Several mammalian animal models of traumatic brain injury have been used, mostly rodents. However, reparative mechanisms in mammalian brain are very limited, and newly formed neurons do not survive for long time. The ...Several mammalian animal models of traumatic brain injury have been used, mostly rodents. However, reparative mechanisms in mammalian brain are very limited, and newly formed neurons do not survive for long time. The brain of adult zebrafish, a teleost fish widely used as vertebrate model, possesses high regenerative properties after injury due to the presence of numerous stem cells niches. The ventricular lining of the zebrafish dorsal telencephalon is the most studied neuronal stem cell niche because its dorso-lateral zone is considered the equivalent to the hippocampus of mammals which contains one of the two constitutive neurogenic niches of mammals. To mimic TBI, stab wound in the dorso-lateral telencephalon of zebrafish was used in studies devoted to fish regenerative properties. Brain-derived neurotrophic factor, which is known to play key roles in the repair process after traumatic brain lesions, persists around the lesioned area of injured telencephalon of adult zebrafish. These results are extensively compared to reparative processes in rodent brain. Considering the complete repair of the damaged area in fish, it could be tempting to consider brain-derived neurotrophic factor as a factor contributing to create a permissive environment that enables the establishment of new neuronal population in damaged brain.展开更多
As three-dimensional“organ-like”aggregates,human cortical organoids have emerged as powerful models for studying human brain evolution and brain disorders with unique advantages of humanspecificity,fidelity and mani...As three-dimensional“organ-like”aggregates,human cortical organoids have emerged as powerful models for studying human brain evolution and brain disorders with unique advantages of humanspecificity,fidelity and manipulation.Human cortical organoids derived from human pluripotent stem cells can elaborately replicate many of the key properties of human cortical development at the molecular,cellular,structural,and functional levels,including the anatomy,functional neural network,and interaction among different brain regions,thus facilitating the discovery of brain development and evolution.In addition to studying the neuro-electrophysiological features of brain cortex development,human cortical organoids have been widely used to mimic the pathophysiological features of cortical-related disease,especially in mimicking malformations of cortical development,thus revealing pathological mechanism and identifying effective drugs.In this review,we provide an overview of the generation of human cortical organoids and the properties of recapitulated cortical development and further outline their applications in modeling malformations of cortical development including pathological phenotype,underlying mechanisms and rescue strategies.展开更多
目的应用嗅觉功能磁共振成像（functional magnetic resonance imaging，fMRI）分析轻度认知障碍（mild cognitive impairment，MCI）患者嗅觉相关脑区的激活情况。方法选取就诊于天津市环湖医院痴呆中心的MCI患者（试验组）及无认知障...目的应用嗅觉功能磁共振成像（functional magnetic resonance imaging，fMRI）分析轻度认知障碍（mild cognitive impairment，MCI）患者嗅觉相关脑区的激活情况。方法选取就诊于天津市环湖医院痴呆中心的MCI患者（试验组）及无认知障碍的健康受试者（对照组）各26例，应用T＆T嗅觉测试法检查所有受试者的嗅觉功能，应用嗅觉刺激仪采用事件相关设计模式进行嗅觉fMRI扫描，了解受试者全脑及嗅觉相关感兴趣区（region of interest associated with olfactory，ROIawo，包括双侧初级嗅觉皮层、双侧海马、双侧眶额回）的激活情况，分析初级嗅觉皮层激活体素数与嗅觉识别阈、认知障碍严重程度的相关性。应用SPSS 19.0软件进行统计学分析。结果试验组T＆T嗅觉识别阈分数明显高于对照组，差异有统计学意义[（3.57±1.29）分（±s，下同）比（1.02±0.35）分，t＝4.372，P〈0.05]。两种性质气味刺激时，试验组比对照组全脑激活范围明显减小，差异有统计学意义（愉快气味147.36±21.45比323.11±39.76，非愉快气味201.86±24.93比447.73±57.22，t愉快气味＝4.241，t非愉快气味＝5.365，P值均〈0.05）；对照组非愉快气味刺激时全脑激活范围较愉快气味更大，差异有统计学意义（447.73±57.22比323.11±39.76，t＝3.936，P〈0.05）。试验组与对照组相比，ROIawo的激活体素数明显减少，差异有统计学意义[愉快气味51.0[8.0，109.0]（M[P25，P75]，下同）比135.0[21.0，321.5]，非愉快气味65.0[6.0，158.0]比205.0[36.5，491.0]，Z愉快气味＝－2.199，Z非愉快气味＝－2.216，P值均〈0.05]；试验组与对照组相比，初级嗅觉皮层的激活体素数明显减少，差异有统计学意义（愉快气味19.0[4.0，35.5]比46.0[9.0，118.5]，非愉快气味26.0[2.0，51.0]比79.0[17.5，189.0]，Z愉快气味＝－1.898，Z非愉快气味＝－2.167，P值均〈0.05）；试验组初级嗅觉皮层激展开更多
