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Sample records for fetal brain neurons

  1. Fetal brain extracellular matrix boosts neuronal network formation in 3D bioengineered model of cortical brain tissue.

    Sood, Disha; Chwalek, Karolina; Stuntz, Emily; Pouli, Dimitra; Du, Chuang; Tang-Schomer, Min; Georgakoudi, Irene; Black, Lauren D; Kaplan, David L

    2016-01-01

    The extracellular matrix (ECM) constituting up to 20% of the organ volume is a significant component of the brain due to its instructive role in the compartmentalization of functional microdomains in every brain structure. The composition, quantity and structure of ECM changes dramatically during the development of an organism greatly contributing to the remarkably sophisticated architecture and function of the brain. Since fetal brain is highly plastic, we hypothesize that the fetal brain ECM may contain cues promoting neural growth and differentiation, highly desired in regenerative medicine. Thus, we studied the effect of brain-derived fetal and adult ECM complemented with matricellular proteins on cortical neurons using in vitro 3D bioengineered model of cortical brain tissue. The tested parameters included neuronal network density, cell viability, calcium signaling and electrophysiology. Both, adult and fetal brain ECM as well as matricellular proteins significantly improved neural network formation as compared to single component, collagen I matrix. Additionally, the brain ECM improved cell viability and lowered glutamate release. The fetal brain ECM induced superior neural network formation, calcium signaling and spontaneous spiking activity over adult brain ECM. This study highlights the difference in the neuroinductive properties of fetal and adult brain ECM and suggests that delineating the basis for this divergence may have implications for regenerative medicine.

  2. Asymmetry of radial and symmetry of tangential neuronal migration pathways in developing human fetal brains

    Yuta eMiyazaki

    2016-01-01

    Full Text Available AbstractThe radial and tangential neural migration pathways are two major neuronal migration streams in humans that are critical during corticogenesis. Corticogenesis is a complex process of neuronal proliferation that is followed by neuronal migration and the formation of axonal connections. Existing histological assessments of these two neuronal migration pathways have limitations inherent to microscopic studies and are confined to small anatomic regions of interest. Thus, little evidence is available about their three-dimensional fiber pathways and development throughout the entire brain. In this study, we imaged and analyzed radial and tangential migration pathways in the whole human brain using high-angular resolution diffusion MR imaging (HARDI tractography. We imaged ten fixed, postmortem fetal (17 gestational weeks (GW, 18 GW, 19 GW, three 20 GW, three 21 GW and 22 GW and eight in vivo newborn (two 30 GW, 34 GW, 35 GW and four 40 GW brains with no neurological/pathological conditions. We statistically compared the volume of the left and right radial and tangential migration pathways, and the volume of the radial migration pathways of the anterior and posterior regions of the brain. In specimens 22 GW or younger, the volume of radial migration pathways of the left hemisphere was significantly larger than that of the right hemisphere. The volume of posterior radial migration pathways was also larger when compared to the anterior pathways in specimens 22 GW or younger. In contrast, no significant differences were observed in the radial migration pathways of brains older than 22 GW. Moreover, our study did not identify any significant differences in volumetric laterality in the tangential migration pathways. These results suggest that these two neuronal migration pathways develop and regress differently, and radial neuronal migration varies regionally based on hemispheric and anterior-posterior laterality, potentially explaining regional

  3. Possible promotion of neuronal differentiation in fetal rat brain neural progenitor cells after sustained exposure to static magnetism.

    Nakamichi, Noritaka; Ishioka, Yukichi; Hirai, Takao; Ozawa, Shusuke; Tachibana, Masaki; Nakamura, Nobuhiro; Takarada, Takeshi; Yoneda, Yukio

    2009-08-15

    We have previously shown significant potentiation of Ca(2+) influx mediated by N-methyl-D-aspartate receptors, along with decreased microtubules-associated protein-2 (MAP2) expression, in hippocampal neurons cultured under static magnetism without cell death. In this study, we investigated the effects of static magnetism on the functionality of neural progenitor cells endowed to proliferate for self-replication and differentiate into neuronal, astroglial, and oligodendroglial lineages. Neural progenitor cells were isolated from embryonic rat neocortex and hippocampus, followed by culture under static magnetism at 100 mT and subsequent determination of the number of cells immunoreactive for a marker protein of particular progeny lineages. Static magnetism not only significantly decreased proliferation of neural progenitor cells without affecting cell viability, but also promoted differentiation into cells immunoreactive for MAP2 with a concomitant decrease in that for an astroglial marker, irrespective of the presence of differentiation inducers. In neural progenitors cultured under static magnetism, a significant increase was seen in mRNA expression of several activator-type proneural genes, such as Mash1, Math1, and Math3, together with decreased mRNA expression of the repressor type Hes5. These results suggest that sustained static magnetism could suppress proliferation for self-renewal and facilitate differentiation into neurons through promoted expression of activator-type proneural genes by progenitor cells in fetal rat brain.

  4. Digital atlas of fetal brain MRI.

    Chapman, Teresa; Matesan, Manuela; Weinberger, Ed; Bulas, Dorothy I

    2010-02-01

    Fetal MRI can be performed in the second and third trimesters. During this time, the fetal brain undergoes profound structural changes. Interpretation of appropriate development might require comparison with normal age-based models. Consultation of a hard-copy atlas is limited by the inability to compare multiple ages simultaneously. To provide images of normal fetal brains from weeks 18 through 37 in a digital format that can be reviewed interactively. This will facilitate recognition of abnormal brain development. T2-W images for the atlas were obtained from fetal MR studies of normal brains scanned for other indications from 2005 to 2007. Images were oriented in standard axial, coronal and sagittal projections, with laterality established by situs. Gestational age was determined by last menstrual period, earliest US measurements and sonogram performed on the same day as the MR. The software program used for viewing the atlas, written in C#, permits linked scrolling and resizing the images. Simultaneous comparison of varying gestational ages is permissible. Fetal brain images across gestational ages 18 to 37 weeks are provided as an interactive digital atlas and are available for free download from http://radiology.seattlechildrens.org/teaching/fetal_brain . Improved interpretation of fetal brain abnormalities can be facilitated by the use of digital atlas cataloging of the normal changes throughout fetal development. Here we provide a description of the atlas and a discussion of normal fetal brain development.

  5. Digital atlas of fetal brain MRI

    Chapman, Teresa; Weinberger, E.; Matesan, Manuela; Bulas, Dorothy I.

    2010-01-01

    Fetal MRI can be performed in the second and third trimesters. During this time, the fetal brain undergoes profound structural changes. Interpretation of appropriate development might require comparison with normal age-based models. Consultation of a hard-copy atlas is limited by the inability to compare multiple ages simultaneously. To provide images of normal fetal brains from weeks 18 through 37 in a digital format that can be reviewed interactively. This will facilitate recognition of abnormal brain development. T2-W images for the atlas were obtained from fetal MR studies of normal brains scanned for other indications from 2005 to 2007. Images were oriented in standard axial, coronal and sagittal projections, with laterality established by situs. Gestational age was determined by last menstrual period, earliest US measurements and sonogram performed on the same day as the MR. The software program used for viewing the atlas, written in C, permits linked scrolling and resizing the images. Simultaneous comparison of varying gestational ages is permissible. Fetal brain images across gestational ages 18 to 37 weeks are provided as an interactive digital atlas and are available for free download. Improved interpretation of fetal brain abnormalities can be facilitated by the use of digital atlas cataloging of the normal changes throughout fetal development. Here we provide a description of the atlas and a discussion of normal fetal brain development. (orig.)

  6. Digital atlas of fetal brain MRI

    Chapman, Teresa; Weinberger, E. [Department of Radiology, Seattle Children' s Hospital, Seattle, WA (United States); Matesan, Manuela [University of Washington, Department of Radiology, Seattle, WA (United States); Bulas, Dorothy I. [Division of Diagnostic Imaging and Radiology, Children' s National Medical Center, Washington, DC (United States)

    2010-02-15

    Fetal MRI can be performed in the second and third trimesters. During this time, the fetal brain undergoes profound structural changes. Interpretation of appropriate development might require comparison with normal age-based models. Consultation of a hard-copy atlas is limited by the inability to compare multiple ages simultaneously. To provide images of normal fetal brains from weeks 18 through 37 in a digital format that can be reviewed interactively. This will facilitate recognition of abnormal brain development. T2-W images for the atlas were obtained from fetal MR studies of normal brains scanned for other indications from 2005 to 2007. Images were oriented in standard axial, coronal and sagittal projections, with laterality established by situs. Gestational age was determined by last menstrual period, earliest US measurements and sonogram performed on the same day as the MR. The software program used for viewing the atlas, written in C, permits linked scrolling and resizing the images. Simultaneous comparison of varying gestational ages is permissible. Fetal brain images across gestational ages 18 to 37 weeks are provided as an interactive digital atlas and are available for free download. Improved interpretation of fetal brain abnormalities can be facilitated by the use of digital atlas cataloging of the normal changes throughout fetal development. Here we provide a description of the atlas and a discussion of normal fetal brain development. (orig.)

  7. MR imaging of the fetal brain

    Glenn, Orit A.

    2010-01-01

    Fetal MRI is clinically performed to evaluate the brain in cases where an abnormality is detected by prenatal sonography. These most commonly include ventriculomegaly, abnormalities of the corpus callosum, and abnormalities of the posterior fossa. Fetal MRI is also increasingly performed to evaluate fetuses who have normal brain findings on prenatal sonogram but who are at increased risk for neurodevelopmental abnormalities, such as complicated monochorionic twin pregnancies. This paper will briefly discuss the common clinical conditions imaged by fetal MRI as well as recent advances in fetal MRI research. (orig.)

  8. MR imaging of the fetal brain

    Glenn, Orit A. [University of California, San Francisco, Department of Radiology, Neuroradiology Section, San Francisco, CA (United States)

    2010-01-15

    Fetal MRI is clinically performed to evaluate the brain in cases where an abnormality is detected by prenatal sonography. These most commonly include ventriculomegaly, abnormalities of the corpus callosum, and abnormalities of the posterior fossa. Fetal MRI is also increasingly performed to evaluate fetuses who have normal brain findings on prenatal sonogram but who are at increased risk for neurodevelopmental abnormalities, such as complicated monochorionic twin pregnancies. This paper will briefly discuss the common clinical conditions imaged by fetal MRI as well as recent advances in fetal MRI research. (orig.)

  9. Populations of subplate and interstitial neurons in fetal and adult human telencephalon.

    Judaš, Miloš; Sedmak, Goran; Pletikos, Mihovil; Jovanov-Milošević, Nataša

    2010-10-01

    In the adult human telencephalon, subcortical (gyral) white matter contains a special population of interstitial neurons considered to be surviving descendants of fetal subplate neurons [Kostovic & Rakic (1980) Cytology and the time of origin of interstitial neurons in the white matter in infant and adult human and monkey telencephalon. J Neurocytol9, 219]. We designate this population of cells as superficial (gyral) interstitial neurons and describe their morphology and distribution in the postnatal and adult human cerebrum. Human fetal subplate neurons cannot be regarded as interstitial, because the subplate zone is an essential part of the fetal cortex, the major site of synaptogenesis and the 'waiting' compartment for growing cortical afferents, and contains both projection neurons and interneurons with distinct input-output connectivity. However, although the subplate zone is a transient fetal structure, many subplate neurons survive postnatally as superficial (gyral) interstitial neurons. The fetal white matter is represented by the intermediate zone and well-defined deep periventricular tracts of growing axons, such as the corpus callosum, anterior commissure, internal and external capsule, and the fountainhead of the corona radiata. These tracts gradually occupy the territory of transient fetal subventricular and ventricular zones.The human fetal white matter also contains distinct populations of deep fetal interstitial neurons, which, by virtue of their location, morphology, molecular phenotypes and advanced level of dendritic maturation, remain distinct from subplate neurons and neurons in adjacent structures (e.g. basal ganglia, basal forebrain). We describe the morphological, histochemical (nicotinamide-adenine dinucleotide phosphate-diaphorase) and immunocytochemical (neuron-specific nuclear protein, microtubule-associated protein-2, calbindin, calretinin, neuropeptide Y) features of both deep fetal interstitial neurons and deep (periventricular

  10. MRI of fetal acquired brain lesions

    Prayer, Daniela; Brugger, Peter C.; Kasprian, Gregor; Witzani, Linde; Helmer, Hanns; Dietrich, Wolfgang; Eppel, Wolfgang; Langer, Martin

    2006-01-01

    Acquired fetal brain damage is suspected in cases of destruction of previously normally formed tissue, the primary cause of which is hypoxia. Fetal brain damage may occur as a consequence of acute or chronic maternal diseases, with acute diseases causing impairment of oxygen delivery to the fetal brain, and chronic diseases interfering with normal, placental development. Infections, metabolic diseases, feto-fetal transfusion syndrome, toxic agents, mechanical traumatic events, iatrogenic accidents, and space-occupying lesions may also qualify as pathologic conditions that initiate intrauterine brain damage. MR manifestations of acute fetal brain injury (such as hemorrhage or acute ischemic lesions) can easily be recognized, as they are hardly different from postnatal lesions. The availability of diffusion-weighted sequences enhances the sensitivity in recognizing acute ischemic lesions. Recent hemorrhages are usually readily depicted on T2 (*) sequences, where they display hypointense signals. Chronic fetal brain injury may be characterized by nonspecific changes that must be attributable to the presence of an acquired cerebral pathology. The workup in suspected acquired fetal brain injury also includes the assessment of extra-CNS organs that may be affected by an underlying pathology. Finally, the placenta, as the organ that mediates oxygen delivery from the maternal circulation to the fetus, must be examined on MR images

  11. MRI of fetal acquired brain lesions

    Prayer, Daniela [Department of Radiodiagnostics, Medical University of Vienna (Austria)]. E-mail: daniela.prayer@meduniwien.ac.at; Brugger, Peter C. [Center of Anatomy and Cell Biology, Medical University of Vienna (Austria); Kasprian, Gregor [Department of Radiodiagnostics, Medical University of Vienna (Austria); Witzani, Linde [Department of Radiodiagnostics, Medical University of Vienna (Austria); Helmer, Hanns [Department of Obstetrics and Gynecology, Medical University of Vienna (Austria); Dietrich, Wolfgang [Department of Neurosurgery, Medical University of Vienna (Austria); Eppel, Wolfgang [Department of Obstetrics and Gynecology, Medical University of Vienna (Austria); Langer, Martin [Department of Obstetrics and Gynecology, Medical University of Vienna (Austria)

    2006-02-15

    Acquired fetal brain damage is suspected in cases of destruction of previously normally formed tissue, the primary cause of which is hypoxia. Fetal brain damage may occur as a consequence of acute or chronic maternal diseases, with acute diseases causing impairment of oxygen delivery to the fetal brain, and chronic diseases interfering with normal, placental development. Infections, metabolic diseases, feto-fetal transfusion syndrome, toxic agents, mechanical traumatic events, iatrogenic accidents, and space-occupying lesions may also qualify as pathologic conditions that initiate intrauterine brain damage. MR manifestations of acute fetal brain injury (such as hemorrhage or acute ischemic lesions) can easily be recognized, as they are hardly different from postnatal lesions. The availability of diffusion-weighted sequences enhances the sensitivity in recognizing acute ischemic lesions. Recent hemorrhages are usually readily depicted on T2 (*) sequences, where they display hypointense signals. Chronic fetal brain injury may be characterized by nonspecific changes that must be attributable to the presence of an acquired cerebral pathology. The workup in suspected acquired fetal brain injury also includes the assessment of extra-CNS organs that may be affected by an underlying pathology. Finally, the placenta, as the organ that mediates oxygen delivery from the maternal circulation to the fetus, must be examined on MR images.

  12. Advanced MRI techniques of the fetal brain

    Schoepf, V.; Dittrich, E.; Berger-Kulemann, V.; Kasprian, G.; Kollndorfer, K.; Prayer, D.

    2013-01-01

    Evaluation of the normal and pathological fetal brain. Magnetic resonance imaging (MRI). Advanced MRI of the fetal brain. Diffusion tensor imaging (DTI) is used in clinical practice, all other methods are used at a research level. Serving as standard methods in the future. Combined structural and functional data for all gestational ages will allow more specific insight into the developmental processes of the fetal brain. This gain of information will help provide a common understanding of complex spatial and temporal procedures of early morphological features and their impact on cognitive and sensory abilities. (orig.) [de

  13. Fetal brain disruption sequence versus fetal brain arrest: A distinct autosomal recessive developmental brain malformation phenotype.

    Abdel-Salam, Ghada M H; Abdel-Hamid, Mohamed S; El-Khayat, Hamed A; Eid, Ola M; Saba, Soliman; Farag, Mona K; Saleem, Sahar N; Gaber, Khaled R

    2015-05-01

    The term fetal brain disruption sequence (FBDS) was coined to describe a number of sporadic conditions caused by numerous external disruptive events presenting with variable imaging findings. However, rare familial occurrences have been reported. We describe five patients (two sib pairs and one sporadic) with congenital severe microcephaly, seizures, and profound intellectual disability. Brain magnetic resonance imaging (MRI) revealed unique and uniform picture of underdeveloped cerebral hemispheres with increased extraxial CSF, abnormal gyral pattern (polymicrogyria-like lesions in two sibs and lissencephaly in the others), loss of white matter, dysplastic ventricles, hypogenesis of corpus callosum, and hypoplasia of the brainstem, but hypoplastic cerebellum in one. Fetal magnetic resonance imaging (FMRI) of two patients showed the same developmental brain malformations in utero. These imaging findings are in accordance with arrested brain development rather than disruption. Molecular analysis excluded mutations in potentially related genes such as NDE1, MKL2, OCLN, and JAM3. These unique clinical and imaging findings were described before among familial reports with FBDS. However, our patients represent a recognizable phenotype of developmental brain malformations, that is, apparently distinguishable from either familial microhydranencephaly or microlissencephaly that were collectively termed FBDS. Thus, the use of the umbrella term FBDS is no longer helpful. Accordingly, we propose the term fetal brain arrest to distinguish them from other familial patients diagnosed as FBDS. The presence of five affected patients from three unrelated consanguineous families suggests an autosomal-recessive mode of inheritance. The spectrum of fetal brain disruption sequence is reviewed. © 2015 Wiley Periodicals, Inc.

  14. Caffeine Augments Anesthesia Neurotoxicity in the Fetal Macaque Brain.

    Noguchi, Kevin K; Johnson, Stephen A; Manzella, Francesca M; Masuoka, Kobe L; Williams, Sasha L; Martin, Lauren D; Dissen, Gregory A; Ikonomidou, Chrysanthy; Schenning, Katie J; Olney, John W; Brambrink, Ansgar M

    2018-03-28

    Caffeine is the most frequently used medication in premature infants. It is the respiratory stimulant of choice for apnea associated with prematurity and has been called the silver bullet in neonatology because of many proven benefits and few known risks. Research has revealed that sedative/anesthetic drugs trigger apoptotic death of neurons and oligodendrocytes in developing mammalian brains. Here we evaluated the influence of caffeine on the neurotoxicity of anesthesia in developing nonhuman primate brains. Fetal macaques (n = 7-8/group), at a neurodevelopmental age comparable to premature human infants, were exposed in utero for 5 hours to no drug (control), isoflurane, or isoflurane + caffeine and examined for evidence of apoptosis. Isoflurane exposure increased apoptosis 3.3 fold for neurons and 3.4 fold for oligodendrocytes compared to control brains. Isoflurane + caffeine caused neuronal apoptosis to increase 8.0 fold compared to control levels but did not augment oligoapoptosis. Neuronal death was particularly pronounced in the basal ganglia and cerebellum. Higher blood levels of caffeine within the range considered therapeutic and safe for human infants correlated with increased neuroapoptosis. Caffeine markedly augments neurotoxicity of isoflurane in the fetal macaque brain and challenges the assumption that caffeine is safe for premature infants.

  15. Fetal MRI of pathological brain development

    Brugger, P.C.; Prayer, D.

    2006-01-01

    Because of the superior tissue contrast, high spatial resolution, and multiplanar capabilities, fetal magnetic resonance imaging (MRI) can depict fetal brain pathologies with high accuracy. Pathological fetal brain development may result from malformations or acquired conditions. Differentiation of these etiologies is important with respect to managing the actual pregnancy or counseling future pregnancies. As a widened ventricular system is a common hallmark of both maldevelopment and acquired conditions, it may cause problems in the differential diagnosis. Fetal MRI can provide detailed morphological information, which allows refinement of the diagnosis of ventricular enlargement in a large number of cases. Systematic work-up of morphological details that may be recognized on MR images provides an approach for achieving a correct diagnosis in cases of ventricle enlargement. (orig.) [de

  16. Normal and abnormal neuronal migration during brain development

    Rakic, P.

    1986-01-01

    Conceptual and factual advances in understanding neuronal migration in the past two decades have provided new insight into the pathogenesis of brain malformations at the cellular, molecular, and functional levels. Some of these results may have direct implications in understanding the consequences of ionizing radiation on the fetal central nervous system in utero. (orig.)

  17. Magnetic resonance imaging of the fetal brain.

    Tee, L Mf; Kan, E Yl; Cheung, J Cy; Leung, W C

    2016-06-01

    This review covers the recent literature on fetal brain magnetic resonance imaging, with emphasis on techniques, advances, common indications, and safety. We conducted a search of MEDLINE for articles published after 2010. The search terms used were "(fetal OR foetal OR fetus OR foetus) AND (MR OR MRI OR [magnetic resonance]) AND (brain OR cerebral)". Consensus statements from major authorities were also included. As a result, 44 relevant articles were included and formed the basis of this review. One major challenge is fetal motion that is largely overcome by ultra-fast sequences. Currently, single-shot fast spin-echo T2-weighted imaging remains the mainstay for motion resistance and anatomical delineation. Recently, a snap-shot inversion recovery sequence has enabled robust T1-weighted images to be obtained, which is previously a challenge for standard gradient-echo acquisitions. Fetal diffusion-weighted imaging, diffusion tensor imaging, and magnetic resonance spectroscopy are also being developed. With multiplanar capabilities, superior contrast resolution and field of view, magnetic resonance imaging does not have the limitations of sonography, and can provide additional important information. Common indications include ventriculomegaly, callosum and posterior fossa abnormalities, and twin complications. There are safety concerns about magnetic resonance-induced heating and acoustic damage but current literature showed no conclusive evidence of deleterious fetal effects. The American College of Radiology guideline states that pregnant patients can be accepted to undergo magnetic resonance imaging at any stage of pregnancy if risk-benefit ratio to patients warrants that the study be performed. Magnetic resonance imaging of the fetal brain is a safe and powerful adjunct to sonography in prenatal diagnosis. It can provide additional information that aids clinical management, prognostication, and counselling.

  18. MRI of normal fetal brain development

    Prayer, Daniela; Kasprian, Gregor; Krampl, Elisabeth; Ulm, Barbara; Witzani, Linde; Prayer, Lucas; Brugger, Peter C.

    2006-01-01

    Normal fetal brain maturation can be studied by in vivo magnetic resonance imaging (MRI) from the 18th gestational week (GW) to term, and relies primarily on T2-weighted and diffusion-weighted (DW) sequences. These maturational changes must be interpreted with a knowledge of the histological background and the temporal course of the respective developmental steps. In addition, MR presentation of developing and transient structures must be considered. Signal changes associated with maturational processes can mainly be ascribed to the following changes in tissue composition and organization, which occur at the histological level: (1) a decrease in water content and increasing cell-density can be recognized as a shortening of T1- and T2-relaxation times, leading to increased T1-weighted and decreased T2-weighted intensity, respectively; (2) the arrangement of microanatomical structures to create a symmetrical or asymmetrical environment, leading to structural differences that may be demonstrated by DW-anisotropy; (3) changes in non-structural qualities, such as the onset of a membrane potential in premyelinating axons. The latter process also influences the appearance of a structure on DW sequences. Thus, we will review the in vivo MR appearance of different maturational states of the fetal brain and relate these maturational states to anatomical, histological, and in vitro MRI data. Then, the development of the cerebral cortex, white matter, temporal lobe, and cerebellum will be reviewed, and the MR appearance of transient structures of the fetal brain will be shown. Emphasis will be placed on the appearance of the different structures with the various sequences. In addition, the possible utility of dynamic fetal sequences in assessing spontaneous fetal movements is discussed

  19. MRI of normal fetal brain development

    Prayer, Daniela [Department of Radiodiagnostics, Medical University of Vienna, Vienna (Austria)]. E-mail: Daniela.prayer@meduniwien.ac.at; Kasprian, Gregor [Department of Radiodiagnostics, Medical University of Vienna, Vienna (Austria); Krampl, Elisabeth [Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna (Austria); Ulm, Barbara [Department of Prenatal Diagnosis, Medical University of Vienna, Vienna (Austria); Witzani, Linde [Department of Radiodiagnostics, Medical University of Vienna, Vienna (Austria); Prayer, Lucas [Diagnosezentrum Urania, Vienna (Austria); Brugger, Peter C. [Center of Anatomy and Cell Biology, Medical University of Vienna, Vienna (Austria)

    2006-02-15

    Normal fetal brain maturation can be studied by in vivo magnetic resonance imaging (MRI) from the 18th gestational week (GW) to term, and relies primarily on T2-weighted and diffusion-weighted (DW) sequences. These maturational changes must be interpreted with a knowledge of the histological background and the temporal course of the respective developmental steps. In addition, MR presentation of developing and transient structures must be considered. Signal changes associated with maturational processes can mainly be ascribed to the following changes in tissue composition and organization, which occur at the histological level: (1) a decrease in water content and increasing cell-density can be recognized as a shortening of T1- and T2-relaxation times, leading to increased T1-weighted and decreased T2-weighted intensity, respectively; (2) the arrangement of microanatomical structures to create a symmetrical or asymmetrical environment, leading to structural differences that may be demonstrated by DW-anisotropy; (3) changes in non-structural qualities, such as the onset of a membrane potential in premyelinating axons. The latter process also influences the appearance of a structure on DW sequences. Thus, we will review the in vivo MR appearance of different maturational states of the fetal brain and relate these maturational states to anatomical, histological, and in vitro MRI data. Then, the development of the cerebral cortex, white matter, temporal lobe, and cerebellum will be reviewed, and the MR appearance of transient structures of the fetal brain will be shown. Emphasis will be placed on the appearance of the different structures with the various sequences. In addition, the possible utility of dynamic fetal sequences in assessing spontaneous fetal movements is discussed.

  20. Neuronal survival in the brain: neuron type-specific mechanisms

    Pfisterer, Ulrich Gottfried; Khodosevich, Konstantin

    2017-01-01

    Neurogenic regions of mammalian brain produce many more neurons that will eventually survive and reach a mature stage. Developmental cell death affects both embryonically produced immature neurons and those immature neurons that are generated in regions of adult neurogenesis. Removal of substantial...... numbers of neurons that are not yet completely integrated into the local circuits helps to ensure that maturation and homeostatic function of neuronal networks in the brain proceed correctly. External signals from brain microenvironment together with intrinsic signaling pathways determine whether...... for survival in a certain brain region. This review focuses on how immature neurons survive during normal and impaired brain development, both in the embryonic/neonatal brain and in brain regions associated with adult neurogenesis, and emphasizes neuron type-specific mechanisms that help to survive for various...

  1. Distribution of melatonin receptor in human fetal brain

    WANG Guo-quan; SHAO Fu-yuan; ZHAO Ying; LIU Zhi-min

    2001-01-01

    Objective: To study the distribution of 2 kinds of melatonin receptor subtypes (mtl and MT2) in human fetal brain. Methods: The fetal brain tissues were sliced and the distribution ofmelatonin receptors in human fetal brain were detected using immunohistochemistry and in situ hybridization. Results: Melatonin receptor mtl existed in the cerebellun and hypothalamus, melatonin receptor MT2 exists in hypothalamus, occipital and medulla. Conclusion: Two kinds of melatonin receptors, mtl and MT2 exist in the membrane and cytosol of brain cells, indicating that human fetal brain is a target organ of melatonin.

  2. Thyroid hormones and fetal brain development.

    Pemberton, H N; Franklyn, J A; Kilby, M D

    2005-08-01

    Thyroid hormones are intricately involved in the developing fetal brain. The fetal central nervous system is sensitive to the maternal thyroid status. Critical amounts of maternal T3 and T4 must be transported across the placenta to the fetus to ensure the correct development of the brain throughout ontogeny. Severe mental retardation of the child can occur due to compromised iodine intake or thyroid disease. This has been reported in areas of the world with iodine insufficiency, New Guinea, and also in mother with thyroid complications such as hypothyroxinaemia and hyperthyroidism. The molecular control of thyroid hormones by deiodinases for the activation of thyroid hormones is critical to ensure the correct amount of active thyroid hormones are temporally supplied to the fetus. These hormones provide timing signals for the induction of programmes for differentiation and maturation at specific stages of development. Understanding these molecular mechanisms further will have profound implications in the clinical management of individuals affected by abnormal maternal of fetal thyroid status.

  3. In vivo MRI of the fetal brain.

    Girard, N; Raybaud, C; Dercole, C; Boubli, L; Chau, C; Cahen, S; Potier, A; Gamerre, M

    1993-01-01

    We report MRI of the brain in 45 fetuses; the findings were confirmed by pathological examination or postnatal neuroradiological studies. MRI necessitates medication to eliminate fetal motion; curare was injected into the umbilical cord, and MRI is therefore limited to cases in which umbilical cord puncture is indicated. T1-weighted images were obtained in axial, sagittal and coronal planes; the last of these were generally as the most useful as regards morphology. We demonstrated cerebral malformations (n = 13), brain haemorrhage (n = 1), a facial angioma (n = 1), a facial mass (n = 1), hydrocephalus (n = 5), unilateral ventricular enlargement (n = 1), atrophy (n = 4), a porencephalic cyst (n = 1) and normal appearances of the brain in 18 cases. Twenty-two of the fetuses were born alive, and the clinical and/or neuroradiological examination confirmed the antenatal findings. The diagnosis was also confirmed in 8 cases in which a neuropathological examination was possible.

  4. Biosynthesis of the D2 cell adhesion molecule: pulse-chase studies in cultured fetal rat neuronal cells

    Lyles, J M; Norrild, B; Bock, E

    1984-01-01

    D2 is a membrane glycoprotein that is believed to function as a cell adhesion molecule (CAM) in neural cells. We have examined its biosynthesis in cultured fetal rat brain neurones. We found D2-CAM to be synthesized initially as two polypeptides: Mr 186,000 (A) and Mr 136,000 (B). With increasing...

  5. Insulin receptors mediate growth effects in cultured fetal neurons. I. Rapid stimulation of protein synthesis

    Heidenreich, K.A.; Toledo, S.P.

    1989-01-01

    In this study we have examined the effects of insulin on protein synthesis in cultured fetal chick neurons. Protein synthesis was monitored by measuring the incorporation of [3H]leucine (3H-leu) into trichloroacetic acid (TCA)-precipitable protein. Upon addition of 3H-leu, there was a 5-min lag before radioactivity occurred in protein. During this period cell-associated radioactivity reached equilibrium and was totally recovered in the TCA-soluble fraction. After 5 min, the incorporation of 3H-leu into protein was linear for 2 h and was inhibited (98%) by the inclusion of 10 micrograms/ml cycloheximide. After 24 h of serum deprivation, insulin increased 3H-leu incorporation into protein by approximately 2-fold. The stimulation of protein synthesis by insulin was dose dependent (ED50 = 70 pM) and seen within 30 min. Proinsulin was approximately 10-fold less potent than insulin on a molar basis in stimulating neuronal protein synthesis. Insulin had no effect on the TCA-soluble fraction of 3H-leu at any time and did not influence the uptake of [3H]aminoisobutyric acid into neurons. The isotope ratio of 3H-leu/14C-leu in the leucyl tRNA pool was the same in control and insulin-treated neurons. Analysis of newly synthesized proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that insulin uniformly increased the incorporation of 14C-leu into all of the resolved neuronal proteins. We conclude from these data that (1) insulin rapidly stimulates overall protein synthesis in fetal neurons independent of amino acid uptake and aminoacyl tRNA precursor pools; (2) stimulation of protein synthesis is mediated by the brain subtype of insulin receptor; and (3) insulin is potentially an important in vivo growth factor for fetal central nervous system neurons

  6. Fetal trauma: brain imaging in four neonates

    Breysem, Luc; Mussen, E.; Demaerel, P.; Smet, M. [Department of Radiology, University Hospitals, Herestraat 49, 3000, Leuven (Belgium); Cossey, V. [Department of Pediatrics, University Hospitals, Leuven (Belgium); Voorde, W. van de [Department of Forensic Medicine, University Hospitals, Leuven (Belgium)

    2004-09-01

    The purpose of this paper is to describe brain pathology in neonates after major traffic trauma in utero during the third trimester. Our patient cohort consisted of four neonates born by emergency cesarean section after car accident in the third trimester of pregnancy. The median gestational age (n=4) was 36 weeks (range: 30-38). Immediate post-natal and follow-up brain imaging consisted of cranial ultrasound (n=4), computed tomography (CT) (n=1) and post-mortem magnetic resonance imaging (MRI) (n=1). Pathology findings were correlated with the imaging findings (n=3). Cranial ultrasound demonstrated a huge subarachnoidal hemorrhage (n=1), subdural hematoma (n=1), brain edema with inversion of the diastolic flow (n=1) and severe ischemic changes (n=1). In one case, CT demonstrated the presence and extension of the subarachnoidal hemorrhage, a parietal fracture and a limited intraventricular hemorrhage. Cerebellar hemorrhage and a small cerebral frontal contusion were seen on post-mortem MRI in a child with a major subarachnoidal hemorrhage on ultrasound. None of these four children survived (three children died within 2 days and one child died after 1 month). Blunt abdominal trauma during pregnancy can cause fetal cranial injury. In our cases, skull fracture, intracranial hemorrhage and hypoxic-ischemic encephalopathy were encountered. (orig.)

  7. Fetal trauma: brain imaging in four neonates

    Breysem, Luc; Mussen, E.; Demaerel, P.; Smet, M.; Cossey, V.; Voorde, W. van de

    2004-01-01

    The purpose of this paper is to describe brain pathology in neonates after major traffic trauma in utero during the third trimester. Our patient cohort consisted of four neonates born by emergency cesarean section after car accident in the third trimester of pregnancy. The median gestational age (n=4) was 36 weeks (range: 30-38). Immediate post-natal and follow-up brain imaging consisted of cranial ultrasound (n=4), computed tomography (CT) (n=1) and post-mortem magnetic resonance imaging (MRI) (n=1). Pathology findings were correlated with the imaging findings (n=3). Cranial ultrasound demonstrated a huge subarachnoidal hemorrhage (n=1), subdural hematoma (n=1), brain edema with inversion of the diastolic flow (n=1) and severe ischemic changes (n=1). In one case, CT demonstrated the presence and extension of the subarachnoidal hemorrhage, a parietal fracture and a limited intraventricular hemorrhage. Cerebellar hemorrhage and a small cerebral frontal contusion were seen on post-mortem MRI in a child with a major subarachnoidal hemorrhage on ultrasound. None of these four children survived (three children died within 2 days and one child died after 1 month). Blunt abdominal trauma during pregnancy can cause fetal cranial injury. In our cases, skull fracture, intracranial hemorrhage and hypoxic-ischemic encephalopathy were encountered. (orig.)

  8. Real-Time Automatic Fetal Brain Extraction in Fetal MRI by Deep Learning

    Salehi, Seyed Sadegh Mohseni; Hashemi, Seyed Raein; Velasco-Annis, Clemente; Ouaalam, Abdelhakim; Estroff, Judy A.; Erdogmus, Deniz; Warfield, Simon K.; Gholipour, Ali

    2017-01-01

    Brain segmentation is a fundamental first step in neuroimage analysis. In the case of fetal MRI, it is particularly challenging and important due to the arbitrary orientation of the fetus, organs that surround the fetal head, and intermittent fetal motion. Several promising methods have been proposed but are limited in their performance in challenging cases and in real-time segmentation. We aimed to develop a fully automatic segmentation method that independently segments sections of the feta...

  9. High vulnerability of the developing fetal brain to ionizing radiation and hyperthermia

    Kameyama, Yoshiro

    1989-01-01

    The developing brain is one of the fetal structures most susceptible to environmental teratogenic insults, because of its long-lasting sensitive period extending from the beginning of embryonic organogenesis to the postnatal infantile period, the great vulnerability of undifferentiated neural cells to a wide range of environmental agents, and the lack of further reproductive capacity of neurons. Among the environmental agents which affect the developing brain, ionizing radiation and hyperthermia are regarded as the most important physical agents. The most prevalent disorders of the brain produced are histogenetic ones such as a deficit of cortical neurons, disorganized cortical architecture, and poor dendritic arborization of the cortical neurons. In this review, emphasis is given to a review of studies on the critical development stage for the induction of histogenetic disorders of the cerebral cortex and on the high vulnerability of developing neuronal cells to the two physical environmental agents mentioned. (author) 59 refs

  10. Fetal frontal cortex transplant (14C) 2-deoxyglucose uptake and histology: survival in cavities of host rat brain motor cortex

    Sharp, F.R.; Gonzalez, M.F.

    1984-01-01

    Fetal frontal neocortex from 18-day-old rat embryonic brain was transplanted into cavities in 30-day-old host motor cortex. Sixty days after transplantation, 5 of 15 transplanted rats had surviving fetal transplants. The fetal cortex transplants were physically attached to the host brain, completely filled the original cavity, and had numerous surviving cells including pyramidal neurons. Cell lamination within the fetal transplant was abnormal. The ( 14 C) 2-deoxyglucose uptake of all five of the fetal neocortex transplants was less than adjacent cortex and contralateral host motor-sensory cortex, but more than adjacent corpus callosum white matter. The results indicate that fetal frontal neocortex can be transplanted into damaged rat motor cortex. The metabolic rate of the transplants suggests they could be partially functional

  11. Fetal, maternal, and placental sources of serotonin and new implications for developmental programming of the brain.

    Bonnin, A; Levitt, P

    2011-12-01

    In addition to its role in neurotransmission, embryonic serotonin (5-HT) has been implicated in the regulation of neurodevelopmental processes. For example, we recently showed that a subset of 5-HT1-receptors expressed in the fetal forebrain mediate a serotonergic modulation of thalamocortical axons response to axon guidance cues, both in vitro and in vivo. This influence of 5-HT signaling on fetal brain wiring raised important questions regarding the source of the ligand during pregnancy. Until recently, it was thought that 5-HT sources impacting brain development arose from maternal transport to the fetus, or from raphe neurons in the brainstem of the fetus. Using genetic mouse models, we uncovered previously unknown differences in 5-HT accumulation between the fore- and hindbrain during early and late fetal stages, through an exogenous source of 5-HT. Using additional genetic strategies, a new technology for studying placental biology ex vivo, and direct manipulation of placental neosynthesis, we investigated the nature of this exogenous source and uncovered a placental 5-HT synthetic pathway from a maternal tryptophan precursor, in both mice and humans. These results implicate a new, direct role for placental metabolic pathways in modulating fetal brain development and suggest an important role for maternal-placental-fetal interactions and 5-HT in the fetal programming of adult mental disorders. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. Vasculo-Neuronal Coupling: Retrograde Vascular Communication to Brain Neurons.

