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SUMMARY: To establish an unprovable diagnostic indicative index reference for ultrasound examination of the fetal cerebral ventricles, based on the morphological characteristics throughout fetal nervous system development. Key ultrasonic morphological indicators of fetal ventricular development, which includes frontal horn width (FHW), occipital horn width (OHW), width of 3rd ventricle, cavity of septum pellucidum (CSP), width and length of 4th ventricle and thalamo-occipital distance (TOD) had been measured and analyzed collectively. All data of the indicators was collected on singleton pregnant woman between 16-39 weeks of gestational age (GA), between November 2017 and June 2021 at the Second Hospital of Dalian Medical University. A total of 235 pregnant women were enrolled in the cross section study; another 36 pregnant women voluntarily joined a timeline-tracking follow-up study (cohort study) under the same examining criteria. A decrease of FHW and OHW of the lateral ventricles was observed as GA increased; while dimensional values of TOD, 3rd ventricle, CSP, as well as 4th ventricle increased with GA. Most of these indicators showed an enhanced variation tendency within a certain period of GA. Moreover, values of FHW and TOD showed asymmetry of the two hemispheres within the whole GA. Our findings revealed the morphological regularity of fetal ventricular development, which would instructively enhance the relative clinical ultrasound diagnosis; moreover, TOD also showed regularly changes as GA increased, suggesting that TOD should be considered as an additional routine ultrasonic indicator for fetal ventricular development.
RESUMEN: El objetivo del estudio fue establecer un índice de referencia indicativo diagnóstico no demostrable para el examen ecográfico de los ventrículos cerebrales fetales, basado en las características morfológicas a lo largo del desarrollo del sistema nervioso fetal. Indicadores morfológicos ultrasónicos clave del desarrollo ventricular fetal, que incluyen el ancho del cuerno frontal (FHW), el ancho del cuerno occipital (OHW), el ancho del tercer ventrículo, la cavidad del septo pelúcido (CSP), el ancho y el largo del cuarto ventrículo y la distancia tálamo-occipital (TOD) fueron medidos y analizados conjuntamente. Todos los datos de los indicadores se recopilaron en mujeres embarazadas de un solo feto entre 16 y 39 semanas de edad gestacional (EG), entre noviembre de 2017 y junio de 2021 en el Segundo Hospital de la Universidad Médica de Dalian. Un total de 235 mujeres embarazadas se inscribieron en el estudio transversal; otras 36 mujeres embarazadas se unieron voluntariamente a un estudio de seguimiento de línea de tiempo (estudio de cohorte) bajo los mismos criterios de examen. Se observó una disminución de FHW y OHW de los ventrículos laterales a medida que aumentaba la GA; mientras que los valores dimensionales de TOD, tercer ventrículo, CSP y cuarto ventrículo aumentaron con GA. La mayoría de estos indicadores mostraron una tendencia de variación mejorada dentro de un cierto período de GA. Además, los valores de FHW y TOD mostraron asimetría de los dos hemisferios dentro de toda la AG. Nuestros hallazgos revelaron la regularidad morfológica del desarrollo ventricular fetal, lo que mejoraría de manera instructiva el diagnóstico clínico de ultrasonido relativo; además, TOD también mostró cambios regulares a medida que aumentaba la GA, lo que sugiere que TOD debe considerarse como un indicador ultrasónico de rutina adicional para el desarrollo ventricular fetal.
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Humanos , Femenino , Embarazo , Ventrículos Cerebrales/crecimiento & desarrollo , Ventrículos Cerebrales/diagnóstico por imagen , Ultrasonografía PrenatalRESUMEN
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with unknown brain etiology. Our knowledge to date about structural brain development across the lifespan in ASD comes mainly from cross-sectional studies, thereby limiting our understanding of true age effects within individuals with the disorder that can only be gained through longitudinal research. The present study describes FreeSurfer-derived volumetric findings from a longitudinal dataset consisting of 607 T1-weighted magnetic resonance imaging (MRI) scans collected from 105 male individuals with ASD (349 MRIs) and 125 typically developing male controls (258 MRIs). Participants were six to forty-five years of age at their first scan, and were scanned up to 5 times over a period of 16 years (average inter-scan interval of 3.7 years). Atypical age-related volumetric trajectories in ASD included enlarged gray matter volume in early childhood that approached levels of the control group by late childhood, an age-related increase in ventricle volume resulting in enlarged ventricles by early adulthood and reduced corpus callosum age-related volumetric increase resulting in smaller corpus callosum volume in adulthood. Larger corpus callosum volume was related to a lower (better) ADOS score at the most recent study visit for the participants with ASD. These longitudinal findings expand our knowledge of volumetric brain-based abnormalities in males with ASD, and highlight the need to continue to examine brain structure across the lifespan and well into adulthood.
