Blast-induced traumatic brain injury(b-TBI)is a kind of significant injury to soldiers in the current military conflicts.However,the mechanism of b-TBI has not been well understood,and even there are some contradictor...Blast-induced traumatic brain injury(b-TBI)is a kind of significant injury to soldiers in the current military conflicts.However,the mechanism of b-TBI has not been well understood,and even there are some contradictory conclusions.It is crucial to reveal the dynamic mechanism of brain volume and shear deformations under blast loading for better understanding of b-TBI.In this paper,the numerical simulation method is adopted to carry out comprehensive and in-depth researches on this issue for the first time.Based on the coupled Eulerian-Lagrangian method,the fluid-structure coupling model of the blast wave and human head is developed to simulate two situations,namely the head subjected to the frontal and lateral impacts.The simulation results are analyzed to obtain the underlying dynamic mechanisms of brain deformation.The brain volume deformation is dominated by the local bending vibration of the skull,and the corresponding frequency for the forehead skull under the frontal impact and the lateral skull faced to the lateral impact is as high as 8 kHz and 5 kHz,respectively.This leads to the high-frequency fluctuation of brain pressure and the large pressure gradient along the skull,totally different from the dynamic response of brain under head collisions.While the brain shear deformation mainly depends on the relative tangential displacement between the skull and brain and the anatomical structure of inner skull,being not related to the brain pressure and its gradient.By further comparing the medical statistics,it is inferred that diffuse axonal injury and brain contusion,the two most common types of b-TBI,are mainly attributed to brain shear deformations.And the von Mises stress can be adopted as the indicator for these two brain injuries.This study can provide theoretical guidance for the diagnosis of b-TBI and the development of protective equipment.展开更多
Research examining the long-term effects of drugs such as AdderallTM, a mixed DL-amphetamine, as a first-line treatment strategy for those diagnosed with attention deficit hyperactivity disorder (ADHD), is very much l...Research examining the long-term effects of drugs such as AdderallTM, a mixed DL-amphetamine, as a first-line treatment strategy for those diagnosed with attention deficit hyperactivity disorder (ADHD), is very much lacking. In order to address this, the present study sought to examine possible behavioral and neuroanatomical effects of chronic oral exposure to DL-amphetamine administered at a relatively low dose to the developing male Sprague Dawley rat. Animals were administered a mixture of chocolate drink and DL-amphetamine at a dose of 1.6 mg/kg for 36 days, beginning at PD 24 and ending at PD 60. Anxiety, a potential side effect of stimulant treatment, was assessed using three paradigms: The open field test (OF), the social interaction test (SI), and the elevated plus maze (EPM). The OF and SI were conducted using repeated testing over the course of five weeks. Testing occurred immediately after drug administration on a given day. The EPM was used only once on the penultimate day of treatment, before the drug was administered. Following drug treatment on PD 60, brain-to-body weight ratios were obtained. Results indicated that there were no group differences in brain-to-body weight ratios nor were differences in locomotor and social behaviors observed. However, rats treated with DL-amphetamine did show an anxiogenic response in the EPM. This was represented as a significant reduction in open arm entries. Overall our findings suggest that while chronic drug treatment fails to alter multiple measures of behavior, or reliable changes in brain volume, such treatment may impact a behavioral index of anxiety. Future research should seek to examine the implications of this heightened anxiogenic response in animals treated chronically with oral, low-dose DL-amphetamine.展开更多
Background This study aimed to investigate the relationship between overall obesity,central obesity and brain volumes,as well as to determine the extent to which cardiometabolic and inflammatory measures act as mediat...Background This study aimed to investigate the relationship between overall obesity,central obesity and brain volumes,as well as to determine the extent to which cardiometabolic and inflammatory measures act as mediators in the association between body mass index(BMI),waist-hip ratio(WHR)and brain volumes.Methods In the context of counterfactual framework,mediation analysis was used to explore the potential mediation in which cardiometabolic and inflammatory measures may mediate the relationship between BMI,WHR,and brain volumes.Results Among 2413 community-dwelling participants,those with high BMI or WHR levels experienced an approximately brain ageing of 4 years.Especially,individuals with high WHR or BMI under the age of 65 exhibited white matter hyperintensity volume(WMHV)differences equivalent to around 5 years of ageing.Conversely,in the high-level WHR population over the age of 65,premature brain ageing in gray matter volume(GMV)exceeded 4.5 years.For GMV,more than 45%of the observed effect of WHR was mediated by glycaemic metabolism indicators.This proportion increases to 78.70%when blood pressure,triglyceride,leucocyte count,and neutrophil count are jointly considered with glycaemic metabolism indicators.Regarding WHR and BMI’s association with WMHV,cardiometabolic and inflammatory indicators,along with high-density lipoprotein cholesterol,mediated 35.50%and 20.20%of the respective effects.Conclusions Overall obesity and central obesity were associated with lower GMV and higher WMHV,a process that is partially mediated by the presence of cardiometabolic and inflammatory measures.展开更多
Background:Brain volume measurement serves as a critical approach for assessing brain health status.Considering the close biological connection between the eyes and brain,this study aims to investigate the feasibility...Background:Brain volume measurement serves as a critical approach for assessing brain health status.Considering the close biological connection between the eyes and brain,this study aims to investigate the feasibility of estimating brain volume through retinal fundus imaging integrated with clinical metadata,and to offer a cost-effective approach for assessing brain health.Methods:Based on clinical information,retinal fundus images,and neuroimaging data derived from a multicenter,population-based cohort study,the Kai Luan Study,we proposed a cross-modal correlation representation(CMCR)network to elucidate the intricate co-degenerative relationships between the eyes and brain for 755 subjects.Specifically,individual clinical information,which has been followed up for as long as 12 years,was encoded as a prompt to enhance the accuracy of brain volume estimation.Independent internal validation and external validation were performed to assess the robustness of the proposed model.Root mean square error(RMSE),peak signal-tonoise ratio(PSNR),and structural similarity index measure(SSIM)metrics were employed to quantitatively evaluate the quality of synthetic brain images derived from retinal imaging data.Results:The proposed framework yielded average RMSE,PSNR,and SSIM values of 98.23,35.78 d B,and 0.64,respectively,which significantly outperformed 5 other methods:multi-channel Variational Autoencoder(mcVAE),Pixelto-Pixel(Pixel2pixel),transformer-based U-Net(Trans UNet),multi-scale transformer network(MT-Net),and residual vision transformer(ResViT).The two-(2D)and three-dimensional(3D)visualization results showed that the shape and texture of the synthetic brain images generated by the proposed method most closely resembled those of actual brain images.Thus,the CMCR framework accurately captured the latent structural correlations between the fundus and the brain.The average difference between predicted and actual brain volumes was 61.36 cm~3,with a relative error of 4.54%.When all of the clinical information(including age and sex,daily habits,cardiovascular factors,metabolic factors,and inflammatory factors)was encoded,the difference was decreased to 53.89 cm~3,with a relative error of 3.98%.Based on the synthesized brain magnetic resonance images from retinal fundus images,the volumes of brain tissues could be estimated with high accuracy.Conclusion:This study provides an innovative,accurate,and cost-effective approach to characterize brain health status through readily accessible retinal fundus images.展开更多