    Kim, Ki Jung; Ramiro Diaz, Juan; Iddings, Jennifer A; Filosa, Jessica A

    2016-12-14

    Continuous cerebral blood flow is essential for neuronal survival, but whether vascular tone influences resting neuronal function is not known. Using a multidisciplinary approach in both rat and mice brain slices, we determined whether flow/pressure-evoked increases or decreases in parenchymal arteriole vascular tone, which result in arteriole constriction and dilation, respectively, altered resting cortical pyramidal neuron activity. We present evidence for intercellular communication in the brain involving a flow of information from vessel to astrocyte to neuron, a direction opposite to that of classic neurovascular coupling and referred to here as vasculo-neuronal coupling (VNC). Flow/pressure increases within parenchymal arterioles increased vascular tone and simultaneously decreased resting pyramidal neuron firing activity. On the other hand, flow/pressure decreases evoke parenchymal arteriole dilation and increased resting pyramidal neuron firing activity. In GLAST-CreERT2; R26-lsl-GCaMP3 mice, we demonstrate that increased parenchymal arteriole tone significantly increased intracellular calcium in perivascular astrocyte processes, the onset of astrocyte calcium changes preceded the inhibition of cortical pyramidal neuronal firing activity. During increases in parenchymal arteriole tone, the pyramidal neuron response was unaffected by blockers of nitric oxide, GABA A , glutamate, or ecto-ATPase. However, VNC was abrogated by TRPV4 channel, GABA B , as well as an adenosine A 1 receptor blocker. Differently to pyramidal neuron responses, increases in flow/pressure within parenchymal arterioles increased the firing activity of a subtype of interneuron. Together, these data suggest that VNC is a complex constitutive active process that enables neurons to efficiently adjust their resting activity according to brain perfusion levels, thus safeguarding cellular homeostasis by preventing mismatches between energy supply and demand. We present evidence for vessel-to-neuron

  13. Fetal antigen 2 in primary and secondary brain tumors

    Rasmussen, H Boje; Teisner, B; Schrøder, H D

    1991-01-01

    Immunohistochemical deposition and distribution of fetal antigen 2 (FA2) was examined in normal brain tissue and in primary and metastatic tumors of the brain. In normal brain tissue FA2 was exclusively found linearly around the vessels, along pia and in arachnoidea. A similar localization was seen...

  14. Developmental disturbances of the fetal brain in guinea-pigs caused by methylmercury

    Inouye, Minoru; Kajiwara, Yuji

    1988-08-01

    Pregnant guinea-pigs of Hartley strain were orally administered methylmercuric chloride once at a dose of 7.5 mg Hg/animal (weighing 500-800 g) on one of days 21, 28, 35, 42 or 49 (3-7 weeks) of gestation. They were killed on day 63 (9 weeks) and their fetuses were removed. Both maternal and fetal blood, brain, liver and kidney, and fetal hair, urine, gastric content and amniotic fluid as well, were sampled for mercury analysis. The fetal brains were also examined pathologically. The maternal kidney contained mercury at a high concentration but the fetal kidney did not. The mercury concentration was strikingly high in the fetal hair, but fairly low in the urine, gastric contents and amniotic fluid. Mercury distributed unevenly in various brain regions of both dams and fetuses after treatment at 6 and 7 weeks of pregnancy (3 and 2 weeks before sampling). The concentration was high in the neopallium and archipallium, followed by the paleopallium, diencephalon and mesencephalon, but low in the rhombencephalon, including cerebellum. Mercury contents were relatively low and distributed almost evenly in various brain regions of both the dams and fetuses following treatment at 3, 4 and 5 weeks of pregnancy. Morphologically, the fetal brains were disturbed in the development following treatment at 3, 4 and 5 weeks of pregnancy. The cerebral cortex was thinned, the nucleus caudatus putamen and the hippocampal formation were reduced in size, and the lateral ventricles were dilated. However, the histological architecture of the cerebral cortex was not strikingly maldeveloped; only a slight disarrangement of the cellular alignment was noted. Following treatment at 6 and 7 weeks of pregnancy, focal degeneration of the neuronal cells was observed in the fetal neocortex; the severe cases showed spongy degeneration and dysgenetic hydrocephalus.

  15. Fetal brain volumetry through MRI volumetric reconstruction and segmentation

    Estroff, Judy A.; Barnewolt, Carol E.; Connolly, Susan A.; Warfield, Simon K.

    2013-01-01

    Purpose Fetal MRI volumetry is a useful technique but it is limited by a dependency upon motion-free scans, tedious manual segmentation, and spatial inaccuracy due to thick-slice scans. An image processing pipeline that addresses these limitations was developed and tested. Materials and methods The principal sequences acquired in fetal MRI clinical practice are multiple orthogonal single-shot fast spin echo scans. State-of-the-art image processing techniques were used for inter-slice motion correction and super-resolution reconstruction of high-resolution volumetric images from these scans. The reconstructed volume images were processed with intensity non-uniformity correction and the fetal brain extracted by using supervised automated segmentation. Results Reconstruction, segmentation and volumetry of the fetal brains for a cohort of twenty-five clinically acquired fetal MRI scans was done. Performance metrics for volume reconstruction, segmentation and volumetry were determined by comparing to manual tracings in five randomly chosen cases. Finally, analysis of the fetal brain and parenchymal volumes was performed based on the gestational age of the fetuses. Conclusion The image processing pipeline developed in this study enables volume rendering and accurate fetal brain volumetry by addressing the limitations of current volumetry techniques, which include dependency on motion-free scans, manual segmentation, and inaccurate thick-slice interpolation. PMID:20625848

  16. Are there fetal stem cells in the maternal brain?

    Osman Demirhan; Necmi (C)ekin; Deniz Ta(s)temir; Erdal Tun(c); Ali irfan Güzel; Demet Meral; Bülent Demirbek

    2013-01-01

    Fetal cells can enter maternal blood during pregnancy but whether they can also cross the blood-brain barrier to enter the maternal brain remains poorly understood. Previous results suggest that fetal cells are summoned to repair damage to the mother's brain. If this is confirmed, it would open up new and safer avenues of treatment for brain damage caused by strokes and neural diseases. In this study, we aimed to investigate whether a baby's stem cells can enter the maternal brain during pregnancy. Deceased patients who had at least one male offspring and no history of abortion and blood transfusion were included in this study. DNA was extracted from brain tissue samples of deceased women using standard phenol-chloroform extraction and ethanol precipitation methods. Genomic DNA was screened by quantitative fluorescent-polymerase chain reaction amplification together with short tandem repeat markers specific to the Y chromosome, and 13, 18, 21 and X. Any foreign DNA residues that could be used to interpret the presence of fetal stem cells in the maternal brain were monitored. Results indicated that fetal stem cells can not cross the blood-brain barrier to enter the maternal brain.

  17. Cross-hemispheric functional connectivity in the human fetal brain.

    Thomason, Moriah E; Dassanayake, Maya T; Shen, Stephen; Katkuri, Yashwanth; Alexis, Mitchell; Anderson, Amy L; Yeo, Lami; Mody, Swati; Hernandez-Andrade, Edgar; Hassan, Sonia S; Studholme, Colin; Jeong, Jeong-Won; Romero, Roberto

    2013-02-20

    Compelling evidence indicates that psychiatric and developmental disorders are generally caused by disruptions in the functional connectivity (FC) of brain networks. Events occurring during development, and in particular during fetal life, have been implicated in the genesis of such disorders. However, the developmental timetable for the emergence of neural FC during human fetal life is unknown. We present the results of resting-state functional magnetic resonance imaging performed in 25 healthy human fetuses in the second and third trimesters of pregnancy (24 to 38 weeks of gestation). We report the presence of bilateral fetal brain FC and regional and age-related variation in FC. Significant bilateral connectivity was evident in half of the 42 areas tested, and the strength of FC between homologous cortical brain regions increased with advancing gestational age. We also observed medial to lateral gradients in fetal functional brain connectivity. These findings improve understanding of human fetal central nervous system development and provide a basis for examining the role of insults during fetal life in the subsequent development of disorders in neural FC.

  18. Genes differentially expressed in medulloblastoma and fetal brain

    Michiels, E. M.; Oussoren, E.; van Groenigen, M.; Pauws, E.; Bossuyt, P. M.; Voûte, P. A.; Baas, F.

    1999-01-01

    Serial analysis of gene expression (SAGE) was used to identify genes that might be involved in the development or growth of medulloblastoma, a childhood brain tumor. Sequence tags from medulloblastoma (10229) and fetal brain (10692) were determined. The distributions of sequence tags in each

  19. Fetal MRI of pathological brain development; Fetale MRT der pathologischen Hirnentwicklung

    Brugger, P.C. [Medizinische Universitaet Wien (Austria). Arbeitsgruppe Integrative Morphologie, Zentrum fuer Anatomie und Zellbiologie; Prayer, D. [Medizinische Universitaet Wien (Austria). Klinik fuer Radiodiagnostik

    2006-02-15

    Because of the superior tissue contrast, high spatial resolution, and multiplanar capabilities, fetal magnetic resonance imaging (MRI) can depict fetal brain pathologies with high accuracy. Pathological fetal brain development may result from malformations or acquired conditions. Differentiation of these etiologies is important with respect to managing the actual pregnancy or counseling future pregnancies. As a widened ventricular system is a common hallmark of both maldevelopment and acquired conditions, it may cause problems in the differential diagnosis. Fetal MRI can provide detailed morphological information, which allows refinement of the diagnosis of ventricular enlargement in a large number of cases. Systematic work-up of morphological details that may be recognized on MR images provides an approach for achieving a correct diagnosis in cases of ventricle enlargement. (orig.) [German] Aufgrund des hervorragenden Gewebekontrastes, der hohen raeumlichen Aufloesung und multiplanaren Moeglichkeiten erlaubt die fetale Magnetresonanztomographie (MRT) eine detaillierte Darstellung fetaler Hirnpathologien. Eine pathologische Hirnentwicklung kann sowohl auf Fehlbildungen als auch waehrend der Schwangerschaft erworbenen Stoerungen beruhen. Nachdem die weiteren Konsequenzen fuer die bestehende, aber auch fuer folgende Schwangerschaften zu einem grossen Teil von einer Differenzierung dieser Aetiologien abhaengig sein kann, ist ein Erkennen der jeweiligen Pathologie wesentlich. Die morphologische Praesentation erworbener und fehlbildungsbedingter Veraenderungen auf MR-Bildern ist u. U. sehr aehnlich. Besondere differenzialdiagnostische Probleme bereitet dabei das Vorliegen eines erweiterten Ventrikelsystems, das als Symptom unterschiedlichster Veraenderungen vorliegen kann. Anhand einer systematischen Darstellung mittels MR-erfassbarer morphologischer Details wird eine Anleitung gegeben, bei Bestehen dieses Leitsymptoms zu einer moeglichst genauen Diagnose zu kommen

  20. Cocaine is pharmacologically active in the nonhuman primate fetal brain

    Benveniste, Helene; Fowler, Joanna S; Rooney, William D

    2010-01-01

    Cocaine use during pregnancy is deleterious to the newborn child, in part via its disruption of placental blood flow. However, the extent to which cocaine can affect the function of the fetal primate brain is still an unresolved question. Here we used PET and MRI and show that in third-trimester ......Cocaine use during pregnancy is deleterious to the newborn child, in part via its disruption of placental blood flow. However, the extent to which cocaine can affect the function of the fetal primate brain is still an unresolved question. Here we used PET and MRI and show that in third......-trimester pregnant nonhuman primates, cocaine at doses typically used by drug abusers significantly increased brain glucose metabolism to the same extent in the mother as in the fetus (approximately 100%). Inasmuch as brain glucose metabolism is a sensitive marker of brain function, the current findings provide...

  1. Metabolomics reveals metabolic alterations by intrauterine growth restriction in the fetal rabbit brain.

    Erwin van Vliet

    Full Text Available Intrauterine Growth Restriction (IUGR due to placental insufficiency occurs in 5-10% of pregnancies and is a major risk factor for abnormal neurodevelopment. The perinatal diagnosis of IUGR related abnormal neurodevelopment represents a major challenge in fetal medicine. The development of clinical biomarkers is considered a promising approach, but requires the identification of biochemical/molecular alterations by IUGR in the fetal brain. This targeted metabolomics study in a rabbit IUGR model aimed to obtain mechanistic insight into the effects of IUGR on the fetal brain and identify metabolite candidates for biomarker development.At gestation day 25, IUGR was induced in two New Zealand rabbits by 40-50% uteroplacental vessel ligation in one horn and the contralateral horn was used as control. At day 30, fetuses were delivered by Cesarian section, weighed and brains collected for metabolomics analysis. Results showed that IUGR fetuses had a significantly lower birth and brain weight compared to controls. Metabolomics analysis using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS and database matching identified 78 metabolites. Comparison of metabolite intensities using a t-test demonstrated that 18 metabolites were significantly different between control and IUGR brain tissue, including neurotransmitters/peptides, amino acids, fatty acids, energy metabolism intermediates and oxidative stress metabolites. Principle component and hierarchical cluster analysis showed cluster formations that clearly separated control from IUGR brain tissue samples, revealing the potential to develop predictive biomarkers. Moreover birth weight and metabolite intensity correlations indicated that the extent of alterations was dependent on the severity of IUGR.IUGR leads to metabolic alterations in the fetal rabbit brain, involving neuronal viability, energy metabolism, amino acid levels, fatty acid profiles and oxidative stress

  2. Fetal magnetic resonance imaging of the brain: technical considerations and normal brain development

    Huisman, Thierry A.G.M.; Kubik-Huch, Rahel; Marincek, Borut [Institute of Diagnostic Radiology, University Hospital Zurich, 8091 Zurich (Switzerland); Martin, Ernst [Department of Neuroradiology and Magnetic Resonance, University Children' s Hospital, 8091 Zurich (Switzerland)

    2002-08-01

    Fetal MRI examines non-invasively the unborn fetus. Ultrafast MRI sequences effectively suppress fetal motion. Multiple case reports and studies have shown that fetal MRI is particularly helpful in the evaluation of the central nervous system. The high contrast-to-noise ratio, the high spatial resolution, the multiplanar capabilities, the large field of view and the simultaneous visualisation of fetal and maternal structures have proven to be advantageous. Fetal MRI is particularly helpful in the evaluation of the normal and pathological development of the brain. Despite the fact that no side effects have been reported or are to be expected, the use of MRI during pregnancy is still limited to the second and third trimester of pregnancy. Magnetic resonance imaging contrast media are not to be used as it passes the placenta. Ultrasound remains the primary screening modality for fetal pathology; fetal MRI can serve as an adjunct or second-line imaging modality. (orig.)

  3. Fetal magnetic resonance imaging of the brain: technical considerations and normal brain development

    Huisman, Thierry A.G.M.; Kubik-Huch, Rahel; Marincek, Borut; Martin, Ernst

    2002-01-01

    Fetal MRI examines non-invasively the unborn fetus. Ultrafast MRI sequences effectively suppress fetal motion. Multiple case reports and studies have shown that fetal MRI is particularly helpful in the evaluation of the central nervous system. The high contrast-to-noise ratio, the high spatial resolution, the multiplanar capabilities, the large field of view and the simultaneous visualisation of fetal and maternal structures have proven to be advantageous. Fetal MRI is particularly helpful in the evaluation of the normal and pathological development of the brain. Despite the fact that no side effects have been reported or are to be expected, the use of MRI during pregnancy is still limited to the second and third trimester of pregnancy. Magnetic resonance imaging contrast media are not to be used as it passes the placenta. Ultrasound remains the primary screening modality for fetal pathology; fetal MRI can serve as an adjunct or second-line imaging modality. (orig.)

  4. Fetal magnetic resonance imaging of the brain: technical considerations and normal brain development.

    Huisman, Thierry A G M; Martin, Ernst; Kubik-Huch, Rahel; Marincek, Borut

    2002-08-01

    Fetal MRI examines non-invasively the unborn fetus. Ultrafast MRI sequences effectively suppress fetal motion. Multiple case reports and studies have shown that fetal MRI is particularly helpful in the evaluation of the central nervous system. The high contrast-to-noise ratio, the high spatial resolution, the multiplanar capabilities, the large field of view and the simultaneous visualisation of fetal and maternal structures have proven to be advantageous. Fetal MRI is particularly helpful in the evaluation of the normal and pathological development of the brain. Despite the fact that no side effects have been reported or are to be expected, the use of MRI during pregnancy is still limited to the second and third trimester of pregnancy. Magnetic resonance imaging contrast media are not to be used as it passes the placenta. Ultrasound remains the primary screening modality for fetal pathology; fetal MRI can serve as an adjunct or second-line imaging modality.

  5. Sectional anatomy of the fetal brain in uterus at term on the sagittal plane

    Fan-Zhen Kong

    2011-06-01

    Conclusion: Through the comparison study between sagittal sections and corresponding MRI of fetal brain at term, we could obtain morphological anatomic structures and MRI of fetal brain, providing morphological demonstration of the intrauterine development of fetal brain and auxiliary diagnosis of ultrasound and MRI in pregnant woman.

  6. File list: His.Neu.20.AllAg.Fetal_brain [Chip-atlas[Archive

    Full Text Available His.Neu.20.AllAg.Fetal_brain hg19 Histone Neural Fetal brain SRX860887,SRX860879,SR...X860886,SRX860883,SRX860881,SRX860885,SRX860884,SRX860880,SRX860888,SRX860882 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Neu.20.AllAg.Fetal_brain.bed ...

  7. File list: ALL.Neu.50.AllAg.Fetal_brain [Chip-atlas[Archive

    Full Text Available ALL.Neu.50.AllAg.Fetal_brain hg19 All antigens Neural Fetal brain SRX142786,SRX2096...60880 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Neu.50.AllAg.Fetal_brain.bed ...

  8. File list: NoD.Neu.50.AllAg.Fetal_brain [Chip-atlas[Archive

    Full Text Available NoD.Neu.50.AllAg.Fetal_brain hg19 No description Neural Fetal brain SRX142786,SRX03...1421,SRX142793,SRX056802,SRX031451,SRX031404,SRX031387 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/NoD.Neu.50.AllAg.Fetal_brain.bed ...

  9. Quantitative analysis of normal fetal brain volume and flow by three-dimensional power Doppler ultrasound

    Ju-Chun Hsu

    2013-09-01

    Conclusion: 3D ultrasound can be used to assess the fetal brain volume and blood flow development quantitatively. Our study indicates that the fetal brain vascularization and blood flow correlates significantly with the advancement of GA. This information may serve as a reference point for further studies of the fetal brain volume and blood flow in abnormal conditions.

  10. File list: NoD.Neu.05.AllAg.Fetal_brain [Chip-atlas[Archive

    Full Text Available NoD.Neu.05.AllAg.Fetal_brain hg19 No description Neural Fetal brain SRX056802,SRX14...2786,SRX142793,SRX031387,SRX031451,SRX031404,SRX031421 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/NoD.Neu.05.AllAg.Fetal_brain.bed ...

  11. File list: ALL.Neu.05.AllAg.Fetal_brain [Chip-atlas[Archive

    Full Text Available ALL.Neu.05.AllAg.Fetal_brain hg19 All antigens Neural Fetal brain SRX056802,SRX1427...60882 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Neu.05.AllAg.Fetal_brain.bed ...

  12. File list: His.Neu.05.AllAg.Fetal_brain [Chip-atlas[Archive

    Full Text Available His.Neu.05.AllAg.Fetal_brain hg19 Histone Neural Fetal brain SRX860887,SRX860886,SR...X860885,SRX860881,SRX860879,SRX860888,SRX860880,SRX860883,SRX860884,SRX860882 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Neu.05.AllAg.Fetal_brain.bed ...

  13. File list: DNS.Neu.50.AllAg.Fetal_brain [Chip-atlas[Archive

    Full Text Available DNS.Neu.50.AllAg.Fetal_brain hg19 DNase-seq Neural Fetal brain SRX040380,SRX040395,...6,SRX121278 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Neu.50.AllAg.Fetal_brain.bed ...

  14. File list: DNS.Neu.20.AllAg.Fetal_brain [Chip-atlas[Archive

    Full Text Available DNS.Neu.20.AllAg.Fetal_brain hg19 DNase-seq Neural Fetal brain SRX040380,SRX040395,...6,SRX121278 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Neu.20.AllAg.Fetal_brain.bed ...

  15. File list: ALL.Neu.20.AllAg.Fetal_brain [Chip-atlas[Archive

    Full Text Available ALL.Neu.20.AllAg.Fetal_brain hg19 All antigens Neural Fetal brain SRX142786,SRX2096...60882 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Neu.20.AllAg.Fetal_brain.bed ...

  16. File list: NoD.Neu.10.AllAg.Fetal_brain [Chip-atlas[Archive

    Full Text Available NoD.Neu.10.AllAg.Fetal_brain hg19 No description Neural Fetal brain SRX142786,SRX05...6802,SRX031451,SRX031387,SRX142793,SRX031404,SRX031421 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/NoD.Neu.10.AllAg.Fetal_brain.bed ...

  17. File list: DNS.Neu.10.AllAg.Fetal_brain [Chip-atlas[Archive

    Full Text Available DNS.Neu.10.AllAg.Fetal_brain hg19 DNase-seq Neural Fetal brain SRX040380,SRX040395,...6,SRX121278 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Neu.10.AllAg.Fetal_brain.bed ...

  18. File list: His.Neu.10.AllAg.Fetal_brain [Chip-atlas[Archive

    Full Text Available His.Neu.10.AllAg.Fetal_brain hg19 Histone Neural Fetal brain SRX860887,SRX860886,SR...X860879,SRX860888,SRX860880,SRX860881,SRX860885,SRX860883,SRX860884,SRX860882 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Neu.10.AllAg.Fetal_brain.bed ...

  19. Retardation of fetal dendritic development induced by gestational hyperglycemia is associated with brain insulin/IGF-I signals.

    Jing, Yu-Hong; Song, Yan-Feng; Yao, Ya-Ming; Yin, Jie; Wang, De-Gui; Gao, Li-Ping

    2014-10-01

    Hyperglycemia is an essential risk factor for mothers and fetuses in gestational diabetes. Clinical observation has indicated that the offspring of mothers with diabetes shows impaired somatosensory function and IQ. However, only a few studies have explored the effects of hyperglycemia on fetal brain development. Neurodevelopment is susceptible to environmental conditions. Thus, this study aims to investigate the effects of maternal hyperglycemia on fetal brain development and to evaluate insulin and insulin-like growth factor-I (IGF-I) signals in fetal brain under hyperglycemia or controlled hyperglycemia. At day 1 of pregnancy, gestational rats were intraperitoneally injected with streptozocin (60 mg/kg). Some of the hyperglycemic gestational rats were injected with insulin (20 IU, two times a day) to control hyperglycemia; the others were injected with saline of equal volume. The gestational rats were sacrificed at days 14, 16, and 18 of embryo development. The dendritic spines of subplate cortex neurons in the fetal brain were detected by Golgi-Cox staining. The mRNA levels of insulin receptors (IRs) and IGF-IR in the fetal brain were measured using qRT-PCR. The protein levels of synaptophysin, IR, and IGF-IR in the fetal brain were detected by western blot. No significant difference in fetal brain formation was observed between the maternal hyperglycemic group and insulin-treated group. By contrast, obvious retardation of dendritic development in the fetus was observed in the maternal hyperglycemic group. Similarly, synaptophysin expression was lower in the fetus of the maternal hyperglycemic group than in that of the insulin-treated group. The mRNA and protein expression levels of IRs in the fetal brain were higher in the hyperglycemic group than in the insulin-treated group. By contrast, the levels of IGF-IR in the brain were lower in the fetus of the maternal hyperglycemic group than in that of the insulin-treated group. These results suggested that

  20. MicroRNAs and fetal brain development: Implications for ethanol teratology during the second trimester period of neurogenesis.

    Rajesh eMiranda

    2012-05-01

    Full Text Available Maternal ethanol consumption during pregnancy can lead to a stereotypic cluster of fetal craniofacial, cardiovascular, skeletal and neurological deficits that are collectively termed the Fetal Alcohol Spectrum Disorder (FASD. Fetal ethanol exposure is a leading non-genetic cause of mental retardation. Mechanisms underlying the etiology of ethanol teratology are varied and complex. This review will focus on the developing brain as an important and vulnerable ethanol target. Near the end of the first trimester, and during the second trimester, fetal neural stem cells (NSCs produce most of the neurons of the adult brain, and ethanol has been shown to influence NSC renewal and maturation. We will discuss the neural developmental and teratological implications of the biogenesis and function of microRNAs (miRNAs, a class of small non-protein-coding RNAs that control the expression of gene networks by translation repression. A small but growing body of research has identified ethanol-sensitive miRNAs at different stages of NSC and brain maturation. While many microRNAs appear to be vulnerable to ethanol at specific developmental stages, a few, like the miR-9 family, appear to exhibit broad vulnerability to ethanol across multiple stages of NSC differentiation. An assessment of the regulation and function of these miRNAs provides important clues about the mechanisms that underlie fetal vulnerability to alterations in the maternal-fetal environment and yields insights into the genesis of FASD.

  1. Differing levels of excision repair in human fetal dermis and brain cells

    Gibson, R.E.; D'Ambrosio, S.M.; Ohio State Univ., Columbus

    1982-01-01

    The levels of DNA excision repair, as measured by unscheduled DNA synthesis (UDS) and the UV-endonuclease sensitive site assay, were compared in cells derived from human fetal brain and dermal tissues. The level of UDS induced following ultraviolet (UV) irradiation was found to be lower (approx. 60%) in the fetal brain cells than in fetal dermal cells. It was determined, using the UV-endonuclease sensitive site assay to confirm the UDS observation, that 50% of the dimers induced by UV in fetal dermal cells were repaired in 8 h. while only 15% were removed in the fetal brain cells during the same period of time. Even after 24 h. only 44% of the dimers induced by UV in the fetal brain cells were repaired, while 65% were removed in the dermal cells. These data suggest that cultured human fetal brain cells exhibit lower levels of excision repair compared to cultured human fetal dermal cells. (author)

  2. Comparative Analysis of Human and Rodent Brain Primary Neuronal Culture Spontaneous Activity Using Micro-Electrode Array Technology.

    Napoli, Alessandro; Obeid, Iyad

    2016-03-01

    Electrical activity in embryonic brain tissue has typically been studied using Micro Electrode Array (MEA) technology to make dozens of simultaneous recordings from dissociated neuronal cultures, brain stem cell progenitors, or brain slices from fetal rodents. Although these rodent neuronal primary culture electrical properties are mostly investigated, it has not been yet established to what extent the electrical characteristics of rodent brain neuronal cultures can be generalized to those of humans. A direct comparison of spontaneous spiking activity between rodent and human primary neurons grown under the same in vitro conditions using MEA technology has never been carried out before and will be described in the present study. Human and rodent dissociated fetal brain neuronal cultures were established in-vitro by culturing on a glass grid of 60 planar microelectrodes neurons under identical conditions. Three different cultures of human neurons were produced from tissue sourced from a single aborted fetus (at 16-18 gestational weeks) and these were compared with seven different cultures of embryonic rat neurons (at 18 gestational days) originally isolated from a single rat. The results show that the human and rodent cultures behaved significantly differently. Whereas the rodent cultures demonstrated robust spontaneous activation and network activity after only 10 days, the human cultures required nearly 40 days to achieve a substantially weaker level of electrical function. These results suggest that rat neuron preparations may yield inferences that do not necessarily transfer to humans. © 2015 Wiley Periodicals, Inc.

  3. MR imaging methods for assessing fetal brain development.

    Rutherford, Mary; Jiang, Shuzhou; Allsop, Joanna; Perkins, Lucinda; Srinivasan, Latha; Hayat, Tayyib; Kumar, Sailesh; Hajnal, Jo

    2008-05-01

    Fetal magnetic resonance imaging provides an ideal tool for investigating growth and development of the brain in vivo. Current imaging methods have been hampered by fetal motion but recent advances in image acquisition can produce high signal to noise, high resolution 3-dimensional datasets suitable for objective quantification by state of the art post acquisition computer programs. Continuing development of imaging techniques will allow a unique insight into the developing brain, more specifically process of cell migration, axonal pathway formation, and cortical maturation. Accurate quantification of these developmental processes in the normal fetus will allow us to identify subtle deviations from normal during the second and third trimester of pregnancy either in the compromised fetus or in infants born prematurely.

  4. Cocaine is pharmacologically active in the nonhuman primate fetal brain

    Benveniste, Helene; Fowler, Joanna S; Rooney, William D

    2010-01-01

    Cocaine use during pregnancy is deleterious to the newborn child, in part via its disruption of placental blood flow. However, the extent to which cocaine can affect the function of the fetal primate brain is still an unresolved question. Here we used PET and MRI and show that in third-trimester ......Cocaine use during pregnancy is deleterious to the newborn child, in part via its disruption of placental blood flow. However, the extent to which cocaine can affect the function of the fetal primate brain is still an unresolved question. Here we used PET and MRI and show that in third...... are influenced by the state of pregnancy. Our findings have clinical implications because they imply that the adverse effects of prenatal cocaine exposure to the newborn child include not only cocaine's deleterious effects to the placental circulation, but also cocaine's direct pharmacological effect...

  5. Mapping fetal brain development in utero using magnetic resonance imaging: the Big Bang of brain mapping.

    Studholme, Colin

    2011-08-15

    The development of tools to construct and investigate probabilistic maps of the adult human brain from magnetic resonance imaging (MRI) has led to advances in both basic neuroscience and clinical diagnosis. These tools are increasingly being applied to brain development in adolescence and childhood, and even to neonatal and premature neonatal imaging. Even earlier in development, parallel advances in clinical fetal MRI have led to its growing use as a tool in challenging medical conditions. This has motivated new engineering developments encompassing optimal fast MRI scans and techniques derived from computer vision, the combination of which allows full 3D imaging of the moving fetal brain in utero without sedation. These promise to provide a new and unprecedented window into early human brain growth. This article reviews the developments that have led us to this point, examines the current state of the art in the fields of fast fetal imaging and motion correction, and describes the tools to analyze dynamically changing fetal brain structure. New methods to deal with developmental tissue segmentation and the construction of spatiotemporal atlases are examined, together with techniques to map fetal brain growth patterns.

  6. Novel applications of quantitative MRI for the fetal brain

    Clouchoux, Cedric [Children' s National Medical Center, Division of Diagnostic Imaging and Radiology, Washington, DC (United States); Limperopoulos, Catherine [Children' s National Medical Center, Division of Diagnostic Imaging and Radiology, Washington, DC (United States); McGill University, McConnell Brain Imaging Center, Montreal Neurological Institute, Montreal (Canada); McGill University, Department of Neurology and Neurosurgery, Montreal (Canada); Children' s National Medical Center, Division of Fetal and Transitional Medicine, Washington, DC (United States)

    2012-01-15

    The advent of ultrafast MRI acquisitions is offering vital insights into the critical maturational events that occur throughout pregnancy. Concurrent with the ongoing enhancement of ultrafast imaging has been the development of innovative image-processing techniques that are enabling us to capture and quantify the exuberant growth, and organizational and remodeling processes that occur during fetal brain development. This paper provides an overview of the role of advanced neuroimaging techniques to study in vivo brain maturation and explores the application of a range of new quantitative imaging biomarkers that can be used clinically to monitor high-risk pregnancies. (orig.)

  7. Fetal alcohol exposure reduces responsiveness of taste nerves and trigeminal chemosensory neurons to ethanol and its flavor components.

    Glendinning, John I; Tang, Joyce; Morales Allende, Ana Paula; Bryant, Bruce P; Youngentob, Lisa; Youngentob, Steven L

    2017-08-01

    Fetal alcohol exposure (FAE) leads to increased intake of ethanol in adolescent rats and humans. We asked whether these behavioral changes may be mediated in part by changes in responsiveness of the peripheral taste and oral trigeminal systems. We exposed the experimental rats to ethanol in utero by administering ethanol to dams through a liquid diet; we exposed the control rats to an isocaloric and isonutritive liquid diet. To assess taste responsiveness, we recorded responses of the chorda tympani (CT) and glossopharyngeal (GL) nerves to lingual stimulation with ethanol, quinine, sucrose, and NaCl. To assess trigeminal responsiveness, we measured changes in calcium levels of isolated trigeminal ganglion (TG) neurons during stimulation with ethanol, capsaicin, mustard oil, and KCl. Compared with adolescent control rats, the adolescent experimental rats exhibited diminished CT nerve responses to ethanol, quinine, and sucrose and GL nerve responses to quinine and sucrose. The reductions in taste responsiveness persisted into adulthood for quinine but not for any of the other stimuli. Adolescent experimental rats also exhibited reduced TG neuron responses to ethanol, capsaicin, and mustard oil. The lack of change in responsiveness of the taste nerves to NaCl and the TG neurons to KCl indicates that FAE altered only a subset of the response pathways within each chemosensory system. We propose that FAE reprograms development of the peripheral taste and trigeminal systems in ways that reduce their responsiveness to ethanol and surrogates for its pleasant (i.e., sweet) and unpleasant (i.e., bitterness, oral burning) flavor attributes. NEW & NOTEWORTHY Pregnant mothers are advised to avoid alcohol. This is because even small amounts of alcohol can alter fetal brain development and increase the risk of adolescent alcohol abuse. We asked how fetal alcohol exposure (FAE) produces the latter effect in adolescent rats by measuring responsiveness of taste nerves and trigeminal

  8. Volumetric MRI study of the intrauterine growth restriction fetal brain

    Polat, A.; Barlow, S.; Ber, R.; Achiron, R.; Katorza, E.

    2017-01-01

    Intrauterine growth restriction (IUGR) is a pathologic fetal condition known to affect the fetal brain regionally and associated with future neurodevelopmental abnormalities. This study employed MRI to assess in utero regional brain volume changes in IUGR fetuses compared to controls. Retrospectively, using MRI images of fetuses at 30-34 weeks gestational age, a total of 8 brain regions - supratentorial brain and cavity, cerebral hemispheres, temporal lobes and cerebellum - were measured for volume in 13 fetuses with IUGR due to placental insufficiency and in 21 controls. Volumes and their ratios were assessed for difference using regression models. Reliability was assessed by intraclass correlation coefficients (ICC) between two observers. In both groups, all structures increase in absolute volume during that gestation period, and the rate of cerebellar growth is higher compared to that of supratentorial structures. All structures' absolute volumes were significantly smaller for the IUGR group. Cerebellar to supratentorial ratios were found to be significantly smaller (P < 0.05) for IUGR compared to controls. No other significant ratio differences were found. ICC showed excellent agreement. The cerebellar to supratentorial volume ratio is affected in IUGR fetuses. Additional research is needed to assess this as a radiologic marker in relation to long-term outcome. (orig.)

  9. Volumetric MRI study of the intrauterine growth restriction fetal brain

    Polat, A.; Barlow, S.; Ber, R.; Achiron, R.; Katorza, E. [Tel Aviv University, Sackler School of Medicine, Department of Obstetrics and Gynecology, Chaim Sheba Medical Center, Tel Hashomer (Israel)

    2017-05-15

    Intrauterine growth restriction (IUGR) is a pathologic fetal condition known to affect the fetal brain regionally and associated with future neurodevelopmental abnormalities. This study employed MRI to assess in utero regional brain volume changes in IUGR fetuses compared to controls. Retrospectively, using MRI images of fetuses at 30-34 weeks gestational age, a total of 8 brain regions - supratentorial brain and cavity, cerebral hemispheres, temporal lobes and cerebellum - were measured for volume in 13 fetuses with IUGR due to placental insufficiency and in 21 controls. Volumes and their ratios were assessed for difference using regression models. Reliability was assessed by intraclass correlation coefficients (ICC) between two observers. In both groups, all structures increase in absolute volume during that gestation period, and the rate of cerebellar growth is higher compared to that of supratentorial structures. All structures' absolute volumes were significantly smaller for the IUGR group. Cerebellar to supratentorial ratios were found to be significantly smaller (P < 0.05) for IUGR compared to controls. No other significant ratio differences were found. ICC showed excellent agreement. The cerebellar to supratentorial volume ratio is affected in IUGR fetuses. Additional research is needed to assess this as a radiologic marker in relation to long-term outcome. (orig.)

