The organization of biological neuronal networks into functional modules has intrigued scientists and inspired engineers to develop artificial systems.These networks are characterized by two key properties.First,they ...The organization of biological neuronal networks into functional modules has intrigued scientists and inspired engineers to develop artificial systems.These networks are characterized by two key properties.First,they exhibit dense interconnectivity(Braitenburg and Schüz,1998;Campagnola et al.,2022).The strength and probability of connectivity depend on cell type,inter-neuronal distance,and species.Still,every cortical neuron receives input from thousands of other neurons while transmitting output to a similar number of neurons.Second,communication between neurons occurs primarily via chemical or electrical synapses.展开更多
Subarachnoid hemorrhage(SAH) is a devastating condition that affects a total of 8 million people worldwide each year(Lauzier and Athiraman, 2024). Etiologies of SAH can be traumatic or nontraumatic, with the majority ...Subarachnoid hemorrhage(SAH) is a devastating condition that affects a total of 8 million people worldwide each year(Lauzier and Athiraman, 2024). Etiologies of SAH can be traumatic or nontraumatic, with the majority of non-traumatic SAH occurring due to intracranial aneurysm rupture(Rutledge et al., 2014).展开更多
The mitogen-activated protein kinase kinase kinase kinases(MAP4Ks)signaling pathway plays a pivotal role in axonal regrowth and neuronal degeneration following insults.Whether targeting this pathway is beneficial to b...The mitogen-activated protein kinase kinase kinase kinases(MAP4Ks)signaling pathway plays a pivotal role in axonal regrowth and neuronal degeneration following insults.Whether targeting this pathway is beneficial to brain injury remains unclear.In this study,we showed that adeno-associated virus-delivery of the Citron homology domain of MAP4Ks effectively reduces traumatic brain injury-induced reactive gliosis,tauopathy,lesion size,and behavioral deficits.Pharmacological inhibition of MAP4Ks replicated the ameliorative effects observed with expression of the Citron homology domain.Mechanistically,the Citron homology domain acted as a dominant-negative mutant,impeding MAP4K-mediated phosphorylation of the dishevelled proteins and thereby controlling the Wnt/β-catenin pathway.These findings implicate a therapeutic potential of targeting MAP4Ks to alleviate the detrimental effects of traumatic brain injury.展开更多
The subcortical visual pathway is generally thought to be involved in dangerous information processing,such as fear processing and defensive behavior.A recent study,published in Human Brain Mapping,shows a new functio...The subcortical visual pathway is generally thought to be involved in dangerous information processing,such as fear processing and defensive behavior.A recent study,published in Human Brain Mapping,shows a new function of the subcortical pathway involved in the fast processing of non-emotional object perception.Rapid object processing is a critical function of visual system.Topological perception theory proposes that the initial perception of objects begins with the extraction of topological property(TP).However,the mechanism of rapid TP processing remains unclear.The researchers investigated the subcortical mechanism of TP processing with transcranial magnetic stimulation(TMS).They find that a subcortical magnocellular pathway is responsible for the early processing of TP,and this subcortical processing of TP accelerates object recognition.Based on their findings,we propose a novel training approach called subcortical magnocellular pathway training(SMPT),aimed at improving the efficiency of the subcortical M pathway to restore visual and attentional functions in disorders associated with subcortical pathway dysfunction.展开更多
Acquired brain injury(ABI)is an injury that affects the brain structure and function.Traditional ABI treatment strategies,including medications and rehabilitation therapy,exhibit their ability to improve its impairmen...Acquired brain injury(ABI)is an injury that affects the brain structure and function.Traditional ABI treatment strategies,including medications and rehabilitation therapy,exhibit their ability to improve its impairments in cognition,emotion,and physical activity.Recently,near-infrared(NIR)photobiomodulation(PBM)has emerged as a promising physical intervention method for ABI,demonstrating that low-level light therapy can modulate cellular metabolic processes,reduce the in flammation and reactive oxygen species of ABI microenvironments,and promote neural repair and regeneration.Preclinical studies using ABI models have been carried out,revealing the potential of PBM in promoting brain injury recovery although its clinical application is still in its early stages.In this review,we first inspected the possible physical and biological mechanisms of NIR-PBM,and then reported the pathophysiology and physiology of ABI underlying NIR-PBM intervention.Therefore,the potential of NIR-PBM as a therapeutic intervention in ABI was demonstrated and it is also expected that further work can facilitate its clinical applications.展开更多