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Trastorno del Espectro Autista , Ventrículos Cerebrales , Cuerpo Calloso , Sustancia Gris , Desarrollo Humano , Adolescente , Adulto , Trastorno del Espectro Autista/diagnóstico por imagen , Trastorno del Espectro Autista/patología , Trastorno del Espectro Autista/fisiopatología , Ventrículos Cerebrales/diagnóstico por imagen , Ventrículos Cerebrales/crecimiento & desarrollo , Ventrículos Cerebrales/patología , Niño , Cuerpo Calloso/diagnóstico por imagen , Cuerpo Calloso/crecimiento & desarrollo , Cuerpo Calloso/patología , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/crecimiento & desarrollo , Sustancia Gris/patología , Desarrollo Humano/fisiología , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Heterogeneity is defined as the quality or state of being diverse in character or content. This article summarizes the natural progression from my studies, reported in the first issue of the Journal of Neuroscience, that identified molecular heterogeneity in precursor cells of the developing primate cerebral cortex to the current state in which differences defined at the molecular, cellular, circuit, and systems levels are building data encyclopedias. The emphasis on heterogeneity has impacted many contributors in the field of developmental neuroscience, who have led a quest to determine the extent to which there is diversity, when it appears developmentally, and what heritable and nonheritable factors mediate nervous system assembly and function. Since the appearance of the article on progenitor cell heterogeneity in the inaugural issue of the Journal of Neuroscience, there have been continuous advances in technologies and data analytics that are contributing to a much better understanding of the origins of neurobiological and behavioral heterogeneity.
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Ventrículos Cerebrales/citología , Células-Madre Neurales/fisiología , Neurogénesis , Neuroglía/fisiología , Animales , Ventrículos Cerebrales/crecimiento & desarrollo , Ventrículos Cerebrales/fisiología , Humanos , Células-Madre Neurales/citología , Neuroglía/citologíaRESUMEN
Even after birth, neuronal production continues in the ventricular-subventricular zone (V-SVZ) and hippocampus in many mammals. The immature new neurons ("neuroblasts") migrate and then mature at their final destination. In humans, neuroblast production and migration toward the neocortex and the olfactory bulb (OB) occur actively only for a few months after birth and then sharply decline with age. However, the precise spatiotemporal profiles and fates of postnatally born neurons remain unclear due to methodological limitations. We previously found that common marmosets, small nonhuman primates, share many features of V-SVZ organization with humans. Here, using marmosets injected with thymidine analogue(s) during various postnatal periods, we demonstrated spatiotemporal changes in neurogenesis during development. V-SVZ progenitor proliferation and neuroblast migration toward the OB and neocortex sharply decreased by 4 months, most strikingly in a V-SVZ subregion from which neuroblasts migrated toward the neocortex. Postnatally born neurons matured within a few months in the OB and hippocampus but remained immature until 6 months in the neocortex. While neurogenic activity was sustained for a month after birth, the distribution and/or differentiation diversity was more restricted in 1-month-born cells than in the neonatal-born population. These findings shed light on distinctive features of postnatal neurogenesis in primates.
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Proliferación Celular , Hipocampo/crecimiento & desarrollo , Ventrículos Laterales/crecimiento & desarrollo , Neocórtex/crecimiento & desarrollo , Células-Madre Neurales/citología , Neurogénesis , Bulbo Olfatorio/crecimiento & desarrollo , Animales , Encéfalo/citología , Encéfalo/crecimiento & desarrollo , Callithrix , Movimiento Celular , Ventrículos Cerebrales/citología , Ventrículos Cerebrales/crecimiento & desarrollo , Hipocampo/citología , Ventrículos Laterales/citología , Neocórtex/citología , Bulbo Olfatorio/citología , Análisis Espacio-TemporalRESUMEN
The brain ventricular system is a series of connected cavities, filled with cerebrospinal fluid (CSF), that forms within the vertebrate central nervous system (CNS). The hollow neural tube is a hallmark of the chordate CNS, and a closed neural tube is essential for normal development. Development and function of the ventricular system is examined, emphasizing three interdigitating components that form a functional system: ventricle walls, CSF fluid properties, and activity of CSF constituent factors. The cellular lining of the ventricle both can produce and is responsive to CSF. Fluid properties and conserved CSF components contribute to normal CNS development. Anomalies of the CSF/ventricular system serve as diagnostics and may cause CNS disorders, further highlighting their importance. This review focuses on the evolution and development of the brain ventricular system, associated function, and connected pathologies. It is geared as an introduction for scholars with little background in the field.
