Children are being exposed to an increasingly greater variety of anesthetics with advances in pediatric and obstetric surgery.Recent animal and retrospective human data suggest that the general anesthetics commonly us...Children are being exposed to an increasingly greater variety of anesthetics with advances in pediatric and obstetric surgery.Recent animal and retrospective human data suggest that the general anesthetics commonly used in pediatric medicine could be damaging to the developing brain when used at clinical concentrations.In vivo primate and rodent models have shown that neonatal exposure to clinical concentrations of anesthetics causes neural apoptosis展开更多
Background:Emerging research supports the idea that exercise positively affects neurodevelopment.However,the mechanisms linking exercise with brain health are largely unknown.We aimed to investigate the effect of exer...Background:Emerging research supports the idea that exercise positively affects neurodevelopment.However,the mechanisms linking exercise with brain health are largely unknown.We aimed to investigate the effect of exercise on(a)blood biomarkers selected based on previous evidence(brainderived neurotrophic factor,β-hydroxybutyrate(BHB),cathepsin B(CTSB),kynurenine,fibroblast growth factor 21(FGF21),soluble vascular cell adhesion molecule-1(sVCAM-1));and(b)a panel of 92 neurology-related proteins(discovery analysis).We also investigated whether changes in these biomarkers mediate the effects of exercise on brain health(hippocampal structure and function,cognitive performance,and mental health).Methods:We randomized 81 overweight/obese children(10.1±1.1 years,41%girls)into 2 groups:either 20 weeks of aerobic plus resistance exercise or control.Candidate biomarkers were assessed using enzyme-linked immunosorbent assay(ELISA)for kynurenine,FGF21,and CTSB;colorimetry forβ-hydroxybutyrate;and XMap for brain-derived neurotrophic factor and soluble vascular cell adhesion molecule-1.The92 neurology-related proteins were analyzed by an antibody-based proteomic analysis.Results:Our intervention had no significant effect on candidate biomarkers(all p>0.05).In the discovery analysis,a reduction in circulating macrophage scavenger receptor type-I was observed(standardized differences between groups=-0.3,p=0.001).This effect was validated using ELISA methods(standardized difference=-0.3,p=0.01).None of the biomarkers mediated the effects of exercise on brain health.Conclusions:Our study does not support a chronic effect of exercise on candidate biomarkers.We observed that while chronic exercise reduced the levels of macrophage scavenger receptor type-Ⅰ,it did not mediate the effects of exercise on brain health.Future studies should explore the implications of this novel biomarker for overall health.展开更多
Circular RNAs(circRNAs)are a class of covalently closed single-stranded RNAs that are expressed during the development of specific cells and tissues.CircRNAs play crucial roles in physiological and pathological proces...Circular RNAs(circRNAs)are a class of covalently closed single-stranded RNAs that are expressed during the development of specific cells and tissues.CircRNAs play crucial roles in physiological and pathological processes by sponging microRNAs,modulating gene transcription,controlling the activity of certain RNA-binding proteins,and producing functional peptides.A key focus of research at present is the functionality of circRNAs in the nervous system and several advances have emerged over the last 2 years.However,the precise role of circRNAs in the nervous system has yet to be comprehensively reviewed.In this review,we first summarize the recently described roles of circRNAs in brain development,maturity,and aging.Then,we focus on the involvement of circRNAs in various diseases of the central nervous system,such as brain cancer,chronic neurodegenerative diseases,acute injuries of the nervous system,and neuropathic pain.A better understanding of the functionality of circRNAs will help us to develop potential diagnostic,prognostic,and therapeutic strategies to treat diseases of the nervous system.展开更多
Brain development and aging are associated with alterations in multiple epigenetic systems,including DNA methylation and demethylation patterns.Here,we observed that the levels of the 5-hydroxymethylcytosine(5hmC)ten-...Brain development and aging are associated with alterations in multiple epigenetic systems,including DNA methylation and demethylation patterns.Here,we observed that the levels of the 5-hydroxymethylcytosine(5hmC)ten-eleven translocation(TET)enzyme-mediated active DNA demethylation products were dynamically changed and involved in postnatal brain development and aging in tree shrews(Tupaia belangeri chinensis).The levels of5hm C in multiple anatomic structures showed a gradual increase throughout postnatal development,whereas a significant decrease in 5hmC was found in several brain regions in aged tree shrews,including in the prefrontal cortex and hippocampus,but not the cerebellum.Active changes in Tet mR NA levels indicated that TET2 and TET3 predominantly contributed to the changes in 5hmC levels.Our findings provide new insight into the dynamic changes in 5hm C levels in tree shrew brains during postnatal development and aging processes.展开更多
Target of research in subarachnoid hemorrhage(SAH):The outcome of aneurysmal SAH remains poor despite advances in the diagnosis and treatment.Although many factors related to patients,aneurysms,and institutions,as wel...Target of research in subarachnoid hemorrhage(SAH):The outcome of aneurysmal SAH remains poor despite advances in the diagnosis and treatment.Although many factors related to patients,aneurysms,and institutions,as well as physiological parameters and medical complications were reported as prognostic factors,the most important determinant of poor展开更多