Transcranial temporal interference stimulation(tTIS)is a novel non-invasive neuromodulation technique with the potential to precisely target deep brain structures.This study explores the neural and behavioral effects ...Transcranial temporal interference stimulation(tTIS)is a novel non-invasive neuromodulation technique with the potential to precisely target deep brain structures.This study explores the neural and behavioral effects of tTIS on the superior colliculus(SC),a region involved in eye movement control,in mice.Computational modeling revealed that tTIS delivers more focused stimulation to the SC than traditional transcranial alternating current stimulation.In vivo experiments,including Ca^(2+)signal recordings and eye movement tracking,showed that tTIS effectively modulates SC neural activity and induces eye movements.A significant correlation was found between stimulation frequency and saccade frequency,suggesting direct tTIS-induced modulation of SC activity.These results demonstrate the precision of tTIS in targeting deep brain regions and regulating eye movements,highlighting its potential for neuroscientific research and therapeutic applications.展开更多
There is growing evidence that lipid metabolism instability in depressive disorder may be a core early pathological event associated with numerous pathogenesis hypotheses.However,spatial distributions and quantitative...There is growing evidence that lipid metabolism instability in depressive disorder may be a core early pathological event associated with numerous pathogenesis hypotheses.However,spatial distributions and quantitative changes of lipids in specific brain regions associated with depressive disorder are far from elucidated.In the present study,lipid profiling characteristics of whole brain sections are systematically determined by using matrix-assisted laser desorption ionization-mass spectrometry imaging(MALDI-MSI)-combined with histomorphological analysis in rats with depressive-like behavior induced by multiple early life stress(mELS)and unstressed control.Lipid dyshomeostasis and different degrees of metabolic disturbance occur in the eight paired representative brain sections from micro-region and molecular level.More specifically,17 lipid molecules show the severe dyshomeostasis between intergroup(control and depressed rats)or intra-group(multiple emotion-regulation-related brain regions).Quite specially,phosphatidylcholine(PC)(39:6)expression in section 7 is significantly upregulated only in the amygdala of depressed rat relative to control rat,by contrast,up-regulated phosphatidylglycerol(PG)(34:2)in section 2 emerges in the medial prefrontal cortex,insular cortex,and nucleus accumbens simultaneously.Linking spatial distribution to quantitative variation of lipids from the whole brain sections contributes the uncovering of new insights in causal mechanism of lipid dyshomeostasis in depression investigation and related targeting interventions.展开更多
Dear Editor,Sturge-Weber Syndrome(SWS)is a rare congenital neurocutaneous syndrome[1,2],with an estimated prevalence of 0.19 in 100,000 annually[3].It is a non-hereditary disease linked to a somatic mutation in the GN...Dear Editor,Sturge-Weber Syndrome(SWS)is a rare congenital neurocutaneous syndrome[1,2],with an estimated prevalence of 0.19 in 100,000 annually[3].It is a non-hereditary disease linked to a somatic mutation in the GNAQ,GNA11,or GNB2 gene[1],leading to vascular malformations in the cutaneous forehead,cerebral cortex,and eye[1,2].Notably,~70%of pediatric patients diagnosed with SWS exhibit brain calcification(BC)[4],though the prevalence of BC ranges from only 1%in young individuals to>20%in the senior population(>60 years old)[5].Similar to the elderly,BC in pediatric SWS patients is identified as vascular calcification[6,7],whereas BC in pediatric patients with tuberous sclerosis and tumors has been previously described as dystrophic calcification[6].展开更多
Dear Editor,The mammalian brain exhibits cross-scale complexity in neuronal morphology and connectivity,the study of which demands high-resolution morphological reconstruction of individual neurons across the entire b...Dear Editor,The mammalian brain exhibits cross-scale complexity in neuronal morphology and connectivity,the study of which demands high-resolution morphological reconstruction of individual neurons across the entire brain[1-4].Current commonly used approaches for such mesoscale brain mapping include two main types of three-dimensional fluorescence microscopy:the block-face methods,and the lightsheet-based methods[5,6].In general,the high imaging speed and light efficiency of light-sheet microscopy make it a suitable tool for high-throughput volumetric imaging,especially when combined with tissue-clearing techniques.However,large brain samples pose major challenges to this approach.展开更多
The brain-gut axis serves as the bidirectional connection between the gut microbiome, the intestinal barrier and the immune system that might be relevant for the pathophysiology of inflammatory demyelinating diseases....The brain-gut axis serves as the bidirectional connection between the gut microbiome, the intestinal barrier and the immune system that might be relevant for the pathophysiology of inflammatory demyelinating diseases. People with multiple sclerosis have been shown to have an altered microbiome, increased intestinal permeability and changes in bile acid metabolism. Experimental evidence suggests that these changes can lead to profound alterations of peripheral and central nervous system immune regulation. Besides being of pathophysiological interest, the brain-gut axis could also open new avenues of therapeutic targets. Modification of the microbiome, the use of probiotics, fecal microbiota transplantation, supplementation with bile acids and intestinal barrier enhancers are all promising candidates. Hopefully, pre-clinical studies and clinical trials will soon yield significant results.展开更多
