Radiation-induced brain injury remains one of the most severe complications of radiotherapy for head and neck tumors,with limited options for prevention and treatment.In situ neural regeneration technology has demonst...Radiation-induced brain injury remains one of the most severe complications of radiotherapy for head and neck tumors,with limited options for prevention and treatment.In situ neural regeneration technology has demonstrated promising therapeutic effects in various neurodegenerative and neurotrauma conditions.In this study,we overexpressed the neural transcription factor NeuroD1 using in situ neural regeneration technology in a radiation-induced brain injury mouse model.This approach converted reactive astrocytes into neurons,increased neuronal density,protected endogenous neurons,decreased microglial activation,reduced peripheral CD8+T cell infiltration,and diminished angiogenesis in the injured area,leading to a significant reduction in lesion volume.Additionally,we explored the potential mechanisms of NeuroD1 in situ neural regeneration technology through bulk RNA sequencing,which showed an upregulation of neurogenesis-related genes and a downregulation of immune response-related and angiogenesis-related genes.Furthermore,our findings suggested that NeuroD1 in situ neural regeneration technology converted reactive astrocytes into neurons and reduced microglial activation in a thalamic hemorrhagic stroke mouse model.In summary,this study supports NeuroD1 in situ neural regeneration technology as a potential therapeutic approach for treating radiation-induced brain injury and hemorrhagic stroke,and offers new insights into the therapeutic role of NeuroD1 in delayed brain injury.展开更多
Medical procedures are inherently invasive and carry the risk of inducing pain to the mind and body.Recently,efforts have been made to alleviate the discomfort associated with invasive medical procedures through the u...Medical procedures are inherently invasive and carry the risk of inducing pain to the mind and body.Recently,efforts have been made to alleviate the discomfort associated with invasive medical procedures through the use of virtual reality(VR)technology.VR has been demonstrated to be an effective treatment for pain associated with medical procedures,as well as for chronic pain conditions for which no effective treatment has been established.The precise mechanism by which the diversion from reality facilitated by VR contributes to the diminution of pain and anxiety has yet to be elucidated.However,the provision of positive images through VR-based visual stimulation may enhance the functionality of brain networks.The salience network is diminished,while the default mode network is enhanced.Additionally,the medial prefrontal cortex may establish a stronger connection with the default mode network,which could result in a reduction of pain and anxiety.Further research into the potential of VR technology to alleviate pain could lead to a reduction in the number of individuals who overdose on painkillers and contribute to positive change in the medical field.展开更多
Sepsis,a life-threatening condition,can lead to acute skin failure characterized by extensive skin damage.This is often due to decreased blood flow,inflammation,and increased susceptibility to infection.Acute skin fai...Sepsis,a life-threatening condition,can lead to acute skin failure characterized by extensive skin damage.This is often due to decreased blood flow,inflammation,and increased susceptibility to infection.Acute skin failure in people with sepsis is often associated with sleep disturbances,anxiety,and poor mood.Inflammatory markers and lactate levels correlate with these psychiatric symptoms,suggesting a link between skin and brain function.The skin and the central nervous system(CNS)have bidirectional communication.The CNS is also in close contact with the digestive tract.The gut,skin,and brain influence each other’s functions thr-ough nervous,hormonal,and immune pathways,forming a gut-skin-brain axis.Understanding the interaction among the gut,skin,and CNS is critical to the diag-nosis and treatment of various skin and neurological disorders.By recognizing individual variations in gut microbiota,immune responses,and neural pathways,treatments can be tailored to specific patient needs,enhancing efficacy and minimizing side effects.The gut plays a large role in mental health.Under-standing the gut skin brain axis,will lead to improved mental health outcomes.展开更多