Glial cells are crucial for maintaining central nervous system(CNS)homeostasis.They actively participate in immune responses,as well as form functional barriers,such as blood-brain barrier(BBB),which restrict the entr...Glial cells are crucial for maintaining central nervous system(CNS)homeostasis.They actively participate in immune responses,as well as form functional barriers,such as blood-brain barrier(BBB),which restrict the entry of pathogens and inflammatory mediators into the CNS.In general,viral infections during the gestational period can alter the embryonic and fetal environment,and the related inflammatory response may affect neurodevelopment and lead to behavioral dysfunction during later stage of life,as highlighted by our group for Zika virus infection.Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)induces a cytokine storm and,during pregnancy,may be related to a more severe form of the coronavirus disease-19(COVID-19)and also to higher preterm birth rates.SARS-CoV-2 can also affect the CNS by inducing neurochemical remodeling in neural cells,which can compromise neuronal plasticity and synaptic function.However,the impact of SARS-CoV-2 infection during pregnancy on postnatal CNS,including brain development during childhood and adulthood,remains undetermined.Our group has recently highlighted the impact of COVID-19 on the expression of molecular markers associated with neuropsychiatric disorders,which are strongly related to the inflammatory response.Thus,based on these relationships,we discussed the impact of SARS-CoV-2 infection either during pregnancy or in critical periods of neurodevelopment as a risk factor for neurological consequences in the offspring later in life,focusing on the potential role of glial cells.Thus,it is important to consider future and long-term public health concerns associated with SARS-CoV-2 infection during pregnancy.展开更多
Food must supply a balance of nutrients to support both brain and body.The human brain makes us uniquely human.Essential fatty acids are part of the metabolic pathways that define tissue structure and function.Omega-6...Food must supply a balance of nutrients to support both brain and body.The human brain makes us uniquely human.Essential fatty acids are part of the metabolic pathways that define tissue structure and function.Omega-6(O6)linoleic acid(LA6)has long been known to be required for skin structure,and as a precursor for inflammatory,thrombotic,immune,and other signaling molecules.Omega-3(O3)alpha-linolenic acid(ALA3)and particularly its long chain product docosahexaenoic acid(DHA3)has a key structural role in the brain,retina,and related neural tissue.In the 20 th century western world,inexpensive,high quality oils primarily from LA6-rich/O3-poor vegetable seed oils became dominant fats produced by the food industry.Provision of LA6-rich/O3-poor oils as the sole source of fat in the diets of pregnant animals causes O3 deficiency and poor brain development,primarily because high LA6 antagonizes metabolism of all O3,creating an artificial metabolic demand for O3.Data developed over the last 2~3 decades show that provision of low LA6 combined with preformed DHA3 optimizes brain function.Recent studies emphasize the importance of nutrition to support brain development,with newer findings showing particular importance of fatty acid balance in malnourished children.The World Health Organization(WHO)through the Codex Alimentarius(“Code for Food”)is increasingly recognizing the primacy of brain health and in part on that basis recently acted to recommend balanced fat for Ready-to-Use-Therapeutic Foods used to treat children with severe acute malnutrition.Similar principles are likely to be important in older persons.Industry now has the tools to adjust the composition of oils to support brain health throughout the life cycle.展开更多
A major basic research projectin the field of neurosciencewas launched on November26 last year at the Shanghai-basedInstitute of Neuroscience of the Chi-nese Academy of Sciences(CAS).
Brain tumors are a diverse group of malignancies that remain refractory to conventional treatment approaches.Molecular neuro-oncologyhas now begun to clarify the transformed phenotype of brain tumors and identify onco...Brain tumors are a diverse group of malignancies that remain refractory to conventional treatment approaches.Molecular neuro-oncologyhas now begun to clarify the transformed phenotype of brain tumors and identify oncogenic pathways that might be amenable to targetedtherapy.Activity of the phosphoinositide 3;kinase(PI3K)/Akt pathway is often upregulated in brain tumors due to excessive stimu-lation by growth factor receptors and Ras.Loss of function of the tumor suppressor gene PTEN also frequently contributesto展开更多
Autism spectrum disorder(ASD)is a group of heterogeneous,multi-factorial,neurodevelopmental disorders resulting from genetic and environmental factors interplay.Infection is a significant trigger of autism,especially ...Autism spectrum disorder(ASD)is a group of heterogeneous,multi-factorial,neurodevelopmental disorders resulting from genetic and environmental factors interplay.Infection is a significant trigger of autism,especially during the critical developmental period.There is a strong interplay between the viral infection as a trigger and a result of ASD.We aim to highlight the mutual relationship between autism and viruses.We performed a thorough literature review and included 158 research in this review.Most of the literature agreed on the possible effects of the viral infection during the critical period of development on the risk of developing autism,especially for specific viral infections such as Rubella,Cytomegalovirus,Herpes Simplex virus,Varicella Zoster Virus,Influenza virus,Zika virus,and severe acute respiratory syndrome coronavirus 2.Viral infection directly infects the brain,triggers immune activation,induces epigenetic changes,and raises the risks of having a child with autism.At the same time,there is some evidence of increased risk of infection,including viral infections in children with autism,due to lots of factors.There is an increased risk of developing autism with a specific viral infection during the early developmental period and an increased risk of viral infections in children with autism.In addition,children with autism are at increased risk of infection,including viruses.Every effort should be made to prevent maternal and early-life infections and reduce the risk of autism.Immune modulation of children with autism should be considered to reduce the risk of infection.展开更多