Our recent findings have demonstrated that rodent models of closed head traumatic brain injury exhibit comprehensive evidence of progressive and enduring orofacial allodynias,a hypersensitive pain response induced by ...Our recent findings have demonstrated that rodent models of closed head traumatic brain injury exhibit comprehensive evidence of progressive and enduring orofacial allodynias,a hypersensitive pain response induced by non-painful stimulation.These allodynias,tested using thermal hyperalgesia,correlated with changes in several known pain signaling receptors and molecules along the trigeminal pain pathway,especially in the trigeminal nucleus caudalis.This study focused to extend our previous work to investigate the changes in monoamine neurotransmitter immunoreactivity changes in spinal trigeminal nucleus oralis,pars interpolaris and nucleus tractus solitaries following mild to moderate closed head traumatic brain injury,which are related to tactile allodynia,touch-pressure sensitivity,and visceral pain.Our results exhibited significant alterations in the excitatory monoamine,serotonin,in spinal trigeminal nucleus oralis and pars interpolaris which usually modulate tactile and mechanical sensitivity in addition to the thermal sensitivity.Moreover,we also detected a robust alteration in the expression of serotonin,and inhibitory molecule norepinephrine in the nucleus tractus solitaries,which might indicate the possibility of an alteration in visceral pain,and existence of other morbidities related to solitary nucleus dysfunction in this rodent model of mild to moderate closed head traumatic brain injury.Collectively,widespread changes in monoamine neurotransmitter may be related to orofacial allodynhias and headache after traumatic brain injury.展开更多
The functional brain network using blood-oxygen-level-dependent（BOLD） functional magnetic resonance imaging（fMRI） has revealed the potentials for probing brain architecture,as well as for identifying clinical biom...The functional brain network using blood-oxygen-level-dependent（BOLD） functional magnetic resonance imaging（fMRI） has revealed the potentials for probing brain architecture,as well as for identifying clinical biomarkers for brain diseases.In the general context of Brainnetome,this review focuses on the development of approaches for modeling and analyzing functional brain networks with BOLD fMRI.The prospects for these approaches are also discussed.展开更多
There is increasing evidence from epidemiological studies indicating that vitamin D deficiency during adulthood is associated with adverse brain outcomes in humans（Ginde et al.,2009）and rodents（Groves et al.,2014）...There is increasing evidence from epidemiological studies indicating that vitamin D deficiency during adulthood is associated with adverse brain outcomes in humans（Ginde et al.,2009）and rodents（Groves et al.,2014）,however,a causal relationship has not yet been established.展开更多
Increasing evidence shows that the human brain is a highly self-organized system that shows attributes of smallworldness,hierarchy and modularity.The ＂connectome＂ was conceived several years ago to identify the unde...Increasing evidence shows that the human brain is a highly self-organized system that shows attributes of smallworldness,hierarchy and modularity.The ＂connectome＂ was conceived several years ago to identify the underpinning physical connectivities of brain networks.The need for an integration of multi-spatial and-temporal approaches is becoming apparent.Therefore,the ＂Brainnetome＂（brain-net-ome） project was proposed.Diffusion magnetic resonance imaging（dMRI） is a non-invasive way to study the anatomy of brain networks.Here,we review the principles of dMRI,its methodologies,and some of its clinical applications for the Brainnetome.Future research in this field is discussed.展开更多
Neuroimaging has opened new opportunities to study the neural correlates of consciousness, and provided additional information concerning diagnosis, prognosis, and therapeutic interventions in patients with disorders ...Neuroimaging has opened new opportunities to study the neural correlates of consciousness, and provided additional information concerning diagnosis, prognosis, and therapeutic interventions in patients with disorders of consciousness. Here, we aim to review neuroimaging studies in chronic disorders of consciousness from the viewpoint of the brain network, focusing on positron emission tomogra- phy, functional MRI, functional near-infrared spectroscopy, electrophysiology, and diffusion MRI. To accelerate basic research on disorders of consciousness and provide a panoramic view of unconsciousness, we propose that it is urgent to integrate different techniques at various spatiotemporal scales, and to merge fragmented findings into a uniform ＂Brainnetome＂ （Brain-net-ome） research framework.展开更多
Human brain development is a complex process that continues between birth and maturity, and monitoring the underlying maturational changes at these stages is crucial for our understanding of typical development as wel...Human brain development is a complex process that continues between birth and maturity, and monitoring the underlying maturational changes at these stages is crucial for our understanding of typical development as well as neurodevelopmental disorders. During the critical periods of brain development, on one hand, many human capacities originate, but on the other hand, a brain undergoing rapid plastic changes may also be vulnerable to neuropsychiatric disorders . Multi-modal magnetic resonance imaging （MRI） has been increasingly used for its ability to noninvasively reveal structural and functional changes in the brain. However, interpretation of the neurobiological processes underlying the findings obtained with MRI is very limited .展开更多