Attention is the cornerstone of effective functioning in a complex and information-rich world.While the neural activity of attention has been extensively studied in the cortex,the brain-wide neural activity patterns a...Attention is the cornerstone of effective functioning in a complex and information-rich world.While the neural activity of attention has been extensively studied in the cortex,the brain-wide neural activity patterns are largely unknown.In this study,we conducted a comprehensive analysis of neural activity across the mouse brain during attentional processing using EEG and c-Fos staining,utilizing hierarchical clustering and c-Fos-based functional network analysis to evaluate the c-Fos activation patterns.Our findings reveal that a wide range of brain regions are activated,notably in the high-order cortex,thalamus,and brain stem regions involved in advanced cognition and arousal regulation,with the central lateral nucleus of the thalamus as a strong hub,suggesting the crucial role of the thalamus in attention control.These results provide valuable insights into the neural network mechanisms underlying attention,offering a foundation for formulating functional hypotheses and conducting circuit-level testing.展开更多
The increasing global prevalence of mild cognitive impairment(MCI)necessitates a paradigm shift in early detection strategies.Conventional neuropsychological assessment methods,predominantly paper-and-pencil tests suc...The increasing global prevalence of mild cognitive impairment(MCI)necessitates a paradigm shift in early detection strategies.Conventional neuropsychological assessment methods,predominantly paper-and-pencil tests such as the Mini-Mental State Examination and the Montreal Cognitive Assessment,exhibit inherent limitations with respect to accessibility,administration burden,and sensitivity to subtle cognitive decline,particularly among diverse populations.This commentary critically examines a recent study that champions a novel approach:The integration of gait and handwriting kinematic parameters analyzed via machine learning for MCI screening.The present study positions itself within the broader landscape of MCI detection,with a view to comparing its advantages against established neuropsychological batteries,advanced neuroimaging(e.g.,positron emission tomography,magnetic resonance imaging),and emerging fluid biomarkers(e.g.,cerebrospinal fluid,blood-based assays).While the study demonstrates promising accuracy(74.44%area under the curve 0.74 with gait and graphic handwriting)and addresses key unmet needs in accessibility and objectivity,we highlight its cross-sectional nature,limited sample diversity,and lack of dual-task assessment as areas for future refinement.This commentary posits that kinematic biomarkers offer a distinctive,scalable,and ecologically valid approach to widespread MCI screening,thereby complementing existing methods by providing real-world functional insights.Future research should prioritize longitudinal validation,expansion to diverse cohorts,integration with multimodal data including dual-tasking,and the development of highly portable,artificial intelligence-driven solutions to achieve the democratization of early MCI detection and enable timely interventions.展开更多
N^(6)-methyladenosine RNA methylation,an essential post-transcriptional modification,dynamically regulates RNA metabolism and plays a crucial role in neuronal function.Growing evidence suggests that dysregulated N^(6)...N^(6)-methyladenosine RNA methylation,an essential post-transcriptional modification,dynamically regulates RNA metabolism and plays a crucial role in neuronal function.Growing evidence suggests that dysregulated N^(6)-methyladenosine modification contributes to the pathogenesis of neurodegenerative diseases,including Alzheimer’s disease,Parkinson’s disease,multiple sclerosis,and amyotrophic lateral sclerosis.However,the precise mechanisms by which N^(6)-methyladenosine modification influences these conditions remain unclear.This review summarizes the role of m6A modification and its associated regulators in neurodegeneration,focusing on their involvement in key pathological processes.In Alzheimer’s disease,m6A modification contributes to synaptic dysfunction,mitochondrial damage,and neuronal apoptosis.Evidence from APP/PS1,5xFAD,tau transgenic,and Drosophila models demonstrates that regulators such as methyltransferase-like 3 and fat mass and obesity-associated protein influence Alzheimer’s disease progression through neuroinflammation,circular RNAs dysregulation,and autophagy-related mechanisms.In Parkinson’s disease,altered N^(6)-methyladenosine regulator expression affects dopaminergic neuron survival and stress responses by modulating mRNA stability and autophagy-related lncRNAs.In multiple sclerosis and amyotrophic lateral sclerosis,N^(6)-methyladenosine affects immune activation,myelin repair,and the regulation of disease-associated genes such as TDP-43.Beyond N^(6)-methyladenosine,other RNA methylation modifications-such as m1A,m5C,m7G,uracil,and pseudouridine-are implicated in neurodegenerative diseases through their regulation of mitochondrial function,RNA metabolism,and neuronal stress responses.Additionally,N^(6)-methyladenosine exhibits cell type-specific functions:in microglia,it regulates inflammatory activation and phagocytic function;in astrocytes,it modulates metabolic homeostasis and glutamate-associated neurotoxicity;in neurons,it affects synaptic function and neurodegeneration-related gene expression;and in adult neural stem cells,it controls differentiation,neurogenesis,and cognitive plasticity.Recently,several small-molecule inhibitors targeting methyltransferase-like 3 or fat mass and obesity-associated protein have been developed to modulate N^(6)-methyladenosine modification,providing new opportunities for disease intervention,with the targeting of N⁶-methyladenosine-related pathways emerging as a promising therapeutic strategy.However,challenges persist in optimizing the specificity and delivery of these therapeutic approaches.展开更多