BACKGROUND： Cholinergic neuron directly participants in human motion, learning and memory and is a target cell for multiple degenerative diseases of central nervous system. OBJECTIVE： To investigate whether the mito...BACKGROUND： Cholinergic neuron directly participants in human motion, learning and memory and is a target cell for multiple degenerative diseases of central nervous system. OBJECTIVE： To investigate whether the mitotic cell is the radial glial cell expressing choline acetyltransferase （CHAT） in ventricle zone （VZ） of telencephalon and whether cholinergic neuron is derived from radial glial cell in ventricle zone of telencephalon. DESIGN： Observational study. SETTING： Department of Histology and Embryology, Basic Medical College of Jilin University. MATERIALS： Nine healthy Wistar rats included 6 females and 3 male. Male and female rats were mated routinely, and the day when spermatozoa or vaginal plug were found was regarded as embryonic 0 （E0）. Primary monoclonal antibodies ChAT and vimentin were provided respectively by Wuhan Boster Company, and Biogenex Company, USA. METHODS： The experiment was carried out in the Laboratory of Cell Culture and Immunohistochemistry, Department of Histology and Embryology from march 2002 to January 2003. Firstly, fluorescence-activated cell sorting （FACS） was used to confirm the time of generation of cholinergic neuron; secondly, telencephalons of rats at embryonic 14 days （E14） were performed coronary sections, then immunohistochemistry double staining for vimentin （a protein marker of radial neuroglia cell） and ChAT （a protein marker of cholinergic neuron） were used to test whether ChAT was expressed in the radial neuroglia cells. MAIN OUTCOME MEASURES： （1） Fluorescence-activated cell numbers of ChAT in telencephalon; （2） results of immunohistochemistry double staining. RESULTS： It is confirmed using by flow cytometer that embryogenesis time of cholinergic neuron was at E12, and shown the population of cells in VZ of dorsal telencephalon of E14 rat co-expressed vimentin and ChAT through immunohistochemistry double staining. A lot of vimentin-positive cells and ChAT-positive cells respectively were observed in VZ of lateral gan展开更多
Background There have been no detailed reports of the three-dimensional structure and the relationship between the external and internal vascularizations observed successively for a long duration in the rat fetus, alt...Background There have been no detailed reports of the three-dimensional structure and the relationship between the external and internal vascularizations observed successively for a long duration in the rat fetus, although many authors have studied the vascular morphology of the developing brain. This study examined the three-dimensional structure of both the external and internal vascularizations of the prenatal rat telencephalon from embryonic days 12 (E12) to 20 (E20).Method A microvascular casting method for scanning electron microscopy (SEM) was used in this study, along with vascular staining using gold-gelatine solution-autometallography (GGS-AMG) after intravascular injection of colloidal gold, as well as hematoxylin-eosin ( HE) staining for paraffin embedded specimens.Results In GGS-AMG stains, E16 fetuses had a few short perforating cortical blood vessels (SPCVs); E17 fetuses had long perforating cortico-medullary vessels (LPCVs). Older fetuses had specific patterns of vascular networks in the cortex and the deeper subcortical part of the telencephalon. In the cortex, fine longitudinal blood vessels were connected by transverse channels. The deep telencephalon had fine blood vessels running in all directions. Using SEM, the external vascularization was already visible in E12 fetuses as arborizations of arterial branches, forming a mesh of fine vascular networks covering the telencephalon. A coralliform fine venous plexus was observed in the external vascularization of E16 fetuses. There were ring-like anastomoses and bud-like protrusions in the network of small blood vessels, most likely the angiogenesis of fetal vessels. From E12 to E16, an immature and incomplete internal vascularization began to appear. There were short blood vessels with ballooned terminals branching from the external vascularization. They penetrated the brain tissue to form networks in the superficial layer, comparable to SPCVs. In E17 to E20 fetuses, tortuous venous branches, straight arterial blood vessels, and a fine network of 展开更多