Alzheimer’s disease is a neurodegenerative disorder characterized by progressive cognitive impairment and neuropathology. Recent preclinical and epidemiological studies proposed statins as a possible therapeutic drug...Alzheimer’s disease is a neurodegenerative disorder characterized by progressive cognitive impairment and neuropathology. Recent preclinical and epidemiological studies proposed statins as a possible therapeutic drug for Alzheimer’s disease, but the exact mechanisms of action are still unknown. Biliverdin reductase-A is a pleiotropic enzyme involved in cellular stress responses. It not only transforms biliverdin-IX alpha into the antioxidant bilirubin-IX alpha but its serine/threonine/ tyrosine kinase activity is able to modulate cell signaling networks. We previously reported the beneficial effects of atorvastatin treatment on biliverdin reductase-A and heme oxygenase-1 in the brains of a well characterized pre-clinical model of Alzheimer’s disease, aged beagles, together with observed improvement in cognition. Here we extend our knowledge of the effects of atorvastatin on inducible nitric oxide synthase in parietal cortex, cerebellum and liver of the same animals. We demonstrated that atorvastatin treatment （80 mg/day for 14.5 months） to aged beagles selectively increased inducible nitric oxide synthase in the parietal cortex but not in the cerebellum. In contrast, inducible nitric oxide synthase protein levels were significantly decreased in the liver. Significant positive correlations were found between biliverdin reductase-A and inducible nitric oxide synthase as well as heme oxygenase-1 protein levels in the parietal cortex. The opposite was observed in the liver. Inducible nitric oxide synthase up-regulation in the parietal cortex was positively associated with improved biliverdin reductase-A functions, whereas the oxidative-induced impairment of biliverdin reductase-A in the liver negatively affected inducible nitric oxide synthase expression, thus suggesting a role for biliverdin reductase-A in atorvastatin-dependent inducible nitric oxide synthase changes. Interestingly, increased inducible nitric oxide synthase levels in the parietal cortex were not associated with higher oxidative/nitrosative stress levels. We hypothesize that biliverdin reductase-A-dependent inducible nitric oxide synthase regulation strongly contributes to the cognitive improvement observed following atorvastatin treatment.展开更多
Military psychiatry, a new subcategory of psychiatry, has become an invaluable, intangible effect of the war. In this review, we begin by examining related military research, summarizing the related epidemiological da...Military psychiatry, a new subcategory of psychiatry, has become an invaluable, intangible effect of the war. In this review, we begin by examining related military research, summarizing the related epidemiological data, neuropathology, and the research achievements of diagnosis and treatment technology, and discussing its comorbidity and sequelae. To date, advances in neuroimaging and molecular biology have greatly boosted the studies on military traumatic brain injury(TBI). In particular, in terms of pathophysiological mechanisms, several preclinical studies have identified abnormal protein accumulation, blood–brain barrier damage, and brain metabolism abnormalities involved in the development of TBI. As an important concept in the field of psychiatry, TBI is based on organic injury, which is largely different from many other mental disorders. Therefore, military TBI is both neuropathic and psychopathic, and is an emerging challenge at the intersection of neurology and psychiatry.展开更多
Brain injuries due to trauma or stroke are major causes of adult death and disability.Unfortunately,few interventions are effective for post-injury repair of brain tissue.After a long debate on whether endogenous neur...Brain injuries due to trauma or stroke are major causes of adult death and disability.Unfortunately,few interventions are effective for post-injury repair of brain tissue.After a long debate on whether endogenous neurogenesis actually happens in the adult human brain,there is now substantial evidence to support its occurrence.Although neurogenesis is usually significantly stimulated by injury,the reparative potential of endogenous differentiation from neural stem/progenitor cells is usually insufficient.Alternatively,exogenous stem cell transplantation has shown promising results in animal models,but limitations such as poor long-term survival and inefficient neuronal differentiation make it still challenging for clinical use.Recently,a high focus was placed on glia-to-neuron conversion under single-factor regulation.Despite some inspiring results,the validity of this strategy is still controversial.In this review,we summarize historical findings and recent advances on neurogenesis strategies for neurorepair after brain injury.We also discuss their advantages and drawbacks,as to provide a comprehensive account of their potentials for further studies.展开更多
Neuroimaging made it possible to quantify brain structure and function.However,there are few neuroimaging biomarkers for the early diagnosis,prognosis,and evaluation of therapy for brain diseases.The development of ne...Neuroimaging made it possible to quantify brain structure and function.However,there are few neuroimaging biomarkers for the early diagnosis,prognosis,and evaluation of therapy for brain diseases.The development of neuroimaging biomarkers for brain diseases faces two major bottleneck problems.First,the neuroimaging datasets of brain diseases are always characterized by small sample size,high dimension,and large heterogeneity.Second,a fine-grained individualized human brain atlas for effective dimensionality reduction has always been lacking.展开更多
基金supported in part by the Rosetrees Trust(#CF-2023-I-2_113)by the Israel Ministry of Innovation,Science,and Technology(#7393)(to ES).