This paper aims to provide an effective overview of ADHD(Attention Deficit Hyperactivity Disorder),so that educators and other individuals who may be involved in the treatment of ADHD patients,especially young patient...This paper aims to provide an effective overview of ADHD(Attention Deficit Hyperactivity Disorder),so that educators and other individuals who may be involved in the treatment of ADHD patients,especially young patients,can effectively obtain basic information about what is ADHD,the causes of ADHD,and the popular treatment methods of ADHD.Various literature and studies were referred to in this paper to review and compare different causes and treatments.Researches held distinct opinions about the causes of ADHD,and the debate focuses on the nature and nurture factors of ADHD.Some studies believe ADHD is inborn and genetic while other studies emphasize the importance of nurture factors during their life,such as the environment that patients grow up in and the lifestyle they have.Depending on distinct arguments,there developed different treatments like using medication to prevent the situation from deteriorating further and changing the environments that patients living in through taking interventions with the family.These arguments and treatments will be discussed in detail in this paper.展开更多
Understanding the fundamental processes of human brain development and diseases is of great importance for our health.However,existing research models such as non-human primate and mouse models remain limited due to t...Understanding the fundamental processes of human brain development and diseases is of great importance for our health.However,existing research models such as non-human primate and mouse models remain limited due to their developmental discrepancies compared with humans.Over the past years,an emerging model,the“brain organoid”integrated from human pluripotent stem cells,has been developed to mimic developmental processes of the human brain and disease-associated phenotypes to some extent,making it possible to better understand the complex structures and functions of the human brain.In this review,we summarize recent advances in brain organoid technologies and their applications in brain development and diseases,including neurodevelopmental,neurodegenerative,psychiatric diseases,and brain tumors.Finally,we also discuss current limitations and the potential of brain organoids.展开更多
The human brain contains billions of highly differentiated and interconnected cells that form intricate neural networks and collectively control the physical activities and high-level cognitive functions,such as memor...The human brain contains billions of highly differentiated and interconnected cells that form intricate neural networks and collectively control the physical activities and high-level cognitive functions,such as memory,decision-making,and social behavior.Big data is required to decipher the complexity of cell types,as well as connectivity and functions of the brain.The newly developed single-cell sequencing technology,which provides a comprehensive landscape of brain cell type diversity by profiling the transcriptome,genome,and/or epigenome of individual cells,has contributed substantially to revealing the complexity and dynamics of the brain and providing new insights into brain development and brain-related disorders.In this review,we first introduce the progresses in both experimental and computational methods of single-cell sequencing technology.Applications of single-cell sequencing-based technologies in brain research,including cell type classification,brain development,and brain disease mechanisms,are then elucidated by representative studies.Lastly,we provided our perspectives into the challenges and future developments in the field of single-cell sequencing.In summary,this mini review aims to provide an overview of how big data generated from single-cell sequencing have empowered the advancements in neuroscience and shed light on the complex problems in understanding brain functions and diseases.展开更多
Neurogenesis is the process in which neurons are generated from neural stem/progenitor cells(NSCs/NPCs).It involves the proliferation and neuronal fate specification/differentiation of NSCs,as well as migration,maturat...Neurogenesis is the process in which neurons are generated from neural stem/progenitor cells(NSCs/NPCs).It involves the proliferation and neuronal fate specification/differentiation of NSCs,as well as migration,maturation and functional integration of the neuronal progeny into neuronal network.NSCs exhibit the two essential properties of stem cells:self-renewal and multi-potency.Contrary to previous dogma that neurogenesis happens only during development,it is generally accepted now that neurogenesis can take place throughout life in mammalian brains.This raises a new therapeutic potential of applying stem cell therapy for stroke,neurodegenerative diseases and other diseases.However,the maintenance and differentiation of NSCs/NPCs are tightly controlled by the extremely intricate molecular networks.Uncovering the underlying mechanisms that drive the differentiation,migration and maturation of specific neuronal lineages for use in regenerative medicine is,therefore,crucial for the application of stem cell for clinical therapy as well as for providing insight into the mechanisms of human neurogenesis.Here,we focus on the role of bone morphogenetic protein(BMP)signaling in NSCs during mammalian brain development.展开更多