  10. Repeated isoflurane exposure and neuroapoptosis in the midgestation fetal sheep brain.

    Olutoye, Olutoyin A; Sheikh, Fariha; Zamora, Irving J; Yu, Ling; Akinkuotu, Adesola C; Adesina, Adekunle M; Olutoye, Oluyinka O

    2016-04-01

    Advances in surgery and technology have resulted in increased in-utero procedures. However, the effect of anesthesia on the fetal brain is not fully known. The inhalational anesthetic agent, isoflurane, other gamma amino butyric acid agonists (benzodiazepines, barbiturates, propofol, other inhalation anesthetics), and N-methyl D aspartate antagonists, eg, ketamine, have been shown to induce neuroapoptosis. The ovine model has been used extensively to study maternal-fetal physiologic interactions and to investigate different surgical interventions on the fetus. The purpose of this study was to determine effects of different doses and duration of isoflurane on neuroapoptosis in midgestation fetal sheep. We hypothesized that repeated anesthetic exposure and high concentrations of isoflurane would result in increased neuroapoptosis. Time-dated, pregnant sheep at 70 days gestation (term 145 days) received either isoflurane 2% × 1 hour, 4% × 3 hours, or 2% × 1 hour every other day for 3 exposures (repeated exposure group). Euthanasia occurred following anesthetic exposure and fetal brains were processed. Neuroapoptosis was detected by immunohistochemistry using anticaspase-3 antibodies. Fetuses unexposed to anesthesia served as controls. Another midgestation group with repeated 2% isoflurane exposure was examined at day 130 (long-term group) and neuronal cell density compared to age-matched controls. Representative sections of the brain were analyzed using Aperio Digital imaging (Leica Microsystems Inc, Buffalo Grove, IL). Data, reported by number of neurons per cubic millimeter of brain tissue are presented as means and SEM. Data were analyzed using the Mann-Whitney U and Kruskal-Wallis tests as appropriate. A total of 34 fetuses were studied. There was no significant difference in neuroapoptosis observed in fetuses exposed to 2% isoflurane for 1 hour or 4% isoflurane for 3 hours. Increased neuroapoptosis was observed in the frontal cortex following repeated 2

  11. MRS of normal and impaired fetal brain development

    Girard, Nadine; Fogliarini, Celine; Viola, Angele; Confort-Gouny, Sylviane; Le Fur, Yann; Viout, Patrick; Chapon, Frederique; Levrier, Olivier; Cozzone, Patrick

    2006-01-01

    Cerebral maturation in the human fetal brain was investigated by in utero localized proton magnetic resonance spectroscopy (MRS). Spectra were acquired on a clinical MR system operating at 1.5 T. Body phased array coils (four coils) were used in combination with spinal coils (two coils). The size of the nominal volume of interest (VOI) was 4.5 cm 3 (20 mm x 15 mm x 15 mm). The MRS acquisitions were performed using a spin echo sequence at short and long echo times (TE = 30 ms and 135 ms) with a VOI located within the cerebral hemisphere at the level of the centrum semiovale. A significant reduction in myo-inositol and choline and an increase in N-acetylaspartate were observed with progressive age. The normal MR spectroscopy data reported here will help to determine whether brain metabolism is altered, especially when subtle anatomic changes are observed on conventional images. Some examples of impaired fetal brain development studied by MRS are illustrated

  12. MRS of normal and impaired fetal brain development

    Girard, Nadine [Service de Neuroradiologie, Assistance Publique-Hopitaux de Marseille, Hopital la Timone, Universite de la Mediterranee, Marseille (France)]. E-mail: nadine.girard@ap-hm.fr; Fogliarini, Celine [Centre de Resonance Magnetique Biologique et Medicale, UMR CNRS 6612, Universite de la Mediterranee, Faculte de Medecine la Timone, Marseille (France); Viola, Angele [Centre de Resonance Magnetique Biologique et Medicale, UMR CNRS 6612, Universite de la Mediterranee, Faculte de Medecine la Timone, Marseille (France); Confort-Gouny, Sylviane [Centre de Resonance Magnetique Biologique et Medicale, UMR CNRS 6612, Universite de la Mediterranee, Faculte de Medecine la Timone, Marseille (France); Le Fur, Yann [Centre de Resonance Magnetique Biologique et Medicale, UMR CNRS 6612, Universite de la Mediterranee, Faculte de Medecine la Timone, Marseille (France); Viout, Patrick [Centre de Resonance Magnetique Biologique et Medicale, UMR CNRS 6612, Universite de la Mediterranee, Faculte de Medecine la Timone, Marseille (France); Chapon, Frederique [Service de Neuroradiologie, Assistance Publique-Hopitaux de Marseille, Hopital la Timone, Universite de la Mediterranee, Marseille (France); Levrier, Olivier [Service de Neuroradiologie, Assistance Publique-Hopitaux de Marseille, Hopital la Timone, Universite de la Mediterranee, Marseille (France); Cozzone, Patrick [Centre de Resonance Magnetique Biologique et Medicale, UMR CNRS 6612, Universite de la Mediterranee, Faculte de Medecine la Timone, Marseille (France)

    2006-02-15

    Cerebral maturation in the human fetal brain was investigated by in utero localized proton magnetic resonance spectroscopy (MRS). Spectra were acquired on a clinical MR system operating at 1.5 T. Body phased array coils (four coils) were used in combination with spinal coils (two coils). The size of the nominal volume of interest (VOI) was 4.5 cm{sup 3} (20 mm x 15 mm x 15 mm). The MRS acquisitions were performed using a spin echo sequence at short and long echo times (TE = 30 ms and 135 ms) with a VOI located within the cerebral hemisphere at the level of the centrum semiovale. A significant reduction in myo-inositol and choline and an increase in N-acetylaspartate were observed with progressive age. The normal MR spectroscopy data reported here will help to determine whether brain metabolism is altered, especially when subtle anatomic changes are observed on conventional images. Some examples of impaired fetal brain development studied by MRS are illustrated.

  13. Generation of human cortical neurons from a new immortal fetal neural stem cell line

    Cacci, E.; Villa, A.; Parmar, M.; Cavallaro, M.; Mandahl, N.; Lindvall, O.; Martinez-Serrano, A.; Kokaia, Z.

    2007-01-01

    Isolation and expansion of neural stem cells (NSCs) of human origin are crucial for successful development of cell therapy approaches in neurodegenerative diseases. Different epigenetic and genetic immortalization strategies have been established for long-term maintenance and expansion of these cells in vitro. Here we report the generation of a new, clonal NSC (hc-NSC) line, derived from human fetal cortical tissue, based on v-myc immortalization. Using immunocytochemistry, we show that these cells retain the characteristics of NSCs after more than 50 passages. Under proliferation conditions, when supplemented with epidermal and basic fibroblast growth factors, the hc-NSCs expressed neural stem/progenitor cell markers like nestin, vimentin and Sox2. When growth factors were withdrawn, proliferation and expression of v-myc and telomerase were dramatically reduced, and the hc-NSCs differentiated into glia and neurons (mostly glutamatergic and GABAergic, as well as tyrosine hydroxylase-positive, presumably dopaminergic neurons). RT-PCR analysis showed that the hc-NSCs retained expression of Pax6, Emx2 and Neurogenin2, which are genes associated with regionalization and cell commitment in cortical precursors during brain development. Our data indicate that this hc-NSC line could be useful for exploring the potential of human NSCs to replace dead or damaged cortical cells in animal models of acute and chronic neurodegenerative diseases. Taking advantage of its clonality and homogeneity, this cell line will also be a valuable experimental tool to study the regulatory role of intrinsic and extrinsic factors in human NSC biology

  14. Diffusion-weighted imaging in normal fetal brain maturation

    Schneider, J.F. [University Children' s Hospital UKBB, Department of Pediatric Radiology, Basel (Switzerland); Confort-Gouny, S.; Le Fur, Y.; Viout, P.; Cozzone, P. [UMR-CNRS 6612, Faculte de Medecine, Universite de la Mediterranee, Centre de Resonance Magnetique Biologique et Medicale, Marseille (France); Bennathan, M.; Chapon, F.; Fogliarini, C.; Girard, N. [Universite de la Mediterranee, Department of Neuroradiology AP-HM Timone, Marseille (France)

    2007-09-15

    Diffusion-weighted imaging (DWI) provides information about tissue maturation not seen on conventional magnetic resonance imaging. The aim of this study is to analyze the evolution over time of the apparent diffusion coefficient (ADC) of normal fetal brain in utero. DWI was performed on 78 fetuses, ranging from 23 to 37 gestational weeks (GW). All children showed at follow-up a normal neurological evaluation. ADC values were obtained in the deep white matter (DWM) of the centrum semiovale, the frontal, parietal, occipital and temporal lobe, in the cerebellar hemisphere, the brainstem, the basal ganglia (BG) and the thalamus. Mean ADC values in supratentorial DWM areas (1.68 {+-} 0.05 mm{sup 2}/s) were higher compared with the cerebellar hemisphere (1.25 {+-} 0.06 mm{sup 2}/s) and lowest in the pons (1.11 {+-} 0.05 mm{sup 2}/s). Thalamus and BG showed intermediate values (1.25 {+-} 0.04 mm{sup 2}/s). Brainstem, cerebellar hemisphere and thalamus showed a linear negative correlation with gestational age. Supratentorial areas revealed an increase in ADC values, followed by a decrease after the 30th GW. This study provides a normative data set that allows insights in the normal fetal brain maturation in utero, which has not yet been observed in previous studies on premature babies. (orig.)

  15. Three-dimensional sonographic measurement of normal fetal brain volume during the second half of pregnancy

    N.M. Roelfsema; W.C.J. Hop (Wim); S.M. Boito; J.W. Wladimiroff (Juriy)

    2004-01-01

    textabstractObjectives: This study was undertaken to develop a three-dimensional (3D) ultrasound method of measuring fetal brain volume. Study design: Serial 3D sonographic measurements of fetal brain volume were made in 68 normal singleton pregnancies at 18 to 34 weeks of gestation. A comparison

  16. [Interference of vitamin E on the brain tissue damage by electromagnetic radiation of cell phone in pregnant and fetal rats].

    Gao, Xian; Luo, Rui; Ma, Bin; Wang, Hui; Liu, Tian; Zhang, Jing; Lian, Zhishun; Cui, Xi

    2013-07-01

    To investigate the interlerence ot vitamin E on brain tissue damage by electromagnetic radiation of cell phone in pregnant and fetal rats. 40 pregnant rats were randomly divided into five groups (positive control, negative control, low, middle and high dosage of vitamin E groups). The low, middle and high dosage of vitamin E groups were supplemented with 5, 15 and 30 mg/ml vitamin E respectively since the first day of pregnancy. And the negative control group and the positive control group were given peanut oil without vitamin E. All groups except for the negative control group were exposed to 900MHz intensity of cell phone radiation for one hour each time, three times per day for 21 days. After accouchement, the right hippocampus tissue of fetal rats in each group was taken and observed under electron microscope. The vitality of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the content of malondialdehyde (MDA) in pregnant and fetal rats' brain tissue were tested. Compared with the negative control group, the chondriosomes in neuron and neuroglia of brain tissues was swelling, mild edema was found around the capillary, chromatin was concentrated and collected, and bubbles were formed in vascular endothelial cells (VEC) in the positive fetal rat control group, whereas the above phenomenon was un-conspicuous in the middle and high dosage of vitamin E groups. We can see uniform chromatin, abundant mitochondrion, rough endoplasmic reticulum and free ribosomes in the high dosage group. The apoptosis has not fond in all groups'sections. In the antioxidase activity analysis, compared with the negative control group, the vitality of SOD and GSH-Px significantly decreased and the content of MDA significantly increased both in the pregnant and fetal rats positive control group (P electromagnetic radiation of cell phone in pregnant rats and fetal rats.

  17. Automatically tracking neurons in a moving and deforming brain.

    Jeffrey P Nguyen

    2017-05-01

    Full Text Available Advances in optical neuroimaging techniques now allow neural activity to be recorded with cellular resolution in awake and behaving animals. Brain motion in these recordings pose a unique challenge. The location of individual neurons must be tracked in 3D over time to accurately extract single neuron activity traces. Recordings from small invertebrates like C. elegans are especially challenging because they undergo very large brain motion and deformation during animal movement. Here we present an automated computer vision pipeline to reliably track populations of neurons with single neuron resolution in the brain of a freely moving C. elegans undergoing large motion and deformation. 3D volumetric fluorescent images of the animal's brain are straightened, aligned and registered, and the locations of neurons in the images are found via segmentation. Each neuron is then assigned an identity using a new time-independent machine-learning approach we call Neuron Registration Vector Encoding. In this approach, non-rigid point-set registration is used to match each segmented neuron in each volume with a set of reference volumes taken from throughout the recording. The way each neuron matches with the references defines a feature vector which is clustered to assign an identity to each neuron in each volume. Finally, thin-plate spline interpolation is used to correct errors in segmentation and check consistency of assigned identities. The Neuron Registration Vector Encoding approach proposed here is uniquely well suited for tracking neurons in brains undergoing large deformations. When applied to whole-brain calcium imaging recordings in freely moving C. elegans, this analysis pipeline located 156 neurons for the duration of an 8 minute recording and consistently found more neurons more quickly than manual or semi-automated approaches.

  18. Intrinsic control of electroresponsive properties of transplanted mammalian brain neurons

    Hounsgaard, J; Yarom, Y

    1985-01-01

    The present study presents the first analysis of neurons in mammalian brain transplants based on intracellular recording. The results, obtained in brain slices including both donor and host tissue, showed that neuronal precursor cells in embryonic transplants retained their ability to complete...... their normal differentiation of cell-type-specific electroresponsive properties. Distortions in cell aggregation and synaptic connectivity did not affect this aspect of neuronal differentiation....

  19. Shaping of neuronal activity through a Brain Computer Interface

    Valero-Aguayo, Luis; Silva-Sauer, Leandro; Velasco-Alvarez, Ricardo; Ron-Angevin, Ricardo

    2014-01-01

    Neuronal responses are human actions which can be measured by an EEG, and which imply changes in waves when neurons are synchronized. This activity could be changed by principles of behaviour analysis. This research tests the efficacy of the behaviour shaping procedure to progressively change neuronal activity, so that those brain responses are adapted according to the differential reinforcement of visual feedback. The Brain Computer Interface (BCI) enables us to record the EEG in real ti...

  20. Adapting Parcellation Schemes to Study Fetal Brain Connectivity in Serial Imaging Studies

    Cheng, Xi; Wilm, Jakob; Seshamani, Sharmishtaa

    2013-01-01

    A crucial step in studying brain connectivity is the definition of the Regions Of Interest (ROI's) which are considered as nodes of a network graph. These ROI's identified in structural imaging reflect consistent functional regions in the anatomies being compared. However in serial studies...... of the developing fetal brain such functional and associated structural markers are not consistently present over time. In this study we adapt two non-atlas based parcellation schemes to study the development of connectivity networks of a fetal monkey brain using Diffusion Weighted Imaging techniques. Results...... demonstrate that the fetal brain network exhibits small-world characteristics and a pattern of increased cluster coefficients and decreased global efficiency. These findings may provide a route to creating a new biomarker for healthy fetal brain development....

  1. Inhibition of Mammary Cancer Progression in Fetal Alcohol Exposed Rats by β-Endorphin Neurons.

    Zhang, Changqing; Franklin, Tina; Sarkar, Dipak K

    2016-01-01

    Fetal alcohol exposure (FAE) increases the susceptibility to carcinogen-induced mammary cancer progression in rodent models. FAE also decreases β-endorphin (β-EP) level and causes hyperstress response, which leads to inhibition of immune function against cancer. Previous studies have shown that injection of nanosphere-attached dibutyryl cyclic adenosine monophosphate (dbcAMP) into the third ventricle increases the number of β-EP neurons in the hypothalamus. In this study, we assessed the therapeutic potential of stress regulation using methods to increase hypothalamic levels of β-EP, a neuropeptide that inhibits stress axis activity, in treatment of carcinogen-induced mammary cancer in fetal alcohol exposed rats. Fetal alcohol exposed and control Sprague Dawley rats were given a dose of N-Nitroso-N-methylurea (MNU) at postnatal day 50 to induce mammary cancer growth. Upon detection of mammary tumors, the animals were either transplanted with β-EP neurons or injected with dbcAMP-delivering nanospheres into the hypothalamus to increase β-EP peptide production. Spleen cytokines were detected using reverse transcription polymerase chain reaction assays. Metastasis study was done by injecting mammary cancer cells MADB106 into jugular vein of β-EP-activated or control fetal alcohol exposed animals. Both transplantation of β-EP neurons and injection of dbcAMP-delivering nanospheres inhibited MNU-induced mammary cancer growth in control rats, and reversed the effect of FAE on the susceptibility to mammary cancer. Similar to the previously reported immune-enhancing and stress-suppressive effects of β-EP transplantation, injection of dbcAMP-delivering nanospheres increased the levels of interferon-γ and granzyme B and decreased the levels of epinephrine and norepinephrine in fetal alcohol exposed rats. Mammary cancer cell metastasis study also showed that FAE increased incidence of lung tumor retention, while β-EP transplantation inhibited lung tumor growth in

  2. Fetal brain damage following maternal carbon monoxide intoxication: an experimental study

    Ginsberg, M D; Myers, R E

    1974-01-01

    Techniques of fetal monitoring, including fetal blood sampling in utero, were employed to study the physiological effects of acute maternal carbon monoxide intoxication on nine term-pregnant female rhesus monkeys exposed to 0.1 to 0.3% inspired carbon monoxide over 1 to 3 hr. The mothers tolerated carboxyhemoglobin levels exceeding 60% without clinical sequelae, whereas the fetuses promptly developed profound hypoxia upon exposure of the mothers to CO. The fetal COHb levels rose only gradually over 1 to 3 hr, and thus contributed only slightly to the development of early fetal hypoxia. The fetal hypoxia was associated with bradycardia, hypotension, and metabolic and respiratory acidosis. Severity of intrauterine hypoxia was closely correlated with the appearance of brain damage. Brain swelling associated with hemorrhagic necrosis of the cerebral hemispheres (severe brain damage) appeared only in fetuses whose arterial oxygen content was reduced below 1.0 ml/100 ml for at least 45 min during the maternal CO intoxication.

  3. Hippocampal neuron populations are reduced in vervet monkeys with fetal alcohol exposure

    Burke, Mark W; Ptito, Maurice; Ervin, Frank R

    2015-01-01

    of pregnancy. Here, we report significant numerical reductions in the principal hippocampal neurons of fetal alcohol-exposed (FAE) offspring, as compared to age-matched, similarly housed conspecifics with isocaloric sucrose exposure. These deficits, particularly marked in CA1 and CA3, are present neonatally......Prenatal exposure to beverage alcohol is a major cause of mild mental retardation and developmental delay. In nonendangered alcohol-preferring vervet monkeys, we modeled the most common nondysmorphic form of fetal alcohol syndrome disorder with voluntary drinking during the third trimester...... and persist through infancy (5 months) and juvenile (2 years) stages. Although the volumes of hippocampal subdivisions in FAE animals are not atypical at birth, by age 2, they are only 65-70% of those estimated in age-matched controls. These data suggest that moderate, naturalistic alcohol consumption during...

  4. Glucose metabolism of fetal rat brain in utero, measured with labeled deoxyglucose

    Dyve, S [Department of General Physiology and Biophysics, Panum Institute, Copenhagen (Denmark); Gjedde, A [Positron Imaging Laboratories, McConnell Brain Imaging Center, Montreal, Quebec (Canada)

    1991-01-01

    Mammals have low cerebral metabolic rates immediately after birth and, by inference, also before birth. In this study, we extended the deoxyglucose method to the fetal rat brain in utero. Rate constants for deoxyglucose transfer across the maternal placental and fetal blood-brain barriers, and lumped constant, have not been reported. Therefore, we applied a new method of determining the lumped constant regionally to the fetal rat brain in utero. The lumped constant averaged 0.55 +- 0.15 relative to the maternal circulation. On this basis, we determined the glucose metabolic rate of the fetal rat brain to be one third of the corresponding maternal value, or 19 +- 2 {mu}mol hg{sup -1} min{sup -1}. (author).

  5. Differential Responses of Human Fetal Brain Neural Stem Cells to Zika Virus Infection

    Erica L. McGrath

    2017-03-01

    Full Text Available Zika virus (ZIKV infection causes microcephaly in a subset of infants born to infected pregnant mothers. It is unknown whether human individual differences contribute to differential susceptibility of ZIKV-related neuropathology. Here, we use an Asian-lineage ZIKV strain, isolated from the 2015 Mexican outbreak (Mex1-7, to infect primary human neural stem cells (hNSCs originally derived from three individual fetal brains. All three strains of hNSCs exhibited similar rates of Mex1-7 infection and reduced proliferation. However, Mex1-7 decreased neuronal differentiation in only two of the three stem cell strains. Correspondingly, ZIKA-mediated transcriptome alterations were similar in these two strains but significantly different from that of the third strain with no ZIKV-induced neuronal reduction. This study thus confirms that an Asian-lineage ZIKV strain infects primary hNSCs and demonstrates a cell-strain-dependent response of hNSCs to ZIKV infection.

  6. Differential Responses of Human Fetal Brain Neural Stem Cells to Zika Virus Infection.

    McGrath, Erica L; Rossi, Shannan L; Gao, Junling; Widen, Steven G; Grant, Auston C; Dunn, Tiffany J; Azar, Sasha R; Roundy, Christopher M; Xiong, Ying; Prusak, Deborah J; Loucas, Bradford D; Wood, Thomas G; Yu, Yongjia; Fernández-Salas, Ildefonso; Weaver, Scott C; Vasilakis, Nikos; Wu, Ping

    2017-03-14

    Zika virus (ZIKV) infection causes microcephaly in a subset of infants born to infected pregnant mothers. It is unknown whether human individual differences contribute to differential susceptibility of ZIKV-related neuropathology. Here, we use an Asian-lineage ZIKV strain, isolated from the 2015 Mexican outbreak (Mex1-7), to infect primary human neural stem cells (hNSCs) originally derived from three individual fetal brains. All three strains of hNSCs exhibited similar rates of Mex1-7 infection and reduced proliferation. However, Mex1-7 decreased neuronal differentiation in only two of the three stem cell strains. Correspondingly, ZIKA-mediated transcriptome alterations were similar in these two strains but significantly different from that of the third strain with no ZIKV-induced neuronal reduction. This study thus confirms that an Asian-lineage ZIKV strain infects primary hNSCs and demonstrates a cell-strain-dependent response of hNSCs to ZIKV infection. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  7. From Neurons to Brain: Adaptive Self-Wiring of Neurons

    Segev, Ronen; Ben-Jacob, Eshel

    1998-01-01

    During embryonic morpho-genesis, a collection of individual neurons turns into a functioning network with unique capabilities. Only recently has this most staggering example of emergent process in the natural world, began to be studied. Here we propose a navigational strategy for neurites growth cones, based on sophisticated chemical signaling. We further propose that the embryonic environment (the neurons and the glia cells) acts as an excitable media in which concentric and spiral chemical ...

  8. Caspase Activation in Fetal Rat Brain Following Experimental Intrauterine Inflammation

    Sharangpani, Aditi; Takanohashi, Asako; Bell, Michael J.

    2009-01-01

    Intrauterine inflammation has been implicated in developmental brain injuries, including the development of periventricular leukomalacia (PVL) and cerebral palsy (CP). Previous studies in our rat model of intrauterine inflammation demonstrated apoptotic cell death in fetal brains within the first 5 days after lipopolysaccharide (LPS) administration to mothers and eventual dysmyelination. Cysteine-containing, aspartate-specific proteases, or caspases, are proteins involved with apoptosis through both intracellular (intrinsic pathway) and extracellular (extrinsic pathway) mechanisms. We hypothesized that cell death in our model would occur mainly via activation of the extrinsic pathway. We further hypothesized that Fas, a member of the tumor necrosis factor receptor (TNFR) superfamily, would be increased and the death inducing signaling complex (DISC) would be detectable. Pregnant rats were injected intracervically with LPS at E15 and immunoblotting, immunohistochemical and immunoprecipitation analyses were performed. The presence of the activated form of the effector caspase (caspase-3) was observed 24 h after LPS administration. Caspase activity assays demonstrated rapid increases in (i) caspases-9 and -10 within 1 h, (ii) caspase-8 at 2 h and (iii) caspase-3 at 4 h. At 24 h after LPS, activated caspase-3+/Fas+ cells were observed within the developing white matter. Lastly, the DISC complex (caspase-8, Fas and Fas-associated Death Domain (FADD)) was observed within 30 min by immunoprecipitation. Apoptosis in our model occurs via both extrinsic and intrinsic pathways, and activation of Fas may play a role. Understanding the mechanisms of cell death in models of intrauterine inflammation may affect development of future strategies to mitigate these injuries in children. PMID:18289516

  9. Optogenetic control of human neurons in organotypic brain cultures

    Andersson, My; Avaliani, Natalia; Svensson, Andreas

    2016-01-01

    Optogenetics is one of the most powerful tools in neuroscience, allowing for selective control of specific neuronal populations in the brain of experimental animals, including mammals. We report, for the first time, the application of optogenetic tools to human brain tissue providing a proof......-of-concept for the use of optogenetics in neuromodulation of human cortical and hippocampal neurons as a possible tool to explore network mechanisms and develop future therapeutic strategies....

  10. Automated fetal brain segmentation from 2D MRI slices for motion correction.

    Keraudren, K; Kuklisova-Murgasova, M; Kyriakopoulou, V; Malamateniou, C; Rutherford, M A; Kainz, B; Hajnal, J V; Rueckert, D

    2014-11-01

    Motion correction is a key element for imaging the fetal brain in-utero using Magnetic Resonance Imaging (MRI). Maternal breathing can introduce motion, but a larger effect is frequently due to fetal movement within the womb. Consequently, imaging is frequently performed slice-by-slice using single shot techniques, which are then combined into volumetric images using slice-to-volume reconstruction methods (SVR). For successful SVR, a key preprocessing step is to isolate fetal brain tissues from maternal anatomy before correcting for the motion of the fetal head. This has hitherto been a manual or semi-automatic procedure. We propose an automatic method to localize and segment the brain of the fetus when the image data is acquired as stacks of 2D slices with anatomy misaligned due to fetal motion. We combine this segmentation process with a robust motion correction method, enabling the segmentation to be refined as the reconstruction proceeds. The fetal brain localization process uses Maximally Stable Extremal Regions (MSER), which are classified using a Bag-of-Words model with Scale-Invariant Feature Transform (SIFT) features. The segmentation process is a patch-based propagation of the MSER regions selected during detection, combined with a Conditional Random Field (CRF). The gestational age (GA) is used to incorporate prior knowledge about the size and volume of the fetal brain into the detection and segmentation process. The method was tested in a ten-fold cross-validation experiment on 66 datasets of healthy fetuses whose GA ranged from 22 to 39 weeks. In 85% of the tested cases, our proposed method produced a motion corrected volume of a relevant quality for clinical diagnosis, thus removing the need for manually delineating the contours of the brain before motion correction. Our method automatically generated as a side-product a segmentation of the reconstructed fetal brain with a mean Dice score of 93%, which can be used for further processing. Copyright

  11. Yeast-2-Hybrid data file showing progranulin interactions in human fetal brain and bone marrow libraries

    Irmgard Tegeder

    2016-12-01

    Full Text Available Progranulin deficiency in humans is associated with neurodegeneration. Its mechanisms are not yet fully understood. We performed a Yeast-2-Hybrid screen using human full-length progranulin as bait to assess the interactions of progranulin. Progranulin was screened against human fetal brain and human bone marrow libraries using the standard Matchmaker technology (Clontech. This article contains the full Y2H data table, including blast results and sequences, a sorted table according to selection criteria for likely positive, putatively positive, likely false and false preys, and tables showing the gene ontology terms associated with the likely and putative preys of the brain and bone marrow libraries. The interactions with autophagy proteins were confirmed and functionally analyzed in "Progranulin overexpression in sensory neurons attenuates neuropathic pain in mice: Role of autophagy" (C. Altmann, S. Hardt, C. Fischer, J. Heidler, H.Y. Lim, A. Haussler, B. Albuquerque, B. Zimmer, C. Moser, C. Behrends, F. Koentgen, I. Wittig, M.H. Schmidt, A.M. Clement, T. Deller, I. Tegeder, 2016 [1].

  12. Yeast-2-Hybrid data file showing progranulin interactions in human fetal brain and bone marrow libraries.

    Tegeder, Irmgard

    2016-12-01

    Progranulin deficiency in humans is associated with neurodegeneration. Its mechanisms are not yet fully understood. We performed a Yeast-2-Hybrid screen using human full-length progranulin as bait to assess the interactions of progranulin. Progranulin was screened against human fetal brain and human bone marrow libraries using the standard Matchmaker technology (Clontech). This article contains the full Y2H data table, including blast results and sequences, a sorted table according to selection criteria for likely positive, putatively positive, likely false and false preys, and tables showing the gene ontology terms associated with the likely and putative preys of the brain and bone marrow libraries. The interactions with autophagy proteins were confirmed and functionally analyzed in "Progranulin overexpression in sensory neurons attenuates neuropathic pain in mice: Role of autophagy" (C. Altmann, S. Hardt, C. Fischer, J. Heidler, H.Y. Lim, A. Haussler, B. Albuquerque, B. Zimmer, C. Moser, C. Behrends, F. Koentgen, I. Wittig, M.H. Schmidt, A.M. Clement, T. Deller, I. Tegeder, 2016) [1].

  13. Fetal guinea pig brain 15-hydroxyprostaglandin dehydrogenase: Ontogeny and effect of ethanol

    Treissman, D.; Brien, J.F.

    1991-01-01

    The objectives of this study were to determine the ontogeny of 15-hydroxyprostaglandin dehydrogenase (15-OH-PGDH) activity in the brain of the fetal guinea pig and to test the hypothesis that acute in vitro ethanol exposure produces concentration-dependent inhibition of fetal brain 15-OH-PGDH activity. Enzyme activity was determined in vitro by measuring the rate of oxidation of PGE2 to 15-keto-PGE2 using an optimized radiometric procedure. The study was conducted utilizing the whole brain of the fetal guinea pig at mean gestational ages of 34, 43 and 62 days (term, about 66 days) and the brain stem (pons and medulla) of the fetal guinea pig at mean gestational ages of 43 and 62 days. The direct effect of acute in vitro exposure to ethanol was assessed by incubating 15-OH-PGDH with ethanol in the concentration range of 10 to 80 mM. 15-OH-PGDH was measurable in the whole brain and brain stem, and the enzyme activity was similar for the gestational ages examined. There was no significant ethanol-induced inhibition of 15-OH-PGDH activity in the whole brain or brain stem. The data demonstrate that the whole brain and brain stem of the fetal guinea pig have the capacity to metabolize PGE2 to 15-keto-PGE2, an inactive metabolite, during the second half of gestation. The data apparently are not consistent with the hypothesis that acute in vitro exposure to ethanol directly inhibits 15-OH-PGDH activity in fetal brain

  14. Fetal growth, cognitive function, and brain volumes in childhood and adolescence.

    Rogne, Tormod; Engstrøm, Andreas Aass; Jacobsen, Geir Wenberg; Skranes, Jon; Østgård, Heidi Furre; Martinussen, Marit

    2015-03-01

    To evaluate the association between fetal growth pattern and cognitive function at 5 and 9 years and regional brain volumes at 15 years. Eighty-three term-born small-for-gestational-age (SGA) neonates and 105 non-SGA neonates in a control group were available for follow-up. Based on serial fetal ultrasound measurements from gestational weeks 25-37, SGA neonates were classified with fetal growth restriction (n=13) or non-fetal growth restriction (n=36). Cognitive function was assessed at 5 and 9 years, and brain volumes were estimated with cerebral magnetic resonance imaging at 15 years. Small-for-gestational-age children had lower performance intelligence quotient at 5 years compared with those in a control group (107.3 compared with 112.5, Pgrowth restriction and control groups, the SGA fetal growth restriction group had significantly lower performance intelligence quotient at 5 years (103.5 compared with 112.5, Pgrowth restriction and control groups for thalamic (17.4 compared with 18.6 cm, Pintelligence quotient scores at 5 and 9 years and smaller brain volumes at 15 years compared with those in the control group, but these findings were only found in those with fetal growth restriction, indicating a possible relationship to decelerated fetal growth. II.

  15. Glial and neuronal control of brain blood flow

    Attwell, David; Buchan, Alastair M; Charpak, Serge

    2010-01-01

    Blood flow in the brain is regulated by neurons and astrocytes. Knowledge of how these cells control blood flow is crucial for understanding how neural computation is powered, for interpreting functional imaging scans of brains, and for developing treatments for neurological disorders. It is now...... in our understanding of cerebral blood flow control have important implications for the development of new therapeutic approaches....

  16. Communication networks in the brain: neurons, receptors, neurotransmitters, and alcohol.

    Lovinger, David M

    2008-01-01

    Nerve cells (i.e., neurons) communicate via a combination of electrical and chemical signals. Within the neuron, electrical signals driven by charged particles allow rapid conduction from one end of the cell to the other. Communication between neurons occurs at tiny gaps called synapses, where specialized parts of the two cells (i.e., the presynaptic and postsynaptic neurons) come within nanometers of one another to allow for chemical transmission. The presynaptic neuron releases a chemical (i.e., a neurotransmitter) that is received by the postsynaptic neuron's specialized proteins called neurotransmitter receptors. The neurotransmitter molecules bind to the receptor proteins and alter postsynaptic neuronal function. Two types of neurotransmitter receptors exist-ligand-gated ion channels, which permit rapid ion flow directly across the outer cell membrane, and G-protein-coupled receptors, which set into motion chemical signaling events within the cell. Hundreds of molecules are known to act as neurotransmitters in the brain. Neuronal development and function also are affected by peptides known as neurotrophins and by steroid hormones. This article reviews the chemical nature, neuronal actions, receptor subtypes, and therapeutic roles of several transmitters, neurotrophins, and hormones. It focuses on neurotransmitters with important roles in acute and chronic alcohol effects on the brain, such as those that contribute to intoxication, tolerance, dependence, and neurotoxicity, as well as maintained alcohol drinking and addiction.

  17. Linking neuronal brain activity to the glucose metabolism

    Göbel, Britta; Oltmanns, Kerstin M; Chung, Matthias

    2013-01-01

    Background Energy homeostasis ensures the functionality of the entire organism. The human brain as a missing link in the global regulation of the complex whole body energy metabolism is subject to recent investigation. The goal of this study is to gain insight into the influence of neuronal brain activity on cerebral and peripheral energy metabolism. In particular, the tight link between brain energy supply and metabolic responses of the organism is of interest. We aim to identifying regul...

  18. A map of octopaminergic neurons in the Drosophila brain.

    Busch, Sebastian; Selcho, Mareike; Ito, Kei; Tanimoto, Hiromu

    2009-04-20

    The biogenic amine octopamine modulates diverse behaviors in invertebrates. At the single neuron level, the mode of action is well understood in the peripheral nervous system owing to its simple structure and accessibility. For elucidating the role of individual octopaminergic neurons in the modulation of complex behaviors, a detailed analysis of the connectivity in the central nervous system is required. Here we present a comprehensive anatomical map of candidate octopaminergic neurons in the adult Drosophila brain: including the supra- and subesophageal ganglia. Application of the Flp-out technique enabled visualization of 27 types of individual octopaminergic neurons. Based on their morphology and distribution of genetic markers, we found that most octopaminergic neurons project to multiple brain structures with a clear separation of dendritic and presynaptic regions. Whereas their major dendrites are confined to specific brain regions, each cell type targets different, yet defined, neuropils distributed throughout the central nervous system. This would allow them to constitute combinatorial modules assigned to the modulation of distinct neuronal processes. The map may provide an anatomical framework for the functional constitution of the octopaminergic system. It also serves as a model for the single-cell organization of a particular neurotransmitter in the brain. 2009 Wiley-Liss, Inc.

  19. Neuron-astrocyte signaling is preserved in the aging brain.

    Gómez-Gonzalo, Marta; Martin-Fernandez, Mario; Martínez-Murillo, Ricardo; Mederos, Sara; Hernández-Vivanco, Alicia; Jamison, Stephanie; Fernandez, Ana P; Serrano, Julia; Calero, Pilar; Futch, Hunter S; Corpas, Rubén; Sanfeliu, Coral; Perea, Gertrudis; Araque, Alfonso

    2017-04-01

    Astrocytes play crucial roles in brain homeostasis and are emerging as regulatory elements of neuronal and synaptic physiology by responding to neurotransmitters with Ca 2+ elevations and releasing gliotransmitters that activate neuronal receptors. Aging involves neuronal and astrocytic alterations, being considered risk factor for neurodegenerative diseases. Most evidence of the astrocyte-neuron signaling is derived from studies with young animals; however, the features of astrocyte-neuron signaling in adult and aging brain remain largely unknown. We have investigated the existence and properties of astrocyte-neuron signaling in physiologically and pathologically aging mouse hippocampal and cortical slices at different lifetime points (0.5 to 20 month-old animals). We found that astrocytes preserved their ability to express spontaneous and neurotransmitter-dependent intracellular Ca 2+ signals from juvenile to aging brains. Likewise, resting levels of gliotransmission, assessed by neuronal NMDAR activation by glutamate released from astrocytes, were largely preserved with similar properties in all tested age groups, but DHPG-induced gliotransmission was reduced in aged mice. In contrast, gliotransmission was enhanced in the APP/PS1 mouse model of Alzheimer's disease, indicating a dysregulation of astrocyte-neuron signaling in pathological conditions. Disruption of the astrocytic IP 3 R2 mediated-signaling, which is required for neurotransmitter-induced astrocyte Ca 2+ signals and gliotransmission, boosted the progression of amyloid plaque deposits and synaptic plasticity impairments in APP/PS1 mice at early stages of the disease. Therefore, astrocyte-neuron interaction is a fundamental signaling, largely conserved in the adult and aging brain of healthy animals, but it is altered in Alzheimer's disease, suggesting that dysfunctions of astrocyte Ca 2+ physiology may contribute to this neurodegenerative disease. GLIA 2017 GLIA 2017;65:569-580. © 2017 Wiley

  20. Bidirectional Microglia-Neuron Communication in the Healthy Brain

    Ukpong B. Eyo

    2013-01-01

    Full Text Available Unlike other resident neural cells that are of neuroectodermal origin, microglia are resident neural cells of mesodermal origin. Traditionally recognized for their immune functions during disease, new roles are being attributed to these cells in the development and maintenance of the central nervous system (CNS including specific communication with neurons. In this review, we highlight some of the recent findings on the bidirectional interaction between neurons and microglia. We discuss these interactions along two lines. First, we review data that suggest that microglial activity is modulated by neuronal signals, focusing on evidence that (i neurons are capable of regulating microglial activation state and influence basal microglial activities; (ii classic neurotransmitters affect microglial behavior; (iii chemotactic signals attract microglia during acute neuronal injury. Next, we discuss some of the recent data on how microglia signal to neurons. Signaling mechanisms include (i direct physical contact of microglial processes with neuronal elements; (ii microglial regulation of neuronal synapse and circuit by fractalkine, complement, and DAP12 signaling. In addition, we discuss the use of microglial depletion strategies in studying the role of microglia in neuronal development and synaptic physiology. Deciphering the mechanisms of bidirectional microglial-neuronal communication provides novel insights in understanding microglial function in both the healthy and diseased brain.

  1. Temporal slice registration and robust diffusion-tensor reconstruction for improved fetal brain structural connectivity analysis.