文摘Several mammalian animal models of traumatic brain injury have been used, mostly rodents. However, reparative mechanisms in mammalian brain are very limited, and newly formed neurons do not survive for long time. The brain of adult zebrafish, a teleost fish widely used as vertebrate model, possesses high regenerative properties after injury due to the presence of numerous stem cells niches. The ventricular lining of the zebrafish dorsal telencephalon is the most studied neuronal stem cell niche because its dorso-lateral zone is considered the equivalent to the hippocampus of mammals which contains one of the two constitutive neurogenic niches of mammals. To mimic TBI, stab wound in the dorso-lateral telencephalon of zebrafish was used in studies devoted to fish regenerative properties. Brain-derived neurotrophic factor, which is known to play key roles in the repair process after traumatic brain lesions, persists around the lesioned area of injured telencephalon of adult zebrafish. These results are extensively compared to reparative processes in rodent brain. Considering the complete repair of the damaged area in fish, it could be tempting to consider brain-derived neurotrophic factor as a factor contributing to create a permissive environment that enables the establishment of new neuronal population in damaged brain.
基金supported by the National Natural Science Foundation of China(Major Project),No.82030110(to CYM)the National Natural Science Foundation(Youth Program),No.82003754(to SNW)+1 种基金Medical Innovation Major Project,No.16CXZ009(to CYM)Shanghai Science and Technology Commission Projects,Nos.20YF1458400(to SNW)and 21140901000(to CYM)。
文摘As three-dimensional“organ-like”aggregates,human cortical organoids have emerged as powerful models for studying human brain evolution and brain disorders with unique advantages of humanspecificity,fidelity and manipulation.Human cortical organoids derived from human pluripotent stem cells can elaborately replicate many of the key properties of human cortical development at the molecular,cellular,structural,and functional levels,including the anatomy,functional neural network,and interaction among different brain regions,thus facilitating the discovery of brain development and evolution.In addition to studying the neuro-electrophysiological features of brain cortex development,human cortical organoids have been widely used to mimic the pathophysiological features of cortical-related disease,especially in mimicking malformations of cortical development,thus revealing pathological mechanism and identifying effective drugs.In this review,we provide an overview of the generation of human cortical organoids and the properties of recapitulated cortical development and further outline their applications in modeling malformations of cortical development including pathological phenotype,underlying mechanisms and rescue strategies.
文摘目的应用嗅觉功能磁共振成像（functional magnetic resonance imaging，fMRI）分析轻度认知障碍（mild cognitive impairment，MCI）患者嗅觉相关脑区的激活情况。方法选取就诊于天津市环湖医院痴呆中心的MCI患者（试验组）及无认知障碍的健康受试者（对照组）各26例，应用T＆T嗅觉测试法检查所有受试者的嗅觉功能，应用嗅觉刺激仪采用事件相关设计模式进行嗅觉fMRI扫描，了解受试者全脑及嗅觉相关感兴趣区（region of interest associated with olfactory，ROIawo，包括双侧初级嗅觉皮层、双侧海马、双侧眶额回）的激活情况，分析初级嗅觉皮层激活体素数与嗅觉识别阈、认知障碍严重程度的相关性。应用SPSS 19.0软件进行统计学分析。结果试验组T＆T嗅觉识别阈分数明显高于对照组，差异有统计学意义[（3.57±1.29）分（±s，下同）比（1.02±0.35）分，t＝4.372，P〈0.05]。两种性质气味刺激时，试验组比对照组全脑激活范围明显减小，差异有统计学意义（愉快气味147.36±21.45比323.11±39.76，非愉快气味201.86±24.93比447.73±57.22，t愉快气味＝4.241，t非愉快气味＝5.365，P值均〈0.05）；对照组非愉快气味刺激时全脑激活范围较愉快气味更大，差异有统计学意义（447.73±57.22比323.11±39.76，t＝3.936，P〈0.05）。试验组与对照组相比，ROIawo的激活体素数明显减少，差异有统计学意义[愉快气味51.0[8.0，109.0]（M[P25，P75]，下同）比135.0[21.0，321.5]，非愉快气味65.0[6.0，158.0]比205.0[36.5，491.0]，Z愉快气味＝－2.199，Z非愉快气味＝－2.216，P值均〈0.05]；试验组与对照组相比，初级嗅觉皮层的激活体素数明显减少，差异有统计学意义（愉快气味19.0[4.0，35.5]比46.0[9.0，118.5]，非愉快气味26.0[2.0，51.0]比79.0[17.5，189.0]，Z愉快气味＝－1.898，Z非愉快气味＝－2.167，P值均〈0.05）；试验组初级嗅觉皮层激