Glioma incidence rates in the United States are near 20000 new cases per year, with a median survival time of 14.6 mo for high-grade gliomas due to limited therapeutic options. The origins of these tumors and their ma...Glioma incidence rates in the United States are near 20000 new cases per year, with a median survival time of 14.6 mo for high-grade gliomas due to limited therapeutic options. The origins of these tumors and their many subtypes remain a matter of investigation. Evidence from mouse models of glioma and human clinical data have provided clues about the cell types and initiating oncogenic mutations that drive gliomagenesis, a topic we review here. There has been mixed evidence as to whether or not the cells of origin are neural stem cells, progenitor cells or differentiated progeny. Many of the existing murine models target cell populations defined by lineage-specific promoters or employ lineagetracing methods to track the potential cells of origin. Our ability to target specific cell populations will likely increase concurrently with the knowledge gleaned from an understanding of neurogenesis in the adult brain. The cell of origin is one variable in tumorigenesis, as oncogenes or tumor suppressor genes may differentially transform the neuroglial cell types. Knowledge of key driver mutations and susceptible cell types will allow us to understand cancer biology from a developmental standpoint and enable early interventional strategies and biomarker discovery.展开更多
A sensitive and rapid liquid chromatography tandem mass spectrometry(LC-MS/MS)method was established for the quantification of total and unbound concentrations of LY3214996,an extracellular signal-regulated kinase inh...A sensitive and rapid liquid chromatography tandem mass spectrometry(LC-MS/MS)method was established for the quantification of total and unbound concentrations of LY3214996,an extracellular signal-regulated kinase inhibitor;abemaciclib,a cyclin-dependent kinase 4/6 inhibitor;and abemaciclib active metabolites,M2 and M20,in human plasma,brain tumor,and cerebrospinal fluid samples.The method was validated over a concentration range of 0.2e500 nM within a total run time of 3.8 min using isocratic elution on a Kinetex^(TM) F_(5) column.Detection was performed on a Sciex QTRAP 6500t mass spectrometer employing multiple reaction monitoring mode under positive electrospray ionization.The intra-and inter-batch accuracy as well as the precision of the method for all matrices was within ±20% and ≤20% at the lower limit of quantification,and within ±15% and ≤15% for other quality control levels for all analytes.The unbound fractions of drugs and metabolites in spiked and patient samples were determined using an optimized equilibrium dialysis.The validated method was successfully applied in a phase 0/2 clinical trial to assess the central nervous system penetration of LY3214996 and abemaciclib.展开更多
Astrocytes are the most abundant glial cells in the central nervous system.They perform a diverse array of functions,with a critical role in structural integrity,synapse formation,and neurotransmission.These cells exh...Astrocytes are the most abundant glial cells in the central nervous system.They perform a diverse array of functions,with a critical role in structural integrity,synapse formation,and neurotransmission.These cells exhibit substantial regional heterogeneity and display variable responses to different neurological diseases.Such diversity in astrocyte morphology and function is essential for understanding both normal brain function and the underlying mechanisms of neurological disorders.To investigate this heterogeneity,we developed a novel method for the selective and sparse labeling of astrocytes in various brain regions.This technique utilizes a dual adeno-associated virus system that allows for the expression of Cre recombinase and enhanced green fluorescent protein under the control of the glial fibrillary acidic protein(GfaABC1D)promoter.The system was tested in C57BL/6J mice and successfully labeled astrocytes across multiple brain regions.The method enabled the detailed visualization of individual astrocytes-including their intricate peripheral processes-through three-dimensional reconstructions from confocal microscopy images.Furthermore,the labeling efficiency of this dual adeno-associated virus technology was validated by examining astrocyte function in a spared nerve injury model and through chemogenetic modulation.This innovative approach holds great promise for future research because it enables a more comprehensive understanding of astrocyte variation not only in spared nerve injury but also in a broad spectrum of neurological diseases.The ability to selectively label and study astrocytes in different brain regions provides a powerful tool for exploring the complexities of these essential cells and their roles in physiological and pathological conditions.展开更多