    Marami, Bahram; Mohseni Salehi, Seyed Sadegh; Afacan, Onur; Scherrer, Benoit; Rollins, Caitlin K; Yang, Edward; Estroff, Judy A; Warfield, Simon K; Gholipour, Ali

    2017-08-01

    Diffusion weighted magnetic resonance imaging, or DWI, is one of the most promising tools for the analysis of neural microstructure and the structural connectome of the human brain. The application of DWI to map early development of the human connectome in-utero, however, is challenged by intermittent fetal and maternal motion that disrupts the spatial correspondence of data acquired in the relatively long DWI acquisitions. Fetuses move continuously during DWI scans. Reliable and accurate analysis of the fetal brain structural connectome requires careful compensation of motion effects and robust reconstruction to avoid introducing bias based on the degree of fetal motion. In this paper we introduce a novel robust algorithm to reconstruct in-vivo diffusion-tensor MRI (DTI) of the moving fetal brain and show its effect on structural connectivity analysis. The proposed algorithm involves multiple steps of image registration incorporating a dynamic registration-based motion tracking algorithm to restore the spatial correspondence of DWI data at the slice level and reconstruct DTI of the fetal brain in the standard (atlas) coordinate space. A weighted linear least squares approach is adapted to remove the effect of intra-slice motion and reconstruct DTI from motion-corrected data. The proposed algorithm was tested on data obtained from 21 healthy fetuses scanned in-utero at 22-38 weeks gestation. Significantly higher fractional anisotropy values in fiber-rich regions, and the analysis of whole-brain tractography and group structural connectivity, showed the efficacy of the proposed method compared to the analyses based on original data and previously proposed methods. The results of this study show that slice-level motion correction and robust reconstruction is necessary for reliable in-vivo structural connectivity analysis of the fetal brain. Connectivity analysis based on graph theoretic measures show high degree of modularity and clustering, and short average

  2. Maternal insulin sensitivity is associated with oral glucose-induced changes in fetal brain activity.

    Linder, Katarzyna; Schleger, Franziska; Ketterer, Caroline; Fritsche, Louise; Kiefer-Schmidt, Isabelle; Hennige, Anita; Häring, Hans-Ulrich; Preissl, Hubert; Fritsche, Andreas

    2014-06-01

    Fetal programming plays an important role in the pathogenesis of type 2 diabetes. The aim of the present study was to investigate whether maternal metabolic changes during OGTT influence fetal brain activity. Thirteen healthy pregnant women underwent an OGTT (75 g). Insulin sensitivity was determined by glucose and insulin measurements at 0, 60 and 120 min. At each time point, fetal auditory evoked fields were recorded with a fetal magnetoencephalographic device and response latencies were determined. Maternal insulin increased from a fasting level of 67 ± 25 pmol/l (mean ± SD) to 918 ± 492 pmol/l 60 min after glucose ingestion and glucose levels increased from 4.4 ± 0.3 to 7.4 ± 1.1 mmol/l. Over the same time period, fetal response latencies decreased from 297 ± 99 to 235 ± 84 ms (p = 0.01) and then remained stable until 120 min (235 ± 84 vs 251 ± 91 ms, p = 0.39). There was a negative correlation between maternal insulin sensitivity and fetal response latencies 60 min after glucose ingestion (r = 0.68, p = 0.02). After a median split of the group based on maternal insulin sensitivity, fetuses of insulin-resistant mothers showed a slower response to auditory stimuli (283 ± 79 ms) than those of insulin-sensitive mothers (178 ± 46 ms, p = 0.03). Lower maternal insulin sensitivity is associated with slower fetal brain responses. These findings provide the first evidence of a direct effect of maternal metabolism on fetal brain activity and suggest that central insulin resistance may be programmed during fetal development.

  3. Fingolimod against endotoxin-induced fetal brain injury in a rat model.

    Yavuz, And; Sezik, Mekin; Ozmen, Ozlem; Asci, Halil

    2017-11-01

    Fingolimod is a sphingosine-1-phosphate receptor modulator used for multiple sclerosis treatment and acts on cellular processes such as apoptosis, endothelial permeability, and inflammation. We hypothesized that fingolimod has a positive effect on alleviating preterm fetal brain injury. Sixteen pregnant rats were divided into four groups of four rats each. On gestational day 17, i.p. endotoxin was injected to induce fetal brain injury, followed by i.p. fingolimod (4 mg/kg maternal weight). Hysterotomy for preterm delivery was performed 6 h after fingolimod. The study groups included (i) vehicle controls (i.p. normal saline only); (ii) positive controls (endotoxin plus saline); (iii) saline plus fingolimod; and (iv) endotoxin plus fingolimod treatment. Brain tissues of the pups were dissected for evaluation of interleukin (IL)-6, caspase-3, and S100β on immunohistochemistry. Maternal fingolimod treatment attenuated endotoxin-related fetal brain injury and led to lower immunoreactions for IL-6, caspase-3, and S100β compared with endotoxin controls (P < 0.0001 for all comparisons). Antenatal maternal fingolimod therapy had fetal neuroprotective effects by alleviating preterm birth-related fetal brain injury with inhibitory effects on inflammation and apoptosis. © 2017 Japan Society of Obstetrics and Gynecology.

  4. Selective neuronal vulnerability to oxidative stress in the brain

    Xinkun Wang

    2010-03-01

    Full Text Available Oxidative stress (OS, caused by the imbalance between the generation and detoxification of reactive oxygen and nitrogen species (ROS/RNS, plays an important role in brain aging, neurodegenerative diseases, and other related adverse conditions, such as ischemia. While ROS/RNS serve as signaling molecules at physiological levels, an excessive amount of these molecules leads to oxidative modification and, therefore, dysfunction of proteins, nucleic acids, and lipids. The response of neurons to this pervasive stress, however, is not uniform in the brain. While many brain neurons can cope with a rise in OS, there are select populations of neurons in the brain that are vulnerable. Because of their selective vulnerability, these neurons are usually the first to exhibit functional decline and cell death during normal aging, or in age-associated neurodegenerative diseases, such as Alzheimer’s disease. Understanding the molecular and cellular mechanisms of selective neuronal vulnerability (SNV to OS is important in the development of future intervention approaches to protect such vulnerable neurons from the stresses of the aging process and the pathological states that lead to neurodegeneration. In this review, the currently known molecular and cellular factors that contribute to SNV to OS are summarized. Included among the major underlying factors are high intrinsic OS, high demand for ROS/RNS-based signaling, low ATP production, mitochondrial dysfunction, and high inflammatory response in vulnerable neurons. The contribution to the selective vulnerability of neurons to OS by other intrinsic or extrinsic factors, such as deficient DNA damage repair, low calcium-buffering capacity, and glutamate excitotoxicity, are also discussed.

  5. Life and death of neurons in the aging brain

    Morrison, J. H.; Hof, P. R.; Bloom, F. E. (Principal Investigator)

    1997-01-01

    Neurodegenerative disorders are characterized by extensive neuron death that leads to functional decline, but the neurobiological correlates of functional decline in normal aging are less well defined. For decades, it has been a commonly held notion that widespread neuron death in the neocortex and hippocampus is an inevitable concomitant of brain aging, but recent quantitative studies suggest that neuron death is restricted in normal aging and unlikely to account for age-related impairment of neocortical and hippocampal functions. In this article, the qualitative and quantitative differences between aging and Alzheimer's disease with respect to neuron loss are discussed, and age-related changes in functional and biochemical attributes of hippocampal circuits that might mediate functional decline in the absence of neuron death are explored. When these data are viewed comprehensively, it appears that the primary neurobiological substrates for functional impairment in aging differ in important ways from those in neurodegenerative disorders such as Alzheimer's disease.

  6. Localisation of the brain in fetal MRI using bundled SIFT features.

    Keraudren, Kevin; Kyriakopoulou, Vanessa; Rutherford, Mary; Hajnal, Joseph V; Rueckert, Daniel

    2013-01-01

    Fetal MRI is a rapidly emerging diagnostic imaging tool. Its main focus is currently on brain imaging, but there is a huge potential for whole body studies. We propose a method for accurate and robust localisation of the fetal brain in MRI when the image data is acquired as a stack of 2D slices misaligned due to fetal motion. We first detect possible brain locations in 2D images with a Bag-of-Words model using SIFT features aggregated within Maximally Stable Extremal Regions (called bundled SIFT), followed by a robust fitting of an axis-aligned 3D box to the selected regions. We rely on prior knowledge of the fetal brain development to define size and shape constraints. In a cross-validation experiment, we obtained a median error distance of 5.7mm from the ground truth and no missed detection on a database of 59 fetuses. This 2D approach thus allows a robust detection even in the presence of substantial fetal motion.

  7. The Gini coefficient: a methodological pilot study to assess fetal brain development employing postmortem diffusion MRI

    Viehweger, Adrian; Sorge, Ina; Hirsch, Wolfgang [University Hospital Leipzig, Department of Pediatric Radiology, Leipzig (Germany); Riffert, Till; Dhital, Bibek; Knoesche, Thomas R.; Anwander, Alfred [Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig (Germany); Stepan, Holger [University Leipzig, Department of Obstetrics, Leipzig (Germany)

    2014-10-15

    Diffusion-weighted imaging (DWI) is important in the assessment of fetal brain development. However, it is clinically challenging and time-consuming to prepare neuromorphological examinations to assess real brain age and to detect abnormalities. To demonstrate that the Gini coefficient can be a simple, intuitive parameter for modelling fetal brain development. Postmortem fetal specimens(n = 28) were evaluated by diffusion-weighted imaging (DWI) on a 3-T MRI scanner using 60 directions, 0.7-mm isotropic voxels and b-values of 0, 150, 1,600 s/mm{sup 2}. Constrained spherical deconvolution (CSD) was used as the local diffusion model. Fractional anisotropy (FA), apparent diffusion coefficient (ADC) and complexity (CX) maps were generated. CX was defined as a novel diffusion metric. On the basis of those three parameters, the Gini coefficient was calculated. Study of fetal brain development in postmortem specimens was feasible using DWI. The Gini coefficient could be calculated for the combination of the three diffusion parameters. This multidimensional Gini coefficient correlated well with age (Adjusted R{sup 2} = 0.59) between the ages of 17 and 26 gestational weeks. We propose a new method that uses an economics concept, the Gini coefficient, to describe the whole brain with one simple and intuitive measure, which can be used to assess the brain's developmental state. (orig.)

  8. The Gini coefficient: a methodological pilot study to assess fetal brain development employing postmortem diffusion MRI

    Viehweger, Adrian; Sorge, Ina; Hirsch, Wolfgang; Riffert, Till; Dhital, Bibek; Knoesche, Thomas R.; Anwander, Alfred; Stepan, Holger

    2014-01-01

    Diffusion-weighted imaging (DWI) is important in the assessment of fetal brain development. However, it is clinically challenging and time-consuming to prepare neuromorphological examinations to assess real brain age and to detect abnormalities. To demonstrate that the Gini coefficient can be a simple, intuitive parameter for modelling fetal brain development. Postmortem fetal specimens(n = 28) were evaluated by diffusion-weighted imaging (DWI) on a 3-T MRI scanner using 60 directions, 0.7-mm isotropic voxels and b-values of 0, 150, 1,600 s/mm 2 . Constrained spherical deconvolution (CSD) was used as the local diffusion model. Fractional anisotropy (FA), apparent diffusion coefficient (ADC) and complexity (CX) maps were generated. CX was defined as a novel diffusion metric. On the basis of those three parameters, the Gini coefficient was calculated. Study of fetal brain development in postmortem specimens was feasible using DWI. The Gini coefficient could be calculated for the combination of the three diffusion parameters. This multidimensional Gini coefficient correlated well with age (Adjusted R 2 = 0.59) between the ages of 17 and 26 gestational weeks. We propose a new method that uses an economics concept, the Gini coefficient, to describe the whole brain with one simple and intuitive measure, which can be used to assess the brain's developmental state. (orig.)

  9. Nanoparticle-mediated transcriptional modification enhances neuronal differentiation of human neural stem cells following transplantation in rat brain.

    Li, Xiaowei; Tzeng, Stephany Y; Liu, Xiaoyan; Tammia, Markus; Cheng, Yu-Hao; Rolfe, Andrew; Sun, Dong; Zhang, Ning; Green, Jordan J; Wen, Xuejun; Mao, Hai-Quan

    2016-04-01

    Strategies to enhance survival and direct the differentiation of stem cells in vivo following transplantation in tissue repair site are critical to realizing the potential of stem cell-based therapies. Here we demonstrated an effective approach to promote neuronal differentiation and maturation of human fetal tissue-derived neural stem cells (hNSCs) in a brain lesion site of a rat traumatic brain injury model using biodegradable nanoparticle-mediated transfection method to deliver key transcriptional factor neurogenin-2 to hNSCs when transplanted with a tailored hyaluronic acid (HA) hydrogel, generating larger number of more mature neurons engrafted to the host brain tissue than non-transfected cells. The nanoparticle-mediated transcription activation method together with an HA hydrogel delivery matrix provides a translatable approach for stem cell-based regenerative therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Why our brains cherish humanity: Mirror neurons and colamus humanitatem

    Skoyles, John R.

    2008-01-01

    Commonsense says we are isolated. After all, our bodies are physically separate. But Seneca’s colamus humanitatem, and John Donne’s observation that “no man is an island” suggests we are neither entirely isolated nor separate. A recent discovery in neuroscience-that of mirror neurons-argues that the brain and the mind is neither built nor functions remote from what happens in other individuals. What are mirror neurons? They are brain cells that process both what happens to or is done by an in...

  11. Linking neuronal brain activity to the glucose metabolism.

    Göbel, Britta; Oltmanns, Kerstin M; Chung, Matthias

    2013-08-29

    Energy homeostasis ensures the functionality of the entire organism. The human brain as a missing link in the global regulation of the complex whole body energy metabolism is subject to recent investigation. The goal of this study is to gain insight into the influence of neuronal brain activity on cerebral and peripheral energy metabolism. In particular, the tight link between brain energy supply and metabolic responses of the organism is of interest. We aim to identifying regulatory elements of the human brain in the whole body energy homeostasis. First, we introduce a general mathematical model describing the human whole body energy metabolism. It takes into account the two central roles of the brain in terms of energy metabolism. The brain is considered as energy consumer as well as regulatory instance. Secondly, we validate our mathematical model by experimental data. Cerebral high-energy phosphate content and peripheral glucose metabolism are measured in healthy men upon neuronal activation induced by transcranial direct current stimulation versus sham stimulation. By parameter estimation we identify model parameters that provide insight into underlying neurophysiological processes. Identified parameters reveal effects of neuronal activity on regulatory mechanisms of systemic glucose metabolism. Our examinations support the view that the brain increases its glucose supply upon neuronal activation. The results indicate that the brain supplies itself with energy according to its needs, and preeminence of cerebral energy supply is reflected. This mechanism ensures balanced cerebral energy homeostasis. The hypothesis of the central role of the brain in whole body energy homeostasis as active controller is supported.

  12. The plastic brain: neoliberalism and the neuronal self.

    Pitts-Taylor, Victoria

    2010-11-01

    Neuroscience-based representations and practices of the brain aimed at lay populations present the brain in ways that both affirm biological determinism and also celebrate plasticity, or the brain's ability to change structure and function. Popular uses of neuroscientific theories of brain plasticity are saturated with a neoliberal vision of the subject. Against more optimistic readings of plasticity, I view the popular deployment of plasticity through the framework of governmentality. I describe how popular brain discourse on plasticity opens up the brain to personal techniques of enhancement and risk avoidance, and how it promotes a neuronal self. I situate brain plasticity in a context of biomedical neoliberalism, where the engineering and modification of biological life is positioned as essential to selfhood and citizenship.

  13. Managing Brain Extracellular K(+) during Neuronal Activity

    Larsen, Brian Roland; Stoica, Anca; MacAulay, Nanna

    2016-01-01

    characteristics required to fulfill their distinct physiological roles in clearance of K(+) from the extracellular space in the face of neuronal activity. Understanding the nature, impact and effects of the various Na(+)/K(+)-ATPase isoform combinations in K(+) management in the central nervous system might...... understanding of the pathological events occurring during disease....

  14. Complement inhibition by hydroxychloroquine prevents placental and fetal brain abnormalities in antiphospholipid syndrome.

    Bertolaccini, Maria Laura; Contento, Gregorio; Lennen, Ross; Sanna, Giovanni; Blower, Philip J; Ma, Michelle T; Sunassee, Kavitha; Girardi, Guillermina

    2016-12-01

    Placental ischemic disease and adverse pregnancy outcomes are frequently observed in patients with antiphospholipid syndrome (APS). Despite the administration of conventional antithrombotic treatment a significant number of women continue to experience adverse pregnancy outcomes, with uncertain prevention and management. Efforts to develop effective pharmacological strategies for refractory obstetric APS cases will be of significant clinical benefit for both mothers and fetuses. Although the antimalarial drug, hydroxychloroquine (HCQ) is increasingly used to treat pregnant women with APS, little is known about its efficacy and mechanism of action of HCQ. Because complement activation plays a crucial and causative role in placental ischemia and abnormal fetal brain development in APS we hypothesised that HCQ prevents these pregnancy complications through inhibition of complement activation. Using a mouse model of obstetric APS that closely resembles the clinical condition, we found that HCQ prevented fetal death and the placental metabolic changes -measured by proton magnetic resonance spectroscopy in APS-mice. Using 111 In labelled antiphospholipid antibodies (aPL) we identified the placenta and the fetal brain as the main organ targets in APS-mice. Using this same method, we found that HCQ does not inhibit aPL binding to tissues as was previously suggested from in vitro studies. While HCQ did not affect aPL binding to fetal brain it prevented fetal brain abnormal cortical development. HCQ prevented complement activation in vivo and in vitro. Complement C5a levels in serum samples from APS patients and APS-mice were lower after treatment with HCQ while the antibodies titres remained unchanged. HCQ prevented not only placental insufficiency but also abnormal fetal brain development in APS. By inhibiting complement activation, HCQ might also be an effective antithrombotic therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Assessment of Autophagy in Neurons and Brain Tissue

    Benito-Cuesta, Irene; Diez, Héctor; Ordoñez, Lara; Wandosell, Francisco

    2017-01-01

    Autophagy is a complex process that controls the transport of cytoplasmic components into lysosomes for degradation. This highly conserved proteolytic system involves dynamic and complex processes, using similar molecular elements and machinery from yeast to humans. Moreover, autophagic dysfunction may contribute to a broad spectrum of mammalian diseases. Indeed, in adult tissues, where the capacity for regeneration or cell division is low or absent (e.g., in the mammalian brain), the accumulation of proteins/peptides that would otherwise be recycled or destroyed may have pathological implications. Indeed, such changes are hallmarks of pathologies, like Alzheimer’s, Prion or Parkinson’s disease, known as proteinopathies. However, it is still unclear whether such dysfunction is a cause or an effect in these conditions. One advantage when analysing autophagy in the mammalian brain is that almost all the markers described in different cell lineages and systems appear to be present in the brain, and even in neurons. By contrast, the mixture of cell types present in the brain and the differentiation stage of such neurons, when compared with neurons in culture, make translating basic research to the clinic less straightforward. Thus, the purpose of this review is to describe and discuss the methods available to monitor autophagy in neurons and in the mammalian brain, a process that is not yet fully understood, focusing primarily on mammalian macroautophagy. We will describe some general features of neuronal autophagy that point to our focus on neuropathologies in which macroautophagy may be altered. Indeed, we centre this review around the hypothesis that enhanced autophagy may be able to provide therapeutic benefits in some brain pathologies, like Alzheimer’s disease, considering this pathology as one of the most prevalent proteinopathies. PMID:28832529

  16. Scaling of brain metabolism with a fixed energy budget per neuron: implications for neuronal activity, plasticity and evolution.

    Herculano-Houzel, Suzana

    2011-03-01

    It is usually considered that larger brains have larger neurons, which consume more energy individually, and are therefore accompanied by a larger number of glial cells per neuron. These notions, however, have never been tested. Based on glucose and oxygen metabolic rates in awake animals and their recently determined numbers of neurons, here I show that, contrary to the expected, the estimated glucose use per neuron is remarkably constant, varying only by 40% across the six species of rodents and primates (including humans). The estimated average glucose use per neuron does not correlate with neuronal density in any structure. This suggests that the energy budget of the whole brain per neuron is fixed across species and brain sizes, such that total glucose use by the brain as a whole, by the cerebral cortex and also by the cerebellum alone are linear functions of the number of neurons in the structures across the species (although the average glucose consumption per neuron is at least 10× higher in the cerebral cortex than in the cerebellum). These results indicate that the apparently remarkable use in humans of 20% of the whole body energy budget by a brain that represents only 2% of body mass is explained simply by its large number of neurons. Because synaptic activity is considered the major determinant of metabolic cost, a conserved energy budget per neuron has several profound implications for synaptic homeostasis and the regulation of firing rates, synaptic plasticity, brain imaging, pathologies, and for brain scaling in evolution.

  17. Scaling of brain metabolism with a fixed energy budget per neuron: implications for neuronal activity, plasticity and evolution.

    Suzana Herculano-Houzel

    Full Text Available It is usually considered that larger brains have larger neurons, which consume more energy individually, and are therefore accompanied by a larger number of glial cells per neuron. These notions, however, have never been tested. Based on glucose and oxygen metabolic rates in awake animals and their recently determined numbers of neurons, here I show that, contrary to the expected, the estimated glucose use per neuron is remarkably constant, varying only by 40% across the six species of rodents and primates (including humans. The estimated average glucose use per neuron does not correlate with neuronal density in any structure. This suggests that the energy budget of the whole brain per neuron is fixed across species and brain sizes, such that total glucose use by the brain as a whole, by the cerebral cortex and also by the cerebellum alone are linear functions of the number of neurons in the structures across the species (although the average glucose consumption per neuron is at least 10× higher in the cerebral cortex than in the cerebellum. These results indicate that the apparently remarkable use in humans of 20% of the whole body energy budget by a brain that represents only 2% of body mass is explained simply by its large number of neurons. Because synaptic activity is considered the major determinant of metabolic cost, a conserved energy budget per neuron has several profound implications for synaptic homeostasis and the regulation of firing rates, synaptic plasticity, brain imaging, pathologies, and for brain scaling in evolution.

  18. Scaling of Brain Metabolism with a Fixed Energy Budget per Neuron: Implications for Neuronal Activity, Plasticity and Evolution

    Herculano-Houzel, Suzana

    2011-01-01

    It is usually considered that larger brains have larger neurons, which consume more energy individually, and are therefore accompanied by a larger number of glial cells per neuron. These notions, however, have never been tested. Based on glucose and oxygen metabolic rates in awake animals and their recently determined numbers of neurons, here I show that, contrary to the expected, the estimated glucose use per neuron is remarkably constant, varying only by 40% across the six species of rodents and primates (including humans). The estimated average glucose use per neuron does not correlate with neuronal density in any structure. This suggests that the energy budget of the whole brain per neuron is fixed across species and brain sizes, such that total glucose use by the brain as a whole, by the cerebral cortex and also by the cerebellum alone are linear functions of the number of neurons in the structures across the species (although the average glucose consumption per neuron is at least 10× higher in the cerebral cortex than in the cerebellum). These results indicate that the apparently remarkable use in humans of 20% of the whole body energy budget by a brain that represents only 2% of body mass is explained simply by its large number of neurons. Because synaptic activity is considered the major determinant of metabolic cost, a conserved energy budget per neuron has several profound implications for synaptic homeostasis and the regulation of firing rates, synaptic plasticity, brain imaging, pathologies, and for brain scaling in evolution. PMID:21390261

  19. T2* relaxometry of fetal brain at 1.5 Tesla using a motion tolerant method.

    Vasylechko, Serge; Malamateniou, Christina; Nunes, Rita G; Fox, Matthew; Allsop, Joanna; Rutherford, Mary; Rueckert, Daniel; Hajnal, Joseph V

    2015-05-01

    The aim of this study was to determine T2* values for the fetal brain in utero and to compare them with previously reported values in preterm and term neonates. Knowledge of T2* may be useful for assessing brain development, brain abnormalities, and for optimizing functional imaging studies. Maternal respiration and unpredictable fetal motion mean that conventional multishot acquisition techniques used in adult T2* relaxometry studies are not practical. Single shot multiecho echo planar imaging was used as a rapid method for measuring fetal T2* by effectively freezing intra-slice motion. T2* determined from a sample of 24 subjects correlated negatively with gestational age with mean values of 220 ms (±45) for frontal white matter, 159 ms (±32) for thalamic gray matter, and 236 ms (±45) for occipital white matter. Fetal T2* values are higher than those previously reported for preterm neonates and decline with a consistent trend across gestational age. The data suggest that longer than usual echo times or direct T2* measurement should be considered when performing fetal fMRI to reach optimal BOLD sensitivity. © 2014 Wiley Periodicals, Inc.

  20. Neuronal Rat Brain Damage Caused by Endogenous and Exogenous Hyperthermia

    Mustafa Aydın

    2012-03-01

    Full Text Available OBJECTIVE: Hyperthermia may induce pathologic alterations within body systems and organs including brain. In this study, neuronal effects of endogenous and exogenous hyperthermia (41°C were studied in rats. METHODS: The endogenous hyperthermia (41°C was induced by lipopolysaccharide and the exogenous by an (electric heater. Possible neuronal damage was evaluated by examining healthy, apoptotic and necrotic cells, and heat shock proteins (HSP 27, HSP 70 in the cerebral cortex, cerebellum and hypothalamus RESULTS: At cellular level, when all neuronal tissues are taken into account; (i a significant increase in the necrotic cells was observed in the both groups (p0.05. CONCLUSION: The neural tissue of brain can show different degree of response to hyperthermia. But we can conclude that endogenous hyperthermia is more harmful to central nervous system than exogenous hyperthermia

  1. Acute Effects of Viral Exposure on P-Glycoprotein Function in the Mouse Fetal Blood-Brain Barrier

    Enrrico Bloise

    2017-02-01

    Full Text Available Background/Aims: Viral infection during pregnancy is known to affect the fetal brain. The toll-like receptor (TLR-3 is a pattern recognition receptor activated by viruses known to elicit adverse fetal neurological outcomes. The P-glycoprotein (P-gp efflux transporter protects the developing fetus by limiting the transfer of substrates across both the placenta and the fetal blood-brain barrier (BBB. As such, inhibition of P-gp at these blood-barrier sites may result in increased exposure of the developing fetus to environmental toxins and xenobiotics present in the maternal circulation. We hypothesized that viral exposure during pregnancy would impair P-gp function in the placenta and in the developing BBB. Here we investigated whether the TLR-3 ligand, polyinosinic:polycytidylic acid (PolyI:C, increased accumulation of one P-gp substrate in the fetus and in the developing fetal brain. Methods: Pregnant C57BL/6 mice (GD15.5 were injected (i.p. with PolyI:C (5 mg/kg or 10 mg/kg or vehicle (saline. [3H]digoxin (P-gp substrate was injected (i.v. 3 or 23h post-treatment and animals were euthanized 1h later. Maternal plasma, ‘fetal-units’ (fetal membranes, amniotic fluid and whole fetus, and fetal brains were collected. Results: PolyI:C exposure (4h significantly elevated maternal plasma IL-6 (P<0.001 and increased [3H]digoxin accumulation in the fetal brain (P<0.05. In contrast, 24h after PolyI:C exposure, no effect on IL-6 or fetal brain accumulation of P-gp substrate was observed. Conclusion: Viral infection modeled by PolyI:C causes acute increases in fetal brain accumulation of P-gp substrates and by doing so, may increase fetal brain exposure to xenobiotics and environmental toxins present in the maternal circulation.

  2. Evolving changes in fetal heart rate variability and brain injury after hypoxia-ischaemia in preterm fetal sheep.

    Yamaguchi, Kyohei; Lear, Christopher A; Beacom, Michael J; Ikeda, Tomoaki; Gunn, Alistair J; Bennet, Laura

    2018-01-08

    Fetal heart rate variability is a critical index of fetal wellbeing. Suppression of heart rate variability may provide prognostic information on the risk of hypoxic-ischaemic brain injury after birth. In the present study, we report the evolution of fetal heart rate variability after both mild and severe hypoxia-ischaemia. Both mild and severe hypoxia-ischaemia were associated with an initial, brief suppression of multiple measures of heart rate variability. This was followed by normal or increased levels of heart rate variability during the latent phase of injury. Severe hypoxia-ischaemia was subsequently associated with the prolonged suppression of measures of heart rate variability during the secondary phase of injury, which is the period of time when brain injury is no longer treatable. These findings suggest that a biphasic pattern of heart rate variability may be an early marker of brain injury when treatment or intervention is probably most effective. Hypoxia-ischaemia (HI) is a major contributor to preterm brain injury, although there are currently no reliable biomarkers for identifying infants who are at risk. We tested the hypothesis that fetal heart rate (FHR) and FHR variability (FHRV) would identify evolving brain injury after HI. Fetal sheep at 0.7 of gestation were subjected to either 15 (n = 10) or 25 min (n = 17) of complete umbilical cord occlusion or sham occlusion (n = 12). FHR and four measures of FHRV [short-term variation, long-term variation, standard deviation of normal to normal R-R intervals (SDNN), root mean square of successive differences) were assessed until 72 h after HI. All measures of FHRV were suppressed for the first 3-4 h in the 15 min group and 1-2 h in the 25 min group. Measures of FHRV recovered to control levels by 4 h in the 15 min group, whereas the 25 min group showed tachycardia and an increase in short-term variation and SDNN from 4 to 6 h after occlusion. The measures of FHRV then progressively

  3. From spiking neurons to brain waves

    Visser, S.

    2013-01-01

    No single model would be able to capture all processes in the brain at once, since its interactions are too numerous and too complex. Therefore, it is common practice to simplify the parts of the system. Typically, the goal is to describe the collective action of many underlying processes, without

  4. Fetal and neonatal brain injury: mechanisms, management, and the risks of practice

    Stevenson, David K; Benitz, William E; Sunshine, Philip

    2003-01-01

    ..., imaging studies, and laboratory measurements can identify the timing and severity of the injury event. Despite these advances, fetal and neonatal brain injury remains a major concern with devastating consequences. It is hoped that this definitive account will provide the clinician not only with a better understanding of the mechanisms involved but also with...

  5. Fetal Growth Restriction with Brain Sparing: Neurocognitive and Behavioral Outcomes at 12 Years of Age

    Beukers, Fenny; Aarnoudse-Moens, Cornelieke S. H.; van Weissenbruch, Mirjam M.; Ganzevoort, Wessel; van Goudoever, Johannes B.; van Wassenaer-Leemhuis, Aleid G.

    2017-01-01

    Objective To study neurocognitive functions and behavior in children with a history of fetal growth restriction (FGR) with brain sparing. We hypothesized that children with FGR would have poorer outcomes on these domains. Study design Subjects were 12-year-old children with a history of FGR born to

  6. Registration-based approach for reconstruction of high-resolution in utero fetal MR brain images.

    Rousseau, Francois; Glenn, Orit A; Iordanova, Bistra; Rodriguez-Carranza, Claudia; Vigneron, Daniel B; Barkovich, James A; Studholme, Colin

    2006-09-01

    This paper describes a novel approach to forming high-resolution MR images of the human fetal brain. It addresses the key problem of fetal motion by proposing a registration-refined compounding of multiple sets of orthogonal fast two-dimensional MRI slices, which are currently acquired for clinical studies, into a single high-resolution MRI volume. A robust multiresolution slice alignment is applied iteratively to the data to correct motion of the fetus that occurs between two-dimensional acquisitions. This is combined with an intensity correction step and a super-resolution reconstruction step, to form a single high isotropic resolution volume of the fetal brain. Experimental validation on synthetic image data with known motion types and underlying anatomy, together with retrospective application to sets of clinical acquisitions, are included. Results indicate that this method promises a unique route to acquiring high-resolution MRI of the fetal brain in vivo allowing comparable quality to that of neonatal MRI. Such data provide a highly valuable window into the process of normal and abnormal brain development, which is directly applicable in a clinical setting.

  7. Regional apparent diffusion coefficient values in 3rd trimester fetal brain

    Hoffmann, Chen; Weisz, Boaz; Lipitz, Shlomo; Katorza, Eldad; Yaniv, Gal; Bergman, Dafi; Biegon, Anat

    2014-01-01

    Apparent diffusion coefficient (ADC) values in the developing fetus can be used in the diagnosis and prognosis of prenatal brain pathologies. To this end, we measured regional ADC in a relatively large cohort of normal fetal brains in utero. Diffusion-weighted imaging (DWI) was performed in 48 non-sedated 3rd trimester fetuses with normal structural MR imaging results. ADC was measured in white matter (frontal, parietal, temporal, and occipital lobes), basal ganglia, thalamus, pons, and cerebellum. Regional ADC values were compared by one-way ANOVA with gestational age as covariate. Regression analysis was used to examine gestational age-related changes in regional ADC. Four other cases of CMV infection were also examined. Median gestational age was 32 weeks (range, 26-33 weeks). There was a highly significant effect of region on ADC, whereby ADC values were highest in white matter, with significantly lower values in basal ganglia and cerebellum and the lowest values in thalamus and pons. ADC did not significantly change with gestational age in any of the regions tested. In the four cases with fetal CMV infection, ADC value was associated with a global decrease. ADC values in normal fetal brain are relatively stable during the third trimester, show consistent regional variation, and can make an important contribution to the early diagnosis and possibly prognosis of fetal brain pathologies. (orig.)

  8. Regional apparent diffusion coefficient values in 3rd trimester fetal brain

    Hoffmann, Chen [Tel Aviv University, Department of Radiology, Sheba Medical Center, Tel Hashomer (affiliated to the Sackler School of Medicine), Tel Aviv (Israel); Sheba Medical Center, Diagnostic Imaging, 52621, Tel Hashomer (Israel); Weisz, Boaz; Lipitz, Shlomo; Katorza, Eldad [Tel Aviv University, Department of Obstetrics and Gynecology, Sheba Medical Center, Tel Hashomer (affiliated to the Sackler School of Medicine), Tel Aviv (Israel); Yaniv, Gal; Bergman, Dafi [Tel Aviv University, Department of Radiology, Sheba Medical Center, Tel Hashomer (affiliated to the Sackler School of Medicine), Tel Aviv (Israel); Biegon, Anat [Stony Brook University School of Medicine, Department of Neurology, Stony Brook, NY (United States)

    2014-07-15

    Apparent diffusion coefficient (ADC) values in the developing fetus can be used in the diagnosis and prognosis of prenatal brain pathologies. To this end, we measured regional ADC in a relatively large cohort of normal fetal brains in utero. Diffusion-weighted imaging (DWI) was performed in 48 non-sedated 3rd trimester fetuses with normal structural MR imaging results. ADC was measured in white matter (frontal, parietal, temporal, and occipital lobes), basal ganglia, thalamus, pons, and cerebellum. Regional ADC values were compared by one-way ANOVA with gestational age as covariate. Regression analysis was used to examine gestational age-related changes in regional ADC. Four other cases of CMV infection were also examined. Median gestational age was 32 weeks (range, 26-33 weeks). There was a highly significant effect of region on ADC, whereby ADC values were highest in white matter, with significantly lower values in basal ganglia and cerebellum and the lowest values in thalamus and pons. ADC did not significantly change with gestational age in any of the regions tested. In the four cases with fetal CMV infection, ADC value was associated with a global decrease. ADC values in normal fetal brain are relatively stable during the third trimester, show consistent regional variation, and can make an important contribution to the early diagnosis and possibly prognosis of fetal brain pathologies. (orig.)

  9. Reduced cell number in the neocortical part of the human fetal brain in Down syndrome

    Larsen, K.B.; Laursen, H.; Graem, N.

    2008-01-01

    Mental retardation is seen in all individuals with Down syndrome (DS) and different brain abnormalities are reported. The aim of this study was to investigate if mental retardation at least in part is a result of a lower cell number in the neocortical part of the human fetal forebrain. We therefore...

  10. Uptake of [3H]testosterone and its metabolites by the brain and pituitary gland of the fetal macaque

    Michael, R.P.; Bonsall, R.W.; Rees, H.D.

    1989-01-01

    Testosterone is secreted by the fetal testis during gestation, and this is thought to influence certain aspects of the brain's subsequent development. To study this action at the neuronal level, nine macaque fetuses were injected with 250 microCi [3H]testosterone via the umbilical vein at about 120 days gestation. After 60 min, samples of brain and peripheral tissue were studied by autoradiography or HPLC. Purified nuclear pellets were prepared, and radioactivity in ether extracts was fractionated by HPLC and identified by coelution with internal standard steroids. Concentrations of radioactivity were significantly higher (P less than 0.05) in the hypothalamus-preoptic area than in amygdala, hippocampus, midbrain, and cerebral and cerebellar cortexes, and most of the radioactivity (75%) in the hypothalamus-preoptic area coeluted with 17 beta-estradiol. Radioactivity coeluting with 17 beta-estradiol was also detected in nuclear fractions from amygdala (44%). In contrast, 80% of the radioactivity extracted from pituitary gland nuclei coeluted with testosterone. Most of the neurons labeled in autoradiograms were located in the hypothalamus and preoptic area, fewer were found in the amygdala, and labeling in the frontal or motor cortex did not exceed chance levels. Results suggested that aromatization and, consequently, estrogen receptors play a role in the effects of testosterone on the hypothalamus and amygdala of the primate fetus at this stage of development

  11. Fetal programming of the human brain: is there a link with insurgence of neurodegenerative disorders in adulthood?

    Faa, G; Marcialis, M A; Ravarino, A; Piras, M; Pintus, M C; Fanos, V

    2014-01-01

    In recent years, evidence is growing on the role played by gestational factors in shaping brain development and on the influence of intrauterine experiences on later development of neurodegenerative diseases including Parkinson's (PD) and Alzheimer's disease (AD). The nine months of intrauterine development and the first three years of postnatal life are appearing to be extremely critical for making connections among neurons and among neuronal and glial cells that will shape a lifetime of experience. Here, the multiple epigenetic factors acting during gestation - including maternal diet, malnutrition, stress, hypertension, maternal diabetes, fetal hypoxia, prematurity, low birth weight, prenatal infection, intrauterine growth restriction, drugs administered to the mother or to the baby - are reported, and their ability to modulate brain development, resulting in interindividual variability in the total neuronal and glial burden at birth is discussed. Data from recent literature suggest that prevention of neurodegeneration should be identified as the one method to halt the diffusion of neurodegenerative diseases. The "two hits" hypothesis, first introduced for PD and successfully applied to AD and other neurodegenerative human pathologies, should focus our attention on a peculiar period of our life: the intrauterine and perinatal periods. The first hit to our nervous system occurs early in life, determining a PD or AD imprinting to our brain that will condition our resistance or, alternatively, our susceptibility to develop a neurodegenerative disease later in life. In conclusion, how early life events contribute to late-life development of adult neurodegenerative diseases, including PD and AD, is emerging as a new fascinating research focus. This assumption implies that research on prevention of neurodegenerative diseases should center on events taking place early in life, during gestation and in the perinatal periods, thus presenting a new challenge to

  12. Combined effects of caffeine and zinc in the maternal diet on fetal brains

    Nakamoto, T.; Gottschalk, S.B.; Yazdani, M.; Joseph, F. Jr. (Louisiana State Univ., New Orleans (United States))

    1991-03-15

    The authors have reported that caffeine (C) intake during the lactational period by dams decreases the Zn content of the brain in their offspring. The objective of the present study is to determine how C plus Zn supplementation to the maternal diet during gestation affects the fetal brains. Timed-pregnant rats at day 3 of gestation were randomly divided into 4 groups (G). G1 was fed a 20% protein diet as a control, G2 was fed a diet supplemented with Zn, G3 was fed a diet with C and G4 was fed a diet with C and Zn. At day 22 of gestation, fetuses were taken out surgically. Fetal brains were removed. Their weights, DNA, Zn, protein, cholesterol, caffeine concentration, and alkaline phosphatase activity were determined. Body and brain weights and cholesterol contents in G4 were greater than in G1, whereas Zn concentration and alkaline phosphatase activity were less. Zn concentration and Zn/DNA in G2 were greater than in G1. Cholesterol content in G4 was higher than in G3. Although mean caffeine concentration in brain and plasma in G4 was greater than in G3, there was no statistical significance between the G due to the wide fluctuation among the pups. It is concluded that supplementation of C and Zn in the maternal diet during gestation could influence fetal brain composition differently than C supplementation alone. Supplementation of Zn alone showed minor effects.