文摘The organization of biological neuronal networks into functional modules has intrigued scientists and inspired engineers to develop artificial systems.These networks are characterized by two key properties.First,they exhibit dense interconnectivity(Braitenburg and Schüz,1998;Campagnola et al.,2022).The strength and probability of connectivity depend on cell type,inter-neuronal distance,and species.Still,every cortical neuron receives input from thousands of other neurons while transmitting output to a similar number of neurons.Second,communication between neurons occurs primarily via chemical or electrical synapses.
文摘Subarachnoid hemorrhage(SAH) is a devastating condition that affects a total of 8 million people worldwide each year(Lauzier and Athiraman, 2024). Etiologies of SAH can be traumatic or nontraumatic, with the majority of non-traumatic SAH occurring due to intracranial aneurysm rupture(Rutledge et al., 2014).
基金supported by the TARCC,Welch Foundation Award(I-1724)the Decherd Foundationthe Pape Adams Foundation,NIH grants NS092616,NS127375,NS117065,NS111776。
文摘The mitogen-activated protein kinase kinase kinase kinases(MAP4Ks)signaling pathway plays a pivotal role in axonal regrowth and neuronal degeneration following insults.Whether targeting this pathway is beneficial to brain injury remains unclear.In this study,we showed that adeno-associated virus-delivery of the Citron homology domain of MAP4Ks effectively reduces traumatic brain injury-induced reactive gliosis,tauopathy,lesion size,and behavioral deficits.Pharmacological inhibition of MAP4Ks replicated the ameliorative effects observed with expression of the Citron homology domain.Mechanistically,the Citron homology domain acted as a dominant-negative mutant,impeding MAP4K-mediated phosphorylation of the dishevelled proteins and thereby controlling the Wnt/β-catenin pathway.These findings implicate a therapeutic potential of targeting MAP4Ks to alleviate the detrimental effects of traumatic brain injury.
文摘The subcortical visual pathway is generally thought to be involved in dangerous information processing,such as fear processing and defensive behavior.A recent study,published in Human Brain Mapping,shows a new function of the subcortical pathway involved in the fast processing of non-emotional object perception.Rapid object processing is a critical function of visual system.Topological perception theory proposes that the initial perception of objects begins with the extraction of topological property(TP).However,the mechanism of rapid TP processing remains unclear.The researchers investigated the subcortical mechanism of TP processing with transcranial magnetic stimulation(TMS).They find that a subcortical magnocellular pathway is responsible for the early processing of TP,and this subcortical processing of TP accelerates object recognition.Based on their findings,we propose a novel training approach called subcortical magnocellular pathway training(SMPT),aimed at improving the efficiency of the subcortical M pathway to restore visual and attentional functions in disorders associated with subcortical pathway dysfunction.
基金supported by the University of Macao(MYRG2022-00054-FHS and MYRGGRG2023-00038-FHS-UMDF)the Macao Science and Technology Development Fund(FDCT0048/2021/AGJ and FDCT0020/2019/AMJ)Natural Science Foundation of Guangdong Province(EF017/FHS-YZ/2021/GDSTC).
文摘Acquired brain injury(ABI)is an injury that affects the brain structure and function.Traditional ABI treatment strategies,including medications and rehabilitation therapy,exhibit their ability to improve its impairments in cognition,emotion,and physical activity.Recently,near-infrared(NIR)photobiomodulation(PBM)has emerged as a promising physical intervention method for ABI,demonstrating that low-level light therapy can modulate cellular metabolic processes,reduce the in flammation and reactive oxygen species of ABI microenvironments,and promote neural repair and regeneration.Preclinical studies using ABI models have been carried out,revealing the potential of PBM in promoting brain injury recovery although its clinical application is still in its early stages.In this review,we first inspected the possible physical and biological mechanisms of NIR-PBM,and then reported the pathophysiology and physiology of ABI underlying NIR-PBM intervention.Therefore,the potential of NIR-PBM as a therapeutic intervention in ABI was demonstrated and it is also expected that further work can facilitate its clinical applications.
基金supported by the National Natural Science Foundation of China(T2394533,32222036,82030038,and 62472206)the National Key Research and Development Program of China(2018YFA0701400)the Shenzhen Science and Technology Innovation Committee(2022410129,KJZD20230923115221044,and KCXFZ20201221173400001).
文摘Transcranial temporal interference stimulation(tTIS)is a novel non-invasive neuromodulation technique with the potential to precisely target deep brain structures.This study explores the neural and behavioral effects of tTIS on the superior colliculus(SC),a region involved in eye movement control,in mice.Computational modeling revealed that tTIS delivers more focused stimulation to the SC than traditional transcranial alternating current stimulation.In vivo experiments,including Ca^(2+)signal recordings and eye movement tracking,showed that tTIS effectively modulates SC neural activity and induces eye movements.A significant correlation was found between stimulation frequency and saccade frequency,suggesting direct tTIS-induced modulation of SC activity.These results demonstrate the precision of tTIS in targeting deep brain regions and regulating eye movements,highlighting its potential for neuroscientific research and therapeutic applications.