Most infants who are later diagnosed with autism show delayed speech and language and/or atypical language profile.There is a large body of research on abnormal speech and language in children with autism.However,audi...Most infants who are later diagnosed with autism show delayed speech and language and/or atypical language profile.There is a large body of research on abnormal speech and language in children with autism.However,auditory development has been relatively under-investigated in autism research,despite its inextricable relationship with language development and despite researchers'ability to detect abnormalities in brain development and behavior in early infancy.In this review,we synthesize research on auditory processing in the prenatal period through infancy and childhood in typically developing children,children at high risk for autism,and children diagnosed with autism.We conclude that there are clear neurobiological and behavioral links between abnormal auditory development and the deficits in social communication seen in autism.We then offer perspectives on the need for a systematic characterization of early auditory development in autism,and identified questions to be addressed in future research on the development of autism.展开更多
The association of Zika virus(ZIKV)infection with microcephaly has raised alarm worldwide.Their causal link has been confirmed in different animal models infected by ZIKV.However,the molecular mechanisms underlying ZI...The association of Zika virus(ZIKV)infection with microcephaly has raised alarm worldwide.Their causal link has been confirmed in different animal models infected by ZIKV.However,the molecular mechanisms underlying ZIKV pathogenesis are far from clear.Hence,we performed global gene expression analysis of ZIKV-infected mouse brains to unveil the biological and molecular networks underpinning microcephaly.We found significant dysregulation of the sub-networks associated with brain development,immune response,cell death,microglial cell activation,and autophagy amongst others.We provided detailed analysis of the related complicated gene networks and the links between them.Additionally,we analyzed the signaling pathways that were likely to be involved.This report provides systemic insights into not only the pathogenesis,but also a path to the development of prophylactic and therapeutic strategies against ZIKV infection.展开更多
Longitudinal image analysis plays an important role in depicting the development of the brain structure,where image regression and interpolation are two commonly used techniques.In this paper,we develop an efficient m...Longitudinal image analysis plays an important role in depicting the development of the brain structure,where image regression and interpolation are two commonly used techniques.In this paper,we develop an efficient model and approach based on a path regression on the image manifold instead of the geodesic regression to avoid the complexity of the geodesic computation.Concretely,first we model the deformation by diffeomorphism;then,a large deformation is represented by a path on the orbit of the diffeomorphism group action.This path is obtained by compositing several small deformations,which can be well approximated by its linearization.Second,we introduce some intermediate images as constraints to the model,which guides to form the best-fitting path.Thirdly,we propose an approximated quadratic model by local linearization method,where a closed form is deduced for the solution.It actually speeds up the algorithm.Finally,we evaluate the proposed model and algorithm on a synthetic data and a real longitudinal MRI data.The results show that our proposed method outperforms several state-of-the-art methods.展开更多
Gliomas are the most common primary malignancies in the adult central nervous system(CNS),and over the course of the last decades a wealth of data on their genomic characterization has been acquired.Nevertheless,attem...Gliomas are the most common primary malignancies in the adult central nervous system(CNS),and over the course of the last decades a wealth of data on their genomic characterization has been acquired.Nevertheless,attempts to stratify patients on the basis of this work has so far conspicuously failed to identify useful treatment targets,and no phase III clinical trials conducted to date have reached a favorable outcome.We suggest that these translational failures are due to inadequacies in classifcation schemes,which fail to capture the range of biologically distinct entities that give rise to gliomas.Treating gliomas of diferent subtypes together,rather than as a set of biologically distinct but related tumors,has resulted in a classifcation scheme rich in unexplained heterogeneities,and has restricted target identifcation eforts to cell cycle and cell growth regulators.We suggest that this failure of detailed genomic characterizations to identify useful treatment targets requires a re-assessment of our assumptions concerning glioma origins.We propose a re-interpretation of glioma subtypes in the light of knowledge of the developmental pathways of the various neural lineages that make up the adult CNS.Such a developmental subtype-specifc classifcation scheme based on dys-regulated cell fate decisions may not only improve classifcation and diagnosis but,more importantly,identify potentially druggable subtype-specifc developmental vulnerabilities.展开更多
基金supported by the Japan Society for the Promotion of Science,Tokyo,JapanGrant No.23890054 and 25861361
文摘Children are being exposed to an increasingly greater variety of anesthetics with advances in pediatric and obstetric surgery.Recent animal and retrospective human data suggest that the general anesthetics commonly used in pediatric medicine could be damaging to the developing brain when used at clinical concentrations.In vivo primate and rodent models have shown that neonatal exposure to clinical concentrations of anesthetics causes neural apoptosis