  13. Why our brains cherish humanity: Mirror neurons and colamus humanitatem

    John R. Skoyles

    2008-06-01

    Full Text Available Commonsense says we are isolated. After all, our bodies are physically separate. But Seneca’s colamus humanitatem, and John Donne’s observation that “no man is an island” suggests we are neither entirely isolated nor separate. A recent discovery in neuroscience—that of mirror neurons—argues that the brain and the mind is neither built nor functions remote from what happens in other individuals. What are mirror neurons? They are brain cells that process both what happens to or is done by an individual, and, as it were, its perceived “refl ection,” when that same thing happens or is done by another individual. Thus, mirror neurons are both activated when an individual does a particular action, and when that individual perceives that same action done by another. The discovery of mirror neurons suggests we need to radically revise our notions of human nature since they offer a means by which we may not be so separated as we think. Humans unlike other apes are adapted to mirror interact nonverbally when together. Notably, our faces have been evolved to display agile and nimble movements. While this is usually explained as enabling nonverbal communication, a better description would be nonverbal commune based upon mirror neurons. I argue we cherish humanity, colamus humanitatem, because mirror neurons and our adapted mirror interpersonal interface blur the physical boundaries that separate us.

  14. In-utero three dimension high resolution fetal brain diffusion tensor imaging.

    Jiang, Shuzhou; Xue, Hui; Counsell, Serena; Anjari, Mustafa; Allsop, Joanna; Rutherford, Mary; Rueckert, Daniel; Hajnal, Joseph V

    2007-01-01

    We present a methodology to achieve 3D high resolution in-utero fetal brain DTI that shows excellent ADC as well as promising FA maps. After continuous DTI scanning to acquire a repeated series of parallel slices with 15 diffusion directions, image registration is used to realign the images to correct for fetal motion. Once aligned, the diffusion images are treated as irregularly sampled data where each voxel is associated with an appropriately rotated diffusion direction, and used to estimate the diffusion tensor on a regular grid. The method has been tested successful on eight fetuses and has been validated on adults imaged at 1.5T.

  15. Thiamin deficiency on fetal brain development with and without prenatal alcohol exposure.

    Kloss, Olena; Eskin, N A Michael; Suh, Miyoung

    2018-04-01

    Adequate thiamin levels are crucial for optimal health through maintenance of homeostasis and viability of metabolic enzymes, which require thiamine as a co-factor. Thiamin deficiency occurs during pregnancy when the dietary intake is inadequate or excessive alcohol is consumed. Thiamin deficiency leads to brain dysfunction because thiamin is involved in the synthesis of myelin and neurotransmitters (e.g., acetylcholine, γ-aminobutyric acid, glutamate), and its deficiency increases oxidative stress by decreasing the production of reducing agents. Thiamin deficiency also leads to neural membrane dysfunction, because thiamin is a structural component of mitochondrial and synaptosomal membranes. Similarly, in-utero exposure to alcohol leads to fetal brain dysfunction, resulting in negative effects such as fetal alcohol spectrum disorder (FASD). Thiamin deficiency and prenatal exposure to alcohol could act synergistically to produce negative effects on fetal development; however, this area of research is currently under-studied. This minireview summarizes the evidence for the potential role of thiamin deficiency in fetal brain development, with or without prenatal exposure to alcohol. Such evidence may influence the development of new nutritional strategies for preventing or mitigating the symptoms of FASD.

  16. Volume of Structures in the Fetal Brain Measured with a New Semiautomated Method.

    Ber, R; Hoffman, D; Hoffman, C; Polat, A; Derazne, E; Mayer, A; Katorza, E

    2017-11-01

    Measuring the volume of fetal brain structures is challenging due to fetal motion, low resolution, and artifacts caused by maternal tissue. Our aim was to introduce a new, simple, Matlab-based semiautomated method to measure the volume of structures in the fetal brain and present normal volumetric curves of the structures measured. The volume of the supratentorial brain, left and right hemispheres, cerebellum, and left and right eyeballs was measured retrospectively by the new semiautomated method in MR imaging examinations of 94 healthy fetuses. Four volume ratios were calculated. Interobserver agreement was calculated with the intraclass correlation coefficient, and a Bland-Altman plot was drawn for comparison of manual and semiautomated method measurements of the supratentorial brain. We present normal volumetric curves and normal percentile values of the structures measured according to gestational age and of the ratios between the cerebellum and the supratentorial brain volume and the total eyeball and the supratentorial brain volume. Interobserver agreement was good or excellent for all structures measured. The Bland-Altman plot between manual and semiautomated measurements showed a maximal relative difference of 7.84%. We present a technologically simple, reproducible method that can be applied prospectively and retrospectively on any MR imaging protocol, and we present normal volumetric curves measured. The method shows results like manual measurements while being less time-consuming and user-dependent. By applying this method on different cranial and extracranial structures, anatomic and pathologic, we believe that fetal volumetry can turn from a research tool into a practical clinical one. © 2017 by American Journal of Neuroradiology.

  17. Exclusive neuronal expression of SUCLA2 in the human brain

    Dobolyi, Arpád; Ostergaard, Elsebet; Bagó, Attila G

    2015-01-01

    associated with SUCLA2 mutations, the precise localization of SUCLA2 protein has never been investigated. Here, we show that immunoreactivity of A-SUCL-β in surgical human cortical tissue samples was present exclusively in neurons, identified by their morphology and visualized by double labeling...... was absent in glial cells, identified by antibodies directed against the glial markers GFAP and S100. Furthermore, in situ hybridization histochemistry demonstrated that SUCLA2 mRNA was present in Nissl-labeled neurons but not glial cells labeled with S100. Immunoreactivity of the GTP-forming β subunit (G......-SUCL-β) encoded by SUCLG2, or in situ hybridization histochemistry for SUCLG2 mRNA could not be demonstrated in either neurons or astrocytes. Western blotting of post mortem brain samples revealed minor G-SUCL-β immunoreactivity that was, however, not upregulated in samples obtained from diabetic versus non...

  18. Brain-wide neuronal dynamics during motor adaptation in zebrafish.

    Ahrens, Misha B; Li, Jennifer M; Orger, Michael B; Robson, Drew N; Schier, Alexander F; Engert, Florian; Portugues, Ruben

    2012-05-09

    A fundamental question in neuroscience is how entire neural circuits generate behaviour and adapt it to changes in sensory feedback. Here we use two-photon calcium imaging to record the activity of large populations of neurons at the cellular level, throughout the brain of larval zebrafish expressing a genetically encoded calcium sensor, while the paralysed animals interact fictively with a virtual environment and rapidly adapt their motor output to changes in visual feedback. We decompose the network dynamics involved in adaptive locomotion into four types of neuronal response properties, and provide anatomical maps of the corresponding sites. A subset of these signals occurred during behavioural adjustments and are candidates for the functional elements that drive motor learning. Lesions to the inferior olive indicate a specific functional role for olivocerebellar circuitry in adaptive locomotion. This study enables the analysis of brain-wide dynamics at single-cell resolution during behaviour.

  19. Glial and neuronal control of brain blood flow

    Attwell, David; Buchan, Alastair M; Charpak, Serge

    2010-01-01

    Blood flow in the brain is regulated by neurons and astrocytes. Knowledge of how these cells control blood flow is crucial for understanding how neural computation is powered, for interpreting functional imaging scans of brains, and for developing treatments for neurological disorders. It is now...... recognized that neurotransmitter-mediated signalling has a key role in regulating cerebral blood flow, that much of this control is mediated by astrocytes, that oxygen modulates blood flow regulation, and that blood flow may be controlled by capillaries as well as by arterioles. These conceptual shifts...

  20. Novel culturing platform for brain slices and neuronal cells

    Svendsen, Winnie Edith; Al Atraktchi, Fatima Al-Zahraa; Bakmand, Tanya

    2015-01-01

    In this paper we demonstrate a novel culturing system for brain slices and neuronal cells, which can control the concentration of nutrients and the waste removal from the culture by adjusting the fluid flow within the device. The entire system can be placed in an incubator. The system has been...... tested successfully with brain slices and PC12 cells. The culture substrate can be modified using metal electrodes and/or nanostructures for conducting electrical measurements while culturing and for better mimicking the in vivo conditions....

  1. Effect of assisted reproductive technology on fetal brain development assessed by prenatal ultrasonography.

    Yin, Linliang; Xu, Yongle; Li, Hong; Ling, Chen; Choy, Kwong Wai; Xia, Fei; Deng, Xuedong

    2015-01-01

    The aim was to evaluate whether assisted reproductive technology (ART) affects the development of the fetal central nervous system (CNS). This study was carried out on women with singleton pregnancies, including 427 women who became pregnant by ART and 32,859 women with natural conceptions (NCs). The cavum septum pellucidum (CSP) width, transverse cerebellar diameter (TCD), cisterna magna (CM) depth, and lateral ventricle width were measured by ultrasound for 72 normal ART fetuses and 201 normal NC fetuses. The malformation rate of CNS was determined for both groups. In both groups, significant positive correlations with gestational age were found for CSP width (ART: r=0.7841, NC: r=0.7864; P0.05). The development and malformation rate of the fetal CNS is not significantly different between ART and NC fetuses, thus, ART does not affect the development of the fetal brain.

  2. Scaling of Brain Metabolism with a Fixed Energy Budget per Neuron: Implications for Neuronal Activity, Plasticity and Evolution

    Herculano-Houzel, Suzana

    2011-01-01

    It is usually considered that larger brains have larger neurons, which consume more energy individually, and are therefore accompanied by a larger number of glial cells per neuron. These notions, however, have never been tested. Based on glucose and oxygen metabolic rates in awake animals and their recently determined numbers of neurons, here I show that, contrary to the expected, the estimated glucose use per neuron is remarkably constant, varying only by 40% across the six species of rodent...

  3. Effect of Testosterone on Neuronal Morphology and Neuritic Growth of Fetal Lamb Hypothalamus-Preoptic Area and Cerebral Cortex in Primary Culture.

    Radhika C Reddy

    Full Text Available Testosterone plays an essential role in sexual differentiation of the male sheep brain. The ovine sexually dimorphic nucleus (oSDN, is 2 to 3 times larger in males than in females, and this sex difference is under the control of testosterone. The effect of testosterone on oSDN volume may result from enhanced expansion of soma areas and/or dendritic fields. To test this hypothesis, cells derived from the hypothalamus-preoptic area (HPOA and cerebral cortex (CTX of lamb fetuses were grown in primary culture to examine the direct morphological effects of testosterone on these cellular components. We found that within two days of plating, neurons derived from both the HPOA and CTX extend neuritic processes and express androgen receptors and aromatase immunoreactivity. Both treated and control neurites continue to grow and branch with increasing time in culture. Treatment with testosterone (10 nM for 3 days significantly (P < 0.05 increased both total neurite outgrowth (35% and soma size (8% in the HPOA and outgrowth (21% and number of branch points (33% in the CTX. These findings indicate that testosterone-induced somal enlargement and neurite outgrowth in fetal lamb neurons may contribute to the development of a fully masculine sheep brain.

  4. Species-Specific Mechanisms of Neuron Subtype Specification Reveal Evolutionary Plasticity of Amniote Brain Development

    Tadashi Nomura

    2018-03-01

    Full Text Available Summary: Highly ordered brain architectures in vertebrates consist of multiple neuron subtypes with specific neuronal connections. However, the origin of and evolutionary changes in neuron specification mechanisms remain unclear. Here, we report that regulatory mechanisms of neuron subtype specification are divergent in developing amniote brains. In the mammalian neocortex, the transcription factors (TFs Ctip2 and Satb2 are differentially expressed in layer-specific neurons. In contrast, these TFs are co-localized in reptilian and avian dorsal pallial neurons. Multi-potential progenitors that produce distinct neuronal subtypes commonly exist in the reptilian and avian dorsal pallium, whereas a cis-regulatory element of avian Ctip2 exhibits attenuated transcription suppressive activity. Furthermore, the neuronal subtypes distinguished by these TFs are not tightly associated with conserved neuronal connections among amniotes. Our findings reveal the evolutionary plasticity of regulatory gene functions that contribute to species differences in neuronal heterogeneity and connectivity in developing amniote brains. : Neuronal heterogeneity is essential for assembling intricate neuronal circuits. Nomura et al. find that species-specific transcriptional mechanisms underlie diversities of excitatory neuron subtypes in mammalian and non-mammalian brains. Species differences in neuronal subtypes and connections suggest functional plasticity of regulatory genes for neuronal specification during amniote brain evolution. Keywords: Ctip2, Satb2, multi-potential progenitors, transcriptional regulation, neuronal connectivity

  5. Effect of alcohol exposure on fetal brain development

    Sudheendran, Narendran; Bake, Shameena; Miranda, Rajesh C.; Larin, Kirill V.

    2013-02-01

    Alcohol consumption during pregnancy can be severely damage to the brain development in fetuses. This study investigates the effects of maternal ethanol consumption on brain development in mice embryos. Pregnant mice at gestational day 12.5 were intragastrically gavaged with ethanol (3g/Kg bwt) twice daily for three consecutive days. On gestational day 14.5, fetuses were collected and fixed in 4% paraformaldehyde and imaged using a swept-source optical coherence tomography (SSOCT) system. 3D images of the mice embryo brain were obtained and the volumes of the left and right ventricles of the brain were measured. The average volumes of the left and the right volumes of 5 embryos each alcohol-exposed and control embryos were measured to be 0.35 and 0.15 mm3, respectively. The results suggest that the left and right ventricle volumes of brain are much larger in the alcohol-exposed embryos as compared to control embryos indicating alcohol-induced developmental delay.

  6. Xenon and sevoflurane provide analgesia during labor and fetal brain protection in a perinatal rat model of hypoxia-ischemia.

    Ting Yang

    Full Text Available It is not possible to identify all pregnancies at risk of neonatal hypoxic-ischemic encephalopathy (HIE. Many women use some form of analgesia during childbirth and some anesthetic agents have been shown to be neuroprotective when used as analgesics at subanesthetic concentrations. In this study we sought to understand the effects of two anesthetic agents with presumptive analgesic activity and known preconditioning-neuroprotective properties (sevoflurane or xenon, in reducing hypoxia-induced brain damage in a model of intrauterine perinatal asphyxia. The analgesic and neuroprotective effects at subanesthetic levels of sevoflurane (0.35% or xenon (35% were tested in a rat model of intrauterine perinatal asphyxia. Analgesic effects were measured by assessing maternal behavior and spinal cord dorsal horn neuronal activation using c-Fos. In separate experiments, intrauterine fetal asphyxia was induced four hours after gas exposure; on post-insult day 3 apoptotic cell death was measured by caspase-3 immunostaining in hippocampal neurons and correlated with the number of viable neurons on postnatal day (PND 7. A separate cohort of pups was nurtured by a surrogate mother for 50 days when cognitive testing with Morris water maze was performed. Both anesthetic agents provided analgesia as reflected by a reduction in the number of stretching movements and decreased c-Fos expression in the dorsal horn of the spinal cord. Both agents also reduced the number of caspase-3 positive (apoptotic neurons and increased cell viability in the hippocampus at PND7. These acute histological changes were mirrored by improved cognitive function measured remotely after birth on PND 50 compared to control group. Subanesthetic doses of sevoflurane or xenon provided both analgesia and neuroprotection in this model of intrauterine perinatal asphyxia. These data suggest that anesthetic agents with neuroprotective properties may be effective in preventing HIE and should be

  7. Aggregation patterns of fetal rat brain cells following exposure to X-irradiation

    Shoji, R.; Suzuki, K.; Lee, I.P.

    1980-01-01

    In our search for a simplified in vitro test system to assess the teratogenic effects of physical factors, we studied the effects of total maternal body X-irradiation on aggregation patterns of enzymatically isolated fetal rat brain cells and on ultrastructural aggregate changes. The fetal brain cells were derived from day 14 gestation fetuses of pregnant Sprague-Dawley (CD strain) rats exposed to X-irradiation (25 - 200 R) one hour prior to sacrifice. Notable changes in the cell aggregates following X-irradiation included a reduction in cell aggregate size and an increase in number. The frequency of cell aggregates was higher in the treated than in the control group, and the mean diameter of cell aggregates was inversely related to increasing X-irradiation doses. Transmission electron microscopy revealed in isolated cells features of degenerative process which were similar to those found in intact fetal brain lesions caused by maternal X-irradiation. Furthermore, scanning electron microscopy revealed that inhibition of cell aggregation following X-irradiation could probably be attributed to inhibition of membrane filopodia development and a consequent failure of cell aggregates to fuse into a greater cell aggregate mass. These results suggest that the membrane factors which influence cell aggregation may be a useful parameter to assess early effects of X-irradiation-induced brain deformity. Presently, the cell aggregation culture system is being further evaluated as a short term test system for environmental teratogens

  8. Evaluation of fetal brain development by magnetic resonance imaging. Subependymal germinal matrix layer and cerebral ventricle

    Kinoshita, Yoshimasa; Yokota, Akira; Okudera, Toshio

    1999-01-01

    Three dimensional data of brain from the formalin-fixed fetuses were collected without isolation, by the 4.7 tesla super high magnetic field MRI and the developmental process of the cerebral parenchyma was studied by 3D images. Subjects were 13 fetal brain and MRI was performed using 3D-steady-state free precession sequence. The isolated brain is very soft and fragile and is deformed by its weight at the imaging. However 3D-MRI can be obtained without isolation, and the deformation is remarkably small. The subependymal germinal matrix layer did not be observed in 7 weeks-old fetus, appeared at 9 weeks-old and increased gradually. Then it rapidly reduced from 28 weeks-old. The volume calculated, from 3D-MRI, increased rapidly from 9 weeks-old to 23 weeks-old, and reached the maximum (2.346 mm 3 ) at 23 weeks-old. The relation between fetal ages and volume of cerebral ventricle also showed similar pattern. This method will be useful to examine the development of the fetal brain without any damage. (K.H.)

  9. Brain renin-angiotensin system: fetal epigenetic programming by maternal protein restriction during pregnancy.

    Goyal, Ravi; Goyal, Dipali; Leitzke, Arthur; Gheorghe, Ciprian P; Longo, Lawrence D

    2010-03-01

    Maternal protein malnutrition during pregnancy can lead to significant alterations in the systemic renin-angiotensin system (RAS) in the fetus. All components of the RAS are present in brain and may be altered in many disease states. Importantly, these disorders are reported to be of higher incidence in prenatally malnourished individuals. In the current study, we tested the hypothesis that antenatal maternal low protein diet (MLPD) leads to epigenetic changes and alterations in gene expression of brain RAS of the mouse fetus. Mice dams were given control and 50% MLPD during second half of the gestation. We analyzed messenger RNA (mRNA), microRNA (miRNA), promoter DNA methylation, and protein expression of various RAS genes in the fetal offspring. As a consequence of 50% MLPD, fetal brains showed increased mRNA expression of angiotensinogen and angiotensin converting enzyme-1 (ACE-1), with a decrease in mRNA levels of angiotensin II type-2 (AT2) receptors. In contrast, while angiotensinogen protein expression was unaltered, the protein levels of ACE-1 and AT2 receptor genes were significantly reduced in the fetal brain from the MLPD dams. Our results also demonstrated hypomethylation of the CpG islands in the promoter regions of ACE-1 gene, and upregulation of the miRNAs, mmu-mir-27a and 27b, which regulate ACE-1 mRNA translation. Furthermore, our study showed reduced expression of the miRNA mmu-mir-330, which putatively regulates AT2 translation. For the developing fetal brain RAS, MLPD leads to significant alterations in the mRNA and protein expression, with changes in DNA methylation and miRNA, key regulators of hypertension in adults.

  10. Region-specific maturation of cerebral cortex in human fetal brain: diffusion tensor imaging and histology

    Trivedi, Richa; Gupta, Rakesh K.; Saksena, Sona; Husain, Nuzhat; Srivastava, Savita; Rathore, Ram K.S.; Sarma, Manoj K.; Malik, Gyanendra K.; Das, Vinita; Pradhan, Mandakini; Pandey, Chandra M.; Narayana, Ponnada A.

    2009-01-01

    In this study, diffusion tensor imaging (DTI) and glial fibrillary acidic protein (GFAP) immunohistochemical analysis in different cortical regions in fetal brains at different gestational age (GA) were performed. DTI was performed on 50 freshly aborted fetal brains with GA ranging from 12 to 42 weeks to compare age-related fractional anisotropy (FA) changes in different cerebral cortical regions that include frontal, parietal, occipital, and temporal lobes at the level of thalami. GFAP immunostaining was performed and the percentage of GFAP-positive areas was quantified. The cortical FA values in the frontal lobe peaked at around 26 weeks of GA, occipital and temporal lobes at around 20 weeks, and parietal lobe at around 23 weeks. A significant, but modest, positive correlation (r=0.31, p=0.02) was observed between cortical FA values and percentage area of GFAP expression in cortical region around the time period during which the migrational events are at its peak, i.e., GA ≤ 28 weeks for frontal cortical region and GA≤22 weeks for rest of the lobes. The DTI-derived FA quantification with its GFAP immunohistologic correlation in cortical regions of the various lobes of the cerebral hemispheres supports region-specific migrational and maturational events in human fetal brain. (orig.)

  11. Region-specific maturation of cerebral cortex in human fetal brain: diffusion tensor imaging and histology

    Trivedi, Richa; Gupta, Rakesh K.; Saksena, Sona [Sanjay Gandhi Post Graduate Institute of Medical Sciences, Department of Radiodiagnosis, Lucknow, UP (India); Husain, Nuzhat; Srivastava, Savita [CSM Medical University, Department of Pathology, Lucknow (India); Rathore, Ram K.S.; Sarma, Manoj K. [Indian Institute of Technology, Department of Mathematics and Statistics, Kanpur (India); Malik, Gyanendra K. [CSM Medical University, Department of Pediatrics, Lucknow (India); Das, Vinita [CSM Medical University, Department of Obstetrics and Gynecology, Lucknow (India); Pradhan, Mandakini [Sanjay Gandhi Postgraduate Institute of Medical Sciences, Department of Medical Genetics, Lucknow (India); Pandey, Chandra M. [Sanjay Gandhi Postgraduate Institute of Medical Sciences, Department of Biostatistics, Lucknow (India); Narayana, Ponnada A. [University of Texas Medical School at Houston, Department of Diagnostic and Interventional Imaging, Houston, TX (United States)

    2009-09-15

    In this study, diffusion tensor imaging (DTI) and glial fibrillary acidic protein (GFAP) immunohistochemical analysis in different cortical regions in fetal brains at different gestational age (GA) were performed. DTI was performed on 50 freshly aborted fetal brains with GA ranging from 12 to 42 weeks to compare age-related fractional anisotropy (FA) changes in different cerebral cortical regions that include frontal, parietal, occipital, and temporal lobes at the level of thalami. GFAP immunostaining was performed and the percentage of GFAP-positive areas was quantified. The cortical FA values in the frontal lobe peaked at around 26 weeks of GA, occipital and temporal lobes at around 20 weeks, and parietal lobe at around 23 weeks. A significant, but modest, positive correlation (r=0.31, p=0.02) was observed between cortical FA values and percentage area of GFAP expression in cortical region around the time period during which the migrational events are at its peak, i.e., GA {<=} 28 weeks for frontal cortical region and GA{<=}22 weeks for rest of the lobes. The DTI-derived FA quantification with its GFAP immunohistologic correlation in cortical regions of the various lobes of the cerebral hemispheres supports region-specific migrational and maturational events in human fetal brain. (orig.)

  12. Advanced MRI techniques of the fetal brain; Zukunftsweisende MRT-Techniken des fetalen Gehirns

    Schoepf, V.; Dittrich, E.; Berger-Kulemann, V.; Kasprian, G.; Kollndorfer, K.; Prayer, D. [Medizinische Universitaet Wien, Abteilung fuer Neuroradiologie und Muskuloskelettale Radiologie, Universitaetsklinik fuer Radiodiagnostik, Wien (Austria)

    2013-02-15

    Evaluation of the normal and pathological fetal brain. Magnetic resonance imaging (MRI). Advanced MRI of the fetal brain. Diffusion tensor imaging (DTI) is used in clinical practice, all other methods are used at a research level. Serving as standard methods in the future. Combined structural and functional data for all gestational ages will allow more specific insight into the developmental processes of the fetal brain. This gain of information will help provide a common understanding of complex spatial and temporal procedures of early morphological features and their impact on cognitive and sensory abilities. (orig.) [German] Evaluierung des gesunden bzw. pathologischen fetalen Gehirns. Die Magnetresonanztomographie. Zukunftsweisende Techniken in der MRT-Bildgebung des fetalen Gehirns. Die Diffusionstensorbildgebung (DTI) befindet sich bereits in der klinischen Anwendung, alle anderen Methoden sind bisher noch als experimentell zu werten. Auf dem Weg zur Etablierung als Standardverfahren. Eine kombinierte Verarbeitung funktioneller und struktureller Daten, modelliert fuer jede Schwangerschaftswoche, wird es zukuenftig ermoeglichen, anhand dieser fusionierten Informationen einen praezisen Einblick in den Entwicklungsprozess des Gehirns zu erlangen. Diese Erkenntnisse und Ergebnisse werden entscheidend zur Klaerung des zeitlichen Verlaufs und des komplexen Aufbaus frueher morphologischer Auffaelligkeiten beitragen sowie deren Einfluss auf kognitive und sensorische Faehigkeiten aufzeigen. (orig.)

  13. Fetal functional brain age assessed from universal developmental indices obtained from neuro-vegetative activity patterns.

    Dirk Hoyer

    Full Text Available Fetal brain development involves the development of the neuro-vegetative (autonomic control that is mediated by the autonomic nervous system (ANS. Disturbances of the fetal brain development have implications for diseases in later postnatal life. In that context, the fetal functional brain age can be altered. Universal principles of developmental biology applied to patterns of autonomic control may allow a functional age assessment. The work aims at the development of a fetal autonomic brain age score (fABAS based on heart rate patterns. We analysed n = 113 recordings in quiet sleep, n = 286 in active sleep, and n = 29 in active awakeness from normals. We estimated fABAS from magnetocardiographic recordings (21.4-40.3 weeks of gestation preclassified in quiet sleep (n = 113, 63 females and active sleep (n = 286, 145 females state by cross-validated multivariate linear regression models in a cross-sectional study. According to universal system developmental principles, we included indices that address increasing fluctuation range, increasing complexity, and pattern formation (skewness, power spectral ratio VLF/LF, pNN5. The resulting models constituted fABAS. fABAS explained 66/63% (coefficient of determination R(2 of training and validation set of the variance by age in quiet, while 51/50% in active sleep. By means of a logistic regression model using fluctuation range and fetal age, quiet and active sleep were automatically reclassified (94.3/93.1% correct classifications. We did not find relevant gender differences. We conclude that functional brain age can be assessed based on universal developmental indices obtained from autonomic control patterns. fABAS reflect normal complex functional brain maturation. The presented normative data are supplemented by an explorative study of 19 fetuses compromised by intrauterine growth restriction. We observed a shift in the state distribution towards active awakeness. The lower WGA

  14. Anatomical distribution of estrogen target neurons in turtle brain

    Kim, Y.S.; Stumpf, W.E.; Sar, M.

    1981-01-01

    Autoradiographic studies with [ 3 H]estradiol-17β in red-eared turtle (Pseudemys scripta elegans) show concentration and retention of radioactivity in nuclei of neurons in certain regions. Accumulations of estrogen target neurons exist in the periventricular brain with relationships to ventral extensions of the forebrain ventricles, including parolfactory, amygdaloid, septal, preoptic, hypothalamic and thalamic areas, as well as the dorsal ventricular ridge, the piriform cortex, and midbrain-pontine periaqueductal structures. The general anatomical pattern of distribution of estrogen target neurons corresponds to those observed not only in another reptile (Anolis carolinensis), but also in birds and mammals, as well as in teleosts and cyclostomes. In Pseudemys, which appears to display an intermediate degree of phylogenetic differentiation, the amygdaloid-septal-preoptic groups of estrogen target neurons constitute a continuum. In phylogenetic ascendency, e.g. in mammals, these cell populations are increasingly separated and distinct, while in phylogenetic descendency, e.g. in teleosts and cyclostomes, an amygdaloid group appears to be absent or contained within the septal-preoptic target cell population. (Auth.)

  15. Anatomical distribution of estrogen target neurons in turtle brain

    Kim, Y.S.; Stumpf, W.E.; Sar, M. (North Carolina Univ., Chapel Hill (USA))

    1981-12-28

    Autoradiographic studies with (/sup 3/H)estradiol-17..beta.. in red-eared turtle (Pseudemys scripta elegans) show concentration and retention of radioactivity in nuclei of neurons in certain regions. Accumulations of estrogen target neurons exist in the periventricular brain with relationships to ventral extensions of the forebrain ventricles, including parolfactory, amygdaloid, septal, preoptic, hypothalamic and thalamic areas, as well as the dorsal ventricular ridge, the piriform cortex, and midbrain-pontine periaqueductal structures. The general anatomical pattern of distribution of estrogen target neurons corresponds to those observed not only in another reptile (Anolis carolinensis), but also in birds and mammals, as well as in teleosts and cyclostomes. In Pseudemys, which appears to display an intermediate degree of phylogenetic differentiation, the amygdaloid-septal-preoptic groups of estrogen target neurons constitute a continuum. In phylogenetic ascendency, e.g. in mammals, these cell populations are increasingly separated and distinct, while in phylogenetic descendency, e.g. in teleosts and cyclostomes, an amygdaloid group appears to be absent or contained within the septal-preoptic target cell population.

  16. Dense reconstruction of brain-wide neuronal population close to the ground truth

    Li, Yun; Zhou, Hang; Li, Shiwei; Li, Jing; Su, Lei; Li, Anan; Feng, Xiong; Li, Ning; Han, Jiacheng; Kang, Hongtao; Chen, Yijun; Fang, Wenqian; Liu, Yidong; Lin, Huimin; Jin, Sen

    2017-01-01

    Neuron is the basic structure and functional unit of the brain, its projection and connections with other neurons provide a basic physical infrastructure for neural signal storage, allocation, processing, and integration. Recent technique progresses allow for labeling and imaging specific neuronal populations at single axonal level across a whole mouse brain. However, digital reconstruction of these neuron individuals needs months of human labor or sometimes is even an impossible task. Here w...

  17. Automatic Measurement of Fetal Brain Development from Magnetic Resonance Imaging: New Reference Data.

    Link, Daphna; Braginsky, Michael B; Joskowicz, Leo; Ben Sira, Liat; Harel, Shaul; Many, Ariel; Tarrasch, Ricardo; Malinger, Gustavo; Artzi, Moran; Kapoor, Cassandra; Miller, Elka; Ben Bashat, Dafna

    2018-01-01

    Accurate fetal brain volume estimation is of paramount importance in evaluating fetal development. The aim of this study was to develop an automatic method for fetal brain segmentation from magnetic resonance imaging (MRI) data, and to create for the first time a normal volumetric growth chart based on a large cohort. A semi-automatic segmentation method based on Seeded Region Growing algorithm was developed and applied to MRI data of 199 typically developed fetuses between 18 and 37 weeks' gestation. The accuracy of the algorithm was tested against a sub-cohort of ground truth manual segmentations. A quadratic regression analysis was used to create normal growth charts. The sensitivity of the method to identify developmental disorders was demonstrated on 9 fetuses with intrauterine growth restriction (IUGR). The developed method showed high correlation with manual segmentation (r2 = 0.9183, p user independent, applicable with retrospective data, and is suggested for use in routine clinical practice. © 2017 S. Karger AG, Basel.

  18. Food and Drug Administration warning on anesthesia and brain development: implications for obstetric and fetal surgery.

    Olutoye, Olutoyin A; Baker, Byron Wycke; Belfort, Michael A; Olutoye, Oluyinka O

    2018-01-01

    There has been growing concern about the detrimental effects of certain anesthetic agents on the developing brain. Preclinical studies in small animal models as well as nonhuman primates suggested loss or death of brain cells and consequent impaired neurocognitive function following anesthetic exposure in neonates and late gestation fetuses. Human studies in this area are limited and currently inconclusive. On Dec. 14, 2016, the US Food and Drug Administration issued a warning regarding impaired brain development in children following exposure to certain anesthetic agents used for general anesthesia, namely the inhalational anesthetics isoflurane, sevoflurane, and desflurane, and the intravenous agents propofol and midazolam, in the third trimester of pregnancy. Furthermore, this warning recommends that health care professionals should balance the benefits of appropriate anesthesia in young children and pregnant women against potential risks, especially for procedures that may last >3 hours or if multiple procedures are required in children surgery in the second and third trimester; this exposure is typically longer than that for cesarean delivery. Very few studies address the effect of anesthetic exposure on the fetus in the second trimester when most nonobstetric and fetal surgical procedures are performed. It is also unclear how the plasticity of the fetal brain at this stage of development will modulate the consequences of anesthetic exposure. Strategies that may circumvent possible untoward long-term neurologic effects of anesthesia in the baby include: (1) use of nonimplicated (nongamma-aminobutyric acid agonist) agents for sedation such as opioids (remifentanil, fentanyl) or the alpha-2 agonist, dexmedetomidine, when appropriate; (2) minimizing the duration of exposure to inhalational anesthetics for fetal, obstetric, and nonobstetric procedures in the pregnant patient, as much as possible within safe limits; and (3) commencing surgery promptly and limiting

  19. The study on morphologic alteration of fetal mice and the change of MeCP2 in fetal brain induced by ionizing radiation

    Chen Feng; Zhang Fengxiang; Tu Yu

    2012-01-01

    Objective: In order to investigate the effect and the possible mechanism of γ-rays on neuro development of fetal brain tissue as bystander effect organ. Methods: pregnant kunming mice were randomly divided into blank control group, 0.5 Gy whole-body exposed group, 0.5 Gy head exposed group, 1.0 Gy whole-body exposed group, 1.0 Gy head exposed group, 2.0 Gy whole-body exposed group and 2.0 Gy head exposed group. The exposed mice were exposed with a vertical single acute dose using 60 Co therapy apparatus on the 9 th day of pregnancy, and cesarean operation were performed to gain fetal mice on the 18 th day of pregnancy. The number, the size, stillbirth, birth defects and abortion, and get fetal brains from live births were observed. Western-blot assay was used to detect the expression of MeCP2 protein. Results: Compared with the blank control group, the rates of stillbirth, birth defects and abortion ascended as the increase of doses; the expression of MeCP2 were upregulated except 0.5 Gy whole-body exposed group, there were no significant differences between groups. Conclusion: When the pregnant mice were exposed to ionizing radiation in the first trimester, bystander effect in fetal brain tissue was induced, within a certain range, the incidence of deterministic effects and stochastic effects ascended as the increase of doses. (authors)

  20. Vaginal Exposure to Zika Virus during Pregnancy Leads to Fetal Brain Infection.

    Yockey, Laura J; Varela, Luis; Rakib, Tasfia; Khoury-Hanold, William; Fink, Susan L; Stutz, Bernardo; Szigeti-Buck, Klara; Van den Pol, Anthony; Lindenbach, Brett D; Horvath, Tamas L; Iwasaki, Akiko

    2016-08-25

    Zika virus (ZIKV) can be transmitted sexually between humans. However, it is unknown whether ZIKV replicates in the vagina and impacts the unborn fetus. Here, we establish a mouse model of vaginal ZIKV infection and demonstrate that, unlike other routes, ZIKV replicates within the genital mucosa even in wild-type (WT) mice. Mice lacking RNA sensors or transcription factors IRF3 and IRF7 resulted in higher levels of local viral replication. Furthermore, mice lacking the type I interferon (IFN) receptor (IFNAR) became viremic and died of infection after a high-dose vaginal ZIKV challenge. Notably, vaginal infection of pregnant dams during early pregnancy led to fetal growth restriction and infection of the fetal brain in WT mice. This was exacerbated in mice deficient in IFN pathways, leading to abortion. Our study highlights the vaginal tract as a highly susceptible site of ZIKV replication and illustrates the dire disease consequences during pregnancy. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Fetal Stress and Programming of Hypoxic/Ischemic-Sensitive Phenotype in the Neonatal Brain: Mechanisms and Possible Interventions

    Li, Yong; Gonzalez, Pablo; Zhang, Lubo

    2012-01-01

    Growing evidence of epidemiological, clinical and experimental studies has clearly shown a close link between adverse in utero environment and the increased risk of neurological, psychological and psychiatric disorders in later life. Fetal stresses, such as hypoxia, malnutrition, and fetal exposure to nicotine, alcohol, cocaine and glucocorticoids may directly or indirectly act at cellular and molecular levels to alter the brain development and result in programming of heightened brain vulnerability to hypoxic-ischemic encephalopathy and the development of neurological diseases in the postnatal life. The underlying mechanisms are not well understood. However, glucocorticoids may play a crucial role in epigenetic programming of neurological disorders of fetal origins. This review summarizes the recent studies about the effects of fetal stress on the abnormal brain development, focusing on the cellular, molecular and epigenetic mechanisms and highlighting the central effects of glucocorticoids on programming of hypoxicischemic-sensitive phenotype in the neonatal brain, which may enhance the understanding of brain pathophysiology resulting from fetal stress and help explore potential targets of timely diagnosis, prevention and intervention in neonatal hypoxic-ischemic encephalopathy and other for brain disorders. PMID:22627492

  2. Fetal stress and programming of hypoxic/ischemic-sensitive phenotype in the neonatal brain: mechanisms and possible interventions.