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Ventrículos Cerebrales/crecimiento & desarrollo , Ventrículos Cerebrales/metabolismo , Líquido Cefalorraquídeo/metabolismo , Animales , Evolución Biológica , Encefalopatías/metabolismo , Ventrículos Cerebrales/citología , Presión del Líquido Cefalorraquídeo/fisiología , Proteínas del Líquido Cefalorraquídeo/metabolismo , Cilios/metabolismo , Epitelio/crecimiento & desarrollo , Epitelio/metabolismo , Humanos , Cinética , Tubo Neural/citología , Tubo Neural/crecimiento & desarrollo , Tubo Neural/metabolismo , Transducción de SeñalRESUMEN
BACKGROUND: The aims of the current analysis were to study the change in ventricular volume (VV) obtained with cranial distraction in patients with craniosynostosis and compare it with the change in total intracranial volume (ICV) and brain volume. METHODS: After institutional review board approval, a retrospective review was performed on patients undergoing cranial distraction over a 5-year period. GE Healthcare AdW 4.3 volume assessment software was utilized to calculate preoperative and postdistraction ICV, VV, and whole-brain volume. Data were also collected on patient demographics, age at the time of distraction, time spent in distraction and consolidation, and length of stay. t Tests were used for comparison. RESULTS: Twenty-three patients met our inclusion criteria. Forty-eight percent of patients (n = 11) had right-sided cranial distraction, 30% (n = 7) had bilateral distraction, and 22% of patients (n = 5) had left-sided distraction. At the preoperative stage, mean head circumference was 42.5 ± 4.7 cm, mean ICV was 810.1 ± 27 cm, mean non-VV (NVV) was 796.2 ± 268 cm, and mean VV was 13.9 ± 9 cm. After a mean of 27.4 mm of distraction, occurring over a mean of 26 days and consolidation period of 149 days, a second computed tomography scan was obtained. Mean postdistraction head circumference was 49.1 ± 3.9 cm, mean ICV was 1074.1 ± 203 cm, mean NVV was 1053.5 ± 197 cm, and VV was 20.6 ± 14 cm. Mean % increase in ICV at this stage was 47.4%; mean % NVV increase was 48.5% as opposed to 60.3% increase in VV. CONCLUSIONS: Cranial distraction is known to effectively increase ICV. Our study suggests that the effect of this volumetric increase is much more pronounced on the VV compared with the brain volume. Further studies are underway to investigate whether this short-term marked increase in VV is sustained over a long-term period.
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Ventrículos Cerebrales/crecimiento & desarrollo , Craneosinostosis/cirugía , Osteogénesis por Distracción , Encéfalo/crecimiento & desarrollo , Femenino , Humanos , Lactante , Masculino , Tamaño de los Órganos , Estudios RetrospectivosRESUMEN
White matter damage persists in hypoxic-ischemic newborns even when treated with hypothermia. We have previously shown that intraventricular delivery of human glial progenitors (GPs) at the neonatal stage is capable of replacing abnormal host glia and rescuing the lifespan of dysmyelinated mice. However, such transplantation in the human brain poses significant challenges as related to high-volume ventricles and long cell migration distances. These challenges can only be studied in large animal model systems. In this study, we developed a three dimensional (3D)-printed model of the ventricular system sized to a newborn pig to investigate the parameters that can maximize a global biodistribution of injected GPs within the ventricular system, while minimizing outflow to the subarachnoid space. Bioluminescent imaging and magnetic resonance imaging were used to image the biodistribution of luciferase-transduced GPs in simple fluid containers and a custom-designed, 3D-printed model of the piglet ventricular system. Seven independent variables were investigated. The results demonstrated that a low volume (0.1 mL) of cell suspension is essential to keep cells within the ventricular system. If higher volumes (1 mL) are needed, a very slow infusion speed (0.01 mL/min) is necessary. Real-time magnetic resonance imaging demonstrated that superparamagnetic iron oxide (SPIO) labeling significantly alters the rheological properties of the GP suspension, such that, even at high speeds and high volumes, the outflow to the subarachnoid space is reduced. Several other factors, including GP species (human vs. mouse), type of catheter tip (end hole vs. side hole), catheter length (0.3 vs. 7.62 m), and cell concentration, had less effect on the overall distribution of GPs. We conclude that the use of a 3D-printed phantom model represents a robust, reproducible, and cost-saving alternative to in vivo large animal studies for determining optimal injection parameters.
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Ventrículos Cerebrales , Modelos Anatómicos , Células-Madre Neurales/citología , Neuroglía/citología , Impresión Tridimensional , Animales , Animales Recién Nacidos , Encéfalo/crecimiento & desarrollo , Encéfalo/metabolismo , Encéfalo/patología , Células Cultivadas , Ventrículos Cerebrales/citología , Ventrículos Cerebrales/crecimiento & desarrollo , Ventrículos Cerebrales/metabolismo , Colorantes Fluorescentes/farmacocinética , Humanos , Nanopartículas de Magnetita/análisis , Ratones , Células-Madre Neurales/fisiología , Neuroglía/fisiología , Porcinos , Distribución TisularRESUMEN
Motile cilia are miniature, propeller-like extensions, emanating from many cell types across the body. Their coordinated beating generates a directional fluid flow, which is essential for various biological processes, from respiration to reproduction. In the nervous system, ependymal cells extend their motile cilia into the brain ventricles and contribute to cerebrospinal fluid (CSF) flow. Although motile cilia are not the only contributors to CSF flow, their functioning is crucial, as patients with motile cilia defects develop clinical features, like hydrocephalus and scoliosis. CSF flow was suggested to primarily deliver nutrients and remove waste, but recent studies emphasized its role in brain development and function. Nevertheless, it remains poorly understood how ciliary beating generates and organizes CSF flow to fulfill these roles. Here, we study motile cilia and CSF flow in the brain ventricles of larval zebrafish. We identified that different populations of motile ciliated cells are spatially organized and generate a directional CSF flow powered by ciliary beating. Our investigations revealed that CSF flow is confined within individual ventricular cavities, with little exchange of fluid between ventricles, despite a pulsatile CSF displacement caused by the heartbeat. Interestingly, our results showed that the ventricular boundaries supporting this compartmentalized CSF flow are abolished during bodily movement, highlighting that multiple physiological processes regulate the hydrodynamics of CSF flow. Finally, we showed that perturbing cilia reduces hydrodynamic coupling between the brain ventricles and disrupts ventricular development. We propose that motile-cilia-generated flow is crucial in regulating the distribution of CSF within and across brain ventricles.