基金supported primarily by the Spanish Ministry of Economy and Competitiveness((MINECO),DEP2017-91544-EXP)the Alicia Koplowitz Foundation+13 种基金supported by additional grants from MINECO(DEP2013-47540,DEP2016-79512-R,PID2020-120249RB-I00)the European Regional Development Fund(ERDF,FEDER in Spanish)the European Commission(No.667302)Further funding was obtained from the Andalusian Operational Programme supported by the ERDF(B-CTS-355-UGR18,B-CTS-500-UGR18 and A-CTS-614-UGR20)partially funded by the University of Granada,Plan Propio de Investigación 2016,Excellence actions:Units of ExcellenceUnit of Excellence on Exercise and Health(UCEES)and by the Regional Government of Andalusia,Regional Ministry of Knowledge,Science,and Universities and the ERDF(SOMM17/6107/UGR)supported by the School of Medicine,Complutense University of Madrid,Mother-Child Health and Development Network(Red SAMID)Ⅲnetwork,Redes temáticas de Investigación Cooperativa en Salud(RETICS),funded by the PN I+D+I 20172021(Spain)funded by the Ramón Areces Foundation.AMG is supported by FPU16/03653supported by the Spanish Ministry of Science and Innovation(RYC2019-027287-I)supported by a grant from Agencia Nacional de Investigación y Desarrollo(No.72180543)from Chilethrough a Margarita Salas grant from the Spanish Ministry Universitiessupported by MINECO and ERDF(grants RYC-2016-21199 and SAF2017-87526-R)the Junta de Andalucia(PAIDI P20_00158,PAIDI P20_00124)supported by the Spanish Ministry of Education,Culture and Sport(FPU 16/02760)。
文摘Background:Emerging research supports the idea that exercise positively affects neurodevelopment.However,the mechanisms linking exercise with brain health are largely unknown.We aimed to investigate the effect of exercise on(a)blood biomarkers selected based on previous evidence(brainderived neurotrophic factor,β-hydroxybutyrate(BHB),cathepsin B(CTSB),kynurenine,fibroblast growth factor 21(FGF21),soluble vascular cell adhesion molecule-1(sVCAM-1));and(b)a panel of 92 neurology-related proteins(discovery analysis).We also investigated whether changes in these biomarkers mediate the effects of exercise on brain health(hippocampal structure and function,cognitive performance,and mental health).Methods:We randomized 81 overweight/obese children(10.1±1.1 years,41%girls)into 2 groups:either 20 weeks of aerobic plus resistance exercise or control.Candidate biomarkers were assessed using enzyme-linked immunosorbent assay(ELISA)for kynurenine,FGF21,and CTSB;colorimetry forβ-hydroxybutyrate;and XMap for brain-derived neurotrophic factor and soluble vascular cell adhesion molecule-1.The92 neurology-related proteins were analyzed by an antibody-based proteomic analysis.Results:Our intervention had no significant effect on candidate biomarkers(all p>0.05).In the discovery analysis,a reduction in circulating macrophage scavenger receptor type-I was observed(standardized differences between groups=-0.3,p=0.001).This effect was validated using ELISA methods(standardized difference=-0.3,p=0.01).None of the biomarkers mediated the effects of exercise on brain health.Conclusions:Our study does not support a chronic effect of exercise on candidate biomarkers.We observed that while chronic exercise reduced the levels of macrophage scavenger receptor type-Ⅰ,it did not mediate the effects of exercise on brain health.Future studies should explore the implications of this novel biomarker for overall health.
基金supported by the National Natural Science Foundation of China,Nos.32270601 and 32070633(to CH)the Chongqing Talents Plan for Young Talents No.cstc2022ycjh-bgzxm0140(to CH)+1 种基金the Innovation Support Program for Overseas Returned Scholars of Chongqing,China,No.cx2019142(to CH)the Natural Science Foundation of Chongqing of China,No.cstc2021jcyj-bshX0121(to MZ)。
文摘Circular RNAs(circRNAs)are a class of covalently closed single-stranded RNAs that are expressed during the development of specific cells and tissues.CircRNAs play crucial roles in physiological and pathological processes by sponging microRNAs,modulating gene transcription,controlling the activity of certain RNA-binding proteins,and producing functional peptides.A key focus of research at present is the functionality of circRNAs in the nervous system and several advances have emerged over the last 2 years.However,the precise role of circRNAs in the nervous system has yet to be comprehensively reviewed.In this review,we first summarize the recently described roles of circRNAs in brain development,maturity,and aging.Then,we focus on the involvement of circRNAs in various diseases of the central nervous system,such as brain cancer,chronic neurodegenerative diseases,acute injuries of the nervous system,and neuropathic pain.A better understanding of the functionality of circRNAs will help us to develop potential diagnostic,prognostic,and therapeutic strategies to treat diseases of the nervous system.
基金supported by the Hundred-Talent Program of Chinese Academy of Sciences(Y4065411411100050210)to J.L.+3 种基金the National Natural Science Foundation of China(8147131391649119)to J.L.the National Natural Science Foundation of China(31260242 to)F.Lthe National Science and Technology Infrastructure Program(2014BAI01B01-04)to S.L.
文摘Brain development and aging are associated with alterations in multiple epigenetic systems,including DNA methylation and demethylation patterns.Here,we observed that the levels of the 5-hydroxymethylcytosine(5hmC)ten-eleven translocation(TET)enzyme-mediated active DNA demethylation products were dynamically changed and involved in postnatal brain development and aging in tree shrews(Tupaia belangeri chinensis).The levels of5hm C in multiple anatomic structures showed a gradual increase throughout postnatal development,whereas a significant decrease in 5hmC was found in several brain regions in aged tree shrews,including in the prefrontal cortex and hippocampus,but not the cerebellum.Active changes in Tet mR NA levels indicated that TET2 and TET3 predominantly contributed to the changes in 5hmC levels.Our findings provide new insight into the dynamic changes in 5hm C levels in tree shrew brains during postnatal development and aging processes.