There are various clinical treatments for traumatic brain injury,including surgery,drug therapy,and rehabilitation therapy;howeve r,the therapeutic effects are limited.Scaffolds combined with exosomes represent a prom...There are various clinical treatments for traumatic brain injury,including surgery,drug therapy,and rehabilitation therapy;howeve r,the therapeutic effects are limited.Scaffolds combined with exosomes represent a promising but challenging method for improving the repair of traumatic brain injury.In this study,we determined the ability of a novel 3D-printed collagen/chitosan scaffold loaded with exosomes derived from neural stem cells pretreated with insulin-like growth factor-1(3D-CC-INEXOS) to improve traumatic brain injury repair and functional recove ry after traumatic brain injury in rats.Composite scaffolds comprising collagen,chitosan,and exosomes derived from neural stem cells pretreated with insulin-like growth fa ctor-1(INEXOS) continuously released exosomes for 2weeks.Transplantation of 3D-CC-INExos scaffolds significantly improved motor and cognitive functions in a rat traumatic brain injury model,as assessed by the Morris water maze test and modified neurological seve rity scores.In addition,immunofluorescence staining and transmission electron microscopy showed that3D-CC-INExos implantation significantly improved the recove ry of damaged nerve tissue in the injured area.In conclusion,this study suggests that transplanted3D-CC-INExos scaffolds might provide a potential strategy for the treatment of traumatic brain injury and lay a solid foundation for clinical translation.展开更多
While brain computer interfaces(BCIs)ofer the potential of allowing those sufering from loss of muscle control to once again fully engage with their environment by bypassing the afected motor system and decoding user ...While brain computer interfaces(BCIs)ofer the potential of allowing those sufering from loss of muscle control to once again fully engage with their environment by bypassing the afected motor system and decoding user intentions directly from brain activity,they are prone to errors.One possible avenue for BCI performance improvement is to detect when the BCI user perceives the BCI to have made an unintended action and thus take corrective actions.Error-related potentials(ErrPs)are neural correlates of error awareness and as such can provide an indication of when a BCI system is not performing according to the user’s intentions.Here,we investigate the brain signals of an implanted BCI user sufering from locked-in syndrome(LIS)due to late-stage ALS that prevents her from being able to speak or move but not from using her BCI at home on a daily basis to communicate,for the presence of error-related signals.We frst establish the presence of an ErrP originating from the dorsolateral pre-frontal cortex(dLPFC)in response to errors made during a discrete feedback task that mimics the click-based spelling software she uses to communicate.Then,we show that this ErrP can also be elicited by cursor movement errors in a continuous BCI cursor control task.This work represents a frst step toward detecting ErrPs during the daily home use of a communications BCI.展开更多
PURPOSE:A phase Ⅱ study of bevacizumab(BVZ) plus irinotecan(CPT-11) was conducted in children with recurrent malignant glioma(MG) and intrinsic brainstem glioma(BSG).PATIENTS AND METHODS:Eligible patients received tw...PURPOSE:A phase Ⅱ study of bevacizumab(BVZ) plus irinotecan(CPT-11) was conducted in children with recurrent malignant glioma(MG) and intrinsic brainstem glioma(BSG).PATIENTS AND METHODS:Eligible patients received two doses of BVZ展开更多
基金the National Natural Science Foundation of China,Nos.81925031(to YT)82330099(to YT)+7 种基金82404189(to KZ)the Key-Area Research and Development Program of Guangdong Province,No.2023B0303040003(to YT)STI 2030-Major Projects,No.2022ZD0211603(to YT)Guangzhou Key Projects of Brain Science and Brain-Like Intelligence Technology,No.202206060002(to GC and YS)Science and Technology Project of Guangdong Province,No.2018B030332001(to GC)Guangdong Provincial Pearl River Project,No.2021ZT09Y552(to GC)the Guangdong Basic and Applied Basic Research Foundation,No.2022A1515110189(to KZ)Sun Yat-sen Pilot Scientific Research Fund,No.YXQH202427(to KZ).