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Encéfalo/fisiología , Ventrículos Cerebrales/crecimiento & desarrollo , Líquido Cefalorraquídeo/fisiología , Cilios/metabolismo , Pez Cebra/fisiología , Animales , Pez Cebra/crecimiento & desarrolloRESUMEN
Nuclear factor-kappaB (NF-κB) is activated in neural progenitor cells in the developing murine cerebral cortex during the neurogenic phase, when it acts to prevent premature neuronal differentiation. Here we show that NF-κB activation continues in mouse neocortical neural progenitor cells during the neurogenic-to-gliogenic switch. Blockade of endogenous NF-κB activity during neocortical gliogenesis leads to the formation of supernumerary committed gliogenic progenitors and premature glial cell differentiation. Conversely, forced NF-κB activation during the neocortical neurogenic-to-gliogenic transition causes delayed gliogenic commitment and decreased astroglial gene expression. NF-κB activation continues in neocortical gliogenic progenitors following commitment and is important to inhibit the differentiation of oligodendrocyte precursor cells and to maintain persistent expression of glial fibrillary acidic protein in maturing astrocytes. These results reveal a number of previously uncharacterized roles for NF-κB during different phases of neocortical gliogenesis and identify NF-κB as an inhibitor of early oligodendrocyte development in the cerebral cortex.
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Corteza Cerebral , Regulación del Desarrollo de la Expresión Génica/genética , FN-kappa B/metabolismo , Neurogénesis/genética , Neuroglía/fisiología , Animales , Animales Recién Nacidos , Diferenciación Celular/fisiología , Células Cultivadas , Corteza Cerebral/citología , Corteza Cerebral/embriología , Corteza Cerebral/crecimiento & desarrollo , Ventrículos Cerebrales/citología , Ventrículos Cerebrales/embriología , Ventrículos Cerebrales/crecimiento & desarrollo , Factor Neurotrófico Ciliar/farmacología , Embrión de Mamíferos , Regulación del Desarrollo de la Expresión Génica/fisiología , Proteína Ácida Fibrilar de la Glía/metabolismo , Quinasa I-kappa B/genética , Quinasa I-kappa B/metabolismo , Antígeno Ki-67/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , FN-kappa B/genética , Proteínas del Tejido Nervioso/metabolismo , Células-Madre Neurales/fisiologíaRESUMEN
The brain ventricular system (BVS) consists of brain ventricles and channels connecting ventricles filled with cerebrospinal fluid (CSF). The disturbance of CSF flow has been linked to neurodegenerative disease including hydrocephalus, which manifests itself as an abnormal expansion of BVS. This relatively common developmental disorder has been observed in human and domesticated animals and linked to functional deficiency of various cells lineages facing BVS, including the choroid plexus or ependymal cells that generate CSF or the ciliated cells that cilia beating generates CSF flow. To understand the underlying causes of hydrocephalus, several animal models were developed, including rodents (mice, rat, and hamster) and zebrafish. At another side of a spectrum of BVS anomalies there is the "slit-ventricle" syndrome, which develops due to insufficient inflation of BVS. Recent advances in functional genetics of zebrafish brought to light novel genetic elements involved in development of BVS and circulation of CSF. This review aims to reveal common elements of morphologically different BVS of zebrafish as a typical representative of teleosts and other vertebrates and illustrate useful features of the zebrafish model for studies of BVS. Along this line, recent analyses of the two novel zebrafish mutants affecting different subunits of the potassium voltage-gated channels allowed to emphasize an important functional convergence of the evolutionarily conserved elements of protein transport essential for BVS development, which were revealed by the zebrafish and mouse studies.
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Ventrículos Cerebrales/embriología , Animales , Ventrículos Cerebrales/crecimiento & desarrollo , Cricetinae , Humanos , Ratones , Ratas , Vertebrados/embriología , Pez CebraRESUMEN
Originating from ectodermal epithelium, radial glial cells (RGCs) retain apico-basolateral polarity and comprise a pseudostratified epithelial layer in the developing cerebral cortex. The apical endfeet of the RGCs faces the fluid-filled ventricles, while the basal processes extend across the entire cortical span towards the pial surface. RGC functions are largely dependent on this polarized structure and the molecular components that define it. In this review, we will dissect existing molecular evidence on RGC polarity establishment and during cerebral cortex development and provide our perspective on the remaining key questions.