基金supported by the China Science and Technology Innovation 2030-Major Project(Nos.2022ZD0211701,2021ZD0200700)the National Natural Science Foundation of China(Nos.82130042,81830040,22176195,82127801)+3 种基金Shenzhen Science and Technology Serial Funds(Nos.GJHZ20210705141400002,KCXFZ20211020164543006,JCYJ20220818101615033,ZDSYS20220606100606014,KQTD 20221101093608028)the National Key R&D Program of China(No.2022YFF0705003)Guangdong Province Zhu Jiang Talents Plan(No.2021QN02Y028)the Guangdong Science and Technology Department(No.2021B1212030004)。
文摘There is growing evidence that lipid metabolism instability in depressive disorder may be a core early pathological event associated with numerous pathogenesis hypotheses.However,spatial distributions and quantitative changes of lipids in specific brain regions associated with depressive disorder are far from elucidated.In the present study,lipid profiling characteristics of whole brain sections are systematically determined by using matrix-assisted laser desorption ionization-mass spectrometry imaging(MALDI-MSI)-combined with histomorphological analysis in rats with depressive-like behavior induced by multiple early life stress(mELS)and unstressed control.Lipid dyshomeostasis and different degrees of metabolic disturbance occur in the eight paired representative brain sections from micro-region and molecular level.More specifically,17 lipid molecules show the severe dyshomeostasis between intergroup(control and depressed rats)or intra-group(multiple emotion-regulation-related brain regions).Quite specially,phosphatidylcholine(PC)(39:6)expression in section 7 is significantly upregulated only in the amygdala of depressed rat relative to control rat,by contrast,up-regulated phosphatidylglycerol(PG)(34:2)in section 2 emerges in the medial prefrontal cortex,insular cortex,and nucleus accumbens simultaneously.Linking spatial distribution to quantitative variation of lipids from the whole brain sections contributes the uncovering of new insights in causal mechanism of lipid dyshomeostasis in depression investigation and related targeting interventions.
基金supported by the Natural Science Foundation of Guangdong Province(2022A1515010297)the National Natural Science Foundation of China(32100765)+1 种基金the Xiamen Medical Health Science and Technology Project(3502Z20194098)the Shenzhen-Hong Kong-Macao Science and Technology Innovation Project(SGDX2020110309280100).
文摘Dear Editor,Sturge-Weber Syndrome(SWS)is a rare congenital neurocutaneous syndrome[1,2],with an estimated prevalence of 0.19 in 100,000 annually[3].It is a non-hereditary disease linked to a somatic mutation in the GNAQ,GNA11,or GNB2 gene[1],leading to vascular malformations in the cutaneous forehead,cerebral cortex,and eye[1,2].Notably,~70%of pediatric patients diagnosed with SWS exhibit brain calcification(BC)[4],though the prevalence of BC ranges from only 1%in young individuals to>20%in the senior population(>60 years old)[5].Similar to the elderly,BC in pediatric SWS patients is identified as vascular calcification[6,7],whereas BC in pediatric patients with tuberous sclerosis and tumors has been previously described as dystrophic calcification[6].
基金supported by the STI 2030-Major Project(2021ZD0204400,2022ZD0205203,2021ZD0200104,2022ZD0211900)the Shenzhen Science and Technology Program(RCYX20210706092100003,RCBS20221008093311027)+3 种基金the Shenzhen Medical Research Funds(A2303005)the Youth Innovation Promotion Association CAS(2022367)the National Natural Science Foundation of China(32100896)NSFC-Guangdong Joint Fund(U20A6005).
文摘Dear Editor,The mammalian brain exhibits cross-scale complexity in neuronal morphology and connectivity,the study of which demands high-resolution morphological reconstruction of individual neurons across the entire brain[1-4].Current commonly used approaches for such mesoscale brain mapping include two main types of three-dimensional fluorescence microscopy:the block-face methods,and the lightsheet-based methods[5,6].In general,the high imaging speed and light efficiency of light-sheet microscopy make it a suitable tool for high-throughput volumetric imaging,especially when combined with tissue-clearing techniques.However,large brain samples pose major challenges to this approach.
基金Supported by the Lejoie-Lake Fellowship(to Camara-Lemarroy CR)awarded by the Hotchkiss Brain Institute
文摘The brain-gut axis serves as the bidirectional connection between the gut microbiome, the intestinal barrier and the immune system that might be relevant for the pathophysiology of inflammatory demyelinating diseases. People with multiple sclerosis have been shown to have an altered microbiome, increased intestinal permeability and changes in bile acid metabolism. Experimental evidence suggests that these changes can lead to profound alterations of peripheral and central nervous system immune regulation. Besides being of pathophysiological interest, the brain-gut axis could also open new avenues of therapeutic targets. Modification of the microbiome, the use of probiotics, fecal microbiota transplantation, supplementation with bile acids and intestinal barrier enhancers are all promising candidates. Hopefully, pre-clinical studies and clinical trials will soon yield significant results.