文摘Radiation-induced brain injury remains one of the most severe complications of radiotherapy for head and neck tumors,with limited options for prevention and treatment.In situ neural regeneration technology has demonstrated promising therapeutic effects in various neurodegenerative and neurotrauma conditions.In this study,we overexpressed the neural transcription factor NeuroD1 using in situ neural regeneration technology in a radiation-induced brain injury mouse model.This approach converted reactive astrocytes into neurons,increased neuronal density,protected endogenous neurons,decreased microglial activation,reduced peripheral CD8+T cell infiltration,and diminished angiogenesis in the injured area,leading to a significant reduction in lesion volume.Additionally,we explored the potential mechanisms of NeuroD1 in situ neural regeneration technology through bulk RNA sequencing,which showed an upregulation of neurogenesis-related genes and a downregulation of immune response-related and angiogenesis-related genes.Furthermore,our findings suggested that NeuroD1 in situ neural regeneration technology converted reactive astrocytes into neurons and reduced microglial activation in a thalamic hemorrhagic stroke mouse model.In summary,this study supports NeuroD1 in situ neural regeneration technology as a potential therapeutic approach for treating radiation-induced brain injury and hemorrhagic stroke,and offers new insights into the therapeutic role of NeuroD1 in delayed brain injury.
文摘Medical procedures are inherently invasive and carry the risk of inducing pain to the mind and body.Recently,efforts have been made to alleviate the discomfort associated with invasive medical procedures through the use of virtual reality(VR)technology.VR has been demonstrated to be an effective treatment for pain associated with medical procedures,as well as for chronic pain conditions for which no effective treatment has been established.The precise mechanism by which the diversion from reality facilitated by VR contributes to the diminution of pain and anxiety has yet to be elucidated.However,the provision of positive images through VR-based visual stimulation may enhance the functionality of brain networks.The salience network is diminished,while the default mode network is enhanced.Additionally,the medial prefrontal cortex may establish a stronger connection with the default mode network,which could result in a reduction of pain and anxiety.Further research into the potential of VR technology to alleviate pain could lead to a reduction in the number of individuals who overdose on painkillers and contribute to positive change in the medical field.
文摘Sepsis,a life-threatening condition,can lead to acute skin failure characterized by extensive skin damage.This is often due to decreased blood flow,inflammation,and increased susceptibility to infection.Acute skin failure in people with sepsis is often associated with sleep disturbances,anxiety,and poor mood.Inflammatory markers and lactate levels correlate with these psychiatric symptoms,suggesting a link between skin and brain function.The skin and the central nervous system(CNS)have bidirectional communication.The CNS is also in close contact with the digestive tract.The gut,skin,and brain influence each other’s functions thr-ough nervous,hormonal,and immune pathways,forming a gut-skin-brain axis.Understanding the interaction among the gut,skin,and CNS is critical to the diag-nosis and treatment of various skin and neurological disorders.By recognizing individual variations in gut microbiota,immune responses,and neural pathways,treatments can be tailored to specific patient needs,enhancing efficacy and minimizing side effects.The gut plays a large role in mental health.Under-standing the gut skin brain axis,will lead to improved mental health outcomes.