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Polaridad Celular , Corteza Cerebral/metabolismo , Ectodermo/metabolismo , Regulación del Desarrollo de la Expresión Génica , Proteínas del Tejido Nervioso/genética , Neuroglía/metabolismo , Citoesqueleto de Actina/metabolismo , Citoesqueleto de Actina/ultraestructura , Uniones Adherentes/metabolismo , Uniones Adherentes/ultraestructura , Animales , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Corteza Cerebral/citología , Corteza Cerebral/crecimiento & desarrollo , Ventrículos Cerebrales/citología , Ventrículos Cerebrales/crecimiento & desarrollo , Ventrículos Cerebrales/metabolismo , Ectodermo/citología , Ectodermo/crecimiento & desarrollo , Embrión de Mamíferos , Epitelio/crecimiento & desarrollo , Epitelio/metabolismo , Matriz Extracelular/metabolismo , Matriz Extracelular/ultraestructura , Humanos , Proteínas del Tejido Nervioso/metabolismo , Neuroglía/citología , Piamadre/citología , Piamadre/crecimiento & desarrollo , Piamadre/metabolismoRESUMEN
The morphogenesis of individual organs and the whole organism occurs under the control of intercellular chemical signals mainly during the perinatal period of ontogenesis in rodents. In this study, we tested our hypothesis that the biologically active concentration of noradrenaline (NA) in blood in perinatal ontogenesis of rats is maintained due to humoral interaction between its central and peripheral sources based on their plasticity. As one of the mechanisms of plasticity, we examined changes in the secretory activity (spontaneous and stimulated release of NA) of NA-producing organs under deficiency of its synthesis in the brain. The destruction of NA-ergic neurons was provoked by administration of a hybrid molecular complex - antibodies against dopamine-ß-hydroxylase associated with the cytotoxin saporin - into the lateral cerebral ventricles of neonatal rats. We found that 72 h after the inhibition of NA synthesis in the brain, its spontaneous release from hypothalamus increased, which was most likely due to a compensatory increase of NA secretion from surviving neurons and can be considered as one of the mechanisms of neuroplasticity aimed at the maintenance of its physiological concentration in peripheral blood. Noradrenaline secretion from peripheral sources (adrenal glands and the organ of Zuckerkandl) also showed a compensatory increase in this model. Thus, during the critical period of morphogenesis, the brain is integrated into the system of NA-producing organs and participates in their reciprocal humoral regulation as manifested in compensatory enhancement of NA secretion in each of the studied sources of NA under specific inhibition of NA production in the brain.
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Glándulas Suprarrenales , Neuronas Adrenérgicas/metabolismo , Ventrículos Cerebrales , Hipotálamo , Norepinefrina/metabolismo , Cuerpos Paraaórticos/metabolismo , Glándulas Suprarrenales/crecimiento & desarrollo , Glándulas Suprarrenales/metabolismo , Animales , Ventrículos Cerebrales/crecimiento & desarrollo , Ventrículos Cerebrales/metabolismo , Dopamina beta-Hidroxilasa/metabolismo , Hipotálamo/crecimiento & desarrollo , Hipotálamo/metabolismo , Masculino , Ratas , Ratas Wistar , Proteínas Inactivadoras de Ribosomas Tipo 1/toxicidad , SaporinasRESUMEN
Transitory cavities associated with the ventricular system represent probably one of the most unique features in the developing mammalian brain. In rodents, the cavities exist transiently in the developing brain and do not appear to be associated with any pathological events. Among the various cavities, the pyramidal-shaped cavum septum pellucidum (CSP) located beneath the corpus callosum and between the lateral ventricles is most well defined. In addition to the CSP are the bilateral subependymal cysts that are consistently associated with the third and fourth ventricles as well as the aqueduct. The cavities/cysts contain a large number of amoeboid microglia expressing surface receptors and hydrolytic enzymes common to tissue macrophages. The significance of these cavities in the developing brain remains a conjecture. Firstly, the cavity walls are free of an apparent epithelial lining; hence, it is speculated that the cavities that appear to communicate with the widened neighboring interstitial tissue spaces may have resulted from physical traction due to the rapid growth of the perinatal brain. Secondly, the cavities contain prominent clusters of amoeboid microglia that may be involved in clearing the debris of degenerating axons and cells resulting from the early brain tissue remodeling. With the increase in brain tissue compactness following the beginning of myelination in the second postnatal week, all cavities are obliterated; concomitantly, the number of amoeboid microglia in them diminishes and all this might signal further maturation of the brain.