基金supported by a Grant-in-Aid for Scientific Research from Mie Medical Research Foundation to HS
文摘Target of research in subarachnoid hemorrhage(SAH):The outcome of aneurysmal SAH remains poor despite advances in the diagnosis and treatment.Although many factors related to patients,aneurysms,and institutions,as well as physiological parameters and medical complications were reported as prognostic factors,the most important determinant of poor
基金The authors are supported by Universidade Federal do Rio Grande do Sul(UFRGS),Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq),Coordenação de Aperfeiçoamento de Pessoal de Nível Superior(CAPES),Fundação de AmparoàPesquisa do Estado do Rio Grande do Sul(FAPERGS),and Instituto Nacional de Ciência e Tecnologia para Excitotoxicidade e Neuroproteção(INCTEN/CNPq).
文摘Glial cells are crucial for maintaining central nervous system(CNS)homeostasis.They actively participate in immune responses,as well as form functional barriers,such as blood-brain barrier(BBB),which restrict the entry of pathogens and inflammatory mediators into the CNS.In general,viral infections during the gestational period can alter the embryonic and fetal environment,and the related inflammatory response may affect neurodevelopment and lead to behavioral dysfunction during later stage of life,as highlighted by our group for Zika virus infection.Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)induces a cytokine storm and,during pregnancy,may be related to a more severe form of the coronavirus disease-19(COVID-19)and also to higher preterm birth rates.SARS-CoV-2 can also affect the CNS by inducing neurochemical remodeling in neural cells,which can compromise neuronal plasticity and synaptic function.However,the impact of SARS-CoV-2 infection during pregnancy on postnatal CNS,including brain development during childhood and adulthood,remains undetermined.Our group has recently highlighted the impact of COVID-19 on the expression of molecular markers associated with neuropsychiatric disorders,which are strongly related to the inflammatory response.Thus,based on these relationships,we discussed the impact of SARS-CoV-2 infection either during pregnancy or in critical periods of neurodevelopment as a risk factor for neurological consequences in the offspring later in life,focusing on the potential role of glial cells.Thus,it is important to consider future and long-term public health concerns associated with SARS-CoV-2 infection during pregnancy.
基金US National Institutes of Health(R01s AT007003,GM103437,GM71534,EY10208,GM49209)Unorthodox Philanthropy+3 种基金Open Philanthropythe Hickey Family Foundationthe Children’s Discovery InstituteWiley Companies。
文摘Food must supply a balance of nutrients to support both brain and body.The human brain makes us uniquely human.Essential fatty acids are part of the metabolic pathways that define tissue structure and function.Omega-6(O6)linoleic acid(LA6)has long been known to be required for skin structure,and as a precursor for inflammatory,thrombotic,immune,and other signaling molecules.Omega-3(O3)alpha-linolenic acid(ALA3)and particularly its long chain product docosahexaenoic acid(DHA3)has a key structural role in the brain,retina,and related neural tissue.In the 20 th century western world,inexpensive,high quality oils primarily from LA6-rich/O3-poor vegetable seed oils became dominant fats produced by the food industry.Provision of LA6-rich/O3-poor oils as the sole source of fat in the diets of pregnant animals causes O3 deficiency and poor brain development,primarily because high LA6 antagonizes metabolism of all O3,creating an artificial metabolic demand for O3.Data developed over the last 2~3 decades show that provision of low LA6 combined with preformed DHA3 optimizes brain function.Recent studies emphasize the importance of nutrition to support brain development,with newer findings showing particular importance of fatty acid balance in malnourished children.The World Health Organization(WHO)through the Codex Alimentarius(“Code for Food”)is increasingly recognizing the primacy of brain health and in part on that basis recently acted to recommend balanced fat for Ready-to-Use-Therapeutic Foods used to treat children with severe acute malnutrition.Similar principles are likely to be important in older persons.Industry now has the tools to adjust the composition of oils to support brain health throughout the life cycle.
文摘A major basic research projectin the field of neurosciencewas launched on November26 last year at the Shanghai-basedInstitute of Neuroscience of the Chi-nese Academy of Sciences(CAS).
文摘Brain tumors are a diverse group of malignancies that remain refractory to conventional treatment approaches.Molecular neuro-oncologyhas now begun to clarify the transformed phenotype of brain tumors and identify oncogenic pathways that might be amenable to targetedtherapy.Activity of the phosphoinositide 3;kinase(PI3K)/Akt pathway is often upregulated in brain tumors due to excessive stimu-lation by growth factor receptors and Ras.Loss of function of the tumor suppressor gene PTEN also frequently contributesto
文摘Autism spectrum disorder(ASD)is a group of heterogeneous,multi-factorial,neurodevelopmental disorders resulting from genetic and environmental factors interplay.Infection is a significant trigger of autism,especially during the critical developmental period.There is a strong interplay between the viral infection as a trigger and a result of ASD.We aim to highlight the mutual relationship between autism and viruses.We performed a thorough literature review and included 158 research in this review.Most of the literature agreed on the possible effects of the viral infection during the critical period of development on the risk of developing autism,especially for specific viral infections such as Rubella,Cytomegalovirus,Herpes Simplex virus,Varicella Zoster Virus,Influenza virus,Zika virus,and severe acute respiratory syndrome coronavirus 2.Viral infection directly infects the brain,triggers immune activation,induces epigenetic changes,and raises the risks of having a child with autism.At the same time,there is some evidence of increased risk of infection,including viral infections in children with autism,due to lots of factors.There is an increased risk of developing autism with a specific viral infection during the early developmental period and an increased risk of viral infections in children with autism.In addition,children with autism are at increased risk of infection,including viruses.Every effort should be made to prevent maternal and early-life infections and reduce the risk of autism.Immune modulation of children with autism should be considered to reduce the risk of infection.