The triple transgenic mouse model of Alzheimer’s disease(3×Tg-AD)is a widely used model that exhibits region-dependent patterns of progressive amyloid-βand tau pathology.Although structural brain abnormalities ...The triple transgenic mouse model of Alzheimer’s disease(3×Tg-AD)is a widely used model that exhibits region-dependent patterns of progressive amyloid-βand tau pathology.Although structural brain abnormalities on magnetic resonance imaging have been observed in 3×Tg-AD mice at later disease stages(>12 months)and as early as 2 months,few studies have investigated changes in these mice during the stage with extensive amyloid-βdeposition and onset of tau pathology(around 9 months).This study aimed to assess brain morphometry and microstructure alterations in 9 month-old 3×Tg-AD mice to better understand the neural mechanisms underlying these specific pathological features.Voxel-based analyses were employed on T2-weighted and diffusion tensor imaging to identify differences between 3×Tg-AD and control mice.Compared with controls,3×Tg-AD mice exhibited lower gray matter volume in several regions including both hippocampal regions,the right thalamus,the left caudoputamen,and the cortex.Reduced white matter volume was observed in fiber tracts including the corpus callosum,internal capsule,stria terminalis,and olfactory tract.Whole-brain diffusion tensor imaging analysis revealed a significant decrease in fractional anisotropy and an increase in both radial and mean diffusivity within the left dentate gyrus of the hippocampal region and right striatum-like amygdala nuclei,with no significant difference in axial diffusivity.Correlation analyses demonstrated significant associations between behavioral performance measures,with both gray and white matter volumes within regions showing significant morphometric differences.Notably,behavioral performance also exhibited significant correlations with diffusion tensor imaging measures particularly within the left dentate gyrus of the hippocampal region and right striatum-like amygdala nuclei.Immunofluorescence analysis confirmed increased amyloid-βplaques and p-Tau protein expression in the hippocampal regions of 3×Tg-AD mice,which corroborated the magnetic resonance imaging findings.Transcriptome analysis in hippocampus tissue identified 1389 differentially expressed genes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that numerous differentially expressed genes were enriched in biological processes relevant to synapse structure,cognition,learning,and memory,with particular emphasis on Wnt and mitogen-activated protein kinase signaling pathways.Collectively,these findings suggest that intricate anatomical and microstructural alterations occur in 3×Tg-AD model mice at the onset of pathology around 9 months,potentially driven by gene expression alterations.Moreover,our results support the potential utility of brain volume and diffusion metrics as biomarkers for Alzheimer’s disease pathology,which could have significant implications for clinical diagnosis of Alzheimer’s disease patients.展开更多
Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microgl...Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microglia play an important role in secondary injury and can be activated in response to traumatic brain injury.In this article,we review the origin and classification of microglia as well as the dynamic changes of microglia in traumatic brain injury.We also clarify the microglial polarization pathways and the therapeutic drugs targeting activated microglia.We found that regulating the signaling pathways involved in pro-inflammatory and anti-inflammatory microglia,such as the Toll-like receptor 4/nuclear factor-kappa B,mitogen-activated protein kinase,Janus kinase/signal transducer and activator of transcription,phosphoinositide 3-kinase/protein kinase B,Notch,and high mobility group box 1 pathways,can alleviate the inflammatory response triggered by microglia in traumatic brain injury,thereby exerting neuroprotective effects.We also reviewed the strategies developed on the basis of these pathways,such as drug and cell replacement therapies.Drugs that modulate inflammatory factors,such as rosuvastatin,have been shown to promote the polarization of antiinflammatory microglia and reduce the inflammatory response caused by traumatic brain injury.Mesenchymal stem cells possess anti-inflammatory properties,and clinical studies have confirmed their significant efficacy and safety in patients with traumatic brain injury.Additionally,advancements in mesenchymal stem cell-delivery methods—such as combinations of novel biomaterials,genetic engineering,and mesenchymal stem cell exosome therapy—have greatly enhanced the efficiency and therapeutic effects of mesenchymal stem cells in animal models.However,numerous challenges in the application of drug and mesenchymal stem cell treatment strategies remain to be addressed.In the future,new technologies,such as single-cell RNA sequencing and transcriptome analysis,can facilitate further experimental studies.Moreover,research involving non-human primates can help translate these treatment strategies to clinical practice.展开更多
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 curr...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,costeffectiveness evaluations,and addressing the needs of patients with comorbidities.A multidisciplinary approach should be used to enhance treatment and improve patient outcomes.展开更多
Stroke is a major cause of death and disability worldwide.It is characterized by a highly interconnected and multiphasic neuropathological cascade of events,in which an intense and protracted inflammatory response pla...Stroke is a major cause of death and disability worldwide.It is characterized by a highly interconnected and multiphasic neuropathological cascade of events,in which an intense and protracted inflammatory response plays a crucial role in worsening brain injury.Neuroinflammation,a key player in the pathophysiology of stroke,has a dual role.In the acute phase of stroke,neuroinflammation exacerbates brain injury,contributing to neuronal damage and blood–brain barrier disruption.This aspect of neuroinflammation is associated with poor neurological outcomes.Conversely,in the recovery phase following stroke,neuroinflammation facilitates brain repair processes,including neurogenesis,angiogenesis,and synaptic plasticity.The transition of neuroinflammation from a harmful to a reparative role is not well understood.Therefore,this review seeks to explore the mechanisms underlying this transition,with the goal of informing the development of therapeutic interventions that are both time-and context-specific.This review aims to elucidate the complex and dual role of neuroinflammation in stroke,highlighting the main actors,biomarkers of the disease,and potential therapeutic approaches.展开更多
Ischemic stroke,a frequently occurring form of stroke,is caused by obstruction of cerebral blood flow,which leads to ischemia,hypoxia,and necrosis of local brain tissue.After ischemic stroke,both astrocytes and the bl...Ischemic stroke,a frequently occurring form of stroke,is caused by obstruction of cerebral blood flow,which leads to ischemia,hypoxia,and necrosis of local brain tissue.After ischemic stroke,both astrocytes and the blood–brain barrier undergo morphological and functional transformations.However,the interplay between astrocytes and the blood–brain barrier has received less attention.This comprehensive review explores the physiological and pathological morphological and functional changes in astrocytes and the blood–brain barrier in ischemic stroke.Post-stroke,the structure of endothelial cells and peripheral cells undergoes alterations,causing disruption of the blood–brain barrier.This disruption allows various pro-inflammatory factors and chemokines to cross the blood–brain barrier.Simultaneously,astrocytes swell and primarily adopt two phenotypic states:A1 and A2,which exhibit different roles at different stages of ischemic stroke.During the acute phase,A1 reactive astrocytes secrete vascular endothelial growth factor,matrix metalloproteinases,lipid carrier protein-2,and other cytokines,exacerbating damage to endothelial cells and tight junctions.Conversely,A2 reactive astrocytes produce pentraxin 3,Sonic hedgehog,angiopoietin-1,and other protective factors for endothelial cells.Furthermore,astrocytes indirectly influence blood–brain barrier permeability through ferroptosis and exosomes.In the middle and late(recovery)stages of ischemic stroke,A1 and A2 astrocytes show different effects on glial scar formation.A1 astrocytes promote glial scar formation and inhibit axon growth via glial fibrillary acidic protein,chondroitin sulfate proteoglycans,and transforming growth factor-β.In contrast,A2 astrocytes facilitate axon growth through platelet-derived growth factor,playing a crucial role in vascular remodeling.Therefore,enhancing our understanding of the pathological changes and interactions between astrocytes and the blood–brain barrier is a vital therapeutic target for preventing further brain damage in acute stroke.These insights may pave the way for innovative therapeutic strategies for ischemic stroke.展开更多
Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have rev...Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota–brain axis.This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury.The NACHT,LRR,and pyrin domain-containing protein 3(NLRP3)inflammasome plays a crucial role in this context.This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome.These mechanisms include metabolic pathways(involving short-chain fatty acids,lipopolysaccharides,lactic acid,bile acids,trimethylamine-N-oxide,and tryptophan),neural pathways(such as the vagus nerve and sympathetic nerve),and immune pathways(involving microglia and T cells).We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage.The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood–brain barrier,inducing neuroinflammation,and interfering with nerve regeneration.Finally,we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury.Our review highlights the critical role of the gut microbiota–brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage,paving the way for exploring potential therapeutic approaches.展开更多
Investigating the mechanisms underlying central nervous system disorders is a major scientific issue in the 21st century.However,the inaccessibility and complexity of the human brain have always represented a challeng...Investigating the mechanisms underlying central nervous system disorders is a major scientific issue in the 21st century.However,the inaccessibility and complexity of the human brain have always represented a challenge in understanding the pathophysiology of the central nervous system.Brain organoids are self-assembled threedimensional aggregates derived from pluripotent stem cells with cell types and structures similar to the embryonic human brain,giving them potential for investigating the atypical cellular,molecular,and genetic characteristics characteristic of central nervous system disorders.Brain organoids also provide a platform for drug screening and serve as a potential source for transplantation therapy for brain injuries.However,the broad application of brain organoids is hampered by several limitations,such as the lack of high-fidelity cell types,insufficient maturation,and considerable heterogeneity,undermining their reliability in specific applications.This review summarizes brain organoid evolution,discusses recent technological and methodological innovations,and reviews their applications in drug screening,transplantation therapy,and disease modeling,as well as clinical research progress.Additionally,we emphasize the limitations of current brain organoid research and explore the potential for advancing the technology to enhance its applicability.展开更多
Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated...Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated with increased levels of circulato ry pro-inflammatory marke rs up to 1 year postTBI(Eagle et al.,2023).展开更多
Brain organoids are artificial neural tissues derived in vitro,containing a variety of cell types,as well as structural and/or functional brain regions.They can partially mimic brain physiological activities and disea...Brain organoids are artificial neural tissues derived in vitro,containing a variety of cell types,as well as structural and/or functional brain regions.They can partially mimic brain physiological activities and diseased processes.Owing to their operability and sample accessibility,brain organoids serve as a bridge between in vitro monolayer cell culture models and in vivo animal models.An increasing number of induction protocols for brain organoids have been developed over the preceding decade.A key future research direction will focus on ensuring the complexity and quality of brain organoids.The integration of powerful technologies,such as the CRISP R/Cas9 genome editing and lineage tra cing systems,shall precipitate practical and broad applications of brain organoids.In this review,we discuss the generation and application of brain organoids,as well as their integration with genome editing technologies,in the study of neural development,disease modeling,and mechanistic investigations.The innovative combination of these two technologies may offer a fresh perspective for exploring the fundamental aspects of the human nervous system and related diseases.展开更多
Traumatic brain injury causes permanent cell death and can lead to long-term cognitive dysfunction,with no available treatments to repair the damaged brain tissue.Methods to track and understand traumatic brain injury...Traumatic brain injury causes permanent cell death and can lead to long-term cognitive dysfunction,with no available treatments to repair the damaged brain tissue.Methods to track and understand traumatic brain injury in humans are severely limited by the inaccessibility of living brain tissue,creating a need for in vitro model systems to study cellular mechanisms of degeneration and regeneration following injury.Here we describe methods to establish a 3D human brain tissue model,consisting of a silk-collagen composite scaffold seeded with human neurons,astrocytes,and microglia,to study neuro-regeneration after traumatic brain injury.Step-by-step fabrication,injury,and analytical assessments of the 3D“triculture”system are described.Using this tissue model system,we demonstrate that glial cells promote regeneration of neuronal networks within the injury site over several weeks post-injury.Further,we found that regenerating networks in the 3D triculture tissues did not secrete early markers of neurodegenerative disease,but displayed signs of excitatory/inhibitory imbalance,suggesting that pro-regenerative treatments for traumatic brain injury in the future may need to direct cell differentiation to promote proper function.The mechanical stability of this model system enables physiologically relevant impact injury and long-term culture capability,while its modular design enables modification of cell contents,extracellular matrix composition,and scaffold properties.This adaptability could allow the integration of patient-derived cells and genetic modifications to bridge research and clinical applications focused on personalized targeted therapies.This in vitro system provides a valuable platform for accelerating therapeutic advancements in traumatic brain injury and neurodegenerative disorders,ultimately improving patient outcomes.展开更多
Transcription factor-mediated cell conversion has been reported in the central nervous system of both rodents and nonhuman primates.In particular,glia-to-neuron conversion has been achieved in the brain and spinal cor...Transcription factor-mediated cell conversion has been reported in the central nervous system of both rodents and nonhuman primates.In particular,glia-to-neuron conversion has been achieved in the brain and spinal cord of animal models for neural regeneration and repair.However,whether glia-to-neuron conversion can be used for brain repair in humans needs to be explored.To investigate the use of glia-to-neuron conversion technology in the human brain,we established a long-term ex vivo culture system using human brain tissue that was surgically removed from epileptic patients to test glia-to-neuron conversion directly.We found that neural transcription factors NeuroD1 and Ascl1 both converted human glial cells into neurons.Immunostaining and electrophysiological recordings showed that the glia-converted neurons demonstrated immature properties during the initial 7-14 days of conversion,and then acquired more mature neuronal properties after 21-27 days of conversion.These ex vivo conversion studies in human brain tissue pave the way toward future clinical trials using a transcription factor-based glia-to-neuron conversion approach to treat neurological disorders.展开更多