基金supported by Merit Review Awards(No.B6570R,B78071,and B1005-R)from the United States(U.S.)Department of Veterans Affairs Rehabilitation Research and Development Service
文摘Our recent findings have demonstrated that rodent models of closed head traumatic brain injury exhibit comprehensive evidence of progressive and enduring orofacial allodynias,a hypersensitive pain response induced by non-painful stimulation.These allodynias,tested using thermal hyperalgesia,correlated with changes in several known pain signaling receptors and molecules along the trigeminal pain pathway,especially in the trigeminal nucleus caudalis.This study focused to extend our previous work to investigate the changes in monoamine neurotransmitter immunoreactivity changes in spinal trigeminal nucleus oralis,pars interpolaris and nucleus tractus solitaries following mild to moderate closed head traumatic brain injury,which are related to tactile allodynia,touch-pressure sensitivity,and visceral pain.Our results exhibited significant alterations in the excitatory monoamine,serotonin,in spinal trigeminal nucleus oralis and pars interpolaris which usually modulate tactile and mechanical sensitivity in addition to the thermal sensitivity.Moreover,we also detected a robust alteration in the expression of serotonin,and inhibitory molecule norepinephrine in the nucleus tractus solitaries,which might indicate the possibility of an alteration in visceral pain,and existence of other morbidities related to solitary nucleus dysfunction in this rodent model of mild to moderate closed head traumatic brain injury.Collectively,widespread changes in monoamine neurotransmitter may be related to orofacial allodynhias and headache after traumatic brain injury.
基金supported by the National Basic Research Development Program(973) of China(2011CB707800)the National Natural Science Foundation of China(91132301 and 81101040)
文摘The functional brain network using blood-oxygen-level-dependent（BOLD） functional magnetic resonance imaging（fMRI） has revealed the potentials for probing brain architecture,as well as for identifying clinical biomarkers for brain diseases.In the general context of Brainnetome,this review focuses on the development of approaches for modeling and analyzing functional brain networks with BOLD fMRI.The prospects for these approaches are also discussed.
文摘There is increasing evidence from epidemiological studies indicating that vitamin D deficiency during adulthood is associated with adverse brain outcomes in humans（Ginde et al.,2009）and rodents（Groves et al.,2014）,however,a causal relationship has not yet been established.
基金supported by the National Basic Research Development Program(973) of China(2011CB707800)the National Natural Science Foundation of China(91132301 and 81000634)
文摘Increasing evidence shows that the human brain is a highly self-organized system that shows attributes of smallworldness,hierarchy and modularity.The ＂connectome＂ was conceived several years ago to identify the underpinning physical connectivities of brain networks.The need for an integration of multi-spatial and-temporal approaches is becoming apparent.Therefore,the ＂Brainnetome＂（brain-net-ome） project was proposed.Diffusion magnetic resonance imaging（dMRI） is a non-invasive way to study the anatomy of brain networks.Here,we review the principles of dMRI,its methodologies,and some of its clinical applications for the Brainnetome.Future research in this field is discussed.
基金supported by the National Natural Science Foundation of China(81471380,31771076,81501550,91432302,31620103905,and 81501179)the Science Frontier Program of the Chinese Academy of Sciences(QYZDJSSW-SMC019)+4 种基金National Key R&D Program of China(2017YFA0105203,2017YFB1002502)Beijing Municipal Science and Technology Commission(Z161100000216152,Z161100000216139,Z171100000117002,and Z161100000516165)the Shenzhen Peacock Plan(KQTD2015033016104926)the Guangdong Pearl River Talents Plan(2016ZT06S220)Youth Innovation Promotion Association,CAS,China
文摘Neuroimaging has opened new opportunities to study the neural correlates of consciousness, and provided additional information concerning diagnosis, prognosis, and therapeutic interventions in patients with disorders of consciousness. Here, we aim to review neuroimaging studies in chronic disorders of consciousness from the viewpoint of the brain network, focusing on positron emission tomogra- phy, functional MRI, functional near-infrared spectroscopy, electrophysiology, and diffusion MRI. To accelerate basic research on disorders of consciousness and provide a panoramic view of unconsciousness, we propose that it is urgent to integrate different techniques at various spatiotemporal scales, and to merge fragmented findings into a uniform ＂Brainnetome＂ （Brain-net-ome） research framework.
