo Yu, Yi Tian, Peng Jiao https://creativecommons.org/licenses/by-nd/4.0
Mazor X Robot-Assisted Pedicle Screw Placement: A Case Series
Pedicle screw placement is a well-established procedure in spine surgeries, and the utilization of robots in spinal surgery has been on the rise. This study aims to investigate the accuracy and screw placement time associated with the use of Mazor X robots in robotic-assisted pedicle screw placement. A retrospective case study was conducted on 12 patients with lumbar spine disease who underwent Mazor X robot-assisted surgery. Screw placement accuracy was assessed using the Gertzbein-Robinson classification. Additionally, total screw placement time and fluoroscopy time were documented for analysis. A total of 60 screws were placed in the 12 patients who received robotic-assisted pedicle screw placement. Of these screws, 98.3% were found to be within the safe zone. As the cases progressed, there was a noticeable decrease in total screw placement time and fluoroscopy time. Our findings suggest that Mazor X robotic-assisted spine surgery boasts high accuracy rates and demonstrates a decreasing trend in screw placement time and fluoroscopy time. To the best of our knowledge, our institution is the first in China to employ the Mazor X robot for pedicle screw placement surgeries and to document its associated characteristics.
Copyright (c) 2023 Hongyi Wang, Yueqi Du, Linpeng Li, Can Zhang, Wanru Duan, Zan Chen https://creativecommons.org/licenses/by-nd/4.0
Anterior controllable antedisplacement and fusion as revision surgery for the treatment of OPLL after anterior and posterior decompression: A case report
Background: In cases of cervical ossification of the posterior longitudinal ligament (OPLL), when initial anterior or posterior decompression fails to yield satisfactory results, the alternative approach is often chosen for revision surgery. Nevertheless, there is a lack of reported information regarding the treatment and prognosis of patients with complex OPLL who have undergone both anterior and posterior decompression but experienced relapse. Case presentation: A 79-year-old male patient presented with numbness, weakness, and muscle atrophy in the right upper extremity, along with weakness in the right lower extremity. Initial assessment on admission revealed a Japanese Orthopaedic Association (JOA) score of 7. The patient previously underwent anterior cervical discectomy and fusion (ACDF) 25 years ago for spinal stenosis, followed by posterior laminectomy as revision surgery. After experiencing recurrent symptoms following a fall one year ago, the patient underwent a second revision surgery using the anterior controllable antedisplacement and fusion (ACAF) technique which led to symptom improvement, and resulted in a postoperative JOA score of 14 at 3 months of follow-up. Conclusions: Treatment of OPLL patients with symptom recurrence after traditional anterior and posterior decompression is challenging. ACAF offers a viable solution for managing this complex case.
Ossification of Posterior Longitudinal Ligament
Anterior Controllable Antedisplacement and Fusion
Copyright (c) 2023 Tianyu Jin, Wanru Duan, Zan Chen https://creativecommons.org/licenses/by-nd/4.0
Exploring Links between Pineal Gland Calcification and Central Nervous System Disease
Central nervous system disease is globally common with dysfunction of the brain and spinal cord, which significantly affects the quality of life, such as sleep disturbances. Pineal gland is pivotal in regulating sleep cycles and circadian rhythms. And melatonin, secreted by pineal gland, promotes neurodevelopment and maintains neurohomeostasis, which is also pivotal in the modulation of central nervous system disorders. In recent years, studies have found that patients with central nervous system damage often have degeneration of the pineal gland, characterized by a decrease in pineal gland volume, reduced melatonin secretion, and even parenchymal calcification. An increasing number of Alzheimer's disease patients have been observed to exhibit pineal gland calcification. Research suggests that sleep disturbances accompanying central nervous system disorders can be attributed to the degeneration of pineal gland function, indicating a potential contribution of gland calcification to central nervous system diseases. Here, we review the recent research on pineal gland calculi and discuss the potential relationship between pineal gland calcification and various central nervous system diseases, contributing to a deeper understanding of the intricate mechanisms underlying neurological disorders.
Copyright (c) 2023 Xinnan Liu, Haotian Liu https://creativecommons.org/licenses/by-nd/4.0
Preclinical Experimental Models for Human Glioma
Gliomas are one of the most common incurable brain tumors in adults with poor prognosis. Attempts at modeling human gliomas over the past decades have not only improved our knowledge of glioma biology but also boosted the development of therapeutic strategies. Despite great endeavors, gliomas are not responsive to the current tumor treatments, such as radiotherapy, chemotherapy, and immunotherapy due to their high inter- and intra-heterogenic tumor microenvironment (TME) and immune suppressive landscape. Therefore, it is significant to utilize suitable models to investigate the tumorigenesis, progression, and invasion of gliomas and evaluate potential therapies. Ideally, glioma models should fully recapitulate the genetic alterations and histological characteristics of the parental tumor, as well as reproduce the interactions between the tumor and its TME. In this review, we will discuss and compare the pros and cons of the current glioma models including traditional mouse models, established cell lines, newly 3D-cultured organoids, and 3D bioprinting glioma models in glioma pathogenesis research and therapy evaluation.
Copyright (c) 2023 Diya Zhang, Yunfan Li, Yucheng Wang, Rui Ju , Lei Guo https://creativecommons.org/licenses/by-nd/4.0