This systematic review aims to comprehensively examine and compare deep learning methods for brain tumor segmentation and classification using MRI and other imaging modalities,focusing on recent trends from 2022 to 20...This systematic review aims to comprehensively examine and compare deep learning methods for brain tumor segmentation and classification using MRI and other imaging modalities,focusing on recent trends from 2022 to 2025.The primary objective is to evaluate methodological advancements,model performance,dataset usage,and existing challenges in developing clinically robust AI systems.We included peer-reviewed journal articles and highimpact conference papers published between 2022 and 2025,written in English,that proposed or evaluated deep learning methods for brain tumor segmentation and/or classification.Excluded were non-open-access publications,books,and non-English articles.A structured search was conducted across Scopus,Google Scholar,Wiley,and Taylor&Francis,with the last search performed in August 2025.Risk of bias was not formally quantified but considered during full-text screening based on dataset diversity,validation methods,and availability of performance metrics.We used narrative synthesis and tabular benchmarking to compare performance metrics(e.g.,accuracy,Dice score)across model types(CNN,Transformer,Hybrid),imaging modalities,and datasets.A total of 49 studies were included(43 journal articles and 6 conference papers).These studies spanned over 9 public datasets(e.g.,BraTS,Figshare,REMBRANDT,MOLAB)and utilized a range of imaging modalities,predominantly MRI.Hybrid models,especially ResViT and UNetFormer,consistently achieved high performance,with classification accuracy exceeding 98%and segmentation Dice scores above 0.90 across multiple studies.Transformers and hybrid architectures showed increasing adoption post2023.Many studies lacked external validation and were evaluated only on a few benchmark datasets,raising concerns about generalizability and dataset bias.Few studies addressed clinical interpretability or uncertainty quantification.Despite promising results,particularly for hybrid deep learning models,widespread clinical adoption remains limited due to lack of validation,interpretability concerns,and real-world deployment barriers.展开更多
Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of kn...Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of knowledge about the underlying modes of action and optimal treatment modalities,a thorough translational investigation of noninvasive brain stimulation in preclinical animal models is urgently needed.Thus,we reviewed the current literature on the mechanistic underpinnings of noninvasive brain stimulation in models of central nervous system impairment,with a particular emphasis on traumatic brain injury and stroke.Due to the lack of translational models in most noninvasive brain stimulation techniques proposed,we found this review to the most relevant techniques used in humans,i.e.,transcranial magnetic stimulation and transcranial direct current stimulation.We searched the literature in Pub Med,encompassing the MEDLINE and PMC databases,for studies published between January 1,2020 and September 30,2024.Thirty-five studies were eligible.Transcranial magnetic stimulation and transcranial direct current stimulation demonstrated distinct strengths in augmenting rehabilitation post-stroke and traumatic brain injury,with emerging mechanistic evidence.Overall,we identified neuronal,inflammatory,microvascular,and apoptotic pathways highlighted in the literature.This review also highlights a lack of translational surrogate parameters to bridge the gap between preclinical findings and their clinical translation.展开更多
Clinical studies on trastuzumab deruxtecan for human epidermal growth factor receptor 2-positive brain metastases Several previous clinical studies have suggested significant intracranial activity of trastuzumab derux...Clinical studies on trastuzumab deruxtecan for human epidermal growth factor receptor 2-positive brain metastases Several previous clinical studies have suggested significant intracranial activity of trastuzumab deruxtecan(T-DXd)in brain metastases(BMs)of human epidermal growth factor receptor 2(HER2)-positive(HER2-positive)metastatic breast cancer(mBC).Pooled analyses from DESTINY-Breast(DB)01,02,and 03 showed that T-DXd outperformed controls in terms of intracranial overall response rate(ORR)and median progression-free survival(mPFS).展开更多
Acute cerebral ischemia caused by stroke,traumatic brain injury(TBI),or systemic acute conditions such as hemorrhagic shock,cardiac arrest,or disseminated intravascular coagulation results in an energy crisis in local...Acute cerebral ischemia caused by stroke,traumatic brain injury(TBI),or systemic acute conditions such as hemorrhagic shock,cardiac arrest,or disseminated intravascular coagulation results in an energy crisis in local sites or the whole brain.The disruption of cerebral blood flow deprives the brain cells of oxygen and glucose,the essential substrates for adenosine triphosphate(ATP)synthesis.As a result,oxidative phosphorylation in the mitochondria fails,forcing cells to rely on anaerobic glycolysis(He et al.,2020).Although this compensatory mechanism maintains short-term energy production under hypoxic conditions,overall ATP production is significantly reduced.Neurons,which are highly susceptible to ischemic injury,deplete their ATP stores faster than glial cells(e.g.,astrocytes),which have some energy reserves.展开更多
Pericytes are multi-functional mural cells of the central nervous system that cover the capillary endothelial cells. Pericytes play a vital role in nervous system development, significantly influencing the formation, ...Pericytes are multi-functional mural cells of the central nervous system that cover the capillary endothelial cells. Pericytes play a vital role in nervous system development, significantly influencing the formation, maturation, and maintenance of the central nervous system. An expanding body of studies has revealed that pericytes establish carefully regulated interactions with oligodendrocytes, microglia, and astrocytes. These communications govern numerous critical brain processes, including angiogenesis, neurovascular unit homeostasis, blood–brain barrier integrity, cerebral blood flow regulation, and immune response initiation. Glial cells and pericytes participate in dynamic and reciprocal interactions, with each influencing and adjusting the functionality of the other. Pericytes have the ability to control astrocyte polarization, trigger differentiation of oligodendrocyte precursor cells, and initiate immunological responses in microglia. Various neurological disorders that compromise the integrity of the blood–brain barrier can disrupt these communications, impair waste clearance, and hinder cerebral blood circulation, contributing to neuroinflammation. In the context of neurodegeneration, these disruptions exacerbate pathological processes, such as neuronal damage, synaptic dysfunction, and impaired tissue repair. This article explores the complex interactions between pericytes and various glial cells in both healthy and pathological states of the central nervous system. It highlights their essential roles in neurovascular function and disease progression, providing important insights that may enhance our understanding of the molecular mechanisms underlying these interactions and guide potential therapeutic strategies for neurodegenerative disorders in future research.展开更多
文摘Blast-induced traumatic brain injury(b-TBI)is a kind of significant injury to soldiers in the current military conflicts.However,the mechanism of b-TBI has not been well understood,and even there are some contradictory conclusions.It is crucial to reveal the dynamic mechanism of brain volume and shear deformations under blast loading for better understanding of b-TBI.In this paper,the numerical simulation method is adopted to carry out comprehensive and in-depth researches on this issue for the first time.Based on the coupled Eulerian-Lagrangian method,the fluid-structure coupling model of the blast wave and human head is developed to simulate two situations,namely the head subjected to the frontal and lateral impacts.The simulation results are analyzed to obtain the underlying dynamic mechanisms of brain deformation.The brain volume deformation is dominated by the local bending vibration of the skull,and the corresponding frequency for the forehead skull under the frontal impact and the lateral skull faced to the lateral impact is as high as 8 kHz and 5 kHz,respectively.This leads to the high-frequency fluctuation of brain pressure and the large pressure gradient along the skull,totally different from the dynamic response of brain under head collisions.While the brain shear deformation mainly depends on the relative tangential displacement between the skull and brain and the anatomical structure of inner skull,being not related to the brain pressure and its gradient.By further comparing the medical statistics,it is inferred that diffuse axonal injury and brain contusion,the two most common types of b-TBI,are mainly attributed to brain shear deformations.And the von Mises stress can be adopted as the indicator for these two brain injuries.This study can provide theoretical guidance for the diagnosis of b-TBI and the development of protective equipment.