文摘Attention is the cornerstone of effective functioning in a complex and information-rich world.While the neural activity of attention has been extensively studied in the cortex,the brain-wide neural activity patterns are largely unknown.In this study,we conducted a comprehensive analysis of neural activity across the mouse brain during attentional processing using EEG and c-Fos staining,utilizing hierarchical clustering and c-Fos-based functional network analysis to evaluate the c-Fos activation patterns.Our findings reveal that a wide range of brain regions are activated,notably in the high-order cortex,thalamus,and brain stem regions involved in advanced cognition and arousal regulation,with the central lateral nucleus of the thalamus as a strong hub,suggesting the crucial role of the thalamus in attention control.These results provide valuable insights into the neural network mechanisms underlying attention,offering a foundation for formulating functional hypotheses and conducting circuit-level testing.
文摘The increasing global prevalence of mild cognitive impairment(MCI)necessitates a paradigm shift in early detection strategies.Conventional neuropsychological assessment methods,predominantly paper-and-pencil tests such as the Mini-Mental State Examination and the Montreal Cognitive Assessment,exhibit inherent limitations with respect to accessibility,administration burden,and sensitivity to subtle cognitive decline,particularly among diverse populations.This commentary critically examines a recent study that champions a novel approach:The integration of gait and handwriting kinematic parameters analyzed via machine learning for MCI screening.The present study positions itself within the broader landscape of MCI detection,with a view to comparing its advantages against established neuropsychological batteries,advanced neuroimaging(e.g.,positron emission tomography,magnetic resonance imaging),and emerging fluid biomarkers(e.g.,cerebrospinal fluid,blood-based assays).While the study demonstrates promising accuracy(74.44%area under the curve 0.74 with gait and graphic handwriting)and addresses key unmet needs in accessibility and objectivity,we highlight its cross-sectional nature,limited sample diversity,and lack of dual-task assessment as areas for future refinement.This commentary posits that kinematic biomarkers offer a distinctive,scalable,and ecologically valid approach to widespread MCI screening,thereby complementing existing methods by providing real-world functional insights.Future research should prioritize longitudinal validation,expansion to diverse cohorts,integration with multimodal data including dual-tasking,and the development of highly portable,artificial intelligence-driven solutions to achieve the democratization of early MCI detection and enable timely interventions.
基金supported by the National Nature Science Foundation of China(General Program),Nos.82271237,82071218(both to JC),and 82230042(to ZY)the Foundation of Key Laboratory of Neurology,Hebei Medical University,Ministry of Education,China,No.2023001(to JC).
文摘N^(6)-methyladenosine RNA methylation,an essential post-transcriptional modification,dynamically regulates RNA metabolism and plays a crucial role in neuronal function.Growing evidence suggests that dysregulated N^(6)-methyladenosine modification contributes to the pathogenesis of neurodegenerative diseases,including Alzheimer’s disease,Parkinson’s disease,multiple sclerosis,and amyotrophic lateral sclerosis.However,the precise mechanisms by which N^(6)-methyladenosine modification influences these conditions remain unclear.This review summarizes the role of m6A modification and its associated regulators in neurodegeneration,focusing on their involvement in key pathological processes.In Alzheimer’s disease,m6A modification contributes to synaptic dysfunction,mitochondrial damage,and neuronal apoptosis.Evidence from APP/PS1,5xFAD,tau transgenic,and Drosophila models demonstrates that regulators such as methyltransferase-like 3 and fat mass and obesity-associated protein influence Alzheimer’s disease progression through neuroinflammation,circular RNAs dysregulation,and autophagy-related mechanisms.In Parkinson’s disease,altered N^(6)-methyladenosine regulator expression affects dopaminergic neuron survival and stress responses by modulating mRNA stability and autophagy-related lncRNAs.In multiple sclerosis and amyotrophic lateral sclerosis,N^(6)-methyladenosine affects immune activation,myelin repair,and the regulation of disease-associated genes such as TDP-43.Beyond N^(6)-methyladenosine,other RNA methylation modifications-such as m1A,m5C,m7G,uracil,and pseudouridine-are implicated in neurodegenerative diseases through their regulation of mitochondrial function,RNA metabolism,and neuronal stress responses.Additionally,N^(6)-methyladenosine exhibits cell type-specific functions:in microglia,it regulates inflammatory activation and phagocytic function;in astrocytes,it modulates metabolic homeostasis and glutamate-associated neurotoxicity;in neurons,it affects synaptic function and neurodegeneration-related gene expression;and in adult neural stem cells,it controls differentiation,neurogenesis,and cognitive plasticity.Recently,several small-molecule inhibitors targeting methyltransferase-like 3 or fat mass and obesity-associated protein have been developed to modulate N^(6)-methyladenosine modification,providing new opportunities for disease intervention,with the targeting of N⁶-methyladenosine-related pathways emerging as a promising therapeutic strategy.However,challenges persist in optimizing the specificity and delivery of these therapeutic approaches.