文摘Human brain development is a complex process that continues between birth and maturity, and monitoring the underlying maturational changes at these stages is crucial for our understanding of typical development as well as neurodevelopmental disorders. During the critical periods of brain development, on one hand, many human capacities originate, but on the other hand, a brain undergoing rapid plastic changes may also be vulnerable to neuropsychiatric disorders . Multi-modal magnetic resonance imaging （MRI） has been increasingly used for its ability to noninvasively reveal structural and functional changes in the brain. However, interpretation of the neurobiological processes underlying the findings obtained with MRI is very limited .
基金Funding for the canine atorvastatin study was through the Alzheimer's Association IIRG-03-5673 to Elizabeth Head
文摘Alzheimer’s disease is a neurodegenerative disorder characterized by progressive cognitive impairment and neuropathology. Recent preclinical and epidemiological studies proposed statins as a possible therapeutic drug for Alzheimer’s disease, but the exact mechanisms of action are still unknown. Biliverdin reductase-A is a pleiotropic enzyme involved in cellular stress responses. It not only transforms biliverdin-IX alpha into the antioxidant bilirubin-IX alpha but its serine/threonine/ tyrosine kinase activity is able to modulate cell signaling networks. We previously reported the beneficial effects of atorvastatin treatment on biliverdin reductase-A and heme oxygenase-1 in the brains of a well characterized pre-clinical model of Alzheimer’s disease, aged beagles, together with observed improvement in cognition. Here we extend our knowledge of the effects of atorvastatin on inducible nitric oxide synthase in parietal cortex, cerebellum and liver of the same animals. We demonstrated that atorvastatin treatment （80 mg/day for 14.5 months） to aged beagles selectively increased inducible nitric oxide synthase in the parietal cortex but not in the cerebellum. In contrast, inducible nitric oxide synthase protein levels were significantly decreased in the liver. Significant positive correlations were found between biliverdin reductase-A and inducible nitric oxide synthase as well as heme oxygenase-1 protein levels in the parietal cortex. The opposite was observed in the liver. Inducible nitric oxide synthase up-regulation in the parietal cortex was positively associated with improved biliverdin reductase-A functions, whereas the oxidative-induced impairment of biliverdin reductase-A in the liver negatively affected inducible nitric oxide synthase expression, thus suggesting a role for biliverdin reductase-A in atorvastatin-dependent inducible nitric oxide synthase changes. Interestingly, increased inducible nitric oxide synthase levels in the parietal cortex were not associated with higher oxidative/nitrosative stress levels. We hypothesize that biliverdin reductase-A-dependent inducible nitric oxide synthase regulation strongly contributes to the cognitive improvement observed following atorvastatin treatment.
基金supported by the Zhejiang Provincial Key Research and Development Program (2021C03107)。
文摘Military psychiatry, a new subcategory of psychiatry, has become an invaluable, intangible effect of the war. In this review, we begin by examining related military research, summarizing the related epidemiological data, neuropathology, and the research achievements of diagnosis and treatment technology, and discussing its comorbidity and sequelae. To date, advances in neuroimaging and molecular biology have greatly boosted the studies on military traumatic brain injury(TBI). In particular, in terms of pathophysiological mechanisms, several preclinical studies have identified abnormal protein accumulation, blood–brain barrier damage, and brain metabolism abnormalities involved in the development of TBI. As an important concept in the field of psychiatry, TBI is based on organic injury, which is largely different from many other mental disorders. Therefore, military TBI is both neuropathic and psychopathic, and is an emerging challenge at the intersection of neurology and psychiatry.
基金supported by the SIAT Innovation Program for Excellent Young Researchers,No.E1G0241001(to XZ)。
文摘Brain injuries due to trauma or stroke are major causes of adult death and disability.Unfortunately,few interventions are effective for post-injury repair of brain tissue.After a long debate on whether endogenous neurogenesis actually happens in the adult human brain,there is now substantial evidence to support its occurrence.Although neurogenesis is usually significantly stimulated by injury,the reparative potential of endogenous differentiation from neural stem/progenitor cells is usually insufficient.Alternatively,exogenous stem cell transplantation has shown promising results in animal models,but limitations such as poor long-term survival and inefficient neuronal differentiation make it still challenging for clinical use.Recently,a high focus was placed on glia-to-neuron conversion under single-factor regulation.Despite some inspiring results,the validity of this strategy is still controversial.In this review,we summarize historical findings and recent advances on neurogenesis strategies for neurorepair after brain injury.We also discuss their advantages and drawbacks,as to provide a comprehensive account of their potentials for further studies.
文摘Neuroimaging made it possible to quantify brain structure and function.However,there are few neuroimaging biomarkers for the early diagnosis,prognosis,and evaluation of therapy for brain diseases.The development of neuroimaging biomarkers for brain diseases faces two major bottleneck problems.First,the neuroimaging datasets of brain diseases are always characterized by small sample size,high dimension,and large heterogeneity.Second,a fine-grained individualized human brain atlas for effective dimensionality reduction has always been lacking.