文摘Research examining the long-term effects of drugs such as AdderallTM, a mixed DL-amphetamine, as a first-line treatment strategy for those diagnosed with attention deficit hyperactivity disorder (ADHD), is very much lacking. In order to address this, the present study sought to examine possible behavioral and neuroanatomical effects of chronic oral exposure to DL-amphetamine administered at a relatively low dose to the developing male Sprague Dawley rat. Animals were administered a mixture of chocolate drink and DL-amphetamine at a dose of 1.6 mg/kg for 36 days, beginning at PD 24 and ending at PD 60. Anxiety, a potential side effect of stimulant treatment, was assessed using three paradigms: The open field test (OF), the social interaction test (SI), and the elevated plus maze (EPM). The OF and SI were conducted using repeated testing over the course of five weeks. Testing occurred immediately after drug administration on a given day. The EPM was used only once on the penultimate day of treatment, before the drug was administered. Following drug treatment on PD 60, brain-to-body weight ratios were obtained. Results indicated that there were no group differences in brain-to-body weight ratios nor were differences in locomotor and social behaviors observed. However, rats treated with DL-amphetamine did show an anxiogenic response in the EPM. This was represented as a significant reduction in open arm entries. Overall our findings suggest that while chronic drug treatment fails to alter multiple measures of behavior, or reliable changes in brain volume, such treatment may impact a behavioral index of anxiety. Future research should seek to examine the implications of this heightened anxiogenic response in animals treated chronically with oral, low-dose DL-amphetamine.
基金supported by National Key R&D Programme of China(No.2022YFC3602500,2022YFC3602505)National Natural Science Foundation of China(81971091)+3 种基金Outstanding Young Talents Project of Capital Medical University(A2105)Capital’s Funds for Health Improvement and Research(2020-1-2041)Key Science&Technologies R&D Programme of Lishui City(2019ZDYF18)Zhejiang Provincial Programme for the Cultivation of High-level Innovative Health talents and AstraZeneca Investment(China)Co.,Ltd.
文摘Background This study aimed to investigate the relationship between overall obesity,central obesity and brain volumes,as well as to determine the extent to which cardiometabolic and inflammatory measures act as mediators in the association between body mass index(BMI),waist-hip ratio(WHR)and brain volumes.Methods In the context of counterfactual framework,mediation analysis was used to explore the potential mediation in which cardiometabolic and inflammatory measures may mediate the relationship between BMI,WHR,and brain volumes.Results Among 2413 community-dwelling participants,those with high BMI or WHR levels experienced an approximately brain ageing of 4 years.Especially,individuals with high WHR or BMI under the age of 65 exhibited white matter hyperintensity volume(WMHV)differences equivalent to around 5 years of ageing.Conversely,in the high-level WHR population over the age of 65,premature brain ageing in gray matter volume(GMV)exceeded 4.5 years.For GMV,more than 45%of the observed effect of WHR was mediated by glycaemic metabolism indicators.This proportion increases to 78.70%when blood pressure,triglyceride,leucocyte count,and neutrophil count are jointly considered with glycaemic metabolism indicators.Regarding WHR and BMI’s association with WMHV,cardiometabolic and inflammatory indicators,along with high-density lipoprotein cholesterol,mediated 35.50%and 20.20%of the respective effects.Conclusions Overall obesity and central obesity were associated with lower GMV and higher WMHV,a process that is partially mediated by the presence of cardiometabolic and inflammatory measures.
基金supported by the National Natural Science Foundation of China(62522119 and 62372358)the Beijing Natural Science Foundation(7242267)+2 种基金the Beijing Scholars Program([2015]160)the Natural Science Basic Research Program of Shaanxi(2023-JC-QN-0719)the Guangdong Basic and Applied Basic Research Foundation(2022A1515110453)。
文摘Background:Brain volume measurement serves as a critical approach for assessing brain health status.Considering the close biological connection between the eyes and brain,this study aims to investigate the feasibility of estimating brain volume through retinal fundus imaging integrated with clinical metadata,and to offer a cost-effective approach for assessing brain health.Methods:Based on clinical information,retinal fundus images,and neuroimaging data derived from a multicenter,population-based cohort study,the Kai Luan Study,we proposed a cross-modal correlation representation(CMCR)network to elucidate the intricate co-degenerative relationships between the eyes and brain for 755 subjects.Specifically,individual clinical information,which has been followed up for as long as 12 years,was encoded as a prompt to enhance the accuracy of brain volume estimation.Independent internal validation and external validation were performed to assess the robustness of the proposed model.Root mean square error(RMSE),peak signal-tonoise ratio(PSNR),and structural similarity index measure(SSIM)metrics were employed to quantitatively evaluate the quality of synthetic brain images derived from retinal imaging data.Results:The proposed framework yielded average RMSE,PSNR,and SSIM values of 98.23,35.78 d B,and 0.64,respectively,which significantly outperformed 5 other methods:multi-channel Variational Autoencoder(mcVAE),Pixelto-Pixel(Pixel2pixel),transformer-based U-Net(Trans UNet),multi-scale transformer network(MT-Net),and residual vision transformer(ResViT).The two-(2D)and three-dimensional(3D)visualization results showed that the shape and texture of the synthetic brain images generated by the proposed method most closely resembled those of actual brain images.Thus,the CMCR framework accurately captured the latent structural correlations between the fundus and the brain.The average difference between predicted and actual brain volumes was 61.36 cm~3,with a relative error of 4.54%.When all of the clinical information(including age and sex,daily habits,cardiovascular factors,metabolic factors,and inflammatory factors)was encoded,the difference was decreased to 53.89 cm~3,with a relative error of 3.98%.Based on the synthesized brain magnetic resonance images from retinal fundus images,the volumes of brain tissues could be estimated with high accuracy.Conclusion:This study provides an innovative,accurate,and cost-effective approach to characterize brain health status through readily accessible retinal fundus images.
基金supported by the National Key R&D Program of China,No.2023YFE0209500(to ZQ)the Natural Science Foundation of Guangdong Province,China,Nos.2023A1515010772(to YL),2025A1515011720(to YL)+1 种基金the Medical Science and Technology Research Foundation of Guangdong Province,No.A2024120(to YL)the National Natural Science Foundation of China,No.U22A20371(to ZQ).