基金Supported by The Medical Scientist Training Program at NYU School of Medicine to Modrek ASNYSTEM Institutional training grant#CO26880 to Bayin NS+1 种基金NIH/NINDS(1 R21 NS087241-01)the NYU Cancer Institute Developmental Projects Program and the NYU Clinical and Translational Science Institute(NYU CTSA grant#UL1TR000038 from the National Center for the Advancement of Translational Science NCATS,NIH)to Placantonakis DG
文摘Glioma incidence rates in the United States are near 20000 new cases per year, with a median survival time of 14.6 mo for high-grade gliomas due to limited therapeutic options. The origins of these tumors and their many subtypes remain a matter of investigation. Evidence from mouse models of glioma and human clinical data have provided clues about the cell types and initiating oncogenic mutations that drive gliomagenesis, a topic we review here. There has been mixed evidence as to whether or not the cells of origin are neural stem cells, progenitor cells or differentiated progeny. Many of the existing murine models target cell populations defined by lineage-specific promoters or employ lineagetracing methods to track the potential cells of origin. Our ability to target specific cell populations will likely increase concurrently with the knowledge gleaned from an understanding of neurogenesis in the adult brain. The cell of origin is one variable in tumorigenesis, as oncogenes or tumor suppressor genes may differentially transform the neuroglial cell types. Knowledge of key driver mutations and susceptible cell types will allow us to understand cancer biology from a developmental standpoint and enable early interventional strategies and biomarker discovery.
基金funding provided by the Ben and Catherine Ivy Foundation.
文摘A sensitive and rapid liquid chromatography tandem mass spectrometry(LC-MS/MS)method was established for the quantification of total and unbound concentrations of LY3214996,an extracellular signal-regulated kinase inhibitor;abemaciclib,a cyclin-dependent kinase 4/6 inhibitor;and abemaciclib active metabolites,M2 and M20,in human plasma,brain tumor,and cerebrospinal fluid samples.The method was validated over a concentration range of 0.2e500 nM within a total run time of 3.8 min using isocratic elution on a Kinetex^(TM) F_(5) column.Detection was performed on a Sciex QTRAP 6500t mass spectrometer employing multiple reaction monitoring mode under positive electrospray ionization.The intra-and inter-batch accuracy as well as the precision of the method for all matrices was within ±20% and ≤20% at the lower limit of quantification,and within ±15% and ≤15% for other quality control levels for all analytes.The unbound fractions of drugs and metabolites in spiked and patient samples were determined using an optimized equilibrium dialysis.The validated method was successfully applied in a phase 0/2 clinical trial to assess the central nervous system penetration of LY3214996 and abemaciclib.
基金National Natural Science Foundation of China,No.32271148(to JW)the National Key Research and the Development Program of China,No.2023M740625(to ML)+1 种基金the Natural Science Foundation of Guangdong Province,Nos.2021B1515120050(to HW)and 2023A1515110782(to ML)and Key R&D Program of Ningxia Hui Autonomous Region,No.2024BEG02027(to JW).