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Encéfalo/crecimiento & desarrollo , Ventrículos Cerebrales/crecimiento & desarrollo , Quistes , Animales , Encéfalo/ultraestructura , Ventrículos Cerebrales/ultraestructura , Cuerpo Calloso/crecimiento & desarrollo , Cuerpo Calloso/ultraestructura , Quistes/ultraestructura , HumanosRESUMEN
Psychological trauma and obesity co-occur frequently and have been identified as major risk factors for psychiatric disorders. Surprisingly, preclinical studies examining how obesity disrupts the ability of the brain to cope with psychological trauma are lacking. The objective of this study was to determine whether an obesogenic Western-like high-fat diet (WD) predisposes rats to post-traumatic stress responsivity. Adolescent Lewis rats (postnatal day 28) were fed ad libitum for 8 weeks with either the experimental WD diet (41.4% kcal from fat) or the control diet (16.5% kcal from fat). We modeled psychological trauma by exposing young adult rats to a cat odor threat. The elevated plus maze and the open field test revealed increased psychological trauma-induced anxiety-like behaviors in the rats that consumed the WD when compared with control animals 1 week after undergoing traumatic stress (p < 0.05). Magnetic resonance imaging showed significant hippocampal atrophy (20% reduction) and lateral ventricular enlargement (50% increase) in the animals fed the WD when compared with controls. These volumetric abnormalities were associated with behavioral indices of anxiety, increased leptin and FK506-binding protein 51 (FKBP51) levels, and reduced hippocampal blood vessel density. We found asymmetric structural vulnerabilities to the WD, particularly the ventral and left hippocampus and lateral ventricle. This study highlights how WD consumption during adolescence impacts key substrates implicated in post-traumatic stress disorder. Understanding how consumption of a WD affects the developmental trajectories of the stress neurocircuitry is critical, as stress susceptibility imposes a marked vulnerability to neuropsychiatric disorders.
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Ventrículos Cerebrales/crecimiento & desarrollo , Ventrículos Cerebrales/patología , Dieta Occidental/efectos adversos , Hipocampo/crecimiento & desarrollo , Hipocampo/patología , Trastornos por Estrés Postraumático/patología , Animales , Ansiedad/diagnóstico por imagen , Ansiedad/patología , Ventrículos Cerebrales/diagnóstico por imagen , Susceptibilidad a Enfermedades/diagnóstico por imagen , Susceptibilidad a Enfermedades/patología , Hipocampo/diagnóstico por imagen , Leptina/metabolismo , Masculino , Memoria , Obesidad/diagnóstico por imagen , Obesidad/etiología , Obesidad/psicología , Tamaño de los Órganos , Distribución Aleatoria , Ratas Endogámicas Lew , Reflejo de Sobresalto , Trastornos por Estrés Postraumático/diagnóstico por imagen , Estrés Psicológico/diagnóstico por imagen , Estrés Psicológico/patologíaRESUMEN
Class III phosphoinositide 3-kinase (PIK3C3 or mammalian vacuolar protein sorting 34 homolog, Vps34) regulates vesicular trafficking, autophagy, and nutrient sensing. Recently, we reported that PIK3C3 is expressed in mouse cerebral cortex throughout the developmental process, especially at early embryonic stage. We thus examined the role of PIK3C3 in the development of the mouse cerebral cortex. Acute silencing of PIK3C3 with in utero electroporation method caused positional defects of excitatory neurons during corticogenesis. Time-lapse imaging revealed that the abnormal positioning was at least partially because of the reduced migration velocity. When PIK3C3 was silenced in cortical neurons in one hemisphere, axon extension to the contralateral hemisphere was also delayed. These aberrant phenotypes were rescued by RNAi-resistant PIK3C3. Notably, knockdown of PIK3C3 did not affect the cell cycle of neuronal progenitors and stem cells at the ventricular zone. Taken together, PIK3C3 was thought to play a crucial role in corticogenesis through the regulation of excitatory neuron migration and axon extension. Meanwhile, when we performed comparative genomic hybridization on a patient with specific learning disorders, a 107 Kb-deletion was identified on 18q12.3 (nt. 39554147-39661206) that encompasses exons 5-23 of PIK3C3. Notably, the above aberrant migration and axon growth phenotypes were not rescued by the disease-related truncation mutant (172 amino acids) lacking the C-terminal kinase domain. Thus, functional defects of PIK3C3 might impair corticogenesis and relate to the pathophysiology of specific learning disorders and other neurodevelopmental disorders. Acute knockdown of Class III phosphoinositide 3-kinase (PIK3C3) evokes migration defects of excitatory neurons during corticogenesis. PIK3C3-knockdown also disrupts axon outgrowth, but not progenitor proliferation in vivo. Involvement of PIK3C3 in neurodevelopmental disorders might be an interesting future subject since a deletion mutation in PIK3C3 was detected in a patient with specific learning disorders (SLD).