    Li, Yong; Gonzalez, Pablo; Zhang, Lubo

    2012-08-01

    Growing evidence of epidemiological, clinical and experimental studies has clearly shown a close link between adverse in utero environment and the increased risk of neurological, psychological and psychiatric disorders in later life. Fetal stresses, such as hypoxia, malnutrition, and fetal exposure to nicotine, alcohol, cocaine and glucocorticoids may directly or indirectly act at cellular and molecular levels to alter the brain development and result in programming of heightened brain vulnerability to hypoxic-ischemic encephalopathy and the development of neurological diseases in the postnatal life. The underlying mechanisms are not well understood. However, glucocorticoids may play a crucial role in epigenetic programming of neurological disorders of fetal origins. This review summarizes the recent studies about the effects of fetal stress on the abnormal brain development, focusing on the cellular, molecular and epigenetic mechanisms and highlighting the central effects of glucocorticoids on programming of hypoxic-ischemic-sensitive phenotype in the neonatal brain, which may enhance the understanding of brain pathophysiology resulting from fetal stress and help explore potential targets of timely diagnosis, prevention and intervention in neonatal hypoxic-ischemic encephalopathy and other brain disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. The capability of high field MRI in demonstrating post-mortem fetal brains at different gestational age

    Zhang Zhonghe; Liu Shuwei; Lin Xiangtao; Gen Hequn; Teng Gaojun; Fang Fang; Zang Fengchao; Yu Taifei; Zhao Bin

    2009-01-01

    Objective: To study the capability of high field MRI in demonstrating the post-mortem fetal brains at different gestational age (GA). Methods: One hundred and eight post-mortem fetal brains of 14-40 weeks GA were evaluated by 3.0 T MRI. Eleven brains of 14 to 27 weeks GA with good 3.0 T MRI images were chosen and scanned by 7.0 T MRI. The developing sulci, layered structures of fetal cerebral cortex and basal nuclei were evaluated on MRI of different Tesla (3.0 T and 7.0 T) and their results analyzed. Results: On T 1 WI of 3.0 T MRI, the layered structures of fetal cerebral cortex were present at 14 weeks GA, the sulci were more accurately identified after 16 weeks GA. The basal nuclei were clearly distinguishable after 20 weeks CA, and these structures were better visualized as the GA increased. On T 2 WI of 7.0 T MRI, the sulci, layered structures of fetal cerebral cortex and basal nuclei were shown more clearly at the same GA when compared to 3.0 T, especially the sulci at the early developmental stages. Conclusions: T 1 WI of 3.0 T MRI could show the developing structures of post-mortem fetal brain well, but the T 2 WI of 7.0 T MRI were comparatively better. (authors)

  4. Toxicogenomic profiling in maternal and fetal rodent brains following gestational exposure to chlorpyrifos

    Moreira, Estefania G.; Yu Xiaozhong; Robinson, Joshua F.; Griffith, Willian; Hong, Sung Woo; Beyer, Richard P.; Bammler, Theo K.; Faustman, Elaine M.

    2010-01-01

    Considering the wide variety of effects that have been reported to occur in the developmental neurotoxicity of chlorpyrifos (CP) and the lack of consensus on their dependence of brain acetylcholinesterase (AChE) activity inhibition, we applied microarray technology to explore dose-dependent alterations in transcriptional response in the fetal and maternal C57BL/6 mouse brain after daily gestational exposure (days 6 to 17) to CP (2, 4, 10, 12 or 15 mg/kg, sc). We identified significantly altered genes across doses and assessed for overrepresentation of Gene Ontology (GO) biological processes and KEGG pathways. We further clustered genes based on their expression profiles across doses and repeated the GO/pathways analysis for each cluster. The dose-effect relationship of CP on gene expression, both at the gene and pathway levels was non-monotonic and not necessarily related to brain AChE inhibition. The largest impact was observed in the 10 mg/kg dose group which was also the LOAEL for brain AChE inhibition. In the maternal brain, lower doses (4 mg/kg) influenced GO categories and pathways such as cell adhesion, behavior, lipid metabolism, long-term potentiation, nervous system development, neurogenesis, synaptic transmission. In the fetal brain, lower doses (2 and/or 4 mg/kg) significantly altered cell division, translation, transmission of nerve impulse, chromatin modification, long-term potentiation. In addition, some genes involved in nervous system development and signaling were shown to be specifically influenced by these lower CP doses. Our approach was sensitive and reflected the diversity of responses known to be disrupted by CP and highlighted possible additional consequences of CP neurotoxicity, such as disturbance of the ubiquitin proteasome system.

  5. Roles of taurine-mediated tonic GABAA receptor activation in the radial migration of neurons in the fetal mouse cerebral cortex

    Tomonori eFurukawa

    2014-03-01

    Full Text Available γ-Aminobutyric acid (GABA depolarizes embryonic cerebrocortical neurons and continuous activation of the GABAA receptor (GABAAR contributes to their tonic depolarization. Although multiple reports have demonstrated a role of GABAAR activation in neocortical development, including in migration, most of these studies have used pharmacological blockers. Herein, we performed in utero electroporation in GABA synthesis-lacking homozygous GAD67-GFP knock-in mice (GAD67GFP/GFP to label neurons born in the ventricular zone. Three days after electroporation, there were no differences in the distribution of labeled cells between the genotypes. The dose-response properties of cells labeled to detect GABA were equivalent among genotypes. However, continuous blockade of GABAAR with the GABAAR antagonist SR95531 accelerated radial migration. This effect of GABAAR blockade in GAD67GFP/GFP mice suggested a role for alternative endogenous GABAAR agonists. Thus, we tested the role of taurine, which is derived from maternal blood but is abundant in the fetal brain. The taurine-evoked currents in labeled cells were mediated by GABAAR. Taurine uptake was blocked by a taurine transporter inhibitor, 2-(guanidinoethanesulfonic acid (GES, and taurine release was blocked by a volume-sensitive anion channel blocker, 4-(2-butyl-6,7-dichlor-2-cyclopentylindan-1-on-5-yl oxobutyric acid (DCPIB, as examined through high-performance liquid chromatography (HPLC. GES increased the extracellular taurine concentration and induced an inward shift of the holding current, which was reversed by SR95531. In a taurine-deficient mouse model, the GABAAR-mediated tonic currents were greatly reduced, and radial migration was accelerated. As the tonic currents were equivalent among the genotypes of GAD67-GFP knock-in mice, taurine, rather than GABA, might play a major role as an endogenous agonist of embryonic tonic GABAAR conductance, regulating the radial migration of neurons in the

  6. Preclinical chorioamnionitis dysregulates CXCL1/CXCR2 signaling throughout the placental-fetal-brain axis.

    Yellowhair, Tracylyn R; Noor, Shahani; Maxwell, Jessie R; Anstine, Christopher V; Oppong, Akosua Y; Robinson, Shenandoah; Milligan, Erin D; Jantzie, Lauren L

    2018-03-01

    In the United States, perinatal brain injury (PBI) is a major cause of infant mortality and childhood disability. For a large proportion of infants with PBI, central nervous system (CNS) injury begins in utero with inflammation (chorioamnionitis/CHORIO) and/or hypoxia-ischemia. While studies show CHORIO contributes to preterm CNS injury and is also a common independent risk factor for brain injury in term infants, the molecular mechanisms mediating inflammation in the placental-fetal-brain axis that result in PBI remain a gap in knowledge. The chemokine (C-X-C motif) ligand 1 (CXCL1), and its cognate receptor, CXCR2, have been clinically implicated in CHORIO and in mature CNS injury, although their specific role in PBI pathophysiology is poorly defined. Given CXCL1/CXCR2 signaling is essential to neural cell development and neutrophil recruitment, a key pathological hallmark of CHORIO, we hypothesized CHORIO would upregulate CXCL1/CXCR2 expression in the placenta and fetal circulation, concomitant with increased CXCL1/CXCR2 signaling in the developing brain, immune cell activation, neutrophilia, and microstructural PBI. On embryonic day 18 (E18), a laparotomy was performed in pregnant Sprague Dawley rats to induce CHORIO. Specifically, uterine arteries were occluded for 60min to induce placental transient systemic hypoxia-ischemia (TSHI), followed by intra-amniotic injection of lipopolysaccharide (LPS). Pups were born at E22. Placentae, serum and brain were collected along an extended time course from E19 to postnatal day (P)15 and analyzed using multiplex electrochemiluminescence (MECI), Western blot, qPCR, flow cytometry (FC) and diffusion tensor imaging (DTI). Results demonstrate that compared to sham, CHORIO increases placental CXCL1 and CXCR2 mRNA levels, concomitant with increased CXCR2 + neutrophils. Interestingly, pup serum CXCL1 expression in CHORIO parallels this increase, with sustained elevation through P15. Analyses of CHORIO brains reveal similarly

  7. Interleukin-1 receptors in mouse brain: Characterization and neuronal localization

    Takao, T.; Tracey, D.E.; Mitchell, W.M.; De Souza, E.B.

    1990-01-01

    The cytokine interleukin-1 (IL-1) has a variety of effects in brain, including induction of fever, alteration of slow wave sleep, and alteration of neuroendocrine activity. To examine the potential sites of action of IL-1 in brain, we used iodine-125-labeled recombinant human interleukin-1 [( 125I]IL-1) to identify and characterize IL-1 receptors in crude membrane preparations of mouse (C57BL/6) hippocampus and to study the distribution of IL-1-binding sites in brain using autoradiography. In preliminary homogenate binding and autoradiographic studies, [125I]IL-1 alpha showed significantly higher specific binding than [125I]IL-1 beta. Thus, [125I]IL-1 alpha was used in all subsequent assays. The binding of [125I]IL-1 alpha was linear over a broad range of membrane protein concentrations, saturable, reversible, and of high affinity, with an equilibrium dissociation constant value of 114 +/- 35 pM and a maximum number of binding sites of 2.5 +/- 0.4 fmol/mg protein. In competition studies, recombinant human IL-1 alpha, recombinant human IL-1 beta, and a weak IL-1 beta analog. IL-1 beta +, inhibited [125I]IL-1 alpha binding to mouse hippocampus in parallel with their relative bioactivities in the T-cell comitogenesis assay, with inhibitory binding affinity constants of 55 +/- 18, 76 +/- 20, and 2940 +/- 742 pM, respectively; rat/human CRF and human tumor necrosis factor showed no effect on [125I]IL-1 alpha binding. Autoradiographic localization studies revealed very low densities of [125I]IL-1 alpha-binding sites throughout the brain, with highest densities present in the molecular and granular layers of the dentate gyrus of the hippocampus and in the choroid plexus. Quinolinic acid lesion studies demonstrated that the [125I]IL-1 alpha-binding sites in the hippocampus were localized to intrinsic neurons

  8. Effect of acute ethanol on beta-endorphin secretion from rat fetal hypothalamic neurons in primary cultures

    Sarkar, D.K.; Minami, S. (Washington State Univ., Pullman (USA))

    1990-01-01

    To characterize the effect of ethanol on the hypothalamic {beta}-endorphin-containing neurons, rat fetal hypothalamic neurons were maintained in primary culture, and the secretion of {beta}-endorphin ({beta}-EP) was determined after ethanol challenges. Constant exposure to ethanol at doses of 6-50 mM produced a dose-dependent increase in basal secretion of {beta}-EP from these cultured cells. These doses of ethanol did not produce any significant effect on cell viability, DNA or protein content. The stimulated secretion of {beta}-EP following constant ethanol exposure is short-lasting. However, intermittent ethanol exposures maintained the ethanol stimulatory action on {beta}-EP secretion for a longer time. The magnitude of the {beta}-EP response to 50 mM ethanol is similar to that of the {beta}-EP response to 56 mM of potassium. Ethanol-stimulated {beta}-EP secretion required extracellular calcium and was blocked by a calcium channel blocker; a sodium channel blocker did not affect ethanol-stimulated secretion. These results suggest that the neuron culture system is a useful model for studying the cellular mechanisms involved in the ethanol-regulated hypothalamic opioid secretion.

  9. Region-specific changes in brain diffusivity in fetal isolated mild ventriculomegaly

    Yaniv, Gal; Katorza, Eldad; Bercovitz, Ronen; Bergman, Dafi; Greenberg, Gahl; Hoffmann, Chen; Biegon, Anat

    2016-01-01

    To evaluate the impact of symmetric and asymmetric isolated mild ventriculomegaly (IMVM, atrial width 10-15 mm) on apparent diffusion coefficient (ADC) values in fetal brain areas. Sixty-seven sequential fetal head magnetic resonance imaging scans (feMRI) of VM cases performed between 2009 and 2014 were compared to 38 normal feMRI scans matched for gestational age (controls). Ultrasound- and MRI-proven IMVM cases were divided into asymmetrical (AVM, ≥2 mm difference in atrial width), symmetrical (SVM, <2 mm difference in atrial width), and asymmetrical IMVM with one normal-sized ventricle (AV1norm). ADC values were significantly elevated in the basal ganglia (BG) of the SVM and AV1norm groups compared to controls (p < 0.004 and p < 0.013, respectively). High diffusivity was constantly detected in the BG ipsilateral to the enlarged atria relative to the normal-sized atria in the AV1norm group (p < 0.03). Frontal lobe ADC values were significantly reduced in the AVM and SVM groups (p < 0.003 and p < 0.003 vs. controls). Temporal lobe ADC values were significantly reduced in the AVM group (p < 0.001 vs. controls). Isolated mild ventriculomegaly is associated with distinct ADC value changes in different brain regions. This phenomenon could reflect the pathophysiology associated with different IMVM patterns. (orig.)

  10. Region-specific changes in brain diffusivity in fetal isolated mild ventriculomegaly

    Yaniv, Gal [Sheba Medical Center, Department of Diagnostic Imaging, Tel Aviv (Israel); The Hebrew University of Jerusalem, The Institute for Research in Military Medicine, The Faculty of Medicine, Jerusalem (Israel); Sheba Medical Center, The Dr. Pinchas Bornstein Talpiot Medical Leadership Program, Tel Aviv (Israel); Katorza, Eldad [Sheba Medical Center, Obstetrics and Gynecology Department, Tel Aviv (Israel); Bercovitz, Ronen; Bergman, Dafi; Greenberg, Gahl; Hoffmann, Chen [Sheba Medical Center, Department of Diagnostic Imaging, Tel Aviv (Israel); Biegon, Anat [Stony Brook University School of Medicine, Department of Neurology, Stony Brook, NY (United States)

    2016-03-15

    To evaluate the impact of symmetric and asymmetric isolated mild ventriculomegaly (IMVM, atrial width 10-15 mm) on apparent diffusion coefficient (ADC) values in fetal brain areas. Sixty-seven sequential fetal head magnetic resonance imaging scans (feMRI) of VM cases performed between 2009 and 2014 were compared to 38 normal feMRI scans matched for gestational age (controls). Ultrasound- and MRI-proven IMVM cases were divided into asymmetrical (AVM, ≥2 mm difference in atrial width), symmetrical (SVM, <2 mm difference in atrial width), and asymmetrical IMVM with one normal-sized ventricle (AV1norm). ADC values were significantly elevated in the basal ganglia (BG) of the SVM and AV1norm groups compared to controls (p < 0.004 and p < 0.013, respectively). High diffusivity was constantly detected in the BG ipsilateral to the enlarged atria relative to the normal-sized atria in the AV1norm group (p < 0.03). Frontal lobe ADC values were significantly reduced in the AVM and SVM groups (p < 0.003 and p < 0.003 vs. controls). Temporal lobe ADC values were significantly reduced in the AVM group (p < 0.001 vs. controls). Isolated mild ventriculomegaly is associated with distinct ADC value changes in different brain regions. This phenomenon could reflect the pathophysiology associated with different IMVM patterns. (orig.)

  11. Learning-based prediction of gestational age from ultrasound images of the fetal brain.

    Namburete, Ana I L; Stebbing, Richard V; Kemp, Bryn; Yaqub, Mohammad; Papageorghiou, Aris T; Alison Noble, J

    2015-04-01

    We propose an automated framework for predicting gestational age (GA) and neurodevelopmental maturation of a fetus based on 3D ultrasound (US) brain image appearance. Our method capitalizes on age-related sonographic image patterns in conjunction with clinical measurements to develop, for the first time, a predictive age model which improves on the GA-prediction potential of US images. The framework benefits from a manifold surface representation of the fetal head which delineates the inner skull boundary and serves as a common coordinate system based on cranial position. This allows for fast and efficient sampling of anatomically-corresponding brain regions to achieve like-for-like structural comparison of different developmental stages. We develop bespoke features which capture neurosonographic patterns in 3D images, and using a regression forest classifier, we characterize structural brain development both spatially and temporally to capture the natural variation existing in a healthy population (N=447) over an age range of active brain maturation (18-34weeks). On a routine clinical dataset (N=187) our age prediction results strongly correlate with true GA (r=0.98,accurate within±6.10days), confirming the link between maturational progression and neurosonographic activity observable across gestation. Our model also outperforms current clinical methods by ±4.57 days in the third trimester-a period complicated by biological variations in the fetal population. Through feature selection, the model successfully identified the most age-discriminating anatomies over this age range as being the Sylvian fissure, cingulate, and callosal sulci. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Central Artery Stiffness, Baroreflex Sensitivity, and Brain White Matter Neuronal Fiber Integrity in Older Adults

    Tarumi, Takashi; de Jong, Daan L.K.; Zhu, David C.; Tseng, Benjamin Y.; Liu, Jie; Hill, Candace; Riley, Jonathan; Womack, Kyle B.; Kerwin, Diana R.; Lu, Hanzhang; Cullum, C. Munro; Zhang, Rong

    2015-01-01

    Cerebral hypoperfusion elevates the risk of brain white matter (WM) lesions and cognitive impairment. Central artery stiffness impairs baroreflex, which controls systemic arterial perfusion, and may deteriorate neuronal fiber integrity of brain WM. The purpose of this study was to examine the associations among brain WM neuronal fiber integrity, baroreflex sensitivity (BRS), and central artery stiffness in older adults. Fifty-four adults (65±6 years) with normal cognitive function or mild cog...

  13. Decreased α1-adrenergic receptor-mediated inositide hydrolysis in neurons from hypertensive rat brain

    Feldstein, J.B.; Gonzales, R.A.; Baker, S.P.; Sumners, C.; Crews, F.T.; Raizada, M.K.

    1986-01-01

    The expression of α 1 -adrenergic receptors and norepinephrine (NE)-stimulated hydrolysis of inositol phospholipid has been studied in neuronal cultures from the brains of normotensive (Wistar-Kyoto, WKY) and spontaneously hypertensive (SH) rats. Binding of 125 I-1-[β-(4-hydroxyphenyl)-ethyl-aminomethyl] tetralone (HEAT) to neuronal membranes was 68-85% specific and was rapid. Competition-inhibition experiments with various agonists and antagonists suggested that 125 I-HEAT bound selectively to α 1 -adrenergic receptors. Specific binding of 125 I-HEAT to neuronal membranes from SH rat brain cultures was 30-45% higher compared with binding in WKY normotensive controls. This increase was attributed to an increase in the number of α 1 -adrenergic receptors on SH rat brain neurons. Incubation of neuronal cultures of rat brain from both strains with NE resulted in a concentration-dependent stimulation of release of inositol phosphates, although neurons from SH rat brains were 40% less responsive compared with WKY controls. The decrease in responsiveness of SH rat brain neurons to NE, even though the α 1 -adrenergic receptors are increased, does not appear to be due to a general defect in membrane receptors and postreceptor signal transduction mechanisms. This is because neither the number of muscarinic-cholinergic receptors nor the carbachol-stimulated release of inositol phosphates is different in neuronal cultures from the brains of SH rats compared with neuronal cultures from the brains of WKY rats. These observations suggest that the increased expression of α 1 -adrenergic receptors does not parallel the receptor-mediated inositol phosphate hydrolysis in neuronal cultures from SH rat brain

  14. From migration to settlement: the pathways, migration modes and dynamics of neurons in the developing brain

    HATANAKA, Yumiko; ZHU, Yan; TORIGOE, Makio; KITA, Yoshiaki; MURAKAMI, Fujio

    2016-01-01

    Neuronal migration is crucial for the construction of the nervous system. To reach their correct destination, migrating neurons choose pathways using physical substrates and chemical cues of either diffusible or non-diffusible nature. Migrating neurons extend a leading and a trailing process. The leading process, which extends in the direction of migration, determines navigation, in particular when a neuron changes its direction of migration. While most neurons simply migrate radially, certain neurons switch their mode of migration between radial and tangential, with the latter allowing migration to destinations far from the neurons’ site of generation. Consequently, neurons with distinct origins are intermingled, which results in intricate neuronal architectures and connectivities and provides an important basis for higher brain function. The trailing process, in contrast, contributes to the late stage of development by turning into the axon, thus contributing to the formation of neuronal circuits. PMID:26755396

  15. GABA regulates synaptic integration of newly generated neurons in the adult brain

    Ge, Shaoyu; Goh, Eyleen L. K.; Sailor, Kurt A.; Kitabatake, Yasuji; Ming, Guo-Li; Song, Hongjun

    2006-02-01

    Adult neurogenesis, the birth and integration of new neurons from adult neural stem cells, is a striking form of structural plasticity and highlights the regenerative capacity of the adult mammalian brain. Accumulating evidence suggests that neuronal activity regulates adult neurogenesis and that new neurons contribute to specific brain functions. The mechanism that regulates the integration of newly generated neurons into the pre-existing functional circuitry in the adult brain is unknown. Here we show that newborn granule cells in the dentate gyrus of the adult hippocampus are tonically activated by ambient GABA (γ-aminobutyric acid) before being sequentially innervated by GABA- and glutamate-mediated synaptic inputs. GABA, the major inhibitory neurotransmitter in the adult brain, initially exerts an excitatory action on newborn neurons owing to their high cytoplasmic chloride ion content. Conversion of GABA-induced depolarization (excitation) into hyperpolarization (inhibition) in newborn neurons leads to marked defects in their synapse formation and dendritic development in vivo. Our study identifies an essential role for GABA in the synaptic integration of newly generated neurons in the adult brain, and suggests an unexpected mechanism for activity-dependent regulation of adult neurogenesis, in which newborn neurons may sense neuronal network activity through tonic and phasic GABA activation.

  16. Absence of PO2 change in fetal brain despite PO2 increase in placenta in response to maternal oxygen challenge.

    Huen, I; Morris, D M; Wright, C; Sibley, C P; Naish, J H; Johnstone, E D

    2014-12-01

    Magnetic resonance imaging allows the noninvasive observation of PO2 changes between air breathing and oxygen breathing through quantification of the magnetic longitudinal relaxation time T1. Changes in PO2 are proportional to changes in the longitudinal relaxation rate ΔR1 (where ΔR1=1/T1oxygen-1/T1air). Knowledge of this response could inform clinical interventions using maternal oxygen administration antenatally to treat fetal growth restriction. We present in vivo measurements of the response of the fetal-placental unit to maternal hyperoxia. Prospective cohort. Large tertiary maternity hospital. Nine women undergoing low-risk pregnancy (21-33 weeks of gestation) and five nonpregnant adults. During imaging the air supply to mothers was changed from medical air (21% oxygen) to medical oxygen (100% oxygen) and T1 was monitored over time in both the placenta and fetal brain using a periodically repeated magnetic resonance imaging sequence. To demonstrate that the method could detect a brain response, brain responses from five normal adult volunteers were measured using a similar imaging protocol. Changes in T1 following oxygen challenge. No significant ΔR1 (P=0.42, paired t-test) was observed in fetal brains. A significant placental ΔR1 (P=0.0002, paired t-test) of 0.02±0.01/s (mean±SD) was simultaneously observed in the same participants. In the brains of the nonpregnant adults, a significant ΔR1 (P=0.01, paired t-test) of 0.005±0.002/s was observed. Short-term maternal oxygen administration does not improve fetal brain oxygenation, in contrast to the response observed in the adult brain. © 2014 Royal College of Obstetricians and Gynaecologists.

  17. The PM1 neurons, movement sensitive centrifugal visual brain neurons in the locust: anatomy, physiology, and modulation by identified octopaminergic neurons.

    Stern, Michael

    2009-02-01

    The locust's optic lobe contains a system of wide-field, multimodal, centrifugal neurons. Two of these cells, the protocerebrum-medulla-neurons PM4a and b, are octopaminergic. This paper describes a second pair of large centrifugal neurons (the protocerebrum-medulla-neurons PM1a and PM1b) from the brain of Locusta migratoria based on intracellular cobalt fills, electrophysiology, and immunocytochemistry. They originate and arborise in the central brain and send processes into the medulla of the optic lobe. Double intracellular recording from the same cell suggests input in the central brain and output in the optic lobe. The neurons show immunoreactivity to gamma-amino-butyric acid and its synthesising enzyme, glutamate decarboxylase. The PM1 cells are movement sensitive and show habituation to repeated visual stimulation. Bath application of octopamine causes the response to dishabituate. A very similar effect is produced by electrical stimulation of one of an octopaminergic PM4 neuron. This effect can be blocked by application of the octopamine antagonists, mianserin and phentolamine. This readily accessible system of four wide-field neurons provides a system suitable for the investigation of octopaminergic effects on the visual system at the cellular level.

  18. Descending brain neurons in larval lamprey: Spinal projection patterns and initiation of locomotion

    Shaw, Albert C.; Jackson, Adam W.; Holmes, Tamra; Thurman, Suzie; Davis, G.R.; McClellan, Andrew D.

    2010-01-01

    In larval lamprey, partial lesions were made in the rostral spinal cord to determine which spinal tracts are important for descending activation of locomotion and to identify descending brain neurons that project in these tracts. In whole animals and in vitro brain/spinal cord preparations, brain-initiated spinal locomotor activity was present when the lateral or intermediate spinal tracts were spared but usually was abolished when the medial tracts were spared. We previously showed that descending brain neurons are located in eleven cell groups, including reticulospinal (RS) neurons in the mesenecephalic reticular nucleus (MRN) as well as the anterior (ARRN), middle (MRRN), and posterior (PRRN) rhombencephalic reticular nuclei. Other descending brain neurons are located in the diencephalic (Di) as well as the anterolateral (ALV), dorsolateral (DLV), and posterolateral (PLV) vagal groups. In the present study, the Mauthner and auxillary Mauthner cells, most neurons in the Di, ALV, DLV, and PLV cell groups, and some neurons in the ARRN and PRRN had crossed descending axons. The majority of neurons projecting in medial spinal tracts included large identified Müller cells and neurons in the Di, MRN, ALV, and DLV. Axons of individual descending brain neurons usually did not switch spinal tracts, have branches in multiple tracts, or cross the midline within the rostral cord. Most neurons that projected in the lateral/intermediate spinal tracts were in the ARRN, MRRN, and PRRN. Thus, output neurons of the locomotor command system are distributed in several reticular nuclei, whose neurons project in relatively wide areas of the cord. PMID:20510243

  19. Fetal functional imaging portrays heterogeneous development of emerging human brain networks

    Andras eJakab

    2014-10-01

    Full Text Available The functional connectivity architecture of the adult human brain enables complex cognitive processes, and exhibits a remarkably complex structure shared across individuals. We are only beginning to understand its heterogeneous structure, ranging from a strongly hierarchical organization in sensorimotor areas to widely distributed networks in areas such as the parieto-frontal cortex. Our study relied on the functional magnetic resonance imaging data of 32 fetuses with no detectable morphological abnormalities. After adapting functional magnetic resonance acquisition, motion correction and nuisance signal reduction procedures of resting-state functional data analysis to fetuses, we extracted neural activity information for major cortical and subcortical structures. Resting fMRI networks were observed for increasing regional functional connectivity from 21st – 38th gestational weeks (GW with a network-based statistical inference approach. The overall connectivity network, short range and interhemispheric connections showed sigmoid expansion curve peaking at the 26-29. GW. In contrast, long-range connections exhibited linear increase with no periods of peaking development. Region-specific increase of functional signal synchrony followed a sequence of occipital (peak: 24.8 GW, temporal (peak: 26 GW, frontal (peak: 26.4 GW and parietal expansion (peak: 27.5 GW. We successfully adapted functional neuroimaging and image post-processing approaches to correlate macroscopical scale activations in the fetal brain with gestational age. This in vivo study reflects the fact that the mid-fetal period hosts events that cause the architecture of the brain circuitry to mature, which presumably manifests in increasing strength of intra- and interhemispheric functional macroconnectivity.

  20. Fetal functional imaging portrays heterogeneous development of emerging human brain networks.

    Jakab, András; Schwartz, Ernst; Kasprian, Gregor; Gruber, Gerlinde M; Prayer, Daniela; Schöpf, Veronika; Langs, Georg

    2014-01-01

    The functional connectivity architecture of the adult human brain enables complex cognitive processes, and exhibits a remarkably complex structure shared across individuals. We are only beginning to understand its heterogeneous structure, ranging from a strongly hierarchical organization in sensorimotor areas to widely distributed networks in areas such as the parieto-frontal cortex. Our study relied on the functional magnetic resonance imaging (fMRI) data of 32 fetuses with no detectable morphological abnormalities. After adapting functional magnetic resonance acquisition, motion correction, and nuisance signal reduction procedures of resting-state functional data analysis to fetuses, we extracted neural activity information for major cortical and subcortical structures. Resting fMRI networks were observed for increasing regional functional connectivity from 21st to 38th gestational weeks (GWs) with a network-based statistical inference approach. The overall connectivity network, short range, and interhemispheric connections showed sigmoid expansion curve peaking at the 26-29 GW. In contrast, long-range connections exhibited linear increase with no periods of peaking development. Region-specific increase of functional signal synchrony followed a sequence of occipital (peak: 24.8 GW), temporal (peak: 26 GW), frontal (peak: 26.4 GW), and parietal expansion (peak: 27.5 GW). We successfully adapted functional neuroimaging and image post-processing approaches to correlate macroscopical scale activations in the fetal brain with gestational age. This in vivo study reflects the fact that the mid-fetal period hosts events that cause the architecture of the brain circuitry to mature, which presumably manifests in increasing strength of intra- and interhemispheric functional macro connectivity.

  1. Focusing on neuronal cell-type specific mechanisms for brain circuit organization, function and dysfunction

    Lu Li

    2017-01-01

    Mammalian brain circuits consist of dynamically interconnected neurons with characteristic morphology, physiology, connectivity and genetics which are often called neuronal cell types. Neuronal cell types have been considered as building blocks of brain circuits, but knowledge of how neuron types or subtypes connect to and interact with each other to perform neural computation is still lacking. Such mechanistic insights are critical not only to our understanding of normal brain functions, such as perception, motion and cognition, but also to brain disorders including Alzheimer's disease, Schizophrenia and epilepsy, to name a few. Thus it is necessary to carry out systematic and standardized studies on neuronal cell-type specific mechanisms for brain circuit organization and function, which will provide good opportunities to bridge basic and clinical research. Here based on recent technology advancements, we discuss the strategy to target and manipulate specific populations of neuronsin vivo to provide unique insights on how neuron types or subtypes behave, interact, and generate emergent properties in a fully connected brain network. Our approach is highlighted by combining transgenic animal models, targeted electrophysiology and imaging with robotics, thus complete and standardized mapping ofin vivo properties of genetically defined neuron populations can be achieved in transgenic mouse models, which will facilitate the development of novel therapeutic strategies for brain disorders.

  2. Birth of projection neurons in adult avian brain may be related to perceptual or motor learning

    Alvarez-Buylla, A.; Kirn, J.R.; Nottebohm, F.

    1990-01-01

    Projection neurons that form part of the motor pathway for song control continue to be produced and to replace older projection neurons in adult canaries and zebra finches. This is shown by combining [3H]thymidine, a cell birth marker, and fluorogold, a retrogradely transported tracer of neuronal connectivity. Species and seasonal comparisons suggest that this process is related to the acquisition of perceptual or motor memories. The ability of an adult brain to produce and replace projection neurons should influence our thinking on brain repair

  3. Molecular fingerprint of neuropeptide S-producing neurons in the mouse brain

    Liu, Xiaobin; Zeng, Joanne; Zhou, Anni

    2011-01-01

    Neuropeptide S (NPS) has been associated with a number of complex brain functions, including anxiety-like behaviors, arousal, sleep-wakefulness regulation, drug-seeking behaviors, and learning and memory. In order to better understand how NPS influences these functions in a neuronal network context...... of incoming neurotransmission, controlling neuronal activity of NPS-producing neurons. Stress-induced functional activation of NPS-producing neurons was detected by staining for the immediate-early gene c-fos, thus supporting earlier findings that NPS might be part of the brain stress response network....

  4. Efficient and rapid derivation of primitive neural stem cells and generation of brain subtype neurons from human pluripotent stem cells.

    Yan, Yiping; Shin, Soojung; Jha, Balendu Shekhar; Liu, Qiuyue; Sheng, Jianting; Li, Fuhai; Zhan, Ming; Davis, Janine; Bharti, Kapil; Zeng, Xianmin; Rao, Mahendra; Malik, Nasir; Vemuri, Mohan C

    2013-11-01

    Human pluripotent stem cells (hPSCs), including human embryonic stem cells and human induced pluripotent stem cells, are unique cell sources for disease modeling, drug discovery screens, and cell therapy applications. The first step in producing neural lineages from hPSCs is the generation of neural stem cells (NSCs). Current methods of NSC derivation involve the time-consuming, labor-intensive steps of an embryoid body generation or coculture with stromal cell lines that result in low-efficiency derivation of NSCs. In this study, we report a highly efficient serum-free pluripotent stem cell neural induction medium that can induce hPSCs into primitive NSCs (pNSCs) in 7 days, obviating the need for time-consuming, laborious embryoid body generation or rosette picking. The pNSCs expressed the neural stem cell markers Pax6, Sox1, Sox2, and Nestin; were negative for Oct4; could be expanded for multiple passages; and could be differentiated into neurons, astrocytes, and oligodendrocytes, in addition to the brain region-specific neuronal subtypes GABAergic, dopaminergic, and motor neurons. Global gene expression of the transcripts of pNSCs was comparable to that of rosette-derived and human fetal-derived NSCs. This work demonstrates an efficient method to generate expandable pNSCs, which can be further differentiated into central nervous system neurons and glia with temporal, spatial, and positional cues of brain regional heterogeneity. This method of pNSC derivation sets the stage for the scalable production of clinically relevant neural cells for cell therapy applications in good manufacturing practice conditions.

  5. Mirror neurons: Enigma of the metaphysical modular brain.

    Acharya, Sourya; Shukla, Samarth

    2012-07-01

    Mirror neurons are one of the most important discoveries in the last decade of neuroscience. These are a variety of visuospatial neurons which indicate fundamentally about human social interaction. Essentially, mirror neurons respond to actions that we observe in others. The interesting part is that mirror neurons fire in the same way when we actually recreate that action ourselves. Apart from imitation, they are responsible for myriad of other sophisticated human behavior and thought processes. Defects in the mirror neuron system are being linked to disorders like autism. This review is a brief introduction to the neurons that shaped our civilization.

  6. Neurons derived from different brain regions are inherently different in vitro: a novel multiregional brain-on-a-chip.

    Dauth, Stephanie; Maoz, Ben M; Sheehy, Sean P; Hemphill, Matthew A; Murty, Tara; Macedonia, Mary Kate; Greer, Angie M; Budnik, Bogdan; Parker, Kevin Kit

    2017-03-01

    Brain in vitro models are critically important to developing our understanding of basic nervous system cellular physiology, potential neurotoxic effects of chemicals, and specific cellular mechanisms of many disease states. In this study, we sought to address key shortcomings of current brain in vitro models: the scarcity of comparative data for cells originating from distinct brain regions and the lack of multiregional brain in vitro models. We demonstrated that rat neurons from different brain regions exhibit unique profiles regarding their cell composition, protein expression, metabolism, and electrical activity in vitro. In vivo, the brain is unique in its structural and functional organization, and the interactions and communication between different brain areas are essential components of proper brain function. This fact and the observation that neurons from different areas of the brain exhibit unique behaviors in vitro underline the importance of establishing multiregional brain in vitro models. Therefore, we here developed a multiregional brain-on-a-chip and observed a reduction of overall firing activity, as well as altered amounts of astrocytes and specific neuronal cell types compared with separately cultured neurons. Furthermore, this multiregional model was used to study the effects of phencyclidine, a drug known to induce schizophrenia-like symptoms in vivo, on individual brain areas separately while monitoring downstream effects on interconnected regions. Overall, this work provides a comparison of cells from different brain regions in vitro and introduces a multiregional brain-on-a-chip that enables the development of unique disease models incorporating essential in vivo features. NEW & NOTEWORTHY Due to the scarcity of comparative data for cells from different brain regions in vitro, we demonstrated that neurons isolated from distinct brain areas exhibit unique behaviors in vitro. Moreover, in vivo proper brain function is dependent on the

  7. Laser capture microdissection of enriched populations of neurons or single neurons for gene expression analysis after traumatic brain injury.