文摘The triple transgenic mouse model of Alzheimer’s disease(3×Tg-AD)is a widely used model that exhibits region-dependent patterns of progressive amyloid-βand tau pathology.Although structural brain abnormalities on magnetic resonance imaging have been observed in 3×Tg-AD mice at later disease stages(>12 months)and as early as 2 months,few studies have investigated changes in these mice during the stage with extensive amyloid-βdeposition and onset of tau pathology(around 9 months).This study aimed to assess brain morphometry and microstructure alterations in 9 month-old 3×Tg-AD mice to better understand the neural mechanisms underlying these specific pathological features.Voxel-based analyses were employed on T2-weighted and diffusion tensor imaging to identify differences between 3×Tg-AD and control mice.Compared with controls,3×Tg-AD mice exhibited lower gray matter volume in several regions including both hippocampal regions,the right thalamus,the left caudoputamen,and the cortex.Reduced white matter volume was observed in fiber tracts including the corpus callosum,internal capsule,stria terminalis,and olfactory tract.Whole-brain diffusion tensor imaging analysis revealed a significant decrease in fractional anisotropy and an increase in both radial and mean diffusivity within the left dentate gyrus of the hippocampal region and right striatum-like amygdala nuclei,with no significant difference in axial diffusivity.Correlation analyses demonstrated significant associations between behavioral performance measures,with both gray and white matter volumes within regions showing significant morphometric differences.Notably,behavioral performance also exhibited significant correlations with diffusion tensor imaging measures particularly within the left dentate gyrus of the hippocampal region and right striatum-like amygdala nuclei.Immunofluorescence analysis confirmed increased amyloid-βplaques and p-Tau protein expression in the hippocampal regions of 3×Tg-AD mice,which corroborated the magnetic resonance imaging findings.Transcriptome analysis in hippocampus tissue identified 1389 differentially expressed genes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that numerous differentially expressed genes were enriched in biological processes relevant to synapse structure,cognition,learning,and memory,with particular emphasis on Wnt and mitogen-activated protein kinase signaling pathways.Collectively,these findings suggest that intricate anatomical and microstructural alterations occur in 3×Tg-AD model mice at the onset of pathology around 9 months,potentially driven by gene expression alterations.Moreover,our results support the potential utility of brain volume and diffusion metrics as biomarkers for Alzheimer’s disease pathology,which could have significant implications for clinical diagnosis of Alzheimer’s disease patients.
基金supported by the Natural Science Foundation of Yunnan Province,No.202401AS070086(to ZW)the National Key Research and Development Program of China,No.2018YFA0801403(to ZW)+1 种基金Yunnan Science and Technology Talent and Platform Plan,No.202105AC160041(to ZW)the Natural Science Foundation of China,No.31960120(to ZW)。
文摘Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microglia play an important role in secondary injury and can be activated in response to traumatic brain injury.In this article,we review the origin and classification of microglia as well as the dynamic changes of microglia in traumatic brain injury.We also clarify the microglial polarization pathways and the therapeutic drugs targeting activated microglia.We found that regulating the signaling pathways involved in pro-inflammatory and anti-inflammatory microglia,such as the Toll-like receptor 4/nuclear factor-kappa B,mitogen-activated protein kinase,Janus kinase/signal transducer and activator of transcription,phosphoinositide 3-kinase/protein kinase B,Notch,and high mobility group box 1 pathways,can alleviate the inflammatory response triggered by microglia in traumatic brain injury,thereby exerting neuroprotective effects.We also reviewed the strategies developed on the basis of these pathways,such as drug and cell replacement therapies.Drugs that modulate inflammatory factors,such as rosuvastatin,have been shown to promote the polarization of antiinflammatory microglia and reduce the inflammatory response caused by traumatic brain injury.Mesenchymal stem cells possess anti-inflammatory properties,and clinical studies have confirmed their significant efficacy and safety in patients with traumatic brain injury.Additionally,advancements in mesenchymal stem cell-delivery methods—such as combinations of novel biomaterials,genetic engineering,and mesenchymal stem cell exosome therapy—have greatly enhanced the efficiency and therapeutic effects of mesenchymal stem cells in animal models.However,numerous challenges in the application of drug and mesenchymal stem cell treatment strategies remain to be addressed.In the future,new technologies,such as single-cell RNA sequencing and transcriptome analysis,can facilitate further experimental studies.Moreover,research involving non-human primates can help translate these treatment strategies to clinical practice.
基金supported by Open Scientific Research Program of Military Logistics,No.BLB20J009(to YZhao).
文摘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,costeffectiveness evaluations,and addressing the needs of patients with comorbidities.A multidisciplinary approach should be used to enhance treatment and improve patient outcomes.
基金supported by European Union-NextGeneration EU under the Italian University and Research(MUR)National Innovation Ecosystem grant ECS00000041-VITALITY-CUP E13C22001060006(to MdA)。
文摘Stroke is a major cause of death and disability worldwide.It is characterized by a highly interconnected and multiphasic neuropathological cascade of events,in which an intense and protracted inflammatory response plays a crucial role in worsening brain injury.Neuroinflammation,a key player in the pathophysiology of stroke,has a dual role.In the acute phase of stroke,neuroinflammation exacerbates brain injury,contributing to neuronal damage and blood–brain barrier disruption.This aspect of neuroinflammation is associated with poor neurological outcomes.Conversely,in the recovery phase following stroke,neuroinflammation facilitates brain repair processes,including neurogenesis,angiogenesis,and synaptic plasticity.The transition of neuroinflammation from a harmful to a reparative role is not well understood.Therefore,this review seeks to explore the mechanisms underlying this transition,with the goal of informing the development of therapeutic interventions that are both time-and context-specific.This review aims to elucidate the complex and dual role of neuroinflammation in stroke,highlighting the main actors,biomarkers of the disease,and potential therapeutic approaches.