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Proteínas Quinasas Dependientes de 3-Fosfoinosítido/genética , Proteínas Quinasas Dependientes de 3-Fosfoinosítido/metabolismo , Encéfalo/enzimología , Encéfalo/crecimiento & desarrollo , Discapacidades para el Aprendizaje/genética , Animales , Axones , Encéfalo/embriología , Movimiento Celular/genética , Corteza Cerebral/embriología , Corteza Cerebral/enzimología , Corteza Cerebral/crecimiento & desarrollo , Ventrículos Cerebrales/citología , Ventrículos Cerebrales/enzimología , Ventrículos Cerebrales/crecimiento & desarrollo , Niño , Exones/genética , Femenino , Eliminación de Gen , Técnicas de Silenciamiento del Gen , Silenciador del Gen , Humanos , Pruebas de Inteligencia , Discapacidades para el Aprendizaje/psicología , Ratones , Células-Madre Neurales , Hibridación de Ácido Nucleico , Embarazo , Interferencia de ARNRESUMEN
Several genome- and proteome-wide studies have associated transcription and translation changes of CRMP2 (collapsing response mediator protein 2) with psychiatric disorders, yet little is known about its function in the developing or adult mammalian brain in vivo. Here we show that brain-specific Crmp2 knockout (cKO) mice display molecular, cellular, structural and behavioural deficits, many of which are reminiscent of neural features and symptoms associated with schizophrenia. cKO mice exhibit enlarged ventricles and impaired social behaviour, locomotor activity, and learning and memory. Loss of Crmp2 in the hippocampus leads to reduced long-term potentiation, abnormal NMDA receptor composition, aberrant dendrite development and defective synapse formation in CA1 neurons. Furthermore, knockdown of crmp2 specifically in newborn neurons results in stage-dependent defects in their development during adult hippocampal neurogenesis. Our findings reveal a critical role for CRMP2 in neuronal plasticity, neural function and behavioural modulation in mice.
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Región CA1 Hipocampal/metabolismo , Péptidos y Proteínas de Señalización Intercelular/deficiencia , Trastornos de la Memoria/genética , Proteínas del Tejido Nervioso/deficiencia , Neurogénesis/genética , Neuronas/metabolismo , Esquizofrenia/genética , Trastorno de la Conducta Social/genética , Animales , Región CA1 Hipocampal/crecimiento & desarrollo , Región CA1 Hipocampal/patología , Ventrículos Cerebrales/crecimiento & desarrollo , Ventrículos Cerebrales/metabolismo , Ventrículos Cerebrales/patología , Modelos Animales de Enfermedad , Regulación del Desarrollo de la Expresión Génica , Péptidos y Proteínas de Señalización Intercelular/genética , Locomoción/genética , Potenciación a Largo Plazo/genética , Masculino , Aprendizaje por Laberinto , Trastornos de la Memoria/metabolismo , Trastornos de la Memoria/patología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas del Tejido Nervioso/genética , Plasticidad Neuronal/genética , Neuronas/patología , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismo , Esquizofrenia/metabolismo , Esquizofrenia/patología , Trastorno de la Conducta Social/metabolismo , Trastorno de la Conducta Social/patología , Sinapsis/genética , Sinapsis/patologíaRESUMEN
Understanding the relationships between the structure and function of the brain largely relies on the qualitative assessment of Magnetic Resonance Images (MRIs) by expert clinicians. Automated analysis systems can support these assessments by providing quantitative measures of brain injury. However, the assessment of deep gray matter structures, which are critical to motor and executive function, remains difficult as a result of large anatomical injuries commonly observed in children with Cerebral Palsy (CP). Hence, this article proposes a robust surrogate marker of the extent of deep gray matter injury based on impingement due to local ventricular enlargement on surrounding anatomy. Local enlargement was computed using a statistical shape model of the lateral ventricles constructed from 44 healthy subjects. Measures of injury on 95 age-matched CP patients were used to train a regression model to predict six clinical measures of function. The robustness of identifying ventricular enlargement was demonstrated by an area under the curve of 0.91 when tested against a dichotomised expert clinical assessment. The measures also showed strong and significant relationships for multiple clinical scores, including: motor function (r2 = 0.62, P < 0.005), executive function (r2 = 0.55, P < 0.005), and communication (r2 = 0.50, P < 0.005), especially compared to using volumes obtained from standard anatomical segmentation approaches. The lack of reliance on accurate anatomical segmentations and its resulting robustness to large anatomical variations is a key feature of the proposed automated approach. This coupled with its strong correlation with clinically meaningful scores, signifies the potential utility to repeatedly assess MRIs for clinicians diagnosing children with CP. Hum Brain Mapp 37:3795-3809, 2016. © 2016 Wiley Periodicals, Inc.