    Boone, Deborah R; Sell, Stacy L; Hellmich, Helen Lee

    2013-04-10

    Long-term cognitive disability after TBI is associated with injury-induced neurodegeneration in the hippocampus-a region in the medial temporal lobe that is critical for learning, memory and executive function. Hence our studies focus on gene expression analysis of specific neuronal populations in distinct subregions of the hippocampus. The technique of laser capture microdissection (LCM), introduced in 1996 by Emmert-Buck, et al., has allowed for significant advances in gene expression analysis of single cells and enriched populations of cells from heterogeneous tissues such as the mammalian brain that contains thousands of functional cell types. We use LCM and a well established rat model of traumatic brain injury (TBI) to investigate the molecular mechanisms that underlie the pathogenesis of TBI. Following fluid-percussion TBI, brains are removed at pre-determined times post-injury, immediately frozen on dry ice, and prepared for sectioning in a cryostat. The rat brains can be embedded in OCT and sectioned immediately, or stored several months at -80 °C before sectioning for laser capture microdissection. Additionally, we use LCM to study the effects of TBI on circadian rhythms. For this, we capture neurons from the suprachiasmatic nuclei that contain the master clock of the mammalian brain. Here, we demonstrate the use of LCM to obtain single identified neurons (injured and degenerating, Fluoro-Jade-positive, or uninjured, Fluoro-Jade-negative) and enriched populations of hippocampal neurons for subsequent gene expression analysis by real time PCR and/or whole-genome microarrays. These LCM-enabled studies have revealed that the selective vulnerability of anatomically distinct regions of the rat hippocampus are reflected in the different gene expression profiles of different populations of neurons obtained by LCM from these distinct regions. The results from our single-cell studies, where we compare the transcriptional profiles of dying and adjacent surviving

  8. Comparative assessments of the effects of alcohol exposure on fetal brain development using optical coherence tomography and ultrasound imaging

    Sudheendran, Narendran; Bake, Shameena; Miranda, Rajesh C.; Larin, Kirill V.

    2013-02-01

    The developing fetal brain is vulnerable to a variety of environmental agents including maternal ethanol consumption. Preclinical studies on the development and amelioration of fetal teratology would be significantly facilitated by the application of high resolution imaging technologies like optical coherence tomography (OCT) and high-frequency ultrasound (US). This study investigates the ability of these imaging technologies to measure the effects of maternal ethanol exposure on brain development, ex vivo, in fetal mice. Pregnant mice at gestational day 12.5 were administered ethanol (3 g/Kg b.wt.) or water by intragastric gavage, twice daily for three consecutive days. On gestational day 14.5, fetuses were collected and imaged. Three-dimensional images of the mice fetus brains were obtained by OCT and high-resolution US, and the volumes of the left and right ventricles of the brain were measured. Ethanol-exposed fetuses exhibited a statistically significant, 2-fold increase in average left and right ventricular volumes compared with the ventricular volume of control fetuses, with OCT-derived measures of 0.38 and 0.18 mm3, respectively, whereas the boundaries of the fetal mouse lateral ventricles were not clearly definable with US imaging. Our results indicate that OCT is a useful technology for assessing ventriculomegaly accompanying alcohol-induced developmental delay. This study clearly demonstrated advantages of using OCT for quantitative assessment of embryonic development compared with US imaging.

  9. Wiring economy and volume exclusion determine neuronal placement in the Drosophila brain.

    Rivera-Alba, Marta; Vitaladevuni, Shiv N; Mishchenko, Yuriy; Mischenko, Yuriy; Lu, Zhiyuan; Takemura, Shin-Ya; Scheffer, Lou; Meinertzhagen, Ian A; Chklovskii, Dmitri B; de Polavieja, Gonzalo G

    2011-12-06

    Wiring economy has successfully explained the individual placement of neurons in simple nervous systems like that of Caenorhabditis elegans [1-3] and the locations of coarser structures like cortical areas in complex vertebrate brains [4]. However, it remains unclear whether wiring economy can explain the placement of individual neurons in brains larger than that of C. elegans. Indeed, given the greater number of neuronal interconnections in larger brains, simply minimizing the length of connections results in unrealistic configurations, with multiple neurons occupying the same position in space. Avoiding such configurations, or volume exclusion, repels neurons from each other, thus counteracting wiring economy. Here we test whether wiring economy together with volume exclusion can explain the placement of neurons in a module of the Drosophila melanogaster brain known as lamina cartridge [5-13]. We used newly developed techniques for semiautomated reconstruction from serial electron microscopy (EM) [14] to obtain the shapes of neurons, the location of synapses, and the resultant synaptic connectivity. We show that wiring length minimization and volume exclusion together can explain the structure of the lamina microcircuit. Therefore, even in brains larger than that of C. elegans, at least for some circuits, optimization can play an important role in individual neuron placement. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Image-guided recording system for spatial and temporal mapping of neuronal activities in brain slice.

    Choi, Geonho; Lee, Jeonghyeon; Kim, Hyeongeun; Jang, Jaemyung; Im, Changkyun; Jeon, Nooli; Jung, Woonggyu

    2018-03-01

    In this study, we introduce the novel image-guided recording system (IGRS) for efficient interpretation of neuronal activities in the brain slice. IGRS is designed to combine microelectrode array (MEA) and optical coherence tomography at the customized upright microscope. It allows to record multi-site neuronal signals and image of the volumetric brain anatomy in a single body configuration. For convenient interconnection between a brain image and neuronal signals, we developed the automatic mapping protocol that enables us to project acquired neuronal signals on a brain image. To evaluate the performance of IGRS, hippocampal signals of the brain slice were monitored, and corresponding with two-dimensional neuronal maps were successfully reconstructed. Our results indicated that IGRS and mapping protocol can provide the intuitive information regarding long-term and multi-sites neuronal signals. In particular, the temporal and spatial mapping capability of neuronal signals would be a very promising tool to observe and analyze the massive neuronal activity and connectivity in MEA-based electrophysiological studies. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Neuroprotection by selective neuronal deletion of Atg7 in neonatal brain injury

    Xie, Cuicui; Ginet, Vanessa; Sun, Yanyan; Koike, Masato; Zhou, Kai; Li, Tao; Li, Hongfu; Li, Qian; Wang, Xiaoyang; Uchiyama, Yasuo; Truttmann, Anita C.; Kroemer, Guido; Puyal, Julien; Blomgren, Klas; Zhu, Changlian

    2016-01-01

    ABSTRACT Perinatal asphyxia induces neuronal cell death and brain injury, and is often associated with irreversible neurological deficits in children. There is an urgent need to elucidate the neuronal death mechanisms occurring after neonatal hypoxia-ischemia (HI). We here investigated the selective neuronal deletion of the Atg7 (autophagy related 7) gene on neuronal cell death and brain injury in a mouse model of severe neonatal hypoxia-ischemia. Neuronal deletion of Atg7 prevented HI-induced autophagy, resulted in 42% decrease of tissue loss compared to wild-type mice after the insult, and reduced cell death in multiple brain regions, including apoptosis, as shown by decreased caspase-dependent and -independent cell death. Moreover, we investigated the lentiform nucleus of human newborns who died after severe perinatal asphyxia and found increased neuronal autophagy after severe hypoxic-ischemic encephalopathy compared to control uninjured brains, as indicated by the numbers of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3)-, LAMP1 (lysosomal-associated membrane protein 1)-, and CTSD (cathepsin D)-positive cells. These findings reveal that selective neuronal deletion of Atg7 is strongly protective against neuronal death and overall brain injury occurring after HI and suggest that inhibition of HI-enhanced autophagy should be considered as a potential therapeutic target for the treatment of human newborns developing severe hypoxic-ischemic encephalopathy. PMID:26727396

  12. Tsc2 Haploinsufficiency Has Limited Effects on Fetal Brain Cytokine Levels during Gestational Immune Activation

    Dan Ehninger

    2014-01-01

    Full Text Available Dysregulated TSC/mTOR signaling may play a pathogenetic role in forms of syndromic autism, such as autism associated with tuberous sclerosis, a genetic disorder caused by heterozygous TSC1 or TSC2 mutations. Environmental risk factors, such as gestational viral infections, may, in some cases, also contribute to the pathogenesis of autism and related neuropsychiatric disorders. We have recently found that a heterozygous Tsc2 mutation and the poly I:C model of maternal immune activation (MIA interactively perturb fetal development and adult social behavior in mice, suggesting that these factors converge on shared pathways. TSC/mTOR signaling plays an important role in the modulation of immune responses, raising the possibility that the damage caused by MIA was greater in Tsc2+/− than in wildtype fetuses because of an exacerbated immune response in the mutants. Here, cytokine antibody arrays were employed to measure relative cytokine abundances in the fetal brain and the placenta during MIA. Cytokines were induced by gestational poly I:C but there was no obvious modulatory effect of Tsc2 haploinsufficiency. The data indicate that cytokine exposure during MIA is comparable in Tsc2 haploinsufficient and wildtype control fetuses, suggesting that downstream molecular and cellular processes may account for the interactive effects of Tsc2 haploinsufficiency and MIA.

  13. Fetal origin of brain damage in 2 infants with a COL4A1 mutation: fetal and neonatal MRI

    Vermeulen, R. J.; Peeters-Scholte, C.; van Vugt, J. J. M.; van Vught, J. J. M. G.; Barkhof, F.; Rizzu, P.; van der Schoor, S. R. D.; van der Knaap, M. S.

    2011-01-01

    Mutations in the gene COL4A1, encoding collagen IV A1, are associated with familial porencephaly. Previously, COL4A1 mutation-associated antenatal hemorrhages have been suggested by early post-natal imaging. We describe 2 children with fetal intracerebral hemorrhages and a COL4A1 mutation. There was

  14. VP-Nets : Efficient automatic localization of key brain structures in 3D fetal neurosonography.

    Huang, Ruobing; Xie, Weidi; Alison Noble, J

    2018-04-23

    Three-dimensional (3D) fetal neurosonography is used clinically to detect cerebral abnormalities and to assess growth in the developing brain. However, manual identification of key brain structures in 3D ultrasound images requires expertise to perform and even then is tedious. Inspired by how sonographers view and interact with volumes during real-time clinical scanning, we propose an efficient automatic method to simultaneously localize multiple brain structures in 3D fetal neurosonography. The proposed View-based Projection Networks (VP-Nets), uses three view-based Convolutional Neural Networks (CNNs), to simplify 3D localizations by directly predicting 2D projections of the key structures onto three anatomical views. While designed for efficient use of data and GPU memory, the proposed VP-Nets allows for full-resolution 3D prediction. We investigated parameters that influence the performance of VP-Nets, e.g. depth and number of feature channels. Moreover, we demonstrate that the model can pinpoint the structure in 3D space by visualizing the trained VP-Nets, despite only 2D supervision being provided for a single stream during training. For comparison, we implemented two other baseline solutions based on Random Forest and 3D U-Nets. In the reported experiments, VP-Nets consistently outperformed other methods on localization. To test the importance of loss function, two identical models are trained with binary corss-entropy and dice coefficient loss respectively. Our best VP-Net model achieved prediction center deviation: 1.8 ± 1.4 mm, size difference: 1.9 ± 1.5 mm, and 3D Intersection Over Union (IOU): 63.2 ± 14.7% when compared to the ground truth. To make the whole pipeline intervention free, we also implement a skull-stripping tool using 3D CNN, which achieves high segmentation accuracy. As a result, the proposed processing pipeline takes a raw ultrasound brain image as input, and output a skull-stripped image with five detected key brain

  15. Effects of endogenous pyrogen and prostaglandin E2 on hypothalamic neurons in rat brain slices.

    Watanabe, T; Morimoto, A; Murakami, N

    1987-06-01

    We investigated the effects of endogenous pyrogen and prostaglandin E2 (PGE2) on the preoptic and anterior hypothalamic (POAH) neurons using brain slice preparations from the rat. Partially purified endogenous pyrogen did not change the activities of most of the neurons in the POAH region when applied locally through a micropipette attached to the recording electrode in proximity to the neurons. This indicates that partially purified endogenous pyrogen does not act directly on the neuronal activity in the POAH region. The partially purified endogenous pyrogen, applied into a culture chamber containing a brain slice, facilitated the activities in 24% of the total neurons tested, regardless of the thermal specificity of the neurons. Moreover, PGE2 added to the culture chamber facilitated 48% of the warm-responsive, 33% of the cold-responsive, and 29% of the thermally insensitive neurons. The direction of change in neuronal activity induced by partially purified endogenous pyrogen appears to be almost the same as that induced by PGE2 when these substances were applied by perfusion to the same neuron in the culture chamber. These results suggest that partially purified pyrogen applied to the perfusate of the culture chamber stimulates some constituents of brain tissue to synthesize and release prostaglandin, which in turn affects the neuronal activity of the POAH region.

  16. Mirror neurons: Enigma of the metaphysical modular brain

    Acharya, Sourya; Shukla, Samarth

    2012-01-01

    Mirror neurons are one of the most important discoveries in the last decade of neuroscience. These are a variety of visuospatial neurons which indicate fundamentally about human social interaction. Essentially, mirror neurons respond to actions that we observe in others. The interesting part is that mirror neurons fire in the same way when we actually recreate that action ourselves. Apart from imitation, they are responsible for myriad of other sophisticated human behavior and thought process...

  17. Intersection based motion correction of multislice MRI for 3-D in utero fetal brain image formation.

    Kim, Kio; Habas, Piotr A; Rousseau, Francois; Glenn, Orit A; Barkovich, Anthony J; Studholme, Colin

    2010-01-01

    In recent years, postprocessing of fast multislice magnetic resonance imaging (MRI) to correct fetal motion has provided the first true 3-D MR images of the developing human brain in utero. Early approaches have used reconstruction based algorithms, employing a two-step iterative process, where slices from the acquired data are realigned to an approximate 3-D reconstruction of the fetal brain, which is then refined further using the improved slice alignment. This two step slice-to-volume process, although powerful, is computationally expensive in needing a 3-D reconstruction, and is limited in its ability to recover subvoxel alignment. Here, we describe an alternative approach which we term slice intersection motion correction (SIMC), that seeks to directly co-align multiple slice stacks by considering the matching structure along all intersecting slice pairs in all orthogonally planned slices that are acquired in clinical imaging studies. A collective update scheme for all slices is then derived, to simultaneously drive slices into a consistent match along their lines of intersection. We then describe a 3-D reconstruction algorithm that, using the final motion corrected slice locations, suppresses through-plane partial volume effects to provide a single high isotropic resolution 3-D image. The method is tested on simulated data with known motions and is applied to retrospectively reconstruct 3-D images from a range of clinically acquired imaging studies. The quantitative evaluation of the registration accuracy for the simulated data sets demonstrated a significant improvement over previous approaches. An initial application of the technique to studying clinical pathology is included, where the proposed method recovered up to 15 mm of translation and 30 degrees of rotation for individual slices, and produced full 3-D reconstructions containing clinically useful additional information not visible in the original 2-D slices.

  18. An efficient sequence for fetal brain imaging at 3T with enhanced T1 contrast and motion robustness.

    Ferrazzi, Giulio; Price, Anthony N; Teixeira, Rui Pedro A G; Cordero-Grande, Lucilio; Hutter, Jana; Gomes, Ana; Padormo, Francesco; Hughes, Emer; Schneider, Torben; Rutherford, Mary; Kuklisova Murgasova, Maria; Hajnal, Joseph V

    2018-07-01

    Ultrafast single-shot T 2 -weighted images are common practice in fetal MR exams. However, there is limited experience with fetal T 1 -weighted acquisitions. This study aims at establishing a robust framework that allows fetal T 1 -weighted scans to be routinely acquired in utero at 3T. A 2D gradient echo sequence with an adiabatic inversion was optimized to be robust to fetal motion and maternal breathing optimizing grey/white matter contrast at the same time. This was combined with slice to volume registration and super resolution methods to produce volumetric reconstructions. The sequence was tested on 22 fetuses. Optimized grey/white matter contrast and robustness to fetal motion and maternal breathing were achieved. Signal from cerebrospinal fluid (CSF) and amniotic fluid was nulled and 0.75 mm isotropic anatomical reconstructions of the fetal brain were obtained using slice-to-volume registration and super resolution techniques. Total acquisition time for a single stack was 56 s, all acquired during free breathing. Enhanced sensitivity to normal anatomy and pathology with respect to established methods is demonstrated. A direct comparison with a 3D spoiled gradient echo sequence and a controlled motion experiment run on an adult volunteer are also shown. This paper describes a robust framework to perform T 1 -weighted acquisitions and reconstructions of the fetal brain in utero. Magn Reson Med 80:137-146, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic

  19. New neurons in the adult brain : The role of sleep and consequences of sleep loss

    Meerlo, Peter; Mistiberger, Ralph E.; Jacobs, Barry L.; Heller, H. Craig; McGinty, Dennis; Mistlberger, Ralph E.

    2009-01-01

    Research over the last few decades has firmly established that new neurons are generated in selected areas of the adult mammalian brain, particularly the dentate gyrus of the hippocampal formation and the subventricular zone of the lateral ventricles. The function of adult-born neurons is still a

  20. Endorphinic neurons are contacting the tuberoinfundibular dopaminergic neurons in the rat brain

    Morel, G.; Pelletier, G.

    1986-01-01

    The anatomical relationships between endorphinic neurons and dopaminergic neurons were evaluated in the rat hypothalamus using a combination of immunocytochemistry and autoradiography. In the arcuate nucleus, endorphinic endings were seen making contacts with dopaminergic cell bodies and dendrites. No synapsis could be observed at the sites of contacts. These results strongly suggest that the endorphinic neurons are directly acting on dopaminergic neurons to modify the release of dopamine into the pituitary portal system

  1. Short-term memory and critical clusterization in brain neurons spike series

    Bershadskii, A.; Dremencov, E.; Yadid, G.

    2003-06-01

    A new phenomenon: critical clusterization, is observed in the neuron firing of a genetically defined rat model of depression. The critical clusterization is studied using a multiscaling analysis of the data obtained from the neurons belonging to the Red Nucleus area of the depressive brains. It is suggested that this critical phenomenon can be partially responsible for the observed ill behavior of the depressive brains: loss of short-term motor memory and slow motor reaction.

  2. Intersection-based registration of slice stacks to form 3D images of the human fetal brain

    Kim, Kio; Hansen, Mads Fogtmann; Habas, Piotr

    2008-01-01

    Clinical fetal MR imaging of the brain commonly makes use of fast 2D acquisitions of multiple sets of approximately orthogonal 2D slices. We and others have previously proposed an iterative slice-to-volume registration process to recover a geometrically consistent 3D image. However......, these approaches depend on a 3D volume reconstruction step during the slice alignment. This is both computationally expensive and makes the convergence of the registration process poorly defined. In this paper our key contribution is a new approach which considers the collective alignment of all slices directly...... of the approach applied to simulated data and clinically acquired fetal images....

  3. Fetal hypothalamic transplants into brain irradiated rats: Graft morphometry and host behavioral responses

    Pearlman, S.H.; Rubin, P.; White, H.C.; Wiegand, S.J.; Gash, D.M.

    1990-01-01

    This study was designed to test the hypothesis that neural implants can ameliorate or prevent some of the long-term changes associated with CNS irradiation. Using a rat model, the initial study focused on establishing motor, regulatory, and morphological changes associated with brain radiation treatments. Secondly, fetal hypothalamic tissue grafts were placed into the third ventricle of rats which had been previously irradiated. Adult male Long Evans rats received one of three radiation doses (15, 22.5, ampersand 30 Gy) or no radiation. Three days after irradiation, 7 animals in each dose group received an embryonic day 17 hypothalamic graft into the third ventricle while the remaining 8-9 animals in each group received injections of vehicle solution (sham). Few changes were observed in the 15 and 22.5 Gy animals, however rats in the 30 Gy treatment group showed stereotypic and ambulatory behavioral hyperactivity 32 weeks after irradiation. Regulatory changes in the high dose group included decreased growth rate and decreased urine osmolalities, but these measures were extremely variable among animals. Morphological results demonstrated that 30 Gy irradiated animals showed extensive necrosis primarily in the fimbria, which extended into the internal capsule, optic nerve, hippocampus, and thalamus. Hemorrhages were found in the hippocampus, thalamus, and fimbria. Defects in the blood-brain barrier also were evident by entry of intravascularly injected horseradish peroxidase into the parenchyma of the brain. Animals in the 30 Gy grafted group showed fewer behavioral changes and less brain damage than their sham grafted counterparts. Specifically, activity measures were comparable to normal levels, and a dilute urine was not found in the 30 Gy implanted rats. Morphological changes support these behavioral results since only two 30 Gy implanted rats showed necrosis

  4. Developmental aspects of the rat brain insulin receptor: loss of sialic acid and fluctuation in number characterize fetal development

    Brennan, W.A. Jr.

    1988-01-01

    In this study, I have investigated the structure of the rat brain insulin receptor during fetal development. There is a progressive decrease in the apparent molecular size of the brain alpha-subunit during development: 130K on day 16 of gestation, 126K at birth, and 120K in the adult. Glycosylation was investigated as a possible reason for the observed differences in the alpha-subunit molecular size. The results show that the developmental decrease in the brain alpha-subunit apparent molecular size is due to a parallel decrease in sialic acid content. This was further confirmed by measuring the retention of autophosphorylated insulin receptors on wheat germ agglutinin (WGA)-Sepharose. An inverse correlation between developmental age and retention of 32 P-labeled insulin receptors on the lectin column was observed. Insulin binding increases 6-fold between 16 and 20 days of gestation [61 +/- 25 (+/- SE) fmol/mg protein and 364 +/- 42 fmol/mg, respectively]. Thereafter, binding in brain membranes decreases to 150 +/- 20 fmol/mg by 2 days after birth, then reaches the adult level of 63 +/- 15 fmol/mg. In addition, the degree of insulin-stimulated autophosphorylation closely parallels the developmental changes in insulin binding. Between 16 and 20 days of fetal life, insulin-stimulated phosphorylation of the beta-subunit increases 6-fold. Thereafter, the extent of phosphorylation decreases rapidly, reaching adult values identical with those in 16-day-old fetal brain. These results suggest that the embryonic brain possesses competent insulin receptors whose expression changes markedly during fetal development. This information should be important in defining the role of insulin in the developing nervous system

  5. Development of fetal brain of 20 weeks gestational age: Assessment with post-mortem Magnetic Resonance Imaging

    Zhang Zhonghe; Liu Shuwei; Lin Xiangtao; Teng Gaojun; Yu Taifei; Fang Fang; Zang Fengchao

    2011-01-01

    Background: The 20th week gestational age (GA) is at mid-gestation and corresponds to the age at which the termination of pregnancy in several countries and the first Magnetic Resonance Imaging (MRI) can be performed, and at which the premature babies may survive. However, at present, very little is known about the exact anatomical character at this GA. Objective: To delineate the developing fetal brain of 20 weeks GA and obtain the three dimensional visualization model. Materials and methods: 20 fetal specimens were scanned by 3.0 T and 7.0 T post-mortem MRI, and the three dimensional visualization model was obtained with Amira 4.1. Results: Most of the sulci or their anlage, except the postcentral sulcus and intraparietal sulcus, were present. The laminar organization, described as layers with different signal intensities, was most clearly distinguished at the parieto-occipital lobe and peripheral regions of the hippocampus. The basal nuclei could be clearly visualized, and the brain stem and cerebellum had formed their common shape. On the visualization model, the shape and relative relationship of the structures could be appropriately delineated. The ranges of normal values of the brain structures were obtained, but no sexual dimorphisms or cerebral asymmetries were found. Conclusions: The developing fetal brain of 20 weeks GA can be clearly delineated on 3.0 T and 7.0 T post-mortem MRIs, and the three dimensional visualization model supplies great help in precise cognition of the immature brain. These results may have positive influences on the evaluation of the fetal brain in the uterus.

  6. Neuronal Culture and labelling of receptors of rat brain by a radioactive molecule labelled with technetium

    Barhoumi, C; Mejri, N.; Saidi, M.; Coulais, Y.; Dunia, D.; Masmoudi, O.; Amri, M.

    2009-01-01

    Alzheimer's disease is a neurodegenerative disease of the brain which causes progressive and irreversible loss of mental function. It is characterized by a decrease of serotoninergic neurons that carry the 5HT1A receptors. In our study, we performed cultures of hippocampal and cortical neurons from brains of young rats. After the differentiation of these neurons, some wells of cell culture were incubated with 8 OH DPAT, a 5HT1A agonist of serotonin, which are located on the surface of neurons.The neurons were then incubated with a molecule labelled with technetium 99m Tc. These neurons are lysed and the radioactivity is read. The results show that for the culture of neurons in the hippocampus, we have levels of radioactivity of cells treated with agonist, below the level of radioactivity of cells treated with the radioactive molecule. Cortical neurons show the same level of radioactivity of cells treated with agonist and for cells treated only with the labelled molecule. Our results show a decrease in the fixation of the labelled molecule on serotoninergic neurons in the hippocampus compared to neurons in the cortex. This work will be continued in humans in order to achieve early diagnosis of Alzheimer's disease

  7. Autologous Adrenal Medullary, Fetal Mesencephalic, and Fetal Adrenal Brain Transplantation in Parkinson's Disease: A Long-Term Postoperative Follow-Up

    Madrazo, Ignacio; Franco-Bourland, Rebecca; Aguilera, Maricarmen; Ostrosky-Solis, Feggy; Madrazo, Mario; Cuevas, Carlos; Catrejon, Hugo; Guizar-Zahagun, Gabriel; Magallon, Eduardo

    1991-01-01

    We report on the clinical status of 5 patients with Parkinson's disease (PD) 3 years after autologous adrenal medullary (AM)-to-caudate nucleus (CN) implanfion, and of 2 PD patients, 2 years after fetal ventral mesencephalon (VM)- and fetal adrenal (A)-to-CN homotransplantation. Current clinical evaluation of 4 of the AM grafted patients revealed sustained bilateral amelioration of their PD signs, most notably of rgidity, postural imbalance and gait disturbances, resulting in a substantial improvement in their quality of life. the disease-related dystonia of one of them disappeared only 2 years after surgery. The levodopa requirements of 2 of these patients and the anticholinergic therapy of another have been reduced. In agreement with the satisfactory clinical evaluation of these 4 patients, their neuropsychological and electrophysiological improvements, initially registered 3 months after surgery, have been maintained for 3 years. After 1 year of significant recovery, the 5th patient of this group has almost returned to her preoperative state. The 2 homotransplanted patients also showed sustained bilateral improvement of their PD signs. Two years after surgery, the most improved signs of the fetal VM case were rigidity, bradykinesia, postural imbalance, gait disturbances and facial expression. The fetal A case has only shown amelioration of rigidity and bradykinesia. Neither of them has shown significant neuropsychological changes. Their current levodopa requirements are less than before surgery. The improvements shown here by PD patients after brain tissue grafts go beyond those obtained using any other therapeutic approach, when levodopa fails. Although more studies and the development of these procedures are obviously required, these initial human trials appear to be resisting the test of time. PMID:1782251

  8. Histograms of Oriented 3D Gradients for Fully Automated Fetal Brain Localization and Robust Motion Correction in 3 T Magnetic Resonance Images.

    Serag, Ahmed; Macnaught, Gillian; Denison, Fiona C; Reynolds, Rebecca M; Semple, Scott I; Boardman, James P

    2017-01-01

    Fetal brain magnetic resonance imaging (MRI) is a rapidly emerging diagnostic imaging tool. However, automated fetal brain localization is one of the biggest obstacles in expediting and fully automating large-scale fetal MRI processing. We propose a method for automatic localization of fetal brain in 3 T MRI when the images are acquired as a stack of 2D slices that are misaligned due to fetal motion. First, the Histogram of Oriented Gradients (HOG) feature descriptor is extended from 2D to 3D images. Then, a sliding window is used to assign a score to all possible windows in an image, depending on the likelihood of it containing a brain, and the window with the highest score is selected. In our evaluation experiments using a leave-one-out cross-validation strategy, we achieved 96% of complete brain localization using a database of 104 MRI scans at gestational ages between 34 and 38 weeks. We carried out comparisons against template matching and random forest based regression methods and the proposed method showed superior performance. We also showed the application of the proposed method in the optimization of fetal motion correction and how it is essential for the reconstruction process. The method is robust and does not rely on any prior knowledge of fetal brain development.

  9. Histograms of Oriented 3D Gradients for Fully Automated Fetal Brain Localization and Robust Motion Correction in 3 T Magnetic Resonance Images

    Ahmed Serag

    2017-01-01

    Full Text Available Fetal brain magnetic resonance imaging (MRI is a rapidly emerging diagnostic imaging tool. However, automated fetal brain localization is one of the biggest obstacles in expediting and fully automating large-scale fetal MRI processing. We propose a method for automatic localization of fetal brain in 3 T MRI when the images are acquired as a stack of 2D slices that are misaligned due to fetal motion. First, the Histogram of Oriented Gradients (HOG feature descriptor is extended from 2D to 3D images. Then, a sliding window is used to assign a score to all possible windows in an image, depending on the likelihood of it containing a brain, and the window with the highest score is selected. In our evaluation experiments using a leave-one-out cross-validation strategy, we achieved 96% of complete brain localization using a database of 104 MRI scans at gestational ages between 34 and 38 weeks. We carried out comparisons against template matching and random forest based regression methods and the proposed method showed superior performance. We also showed the application of the proposed method in the optimization of fetal motion correction and how it is essential for the reconstruction process. The method is robust and does not rely on any prior knowledge of fetal brain development.

  10. Brain scaling in mammalian evolution as a consequence of concerted and mosaic changes in numbers of neurons and average neuronal cell size

    Suzana eHerculano-Houzel

    2014-08-01

    Full Text Available Enough species have now been subject to systematic quantitative analysis of the relationship between the morphology and cellular composition of their brain that patterns begin to emerge and shed light on the evolutionary path that led to mammalian brain diversity. Based on an analysis of the shared and clade-specific characteristics of 41 modern mammalian species in 6 clades, and in light of the phylogenetic relationships among them, here we propose that ancestral mammal brains were composed and scaled in their cellular composition like modern afrotherian and glire brains: with an addition of neurons that is accompanied by a decrease in neuronal density and very little modification in glial cell density, implying a significant increase in average neuronal cell size in larger brains, and the allocation of approximately 2 neurons in the cerebral cortex and 8 neurons in the cerebellum for every neuron allocated to the rest of brain. We also propose that in some clades the scaling of different brain structures has diverged away from the common ancestral layout through clade-specific (or clade-defining changes in how average neuronal cell mass relates to numbers of neurons in each structure, and how numbers of neurons are differentially allocated to each structure relative to the number of neurons in the rest of brain. Thus, the evolutionary expansion of mammalian brains has involved both concerted and mosaic patterns of scaling across structures. This is, to our knowledge, the first mechanistic model that explains the generation of brains large and small in mammalian evolution, and it opens up new horizons for seeking the cellular pathways and genes involved in brain evolution.

  11. Impacts of brain serotonin deficiency following Tph2 inactivation on development and raphe neuron serotonergic specification.

    Lise Gutknecht

    Full Text Available Brain serotonin (5-HT is implicated in a wide range of functions from basic physiological mechanisms to complex behaviors, including neuropsychiatric conditions, as well as in developmental processes. Increasing evidence links 5-HT signaling alterations during development to emotional dysregulation and psychopathology in adult age. To further analyze the importance of brain 5-HT in somatic and brain development and function, and more specifically differentiation and specification of the serotonergic system itself, we generated a mouse model with brain-specific 5-HT deficiency resulting from a genetically driven constitutive inactivation of neuronal tryptophan hydroxylase-2 (Tph2. Tph2 inactivation (Tph2-/- resulted in brain 5-HT deficiency leading to growth retardation and persistent leanness, whereas a sex- and age-dependent increase in body weight was observed in Tph2+/- mice. The conserved expression pattern of the 5-HT neuron-specific markers (except Tph2 and 5-HT demonstrates that brain 5-HT synthesis is not a prerequisite for the proliferation, differentiation and survival of raphe neurons subjected to the developmental program of serotonergic specification. Furthermore, although these neurons are unable to synthesize 5-HT from the precursor tryptophan, they still display electrophysiological properties characteristic of 5-HT neurons. Moreover, 5-HT deficiency induces an up-regulation of 5-HT(1A and 5-HT(1B receptors across brain regions as well as a reduction of norepinephrine concentrations accompanied by a reduced number of noradrenergic neurons. Together, our results characterize developmental, neurochemical, neurobiological and electrophysiological consequences of brain-specific 5-HT deficiency, reveal a dual dose-dependent role of 5-HT in body weight regulation and show that differentiation of serotonergic neuron phenotype is independent from endogenous 5-HT synthesis.

  12. In utero diffusion tensor imaging of the fetal brain: A reproducibility study.

    Jakab, András; Tuura, Ruth; Kellenberger, Christian; Scheer, Ianina

    2017-01-01

    Our purpose was to evaluate the within-subject reproducibility of in utero diffusion tensor imaging (DTI) metrics and the visibility of major white matter structures. Images for 30 fetuses (20-33. postmenstrual weeks, normal neurodevelopment: 6 cases, cerebral pathology: 24 cases) were acquired on 1.5 T or 3.0 T MRI. DTI with 15 diffusion-weighting directions was repeated three times for each case, TR/TE: 2200/63 ms, voxel size: 1 ∗ 1 mm, slice thickness: 3-5 mm, b-factor: 700 s/mm 2 . Reproducibility was evaluated from structure detectability, variability of DTI measures using the coefficient of variation (CV), image correlation and structural similarity across repeated scans for six selected structures. The effect of age, scanner type, presence of pathology was determined using Wilcoxon rank sum test. White matter structures were detectable in the following percentage of fetuses in at least two of the three repeated scans: corpus callosum genu 76%, splenium 64%, internal capsule, posterior limb 60%, brainstem fibers 40% and temporooccipital association pathways 60%. The mean CV of DTI metrics ranged between 3% and 14.6% and we measured higher reproducibility in fetuses with normal brain development. Head motion was negatively correlated with reproducibility, this effect was partially ameliorated by motion-correction algorithm using image registration. Structures on 3.0 T had higher variability both with- and without motion correction. Fetal DTI is reproducible for projection and commissural bundles during mid-gestation, however, in 16-30% of the cases, data were corrupted by artifacts, resulting in impaired detection of white matter structures. To achieve robust results for the quantitative analysis of diffusivity and anisotropy values, fetal-specific image processing is recommended and repeated DTI is needed to ensure the detectability of fiber pathways.

  13. Kaleido: Visualizing Big Brain Data with Automatic Color Assignment for Single-Neuron Images.

    Wang, Ting-Yuan; Chen, Nan-Yow; He, Guan-Wei; Wang, Guo-Tzau; Shih, Chi-Tin; Chiang, Ann-Shyn

    2018-03-03

    Effective 3D visualization is essential for connectomics analysis, where the number of neural images easily reaches over tens of thousands. A formidable challenge is to simultaneously visualize a large number of distinguishable single-neuron images, with reasonable processing time and memory for file management and 3D rendering. In the present study, we proposed an algorithm named "Kaleido" that can visualize up to at least ten thousand single neurons from the Drosophila brain using only a fraction of the memory traditionally required, without increasing computing time. Adding more brain neurons increases memory only nominally. Importantly, Kaleido maximizes color contrast between neighboring neurons so that individual neurons can be easily distinguished. Colors can also be assigned to neurons based on biological relevance, such as gene expression, neurotransmitters, and/or development history. For cross-lab examination, the identity of every neuron is retrievable from the displayed image. To demonstrate the effectiveness and tractability of the method, we applied Kaleido to visualize the 10,000 Drosophila brain neurons obtained from the FlyCircuit database ( http://www.flycircuit.tw/modules.php?name=kaleido ). Thus, Kaleido visualization requires only sensible computer memory for manual examination of big connectomics data.

  14. Hydrophobically Modified siRNAs Silence Huntingtin mRNA in Primary Neurons and Mouse Brain

    Julia F Alterman

    2015-01-01

    Full Text Available Applications of RNA interference for neuroscience research have been limited by a lack of simple and efficient methods to deliver oligonucleotides to primary neurons in culture and to the brain. Here, we show that primary neurons rapidly internalize hydrophobically modified siRNAs (hsiRNAs added directly to the culture medium without lipid formulation. We identify functional hsiRNAs targeting the mRNA of huntingtin, the mutation of which is responsible for Huntington's disease, and show that direct uptake in neurons induces potent and specific silencing in vitro. Moreover, a single injection of unformulated hsiRNA into mouse brain silences Htt mRNA with minimal neuronal toxicity. Thus, hsiRNAs embody a class of therapeutic oligonucleotides that enable simple and straightforward functional studies of genes involved in neuronal biology and neurodegenerative disorders in a native biological context.

  15. An immunocytochemical study of the germinal layer vasculature in the developing fetal brain using Ulex europaeus 1 lectin.

    Gould, S J; Howard, S

    1988-10-01

    The characteristics of the germinal matrix vasculature were studied in the developing fetal brain using immunocytochemical methods. A preliminary comparative immunocytochemical study was made on six fetal brains to compare endothelial staining by Ulex europaeus I lectin with that of antibody to Factor VIII related antigen. Ulex was found to stain germinal layer vessels better than Factor VIII related antigen. Subsequently, the germinal layers of a further 15 fetal and preterm infant brains ranging from 13 to 35 weeks' gestation were stained with Ulex europaeus I to demonstrate the vasculature. With increasing gestation, there was a gradual increase in vessel density, particularly of capillaries. This was not a uniform process. A plexus of capillaries was prominent immediately beneath the ependyma while the more central parts of the germinal matrix contained fewer, but often larger diameter, vessels. The variation in vessel density which was a feature of the later gestation brains may have implications for local blood flow and may be a factor in haemorrhage at this site.

  16. Fetal brain 11β-hydroxysteroid dehydrogenase type 2 selectively determines programming of adult depressive-like behaviors and cognitive function, but not anxiety behaviors in male mice.

    Wyrwoll, Caitlin; Keith, Marianne; Noble, June; Stevenson, Paula L; Bombail, Vincent; Crombie, Sandra; Evans, Louise C; Bailey, Matthew A; Wood, Emma; Seckl, Jonathan R; Holmes, Megan C

    2015-09-01

    Stress or elevated glucocorticoids during sensitive windows of fetal development increase the risk of neuropsychiatric disorders in adult rodents and humans, a phenomenon known as glucocorticoid programming. 11β-Hydroxysteroid dehydrogenase type 2 (11β-HSD2), which catalyses rapid inactivation of glucocorticoids in the placenta, controls access of maternal glucocorticoids to the fetal compartment, placing it in a key position to modulate glucocorticoid programming of behavior. However, the importance of the high expression of 11β-HSD2 within the midgestational fetal brain is unknown. To examine this, a brain-specific knockout of 11β-HSD2 (HSD2BKO) was generated and compared to wild-type littermates. HSD2BKO have markedly diminished fetal brain 11β-HSD2, but intact fetal body and placental 11β-HSD2 and normal fetal and placental growth. Despite normal fetal plasma corticosterone, HSD2BKO exhibit elevated fetal brain corticosterone levels at midgestation. As adults, HSD2BKO show depressive-like behavior and have cognitive impairments. However, unlike complete feto-placental deficiency, HSD2BKO show no anxiety-like behavioral deficits. The clear mechanistic separation of the programmed components of depression and cognition from anxiety implies distinct mechanisms of pathogenesis, affording potential opportunities for stratified interventions. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  17. Fetal liver blood flow distribution: role in human developmental strategy to prioritize fat deposition versus brain development.