文摘This paper aims to provide an effective overview of ADHD(Attention Deficit Hyperactivity Disorder),so that educators and other individuals who may be involved in the treatment of ADHD patients,especially young patients,can effectively obtain basic information about what is ADHD,the causes of ADHD,and the popular treatment methods of ADHD.Various literature and studies were referred to in this paper to review and compare different causes and treatments.Researches held distinct opinions about the causes of ADHD,and the debate focuses on the nature and nurture factors of ADHD.Some studies believe ADHD is inborn and genetic while other studies emphasize the importance of nurture factors during their life,such as the environment that patients grow up in and the lifestyle they have.Depending on distinct arguments,there developed different treatments like using medication to prevent the situation from deteriorating further and changing the environments that patients living in through taking interventions with the family.These arguments and treatments will be discussed in detail in this paper.
基金supported by the National Natural Science Foundation of China(32130035 and 92168107)STI2030-Major Projects(2021ZD0202500)+2 种基金the Frontier Key Project of the Chinese Academy of Sciences(QYZDJ-SSW-SMC025)Shanghai Municipal Science and Technology Projects(2018SHZDZX05)Shanghai Frontiers Science Center for Biomacromolecules and Precision Medicine at ShanghaiTech University.
文摘Understanding the fundamental processes of human brain development and diseases is of great importance for our health.However,existing research models such as non-human primate and mouse models remain limited due to their developmental discrepancies compared with humans.Over the past years,an emerging model,the“brain organoid”integrated from human pluripotent stem cells,has been developed to mimic developmental processes of the human brain and disease-associated phenotypes to some extent,making it possible to better understand the complex structures and functions of the human brain.In this review,we summarize recent advances in brain organoid technologies and their applications in brain development and diseases,including neurodevelopmental,neurodegenerative,psychiatric diseases,and brain tumors.Finally,we also discuss current limitations and the potential of brain organoids.
基金supported by the Research Grants Council (RGC) (Grant No. 26102719),Hong Kong Special Administrative Region (SAR), Chinathe National Natural Science Foundation of China (NSFC) (No. 31922088)+3 种基金NSFC-RGC Joint Research Scheme (Grant No. N_HKUST606/17), Hong Kong SAR, Chinathe Collaborative Research Fund (CRF) (Grant Nos. C6002-17GF and C7065-18GF), Hong Kong SAR, Chinathe Hong Kong Epigenomics Project (Epi HK)the Innovation and Technology Commission (ITCPD/17-9, ITS/480/18FP), Hong Kong SAR, China
文摘The human brain contains billions of highly differentiated and interconnected cells that form intricate neural networks and collectively control the physical activities and high-level cognitive functions,such as memory,decision-making,and social behavior.Big data is required to decipher the complexity of cell types,as well as connectivity and functions of the brain.The newly developed single-cell sequencing technology,which provides a comprehensive landscape of brain cell type diversity by profiling the transcriptome,genome,and/or epigenome of individual cells,has contributed substantially to revealing the complexity and dynamics of the brain and providing new insights into brain development and brain-related disorders.In this review,we first introduce the progresses in both experimental and computational methods of single-cell sequencing technology.Applications of single-cell sequencing-based technologies in brain research,including cell type classification,brain development,and brain disease mechanisms,are then elucidated by representative studies.Lastly,we provided our perspectives into the challenges and future developments in the field of single-cell sequencing.In summary,this mini review aims to provide an overview of how big data generated from single-cell sequencing have empowered the advancements in neuroscience and shed light on the complex problems in understanding brain functions and diseases.
文摘Neurogenesis is the process in which neurons are generated from neural stem/progenitor cells(NSCs/NPCs).It involves the proliferation and neuronal fate specification/differentiation of NSCs,as well as migration,maturation and functional integration of the neuronal progeny into neuronal network.NSCs exhibit the two essential properties of stem cells:self-renewal and multi-potency.Contrary to previous dogma that neurogenesis happens only during development,it is generally accepted now that neurogenesis can take place throughout life in mammalian brains.This raises a new therapeutic potential of applying stem cell therapy for stroke,neurodegenerative diseases and other diseases.However,the maintenance and differentiation of NSCs/NPCs are tightly controlled by the extremely intricate molecular networks.Uncovering the underlying mechanisms that drive the differentiation,migration and maturation of specific neuronal lineages for use in regenerative medicine is,therefore,crucial for the application of stem cell for clinical therapy as well as for providing insight into the mechanisms of human neurogenesis.Here,we focus on the role of bone morphogenetic protein(BMP)signaling in NSCs during mammalian brain development.