基金supported by the National Natural Science Foundation of China,No.U21A20400(to QW)the National Natural Science Foundation of China,No.82104560(to CL)+1 种基金the Natural Science Foundation of Beijing,No.7232279(to XW)the Project of Beijing University of Chinese Medicine,Nos.2024-JYB-JBZD-043(to CL),2022-JYB-JBZR-004(to XW)。
文摘Ischemic stroke,a frequently occurring form of stroke,is caused by obstruction of cerebral blood flow,which leads to ischemia,hypoxia,and necrosis of local brain tissue.After ischemic stroke,both astrocytes and the blood–brain barrier undergo morphological and functional transformations.However,the interplay between astrocytes and the blood–brain barrier has received less attention.This comprehensive review explores the physiological and pathological morphological and functional changes in astrocytes and the blood–brain barrier in ischemic stroke.Post-stroke,the structure of endothelial cells and peripheral cells undergoes alterations,causing disruption of the blood–brain barrier.This disruption allows various pro-inflammatory factors and chemokines to cross the blood–brain barrier.Simultaneously,astrocytes swell and primarily adopt two phenotypic states:A1 and A2,which exhibit different roles at different stages of ischemic stroke.During the acute phase,A1 reactive astrocytes secrete vascular endothelial growth factor,matrix metalloproteinases,lipid carrier protein-2,and other cytokines,exacerbating damage to endothelial cells and tight junctions.Conversely,A2 reactive astrocytes produce pentraxin 3,Sonic hedgehog,angiopoietin-1,and other protective factors for endothelial cells.Furthermore,astrocytes indirectly influence blood–brain barrier permeability through ferroptosis and exosomes.In the middle and late(recovery)stages of ischemic stroke,A1 and A2 astrocytes show different effects on glial scar formation.A1 astrocytes promote glial scar formation and inhibit axon growth via glial fibrillary acidic protein,chondroitin sulfate proteoglycans,and transforming growth factor-β.In contrast,A2 astrocytes facilitate axon growth through platelet-derived growth factor,playing a crucial role in vascular remodeling.Therefore,enhancing our understanding of the pathological changes and interactions between astrocytes and the blood–brain barrier is a vital therapeutic target for preventing further brain damage in acute stroke.These insights may pave the way for innovative therapeutic strategies for ischemic stroke.
基金supported by the Guangdong Basic and Applied Basic Research Foundation,No.2023A1515030045(to HS)Presidential Foundation of Zhujiang Hospital of Southern Medical University,No.yzjj2022ms4(to HS)。
文摘Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota–brain axis.This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury.The NACHT,LRR,and pyrin domain-containing protein 3(NLRP3)inflammasome plays a crucial role in this context.This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome.These mechanisms include metabolic pathways(involving short-chain fatty acids,lipopolysaccharides,lactic acid,bile acids,trimethylamine-N-oxide,and tryptophan),neural pathways(such as the vagus nerve and sympathetic nerve),and immune pathways(involving microglia and T cells).We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage.The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood–brain barrier,inducing neuroinflammation,and interfering with nerve regeneration.Finally,we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury.Our review highlights the critical role of the gut microbiota–brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage,paving the way for exploring potential therapeutic approaches.
基金supported by Guizhou Provincial Higher Education Science and Technological Innovation Team,No.[2023]072 (to LX)Graduate Education and Teaching Innovation Program of Zunyi Medical University,No.ZYK262 (to QW)the Guizhou Graduate Research Fund,No.2024YJSKYJJ333 (to QW)
文摘Investigating the mechanisms underlying central nervous system disorders is a major scientific issue in the 21st century.However,the inaccessibility and complexity of the human brain have always represented a challenge in understanding the pathophysiology of the central nervous system.Brain organoids are self-assembled threedimensional aggregates derived from pluripotent stem cells with cell types and structures similar to the embryonic human brain,giving them potential for investigating the atypical cellular,molecular,and genetic characteristics characteristic of central nervous system disorders.Brain organoids also provide a platform for drug screening and serve as a potential source for transplantation therapy for brain injuries.However,the broad application of brain organoids is hampered by several limitations,such as the lack of high-fidelity cell types,insufficient maturation,and considerable heterogeneity,undermining their reliability in specific applications.This review summarizes brain organoid evolution,discusses recent technological and methodological innovations,and reviews their applications in drug screening,transplantation therapy,and disease modeling,as well as clinical research progress.Additionally,we emphasize the limitations of current brain organoid research and explore the potential for advancing the technology to enhance its applicability.
文摘Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated with increased levels of circulato ry pro-inflammatory marke rs up to 1 year postTBI(Eagle et al.,2023).
基金Special Projectfor Clinical Research of Shanghai Municipal Health Commission,No.202140403Key Disciplines Group Construction Project of Pudong Health Bureau of Shanghai,No.PWZxq2022-05+2 种基金Natural Science Foundation of Ningxia Hui Autonomous Region,No.2024AAC05084Ningxia Hui Autonomous Region Key Research and Development Program,No.2021BEG03084National Natural Science Foundation of China,Nos.32370895,32070862。
文摘Brain organoids are artificial neural tissues derived in vitro,containing a variety of cell types,as well as structural and/or functional brain regions.They can partially mimic brain physiological activities and diseased processes.Owing to their operability and sample accessibility,brain organoids serve as a bridge between in vitro monolayer cell culture models and in vivo animal models.An increasing number of induction protocols for brain organoids have been developed over the preceding decade.A key future research direction will focus on ensuring the complexity and quality of brain organoids.The integration of powerful technologies,such as the CRISP R/Cas9 genome editing and lineage tra cing systems,shall precipitate practical and broad applications of brain organoids.In this review,we discuss the generation and application of brain organoids,as well as their integration with genome editing technologies,in the study of neural development,disease modeling,and mechanistic investigations.The innovative combination of these two technologies may offer a fresh perspective for exploring the fundamental aspects of the human nervous system and related diseases.
基金supported by funding from the U.S.Department of Defense,Nos.W911NF-23-1-0276,W81XWH2211065the NIH,No.P41EB027062(all to DLK).
文摘Traumatic brain injury causes permanent cell death and can lead to long-term cognitive dysfunction,with no available treatments to repair the damaged brain tissue.Methods to track and understand traumatic brain injury in humans are severely limited by the inaccessibility of living brain tissue,creating a need for in vitro model systems to study cellular mechanisms of degeneration and regeneration following injury.Here we describe methods to establish a 3D human brain tissue model,consisting of a silk-collagen composite scaffold seeded with human neurons,astrocytes,and microglia,to study neuro-regeneration after traumatic brain injury.Step-by-step fabrication,injury,and analytical assessments of the 3D“triculture”system are described.Using this tissue model system,we demonstrate that glial cells promote regeneration of neuronal networks within the injury site over several weeks post-injury.Further,we found that regenerating networks in the 3D triculture tissues did not secrete early markers of neurodegenerative disease,but displayed signs of excitatory/inhibitory imbalance,suggesting that pro-regenerative treatments for traumatic brain injury in the future may need to direct cell differentiation to promote proper function.The mechanical stability of this model system enables physiologically relevant impact injury and long-term culture capability,while its modular design enables modification of cell contents,extracellular matrix composition,and scaffold properties.This adaptability could allow the integration of patient-derived cells and genetic modifications to bridge research and clinical applications focused on personalized targeted therapies.This in vitro system provides a valuable platform for accelerating therapeutic advancements in traumatic brain injury and neurodegenerative disorders,ultimately improving patient outcomes.