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Parálisis Cerebral/diagnóstico por imagen , Ventrículos Cerebrales/diagnóstico por imagen , Sustancia Gris/diagnóstico por imagen , Interpretación de Imagen Asistida por Computador/métodos , Reconocimiento de Normas Patrones Automatizadas , Adolescente , Área Bajo la Curva , Parálisis Cerebral/fisiopatología , Parálisis Cerebral/psicología , Ventrículos Cerebrales/crecimiento & desarrollo , Niño , Preescolar , Comunicación , Función Ejecutiva , Femenino , Sustancia Gris/crecimiento & desarrollo , Humanos , Imagen por Resonancia Magnética , Masculino , Modelos Anatómicos , Modelos Neurológicos , Actividad Motora , Tamaño de los Órganos , Curva ROC , Análisis de RegresiónRESUMEN
The development of ventricles in the brain of H. huso (Beluga sturgeon) from 1 to 54 days old is presented in this study. The components observed in the 1-day-old ventricular system were the telencephalic, tectal, and cerebellar ventricles. These ventricles were not observed to have any recess or sulcus. They were surrounded by copious ependymal and embryonic cells. Two different parts were detected in the 6-day-old telencephalic ventricle: the olfactory and lateral ventricle. The olfactory ventricle was observed as a cranial extension of the telencephalic ventricle from 6 days old, as was the inner cell layer of the olfactory bulb (ic) adjacent to this extension. In the preoptic region, the lateral ventricle was connected to the preoptic recess from 15 days old, and this recess was connected by the interventricular foramen to the third ventricle in the diencephalon. At 6 days old, the third ventricle in the diencephalon was visible at the caudal part of the lateral ventricle, and the third ventricle had a recess near to the inferior lobe of the hypothalamus. At 6 days old, the tectal ventricle was observed to have bilateral extensions which proceeded to grow with age. The cerebellar ventricle, situated between the two lobes of the cerebellum, was observed from 1 day old. The cerebellar ventricle grew with age, extending laterally from 6 days old. The connection of the cerebellar ventricle to the fourth ventricle in the medulla oblongata was visible from 6 days old. Upon dividing the ventricular system into three regions (forebrain, midbrain, and hindbrain), stereological studies performed utiizing Cavalieri's principle indicated that the forebrain ventricular region had the smallest volume while the hindbrain ventricular region had the largest.
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Ventrículos Cerebrales/anatomía & histología , Ventrículos Cerebrales/crecimiento & desarrollo , Peces/anatomía & histología , Peces/crecimiento & desarrollo , Animales , Ventrículos Cerebrales/citologíaRESUMEN
Ventricle sizes are important for the early diagnosis of hydrocephalus or for follow-up after ventriculostomy. Diameters of ventricles may change, especially in childhood. This study aims to provide normative data about ventricle diameters. Among 14,854 cranial MRI performed between 2011 and 2013, 2,755 images of Turkish children aged 0-18 years were obtained. After exclusions, 517 images were left. Four radiologists were trained by a pediatric radiologist. Twenty images were assessed by all radiologists for a pilot study to see that there was no interobserver variation. There were 10-22 children in each age group. The maximum width of the third ventricle was 5.54 ± 1.29 mm in males in age group 1 and 4.98 ± 1.08 mm in females in age group 2. The Evans' index was <0.3 and consistent with the literature. The third ventricle/basilar artery width ratio was found to be >1 and <2 in all age groups and both gender groups. Our study showed the ventricle size data of children in various age groups from newborn to adolescent. The ventricle volume/cerebral parenchyma ratio seems to decrease with age. We think that these data can be applied in clinical practice, especially for the early diagnosis of hydrocephalus.
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Cuarto Ventrículo/anatomía & histología , Ventrículos Laterales/anatomía & histología , Tercer Ventrículo/anatomía & histología , Adolescente , Factores de Edad , Ventrículos Cerebrales/anatomía & histología , Ventrículos Cerebrales/crecimiento & desarrollo , Niño , Preescolar , Femenino , Cuarto Ventrículo/crecimiento & desarrollo , Humanos , Hidrocefalia/diagnóstico , Lactante , Recién Nacido , Ventrículos Laterales/crecimiento & desarrollo , Imagen por Resonancia Magnética/métodos , Masculino , Tamaño de los Órganos , Tercer Ventrículo/crecimiento & desarrolloRESUMEN
Metatherians and monotremes are born in an immature state, followed by prolonged nurturing by maternal lactation. Quantitative analysis of isocortical sections held in the collections at the Museum für Naturkunde, Berlin was used to compare the pace of somatosensory cortex development relative to body size and pallial thickness between metatherian groups, monotremes, and the laboratory rat. Analysis indicated that the pace of pallial growth in the monotremes is much lower than that in the metatherians or laboratory rat, with an estimated 8.6-fold increase in parietal cortex thickness between 10 and 100 mm body length, compared to a 10- to 20-fold increase among the metatherians and the rat. It was found that aggregation of cortical plate neurons occurs at similar embryo size in the mammals studied (around 8-14 mm body length) and a similar pallial thickness (around 200 µm), but that proliferative zone involution occurs at a much higher body size and pallial thickness in the monotremes compared to the metatherians and the laboratory rat. The observations suggest that cortical development in the monotremes is slower and subject to different regulatory signals to the therians studied. The slow pace may be related to either generally slower metabolism in monotremes or less efficient nutrient supply to the offspring due to the lack of teats.