基金supported by the National Natural Science Foundation of China(31830034,82021004,81620108016,31221003,31521063,81671767,82071998,81971690,32130045,and 61761166004)Changjiang Scholar Professorship Award(T2015027)+3 种基金the National Key Research and Development Project of China(2018YFA0701402)Beijing Nova Program(Z191100001119023)the Beijing Brain Initiative of Beijing Municipal Science&Technology Commission(Z181100001518003)the Fundamental Research Funds for the Central Universities(2020NTST29)。
基金supported by the National Natural Science Foundation of China(31900775,31571136)the SCNU Young Faculty Research Award(18KJ09)the Key Realm R&D Program of Guangdong Province(2019B030335001)。
文摘Most infants who are later diagnosed with autism show delayed speech and language and/or atypical language profile.There is a large body of research on abnormal speech and language in children with autism.However,auditory development has been relatively under-investigated in autism research,despite its inextricable relationship with language development and despite researchers'ability to detect abnormalities in brain development and behavior in early infancy.In this review,we synthesize research on auditory processing in the prenatal period through infancy and childhood in typically developing children,children at high risk for autism,and children diagnosed with autism.We conclude that there are clear neurobiological and behavioral links between abnormal auditory development and the deficits in social communication seen in autism.We then offer perspectives on the need for a systematic characterization of early auditory development in autism,and identified questions to be addressed in future research on the development of autism.
基金This work was supported by the Strategic Priority Research Program and Innovation Program of the Chinese Academy of Sciences,China(Grant Nos.XDB32020100,XDA16010306,QYZDJ-SSW-SMC007,and GJHZ1827)the National Natural Science Foundation of China(Grant Nos.31730108,31430037,31571038,and 31871329)the Natural Science Foundation of Shanghai,China(Grant No.17ZR1413900).
文摘The association of Zika virus(ZIKV)infection with microcephaly has raised alarm worldwide.Their causal link has been confirmed in different animal models infected by ZIKV.However,the molecular mechanisms underlying ZIKV pathogenesis are far from clear.Hence,we performed global gene expression analysis of ZIKV-infected mouse brains to unveil the biological and molecular networks underpinning microcephaly.We found significant dysregulation of the sub-networks associated with brain development,immune response,cell death,microglial cell activation,and autophagy amongst others.We provided detailed analysis of the related complicated gene networks and the links between them.Additionally,we analyzed the signaling pathways that were likely to be involved.This report provides systemic insights into not only the pathogenesis,but also a path to the development of prophylactic and therapeutic strategies against ZIKV infection.
基金The research was supported by the National Natural Science Foundation of China(Nos.11771276,11471208)the Capacity Construction Project of Local Universities in Shanghai(No.18010500600).
文摘Longitudinal image analysis plays an important role in depicting the development of the brain structure,where image regression and interpolation are two commonly used techniques.In this paper,we develop an efficient model and approach based on a path regression on the image manifold instead of the geodesic regression to avoid the complexity of the geodesic computation.Concretely,first we model the deformation by diffeomorphism;then,a large deformation is represented by a path on the orbit of the diffeomorphism group action.This path is obtained by compositing several small deformations,which can be well approximated by its linearization.Second,we introduce some intermediate images as constraints to the model,which guides to form the best-fitting path.Thirdly,we propose an approximated quadratic model by local linearization method,where a closed form is deduced for the solution.It actually speeds up the algorithm.Finally,we evaluate the proposed model and algorithm on a synthetic data and a real longitudinal MRI data.The results show that our proposed method outperforms several state-of-the-art methods.
基金funded by National Natural Science Foundation of China (Grants 81773015,82072789,81472348,81072080 and 31711530156)the National Key Research and Development Program of China (Grants 2012DFA30470,2016YFC0902500 and 2019YFE0108100)the Erik Philip-Sörensen Foundation.
文摘Gliomas are the most common primary malignancies in the adult central nervous system(CNS),and over the course of the last decades a wealth of data on their genomic characterization has been acquired.Nevertheless,attempts to stratify patients on the basis of this work has so far conspicuously failed to identify useful treatment targets,and no phase III clinical trials conducted to date have reached a favorable outcome.We suggest that these translational failures are due to inadequacies in classifcation schemes,which fail to capture the range of biologically distinct entities that give rise to gliomas.Treating gliomas of diferent subtypes together,rather than as a set of biologically distinct but related tumors,has resulted in a classifcation scheme rich in unexplained heterogeneities,and has restricted target identifcation eforts to cell cycle and cell growth regulators.We suggest that this failure of detailed genomic characterizations to identify useful treatment targets requires a re-assessment of our assumptions concerning glioma origins.We propose a re-interpretation of glioma subtypes in the light of knowledge of the developmental pathways of the various neural lineages that make up the adult CNS.Such a developmental subtype-specifc classifcation scheme based on dys-regulated cell fate decisions may not only improve classifcation and diagnosis but,more importantly,identify potentially druggable subtype-specifc developmental vulnerabilities.