基金supported by the Key Project of Guangzhou City,No.202206060002(to GC)the Guangdong Province Science and Technology Project of China,No.2018B030332001(to GC)+1 种基金the Natural Science Foundation of Guangdong Province of China,No.2020A1515010854(to QW)the Yi-Liang Liu Endowment Fund from Jinan University Education Development Foundation。
文摘Transcription factor-mediated cell conversion has been reported in the central nervous system of both rodents and nonhuman primates.In particular,glia-to-neuron conversion has been achieved in the brain and spinal cord of animal models for neural regeneration and repair.However,whether glia-to-neuron conversion can be used for brain repair in humans needs to be explored.To investigate the use of glia-to-neuron conversion technology in the human brain,we established a long-term ex vivo culture system using human brain tissue that was surgically removed from epileptic patients to test glia-to-neuron conversion directly.We found that neural transcription factors NeuroD1 and Ascl1 both converted human glial cells into neurons.Immunostaining and electrophysiological recordings showed that the glia-converted neurons demonstrated immature properties during the initial 7-14 days of conversion,and then acquired more mature neuronal properties after 21-27 days of conversion.These ex vivo conversion studies in human brain tissue pave the way toward future clinical trials using a transcription factor-based glia-to-neuron conversion approach to treat neurological disorders.
文摘This systematic review aims to comprehensively examine and compare deep learning methods for brain tumor segmentation and classification using MRI and other imaging modalities,focusing on recent trends from 2022 to 2025.The primary objective is to evaluate methodological advancements,model performance,dataset usage,and existing challenges in developing clinically robust AI systems.We included peer-reviewed journal articles and highimpact conference papers published between 2022 and 2025,written in English,that proposed or evaluated deep learning methods for brain tumor segmentation and/or classification.Excluded were non-open-access publications,books,and non-English articles.A structured search was conducted across Scopus,Google Scholar,Wiley,and Taylor&Francis,with the last search performed in August 2025.Risk of bias was not formally quantified but considered during full-text screening based on dataset diversity,validation methods,and availability of performance metrics.We used narrative synthesis and tabular benchmarking to compare performance metrics(e.g.,accuracy,Dice score)across model types(CNN,Transformer,Hybrid),imaging modalities,and datasets.A total of 49 studies were included(43 journal articles and 6 conference papers).These studies spanned over 9 public datasets(e.g.,BraTS,Figshare,REMBRANDT,MOLAB)and utilized a range of imaging modalities,predominantly MRI.Hybrid models,especially ResViT and UNetFormer,consistently achieved high performance,with classification accuracy exceeding 98%and segmentation Dice scores above 0.90 across multiple studies.Transformers and hybrid architectures showed increasing adoption post2023.Many studies lacked external validation and were evaluated only on a few benchmark datasets,raising concerns about generalizability and dataset bias.Few studies addressed clinical interpretability or uncertainty quantification.Despite promising results,particularly for hybrid deep learning models,widespread clinical adoption remains limited due to lack of validation,interpretability concerns,and real-world deployment barriers.
基金funded by the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation):project ID 431549029-SFB 1451the Marga-und-Walter-Boll-Stiftung(#210-10-15)(to MAR)a stipend from the'Gerok Program'(Faculty of Medicine,University of Cologne,Germany)。
文摘Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of knowledge about the underlying modes of action and optimal treatment modalities,a thorough translational investigation of noninvasive brain stimulation in preclinical animal models is urgently needed.Thus,we reviewed the current literature on the mechanistic underpinnings of noninvasive brain stimulation in models of central nervous system impairment,with a particular emphasis on traumatic brain injury and stroke.Due to the lack of translational models in most noninvasive brain stimulation techniques proposed,we found this review to the most relevant techniques used in humans,i.e.,transcranial magnetic stimulation and transcranial direct current stimulation.We searched the literature in Pub Med,encompassing the MEDLINE and PMC databases,for studies published between January 1,2020 and September 30,2024.Thirty-five studies were eligible.Transcranial magnetic stimulation and transcranial direct current stimulation demonstrated distinct strengths in augmenting rehabilitation post-stroke and traumatic brain injury,with emerging mechanistic evidence.Overall,we identified neuronal,inflammatory,microvascular,and apoptotic pathways highlighted in the literature.This review also highlights a lack of translational surrogate parameters to bridge the gap between preclinical findings and their clinical translation.
基金supported by the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(No.2023-JKCS-23)the Special Research Fund for Central Universities,Peking Union Medical College(No.2022-I2M-C&T-A-014).
文摘Clinical studies on trastuzumab deruxtecan for human epidermal growth factor receptor 2-positive brain metastases Several previous clinical studies have suggested significant intracranial activity of trastuzumab deruxtecan(T-DXd)in brain metastases(BMs)of human epidermal growth factor receptor 2(HER2)-positive(HER2-positive)metastatic breast cancer(mBC).Pooled analyses from DESTINY-Breast(DB)01,02,and 03 showed that T-DXd outperformed controls in terms of intracranial overall response rate(ORR)and median progression-free survival(mPFS).
基金supported by the Russian Science Foundation,grant 24-75-10013(to NVA).
文摘Acute cerebral ischemia caused by stroke,traumatic brain injury(TBI),or systemic acute conditions such as hemorrhagic shock,cardiac arrest,or disseminated intravascular coagulation results in an energy crisis in local sites or the whole brain.The disruption of cerebral blood flow deprives the brain cells of oxygen and glucose,the essential substrates for adenosine triphosphate(ATP)synthesis.As a result,oxidative phosphorylation in the mitochondria fails,forcing cells to rely on anaerobic glycolysis(He et al.,2020).Although this compensatory mechanism maintains short-term energy production under hypoxic conditions,overall ATP production is significantly reduced.Neurons,which are highly susceptible to ischemic injury,deplete their ATP stores faster than glial cells(e.g.,astrocytes),which have some energy reserves.
文摘Pericytes are multi-functional mural cells of the central nervous system that cover the capillary endothelial cells. Pericytes play a vital role in nervous system development, significantly influencing the formation, maturation, and maintenance of the central nervous system. An expanding body of studies has revealed that pericytes establish carefully regulated interactions with oligodendrocytes, microglia, and astrocytes. These communications govern numerous critical brain processes, including angiogenesis, neurovascular unit homeostasis, blood–brain barrier integrity, cerebral blood flow regulation, and immune response initiation. Glial cells and pericytes participate in dynamic and reciprocal interactions, with each influencing and adjusting the functionality of the other. Pericytes have the ability to control astrocyte polarization, trigger differentiation of oligodendrocyte precursor cells, and initiate immunological responses in microglia. Various neurological disorders that compromise the integrity of the blood–brain barrier can disrupt these communications, impair waste clearance, and hinder cerebral blood circulation, contributing to neuroinflammation. In the context of neurodegeneration, these disruptions exacerbate pathological processes, such as neuronal damage, synaptic dysfunction, and impaired tissue repair. This article explores the complex interactions between pericytes and various glial cells in both healthy and pathological states of the central nervous system. It highlights their essential roles in neurovascular function and disease progression, providing important insights that may enhance our understanding of the molecular mechanisms underlying these interactions and guide potential therapeutic strategies for neurodegenerative disorders in future research.