基金the Scientific Research Foundation of the Higher Education Institutions, No. 20030183048
文摘BACKGROUND： Cholinergic neuron directly participants in human motion, learning and memory and is a target cell for multiple degenerative diseases of central nervous system. OBJECTIVE： To investigate whether the mitotic cell is the radial glial cell expressing choline acetyltransferase （CHAT） in ventricle zone （VZ） of telencephalon and whether cholinergic neuron is derived from radial glial cell in ventricle zone of telencephalon. DESIGN： Observational study. SETTING： Department of Histology and Embryology, Basic Medical College of Jilin University. MATERIALS： Nine healthy Wistar rats included 6 females and 3 male. Male and female rats were mated routinely, and the day when spermatozoa or vaginal plug were found was regarded as embryonic 0 （E0）. Primary monoclonal antibodies ChAT and vimentin were provided respectively by Wuhan Boster Company, and Biogenex Company, USA. METHODS： The experiment was carried out in the Laboratory of Cell Culture and Immunohistochemistry, Department of Histology and Embryology from march 2002 to January 2003. Firstly, fluorescence-activated cell sorting （FACS） was used to confirm the time of generation of cholinergic neuron; secondly, telencephalons of rats at embryonic 14 days （E14） were performed coronary sections, then immunohistochemistry double staining for vimentin （a protein marker of radial neuroglia cell） and ChAT （a protein marker of cholinergic neuron） were used to test whether ChAT was expressed in the radial neuroglia cells. MAIN OUTCOME MEASURES： （1） Fluorescence-activated cell numbers of ChAT in telencephalon; （2） results of immunohistochemistry double staining. RESULTS： It is confirmed using by flow cytometer that embryogenesis time of cholinergic neuron was at E12, and shown the population of cells in VZ of dorsal telencephalon of E14 rat co-expressed vimentin and ChAT through immunohistochemistry double staining. A lot of vimentin-positive cells and ChAT-positive cells respectively were observed in VZ of lateral gan
文摘Background There have been no detailed reports of the three-dimensional structure and the relationship between the external and internal vascularizations observed successively for a long duration in the rat fetus, although many authors have studied the vascular morphology of the developing brain. This study examined the three-dimensional structure of both the external and internal vascularizations of the prenatal rat telencephalon from embryonic days 12 (E12) to 20 (E20).Method A microvascular casting method for scanning electron microscopy (SEM) was used in this study, along with vascular staining using gold-gelatine solution-autometallography (GGS-AMG) after intravascular injection of colloidal gold, as well as hematoxylin-eosin ( HE) staining for paraffin embedded specimens.Results In GGS-AMG stains, E16 fetuses had a few short perforating cortical blood vessels (SPCVs); E17 fetuses had long perforating cortico-medullary vessels (LPCVs). Older fetuses had specific patterns of vascular networks in the cortex and the deeper subcortical part of the telencephalon. In the cortex, fine longitudinal blood vessels were connected by transverse channels. The deep telencephalon had fine blood vessels running in all directions. Using SEM, the external vascularization was already visible in E12 fetuses as arborizations of arterial branches, forming a mesh of fine vascular networks covering the telencephalon. A coralliform fine venous plexus was observed in the external vascularization of E16 fetuses. There were ring-like anastomoses and bud-like protrusions in the network of small blood vessels, most likely the angiogenesis of fetal vessels. From E12 to E16, an immature and incomplete internal vascularization began to appear. There were short blood vessels with ballooned terminals branching from the external vascularization. They penetrated the brain tissue to form networks in the superficial layer, comparable to SPCVs. In E17 to E20 fetuses, tortuous venous branches, straight arterial blood vessels, and a fine network of