文摘Astrocytes are the most abundant glial cells in the central nervous system.They perform a diverse array of functions,with a critical role in structural integrity,synapse formation,and neurotransmission.These cells exhibit substantial regional heterogeneity and display variable responses to different neurological diseases.Such diversity in astrocyte morphology and function is essential for understanding both normal brain function and the underlying mechanisms of neurological disorders.To investigate this heterogeneity,we developed a novel method for the selective and sparse labeling of astrocytes in various brain regions.This technique utilizes a dual adeno-associated virus system that allows for the expression of Cre recombinase and enhanced green fluorescent protein under the control of the glial fibrillary acidic protein(GfaABC1D)promoter.The system was tested in C57BL/6J mice and successfully labeled astrocytes across multiple brain regions.The method enabled the detailed visualization of individual astrocytes-including their intricate peripheral processes-through three-dimensional reconstructions from confocal microscopy images.Furthermore,the labeling efficiency of this dual adeno-associated virus technology was validated by examining astrocyte function in a spared nerve injury model and through chemogenetic modulation.This innovative approach holds great promise for future research because it enables a more comprehensive understanding of astrocyte variation not only in spared nerve injury but also in a broad spectrum of neurological diseases.The ability to selectively label and study astrocytes in different brain regions provides a powerful tool for exploring the complexities of these essential cells and their roles in physiological and pathological conditions.
基金supported by the National Major Scientific and Technological Special Project for Significant New Drugs Development,No.2019ZX09301-147 (to LXZ)。
文摘There are various clinical treatments for traumatic brain injury,including surgery,drug therapy,and rehabilitation therapy;howeve r,the therapeutic effects are limited.Scaffolds combined with exosomes represent a promising but challenging method for improving the repair of traumatic brain injury.In this study,we determined the ability of a novel 3D-printed collagen/chitosan scaffold loaded with exosomes derived from neural stem cells pretreated with insulin-like growth factor-1(3D-CC-INEXOS) to improve traumatic brain injury repair and functional recove ry after traumatic brain injury in rats.Composite scaffolds comprising collagen,chitosan,and exosomes derived from neural stem cells pretreated with insulin-like growth fa ctor-1(INEXOS) continuously released exosomes for 2weeks.Transplantation of 3D-CC-INExos scaffolds significantly improved motor and cognitive functions in a rat traumatic brain injury model,as assessed by the Morris water maze test and modified neurological seve rity scores.In addition,immunofluorescence staining and transmission electron microscopy showed that3D-CC-INExos implantation significantly improved the recove ry of damaged nerve tissue in the injured area.In conclusion,this study suggests that transplanted3D-CC-INExos scaffolds might provide a potential strategy for the treatment of traumatic brain injury and lay a solid foundation for clinical translation.
文摘While brain computer interfaces(BCIs)ofer the potential of allowing those sufering from loss of muscle control to once again fully engage with their environment by bypassing the afected motor system and decoding user intentions directly from brain activity,they are prone to errors.One possible avenue for BCI performance improvement is to detect when the BCI user perceives the BCI to have made an unintended action and thus take corrective actions.Error-related potentials(ErrPs)are neural correlates of error awareness and as such can provide an indication of when a BCI system is not performing according to the user’s intentions.Here,we investigate the brain signals of an implanted BCI user sufering from locked-in syndrome(LIS)due to late-stage ALS that prevents her from being able to speak or move but not from using her BCI at home on a daily basis to communicate,for the presence of error-related signals.We frst establish the presence of an ErrP originating from the dorsolateral pre-frontal cortex(dLPFC)in response to errors made during a discrete feedback task that mimics the click-based spelling software she uses to communicate.Then,we show that this ErrP can also be elicited by cursor movement errors in a continuous BCI cursor control task.This work represents a frst step toward detecting ErrPs during the daily home use of a communications BCI.
文摘PURPOSE:A phase Ⅱ study of bevacizumab(BVZ) plus irinotecan(CPT-11) was conducted in children with recurrent malignant glioma(MG) and intrinsic brainstem glioma(BSG).PATIENTS AND METHODS:Eligible patients received two doses of BVZ