    Keith M Godfrey

    Full Text Available Among primates, human neonates have the largest brains but also the highest proportion of body fat. If placental nutrient supply is limited, the fetus faces a dilemma: should resources be allocated to brain growth, or to fat deposition for use as a potential postnatal energy reserve? We hypothesised that resolving this dilemma operates at the level of umbilical blood distribution entering the fetal liver. In 381 uncomplicated pregnancies in third trimester, we measured blood flow perfusing the fetal liver, or bypassing it via the ductus venosus to supply the brain and heart using ultrasound techniques. Across the range of fetal growth and independent of the mother's adiposity and parity, greater liver blood flow was associated with greater offspring fat mass measured by dual-energy X-ray absorptiometry, both in the infant at birth (r = 0.43, P<0.001 and at age 4 years (r = 0.16, P = 0.02. In contrast, smaller placentas less able to meet fetal demand for essential nutrients were associated with a brain-sparing flow pattern (r = 0.17, p = 0.02. This flow pattern was also associated with a higher degree of shunting through ductus venosus (P = 0.04. We propose that humans evolved a developmental strategy to prioritize nutrient allocation for prenatal fat deposition when the supply of conditionally essential nutrients requiring hepatic inter-conversion is limited, switching resource allocation to favour the brain if the supply of essential nutrients is limited. Facilitated placental transfer mechanisms for glucose and other nutrients evolved in environments less affluent than those now prevalent in developed populations, and we propose that in circumstances of maternal adiposity and nutrient excess these mechanisms now also lead to prenatal fat deposition. Prenatal developmental influences play important roles in the human propensity to deposit fat.

  18. Area-specific migration and recruitment of new neurons in the adult songbird brain

    Vellema, Michiel; Van der Linden, Annemie; Gahr, Manfred

    2010-01-01

    sensitive to plastic changes, such as nucleus higher vocal center (HVC) and area X, recruited similar numbers of new neurons as their surrounding brain tissues, employing no specific directional mechanisms. The distribution pattern in and around HVC could best be described by a random displacement model......Neuron recruitment has been implicated in morphological and functional plasticity in the adult brain. Whereas mammals restrict neuron recruitment specifically to two regions of known plasticity, the hippocampus and olfactory bulb, newborn neurons are found throughout the forebrain of adult...... songbirds. In order to study the area-specificity of the widespread proliferation and recruitment in the songbird brain, six adult male canaries received repetitive intraperitoneal injections of the mitotic marker BrdU (5-bromo-2-deoxyuridine) and were sacrificed after 24 hours to study proliferation...

  19. Stable long-term chronic brain mapping at the single-neuron level.

    Fu, Tian-Ming; Hong, Guosong; Zhou, Tao; Schuhmann, Thomas G; Viveros, Robert D; Lieber, Charles M

    2016-10-01

    Stable in vivo mapping and modulation of the same neurons and brain circuits over extended periods is critical to both neuroscience and medicine. Current electrical implants offer single-neuron spatiotemporal resolution but are limited by such factors as relative shear motion and chronic immune responses during long-term recording. To overcome these limitations, we developed a chronic in vivo recording and stimulation platform based on flexible mesh electronics, and we demonstrated stable multiplexed local field potentials and single-unit recordings in mouse brains for at least 8 months without probe repositioning. Properties of acquired signals suggest robust tracking of the same neurons over this period. This recording and stimulation platform allowed us to evoke stable single-neuron responses to chronic electrical stimulation and to carry out longitudinal studies of brain aging in freely behaving mice. Such advantages could open up future studies in mapping and modulating changes associated with learning, aging and neurodegenerative diseases.

  20. Fetal MRI; Fetales MRT

    Blondin, D. [Inst. fuer Diagn. Radiologie, Uniklinikum Duesseldorf (Germany); Turowski, B. [Inst. fuer Diagn. Radiologie, Neuroradiologie, Uniklinikum Duesseldorf (Germany); Schaper, J. [Inst. fuer Diagn. Radiologie, Kinderradiologie, Uniklinikum Duesseldorf (Germany)

    2007-02-15

    Ultrasonography is the method of choice for prenatal malformation screening, but it does not always provide sufficient information for correct diagnosis or adequate abnormality evaluation. Fetal MRI is increasingly being used to complete sonographic findings. It was initially used for evaluation of cerebral abnormalities but is increasingly being applied to other fetal areas. In vivo investigation of fetal brain maturation has been enhanced by MRI. An adequate analysis of fetal chest and abdomen can be achieved with fast T2-, T1-weighted and diffusion-weighted imaging (DWI). The advantages include the great field of view and the excellent soft tissue contrast. This allows correct diagnosis of congenital diaphragmatic hernia and evaluation of the consequences on pulmonary growth. Other pulmonary malformations, such as cystic adenomatoid malformation, sequestration and brochogenic cysts, can also be easily identified. Renal position can be quickly determined using DWI sequences and renal agenesia can be easily diagnosed with only one sequence. Prenatal MRI is virtually as effective as postnatal examination, dispenses with transport of a potentially very ill newborn, and provides logistic advantages. Therefore, prenatal MRI is useful for adequate postnatal treatment of newborns with malformations. (orig.)

  1. Neuron-Type-Specific Utility in a Brain-Machine Interface: a Pilot Study.

    Garcia-Garcia, Martha G; Bergquist, Austin J; Vargas-Perez, Hector; Nagai, Mary K; Zariffa, Jose; Marquez-Chin, Cesar; Popovic, Milos R

    2017-11-01

    Firing rates of single cortical neurons can be volitionally modulated through biofeedback (i.e. operant conditioning), and this information can be transformed to control external devices (i.e. brain-machine interfaces; BMIs). However, not all neurons respond to operant conditioning in BMI implementation. Establishing criteria that predict neuron utility will assist translation of BMI research to clinical applications. Single cortical neurons (n=7) were recorded extracellularly from primary motor cortex of a Long-Evans rat. Recordings were incorporated into a BMI involving up-regulation of firing rate to control the brightness of a light-emitting-diode and subsequent reward. Neurons were classified as 'fast-spiking', 'bursting' or 'regular-spiking' according to waveform-width and intrinsic firing patterns. Fast-spiking and bursting neurons were found to up-regulate firing rate by a factor of 2.43±1.16, demonstrating high utility, while regular-spiking neurons decreased firing rates on average by a factor of 0.73±0.23, demonstrating low utility. The ability to select neurons with high utility will be important to minimize training times and maximize information yield in future clinical BMI applications. The highly contrasting utility observed between fast-spiking and bursting neurons versus regular-spiking neurons allows for the hypothesis to be advanced that intrinsic electrophysiological properties may be useful criteria that predict neuron utility in BMI implementation.

  2. Cortical neurogenesis in adult rats after ischemic brain injury: most new neurons fail to mature

    Qing-quan Li

    2015-01-01

    Full Text Available The present study examines the hypothesis that endogenous neural progenitor cells isolated from the neocortex of ischemic brain can differentiate into neurons or glial cells and contribute to neural regeneration. We performed middle cerebral artery occlusion to establish a model of cerebral ischemia/reperfusion injury in adult rats. Immunohistochemical staining of the cortex 1, 3, 7, 14 or 28 days after injury revealed that neural progenitor cells double-positive for nestin and sox-2 appeared in the injured cortex 1 and 3 days post-injury, and were also positive for glial fibrillary acidic protein. New neurons were labeled using bromodeoxyuridine and different stages of maturity were identified using doublecortin, microtubule-associated protein 2 and neuronal nuclei antigen immunohistochemistry. Immature new neurons coexpressing doublecortin and bromodeoxyuridine were observed in the cortex at 3 and 7 days post-injury, and semi-mature and mature new neurons double-positive for microtubule-associated protein 2 and bromodeoxyuridine were found at 14 days post-injury. A few mature new neurons coexpressing neuronal nuclei antigen and bromodeoxyuridine were observed in the injured cortex 28 days post-injury. Glial fibrillary acidic protein/bromodeoxyuridine double-positive astrocytes were also found in the injured cortex. Our findings suggest that neural progenitor cells are present in the damaged cortex of adult rats with cerebral ischemic brain injury, and that they differentiate into astrocytes and immature neurons, but most neurons fail to reach the mature stage.

  3. THE TOPOLOGICAL AND DYNAMIC CHARACTERISTICS OF NEURONIC ENSEMBLES IN THE BRAIN AS PERCOLATING FRACTAL SETS

    Sergey L’vovich Molchatsky

    2017-10-01

    Full Text Available The objective of the research was to determine of neuronic ensembles in the brain. The research was based that neuronic ensembles of a brain are considered as the percolating clusters. In the basic part of the study the main concern was determination of the following parameters: fractal dimension on a passing threshold df; for geodetic lines on a fractal dθ and for trajectories of particles in a turbulence field dw. In the same part of a research the index of a compendency (θ of neuronic ensembles of animals and the human brain is defined. As well as it was supposed has a negative value θ 1. Numerical calculations with use of results of computer analysis frontal section images of a hypothalamus of a brain of animals and human are shown, that the considered objects can be ranked to the special class of fractal objects. Such class of objects is called asymptotically arcwise connected.

  4. Direct Signaling from Astrocytes to Neurons in Cultures of Mammalian Brain Cells

    Nedergaard, Maiken

    1994-03-01

    Although astrocytes have been considered to be supportive, rather than transmissive, in the adult nervous system, recent studies have challenged this assumption by demonstrating that astrocytes possess functional neurotransmitter receptors. Astrocytes are now shown to directly modulate the free cytosolic calcium, and hence transmission characteristics, of neighboring neurons. When a focal electric field potential was applied to single astrocytes in mixed cultures of rat forebrain astrocytes and neurons, a prompt elevation of calcium occurred in the target cell. This in turn triggered a wave of calcium increase, which propagated from astrocyte to astrocyte. Neurons resting on these astrocytes responded with large increases in their concentration of cytosolic calcium. The gap junction blocker octanol attenuated the neuronal response, which suggests that the astrocytic-neuronal signaling is mediated through intercellular connections rather than synaptically. This neuronal response to local astrocytic stimulation may mediate local intercellular communication within the brain.

  5. Role of Non-neuronal Cells in Tauopathies After Brain Injury

    2017-09-01

    AWARD NUMBER: W81XWH-15-1-0422 TITLE: Role of Nonneuronal Cells in Tauopathies After Brain Injury PRINCIPAL INVESTIGATOR: Sally A. Frautschy...AND SUBTITLE 5a. CONTRACT NUMBER Role of Non-neuronal Cells in Tauopathies After Brain Injury 5b. GRANT NUMBER W81XWH-15-1-0422 5c. PROGRAM...traumatic brain injury (TBI), specific inflammatory factors (complement proteins) elevated during long asymptomatic prodromal period are responsible

  6. Effect of sevoflurane on neuronal activity during deep brain stimulation surgery for epilepsy: A case report

    Michaël J. Bos, MD; Linda Ackermans, MD, PhD; Frédéric L.W.V.J. Schaper, MD; Rob P.W. Rouhl, MD, PhD; Vivianne H.J.M. van Kranen-Mastenbroek, MD, PhD; Wolfgang F. Buhre, MD, PhD; Marcus L.F. Janssen, MD, PhD

    2018-01-01

    Deep brain stimulation of the anterior nucleus of the thalamus is an effective treatment for patients with refractory epilepsy who do not respond sufficiently to medical therapy. Optimal therapeutic effects of deep brain stimulation probably depend on accurate positioning of the stimulating electrodes. Microelectrode recordings show bursty firing neurons in the anterior nucleus of the thalamus region, which confirms the anatomical target determined by the surgeon. Deep brain stimulation elect...

  7. Robust motion correction and outlier rejection of in vivo functional MR images of the fetal brain and placenta during maternal hyperoxia

    You, Wonsang; Serag, Ahmed; Evangelou, Iordanis E.; Andescavage, Nickie; Limperopoulos, Catherine

    2017-01-01

    Subject motion is a major challenge in functional magnetic resonance imaging studies (fMRI) of the fetal brain and placenta during maternal hyperoxia. We propose a motion correction and volume outlier rejection method for the correction of severe motion artifacts in both fetal brain and placenta. The method is optimized to the experimental design by processing different phases of acquisition separately. It also automatically excludes high-motion volumes and all the missing data are regressed ...

  8. Robust motion correction and outlier rejection of in vivo functional MR images of the fetal brain and placenta during maternal hyperoxia

    You, Wonsang; Serag, Ahmed; Evangelou, Iordanis E.; Andescavage, Nickie; Limperopoulos, Catherine

    2015-01-01

    Subject motion is a major challenge in functional magnetic resonance imaging studies (fMRI) of the fetal brain and placenta during maternal hyperoxia. We propose a motion correction and volume outlier rejection method for the correction of severe motion artifacts in both fetal brain and placenta. The method is optimized to the experimental design by processing different phases of acquisition separately. It also automatically excludes high-motion volumes and all the missing data are regressed ...

  9. A High Density Electrophysiological Data Analysis System for a Peripheral Nerve Interface Communicating with Individual Neurons in the Brain

    2016-11-14

    of-the-art instrumentation to communicate with individual neurons in the brain and the peripheral nervous system. The major theme of the research is...Nerve Interface Communicating with Individual Neurons in the Brain The views, opinions and/or findings contained in this report are those of the author... Communicating with Individual Neurons in the Brain Report Title The high density electrophysiological data acquisition system obtained through this

  10. Brain pericyte-derived soluble factors enhance insulin sensitivity in GT1-7 hypothalamic neurons.

    Takahashi, Hiroyuki; Takata, Fuyuko; Matsumoto, Junichi; Machida, Takashi; Yamauchi, Atsushi; Dohgu, Shinya; Kataoka, Yasufumi

    2015-02-20

    Insulin signaling in the hypothalamus plays an important role in food intake and glucose homeostasis. Hypothalamic neuronal functions are modulated by glial cells; these form an extensive network connecting the neurons and cerebral vasculature, known as the neurovascular unit (NVU). Brain pericytes are periendothelial accessory structures of the blood-brain barrier and integral members of the NVU. However, the interaction between pericytes and neurons is largely unexplored. Here, we investigate whether brain pericytes could affect hypothalamic neuronal insulin signaling. Our immunohistochemical observations demonstrated the existence of pericytes in the mouse hypothalamus, exhibiting immunoreactivity of platelet-derived growth factor receptor β (a pericyte marker), and laminin, a basal lamina marker. We then exposed a murine hypothalamic neuronal cell line, GT1-7, to conditioned medium obtained from primary cultures of rat brain pericytes. Pericyte-conditioned medium (PCM), but not astrocyte- or aortic smooth muscle cell-conditioned medium, increased the insulin-stimulated phosphorylation of Akt in GT1-7 cells in a concentration-dependent manner. PCM also enhanced insulin-stimulated tyrosine phosphorylation of insulin receptor β without changing its expression or localization in cytosolic or plasma membrane fractions. These results suggest that pericytes, rather than astrocytes, increase insulin sensitivity in hypothalamic neurons by releasing soluble factors under physiological conditions in the NVU. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Insulin receptors mediate growth effects in cultured fetal neurons. II. Activation of a protein kinase that phosphorylates ribosomal protein S6

    Heidenreich, K.A.; Toledo, S.P.

    1989-01-01

    As an initial attempt to identify early steps in insulin action that may be involved in the growth responses of neurons to insulin, we investigated whether insulin receptor activation increases the phosphorylation of ribosomal protein S6 in cultured fetal neurons and whether activation of a protein kinase is involved in this process. When neurons were incubated for 2 h with 32Pi, the addition of insulin (100 ng/ml) for the final 30 min increased the incorporation of 32Pi into a 32K microsomal protein. The incorporation of 32Pi into the majority of other neuronal proteins was unaltered by the 30-min exposure to insulin. Cytosolic extracts from insulin-treated neurons incubated in the presence of exogenous rat liver 40S ribosomes and [gamma-32P]ATP displayed a 3- to 8-fold increase in the phosphorylation of ribosomal protein S6 compared to extracts from untreated cells. Inclusion of cycloheximide during exposure of the neurons to insulin did not inhibit the increased cytosolic kinase activity. Activation of S6 kinase activity by insulin was dose dependent (seen at insulin concentration as low as 0.1 ng/ml) and reached a maximum after 20 min of incubation. Addition of phosphatidylserine, diolein, and Ca2+ to the in vitro kinase reaction had no effect on the phosphorylation of ribosomal protein S6. Likewise, treatment of neurons with (Bu)2cAMP did not alter the phosphorylation of ribosomal protein S6 by neuronal cytosolic extracts. We conclude that insulin activates a cytosolic protein kinase that phosphorylates ribosomal S6 in neurons and is distinct from protein kinase-C and cAMP-dependent protein kinase. Stimulation of this kinase may play a role in insulin signal transduction in neurons

  12. Maternal pravastatin prevents altered fetal brain development in a preeclamptic CD-1 mouse model.

    Alissa R Carver

    Full Text Available Using an animal model, we have previously shown that preeclampsia results in long-term adverse neuromotor outcomes in the offspring, and this phenotype was prevented by antenatal treatment with pravastatin. This study aims to localize the altered neuromotor programming in this animal model and to evaluate the role of pravastatin in its prevention.For the preeclampsia model, pregnant CD-1 mice were randomly allocated to injection of adenovirus carrying sFlt-1 or its control virus carrying mFc into the tail vein. Thereafter they received pravastatin (sFlt-1-pra "experimental group" or water (sFlt-1 "positive control" until weaning. The mFc group ("negative control" received water. Offspring at 6 months of age were sacrificed, and whole brains underwent magnetic resonance imaging (MRI. MRIs were performed using an 11.7 Tesla vertical bore MRI scanner. T2 weighted images were acquired to evaluate the volumes of 28 regions of interest, including areas involved in adaptation and motor, spatial and sensory function. Cytochemistry and cell quantification was performed using neuron-specific Nissl stain. One-way ANOVA with multiple comparison testing was used for statistical analysis.Compared with control offspring, male sFlt-1 offspring have decreased volumes in the fimbria, periaquaductal gray, stria medullaris, and ventricles and increased volumes in the lateral globus pallidus and neocortex; however, female sFlt-1 offspring showed increased volumes in the ventricles, stria medullaris, and fasciculus retroflexus and decreased volumes in the inferior colliculus, thalamus, and lateral globus pallidus. Neuronal quantification via Nissl staining exhibited decreased cell counts in sFlt-1 offspring neocortex, more pronounced in males. Prenatal pravastatin treatment prevented these changes.Preeclampsia alters brain development in sex-specific patterns, and prenatal pravastatin therapy prevents altered neuroanatomic programming in this animal model.

  13. Effects of hypoglycaemia on neuronal metabolism in the adult brain: role of alternative substrates to glucose.

    Amaral, Ana I

    2013-07-01

    Hypoglycaemia is characterized by decreased blood glucose levels and is associated with different pathologies (e.g. diabetes, inborn errors of metabolism). Depending on its severity, it might affect cognitive functions, including impaired judgment and decreased memory capacity, which have been linked to alterations of brain energy metabolism. Glucose is the major cerebral energy substrate in the adult brain and supports the complex metabolic interactions between neurons and astrocytes, which are essential for synaptic activity. Therefore, hypoglycaemia disturbs cerebral metabolism and, consequently, neuronal function. Despite the high vulnerability of neurons to hypoglycaemia, important neurochemical changes enabling these cells to prolong their resistance to hypoglycaemia have been described. This review aims at providing an overview over the main metabolic effects of hypoglycaemia on neurons, covering in vitro and in vivo findings. Recent studies provided evidence that non-glucose substrates including pyruvate, glycogen, ketone bodies, glutamate, glutamine, and aspartate, are metabolized by neurons in the absence of glucose and contribute to prolong neuronal function and delay ATP depletion during hypoglycaemia. One of the pathways likely implicated in the process is the pyruvate recycling pathway, which allows for the full oxidation of glutamate and glutamine. The operation of this pathway in neurons, particularly after hypoglycaemia, has been re-confirmed recently using metabolic modelling tools (i.e. Metabolic Flux Analysis), which allow for a detailed investigation of cellular metabolism in cultured cells. Overall, the knowledge summarized herein might be used for the development of potential therapies targeting neuronal protection in patients vulnerable to hypoglycaemic episodes.

  14. Hippocampal Neuron Number Is Unchanged 1 Year After Fractionated Whole-Brain Irradiation at Middle Age

    Shi Lei; Molina, Doris P.; Robbins, Michael E.; Wheeler, Kenneth T.; Brunso-Bechtold, Judy K.

    2008-01-01

    Purpose: To determine whether hippocampal neurons are lost 12 months after middle-aged rats received a fractionated course of whole-brain irradiation (WBI) that is expected to be biologically equivalent to the regimens used clinically in the treatment of brain tumors. Methods and Materials: Twelve-month-old Fischer 344 X Brown Norway male rats were divided into WBI and control (CON) groups (n = 6 per group). Anesthetized WBI rats received 45 Gy of 137 Cs γ rays delivered as 9 5-Gy fractions twice per week for 4.5 weeks. Control rats were anesthetized but not irradiated. Twelve months after WBI completion, all rats were anesthetized and perfused with paraformaldehyde, and hippocampal sections were immunostained with the neuron-specific antibody NeuN. Using unbiased stereology, total neuron number and the volume of the neuronal and neuropil layers were determined in the dentate gyrus, CA3, and CA1 subregions of hippocampus. Results: No differences in tissue integrity or neuron distribution were observed between the WBI and CON groups. Moreover, quantitative analysis demonstrated that neither total neuron number nor the volume of neuronal or neuropil layers differed between the two groups for any subregion. Conclusions: Impairment on a hippocampal-dependent learning and memory test occurs 1 year after fractionated WBI at middle age. The same WBI regimen, however, does not lead to a loss of neurons or a reduction in the volume of hippocampus

  15. Neuronal coupling by endogenous electric fields: cable theory and applications to coincidence detector neurons in the auditory brain stem.

    Goldwyn, Joshua H; Rinzel, John

    2016-04-01

    The ongoing activity of neurons generates a spatially and time-varying field of extracellular voltage (Ve). This Ve field reflects population-level neural activity, but does it modulate neural dynamics and the function of neural circuits? We provide a cable theory framework to study how a bundle of model neurons generates Ve and how this Ve feeds back and influences membrane potential (Vm). We find that these "ephaptic interactions" are small but not negligible. The model neural population can generate Ve with millivolt-scale amplitude, and this Ve perturbs the Vm of "nearby" cables and effectively increases their electrotonic length. After using passive cable theory to systematically study ephaptic coupling, we explore a test case: the medial superior olive (MSO) in the auditory brain stem. The MSO is a possible locus of ephaptic interactions: sounds evoke large (millivolt scale)Vein vivo in this nucleus. The Ve response is thought to be generated by MSO neurons that perform a known neuronal computation with submillisecond temporal precision (coincidence detection to encode sound source location). Using a biophysically based model of MSO neurons, we find millivolt-scale ephaptic interactions consistent with the passive cable theory results. These subtle membrane potential perturbations induce changes in spike initiation threshold, spike time synchrony, and time difference sensitivity. These results suggest that ephaptic coupling may influence MSO function. Copyright © 2016 the American Physiological Society.

  16. Reelin signaling in the migration of ventral brain stem and spinal cord neurons

    Sandra eBlaess

    2016-03-01

    Full Text Available The extracellular matrix protein Reelin is an important orchestrator of neuronal migration during the development of the central nervous system. While its role and mechanism of action have been extensively studied and reviewed in the formation of dorsal laminar brain structures like the cerebral cortex, hippocampus, and cerebellum, its functions during the neuronal migration events that result in the nuclear organization of the ventral central nervous system are less well understood. In an attempt to delineate an underlying pattern of Reelin action in the formation of neuronal cell clusters, this review highlights the role of Reelin signaling in the migration of neuronal populations that originate in the ventral brain stem and the spinal cord.

  17. Glucose metabolism and astrocyte-neuron interactions in the neonatal brain.

    Brekke, Eva; Morken, Tora Sund; Sonnewald, Ursula

    2015-03-01

    Glucose is essentially the sole fuel for the adult brain and the mapping of its metabolism has been extensive in the adult but not in the neonatal brain, which is believed to rely mainly on ketone bodies for energy supply. However, glucose is absolutely indispensable for normal development and recent studies have shed light on glycolysis, the pentose phosphate pathway and metabolic interactions between astrocytes and neurons in the 7-day-old rat brain. Appropriately (13)C labeled glucose was used to distinguish between glycolysis and the pentose phosphate pathway during development. Experiments using (13)C labeled acetate provided insight into the GABA-glutamate-glutamine cycle between astrocytes and neurons. It could be shown that in the neonatal brain the part of this cycle that transfers glutamine from astrocytes to neurons is operating efficiently while, in contrast, little glutamate is shuttled from neurons to astrocytes. This lack of glutamate for glutamine synthesis is compensated for by anaplerosis via increased pyruvate carboxylation relative to that in the adult brain. Furthermore, compared to adults, relatively more glucose is prioritized to the pentose phosphate pathway than glycolysis and pyruvate dehydrogenase activity. The reported developmental differences in glucose metabolism and neurotransmitter synthesis may determine the ability of the brain at various ages to resist excitotoxic insults such as hypoxia-ischemia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Inflammatory-induced hibernation in the fetus: priming of fetal sheep metabolism correlates with developmental brain injury.

    Matthias Keller

    Full Text Available Prenatal inflammation is considered an important factor contributing to preterm birth and neonatal mortality and morbidity. The impact of prenatal inflammation on fetal bioenergetic status and the correlation of specific metabolites to inflammatory-induced developmental brain injury are unknown. We used a global metabolomics approach to examine plasma metabolites differentially regulated by intrauterine inflammation. Preterm-equivalent sheep fetuses were randomized to i.v. bolus infusion of either saline-vehicle or LPS. Blood samples were collected at baseline 2 h, 6 h and daily up to 10 days for metabolite quantification. Animals were killed at 10 days after LPS injection, and brain injury was assessed by histopathology. We detected both acute and delayed effects of LPS on fetal metabolism, with a long-term down-regulation of fetal energy metabolism. Within the first 3 days after LPS, 121 metabolites were up-regulated or down-regulated. A transient phase (4-6 days, in which metabolite levels recovered to baseline, was followed by a second phase marked by an opposing down-regulation of energy metabolites, increased pO(2 and increased markers of inflammation and ADMA. The characteristics of the metabolite response to LPS in these two phases, defined as 2 h to 2 days and at 6-9 days, respectively, were strongly correlated with white and grey matter volumes at 10 days recovery. Based on these results we propose a novel concept of inflammatory-induced hibernation of the fetus. Inflammatory priming of fetal metabolism correlated with measures of brain injury, suggesting potential for future biomarker research and the identification of therapeutic targets.

  19. Cholesterol efflux is differentially regulated in neurons and astrocytes: implications for brain cholesterol homeostasis

    Chen, Jing; Zhang, Xiaolu; Kusumo, Handojo; Costa, Lucio G.; Guizzetti, Marina

    2012-01-01

    Disruption of cholesterol homeostasis in the central nervous system (CNS) has been associated with neurological, neurodegenerative, and neurodevelopmental disorders. The CNS is a closed system with regard to cholesterol homeostasis, as cholesterol-delivering lipoproteins from the periphery cannot pass the blood-brain-barrier and enter the brain. Different cell types in the brain have different functions in the regulation of cholesterol homeostasis, with astrocytes producing and releasing apolipoprotein E and lipoproteins, and neurons metabolizing cholesterol to 24(S)-hydroxycholesterol. We present evidence that astrocytes and neurons adopt different mechanisms also in regulating cholesterol efflux. We found that in astrocytes cholesterol efflux is induced by both lipid-free apolipoproteins and lipoproteins, while cholesterol removal from neurons is triggered only by lipoproteins. The main pathway by which apolipoproteins induce cholesterol efflux is through ABCA1. By upregulating ABCA1 levels and by inhibiting its activity and silencing its expression, we show that ABCA1 is involved in cholesterol efflux from astrocytes but not from neurons. Furthermore, our results suggest that ABCG1 is involved in cholesterol efflux to apolipoproteins and lipoproteins from astrocytes but not from neurons, while ABCG4, whose expression is much higher in neurons than astrocytes, is involved in cholesterol efflux from neurons but not astrocytes. These results indicate that different mechanisms regulate cholesterol efflux from neurons and astrocytes, reflecting the different roles that these cell types play in brain cholesterol homeostasis. These results are important in understanding cellular targets of therapeutic drugs under development for the treatments of conditions associated with altered cholesterol homeostasis in the CNS. PMID:23010475

  20. The digital bee brain: integrating and managing neurons in a common 3D reference system

    Jürgen Rybak

    2010-07-01

    Full Text Available The honeybee standard brain (HSB serves as an interactive tool for relating morphologies of bee brain neurons and provides a reference system for functional and bibliographical properties (http://www.neurobiologie.fu-berlin.de/beebrain/. The ultimate goal is to document not only the morphological network properties of neurons collected from separate brains, but also to establish a graphical user interface for a neuron-related data base. Here, we review the current methods and protocols used to incorporate neuronal reconstructions into the HSB. Our registration protocol consists of two separate steps applied to imaging data from two-channel confocal microscopy scans: (1 The reconstruction of the neuron, facilitated by an automatic extraction of the neuron’s skeleton based on threshold segmentation, and (2 the semi-automatic 3D segmentation of the neuropils and their registration with the HSB. The integration of neurons in the HSB is performed by applying the transformation computed in step (2 to the reconstructed neurons of step (1. The most critical issue of this protocol in terms of user interaction time – the segmentation process – is drastically improved by the use of a model-based segmentation process. Furthermore, the underlying statistical shape models (SSM allow the visualization and analysis of characteristic variations in large sets of bee brain data. The anatomy of neural networks composed of multiple neurons that are registered into the HSB are visualized by depicting the 3D reconstructions together with semantic information with the objective to integrate data from multiple sources (electrophysiology, imaging, immunocytochemistry, molecular biology. Ultimately, this will allow the user to specify cell types and retrieve their morphologies along with physiological characterizations.

  1. [Power metabolism from neurons and a glia to the whole brain: norm, pathology and correction].

    Zil'berter, Iu I; Zil'berter, T M

    2012-01-01

    The review outlines current state of the thepretical, methodological and applies aspects of brain's energy homeostasis. Authors suggest reconsidering the exclusive role of glucose as an energy substrate (ES) at both neuronal and systemic levels discussing recent research data on qualitative composition of ES pool in the brain. The role of ES alternative to glucose, e.g., lactate and ketone bodies, is examined. The hypotheses of intracellular and astrocyte-neuron lactate shuttles are discussed along with the hypotheses of astrocyte-neuron shuttle of ketone bodies, the selfish brain theory and suppositions on homeostatic versus non-homeostatic ES supply chains. In conclusion, authors argue that exogenous native ES may be used for prevention and treatment of neurodegenerative diseases.

  2. Cellular scaling rules for the brain of Artiodactyla include a highly folded cortex with few neurons

    Rodrigo eSiqueira Kazu

    2014-11-01

    Full Text Available Quantitative analysis of the cellular composition of rodent, primate, insectivore and afrotherian brains has shown that nonneuronal scaling rules are similar across these mammalian orders that diverged about 95 million years ago, and therefore appear to be conserved in evolution, while neuronal scaling rules appear to be free to vary in a clade-specific manner. Here we analyze the cellular scaling rules that apply to the brain of artiodactyls, a group within the order Cetartiodactyla, believed to be a relatively recent radiation from the common Eutherian ancestor. We find that artiodactyls share nonneuronal scaling rules with all groups analyzed previously. Artiodactyls share with afrotherians and rodents, but not with primates, the neuronal scaling rules that apply to the cerebral cortex and cerebellum. The neuronal scaling rules that apply to the remaining brain areas are however distinct in artiodactyls. Importantly, we show that the folding index of the cerebral cortex scales with the number of neurons in the cerebral cortex in distinct fashions across artiodactyls, afrotherians, rodents, and primates, such that the artiodactyl cerebral cortex is more convoluted than primate cortices of similar numbers of neurons. Our findings suggest that the scaling rules found to be shared across modern afrotherians, glires and artiodactyls applied to the common Eutherian ancestor, such as the relationship between the mass of the cerebral cortex as a whole and its number of neurons. In turn, the distribution of neurons along the surface of the cerebral cortex, which is related to its degree of gyrification, appears to be a clade-specific characteristic. If the neuronal scaling rules for artiodactyls extend to all cetartiodactyls, we predict that the large cerebral cortex of cetaceans will still have fewer neurons than the human cerebral cortex.

  3. Evolvable Neuronal Paths: A Novel Basis for Information and Search in the Brain

    Fernando, Chrisantha; Vasas, Vera; Szathmáry, Eörs; Husbands, Phil

    2011-01-01

    We propose a previously unrecognized kind of informational entity in the brain that is capable of acting as the basis for unlimited hereditary variation in neuronal networks. This unit is a path of activity through a network of neurons, analogous to a path taken through a hidden Markov model. To prove in principle the capabilities of this new kind of informational substrate, we show how a population of paths can be used as the hereditary material for a neuronally implemented genetic algorithm, (the swiss-army knife of black-box optimization techniques) which we have proposed elsewhere could operate at somatic timescales in the brain. We compare this to the same genetic algorithm that uses a standard ‘genetic’ informational substrate, i.e. non-overlapping discrete genotypes, on a range of optimization problems. A path evolution algorithm (PEA) is defined as any algorithm that implements natural selection of paths in a network substrate. A PEA is a previously unrecognized type of natural selection that is well suited for implementation by biological neuronal networks with structural plasticity. The important similarities and differences between a standard genetic algorithm and a PEA are considered. Whilst most experiments are conducted on an abstract network model, at the conclusion of the paper a slightly more realistic neuronal implementation of a PEA is outlined based on Izhikevich spiking neurons. Finally, experimental predictions are made for the identification of such informational paths in the brain. PMID:21887266

  4. The circuitry of olfactory projection neurons in the brain of the honeybee, Apis mellifera

    Hanna Zwaka

    2016-09-01

    Full Text Available In the honeybee brain, two prominent tracts - the medial and the lateral antennal lobe tract - project from the primary olfactory center, the antennal lobes, to the central brain, the mushroom bodies, and the protocerebral lobe. Intracellularly stained uniglomerular projection neurons (uPN were reconstructed, registered to the 3D honeybee standard brain atlas, and then used to derive the spatial properties and quantitative morphology of the neurons of both tracts. We evaluated putative synaptic contacts of projection neurons using confocal microscopy. Analysis of the patterns of axon terminals revealed a domain-like innervation within the mushroom body lip neuropil. Projection neurons of the lateral tract arborized more sparsely within the lips and exhibited fewer synaptic boutons, while medial tract neurons occupied broader regions in the mushroom body calyces and the protocerebral lobe. Our data show that uPNs from the medial and lateral tract innervate both the core and the cortex of the ipsilateral mushroom body lip but differ in their innervation patterns in these regions. In the mushroombody neuropil collar we found evidence for ALT boutons suggesting the collar as a multi modal input site including olfactory input similar to lip and basal ring. In addition, our data support the conclusion drawn in previous studies that reciprocal synapses exist between projection neurons, octopaminergic-, and GABAergic cells in the mushroom body calyces. For the first time, we found evidence for connections between both tracts within the antennal lobe.

  5. Childhood obstructive sleep apnea associates with neuropsychological deficits and neuronal brain injury.

    Ann C Halbower

    2006-08-01

    Full Text Available Childhood obstructive sleep apnea (OSA is associated with neuropsychological deficits of memory, learning, and executive function. There is no evidence of neuronal brain injury in children with OSA. We hypothesized that childhood OSA is associated with neuropsychological performance dysfunction, and with neuronal metabolite alterations in the brain, indicative of neuronal injury in areas corresponding to neuropsychological function.We conducted a cross-sectional study of 31 children (19 with OSA and 12 healthy controls, aged 6-16 y group-matched by age, ethnicity, gender, and socioeconomic status. Participants underwent polysomnography and neuropsychological assessments. Proton magnetic resonance spectroscopic imaging was performed on a subset of children with OSA and on matched controls. Neuropsychological test scores and mean neuronal metabolite ratios of target brain areas were compared. Relative to controls, children with severe OSA had significant deficits in IQ and executive functions (verbal working memory and verbal fluency. Children with OSA demonstrated decreases of the mean neuronal metabolite ratio N-acetyl aspartate/choline in the left hippocampus (controls: 1.29, standard deviation [SD] 0.21; OSA: 0.91, SD 0.05; p = 0.001 and right frontal cortex (controls: 2.2, SD 0.4; OSA: 1.6, SD 0.4; p = 0.03.Childhood OSA is associated with deficits of IQ and executive function and also with possible neuronal injury in the hippocampus and frontal cortex. We speculate that untreated childhood OSA could permanently alter a developing child's cognitive potential.

  6. Absence of Tangentially Migrating Glutamatergic Neurons in the Developing Avian Brain

    Fernando García-Moreno

    2018-01-01

    Full Text Available Summary: Several neuronal populations orchestrate neocortical development during mammalian embryogenesis. These include the glutamatergic subplate-, Cajal-Retzius-, and ventral pallium-derived populations, which coordinate cortical wiring, migration, and proliferation, respectively. These transient populations are primarily derived from other non-cortical pallial sources that migrate to the dorsal pallium. Are these migrations to the dorsal pallium conserved in amniotes or are they specific to mammals? Using in ovo electroporation, we traced the entire lineage of defined chick telencephalic progenitors. We found that several pallial sources that produce tangential migratory neurons in mammals only produced radially migrating neurons in the avian brain. Moreover, ectopic expression of VP-specific mammalian Dbx1 in avian brains altered neurogenesis but did not convert the migration into a mammal-like tangential movement. Together, these data indicate that tangential cellular contributions of glutamatergic neurons originate from outside the dorsal pallium and that pallial Dbx1 expression may underlie the generation of the mammalian neocortex during evolution. : Neocortical formation crucially depends on the early tangential arrival of several transient glutamatergic neuronal populations. García-Moreno et al. find that these neuronal migrations are absent in the developing brain of chicks. The mammalian uniqueness of these developing migrations suggests a crucial role of these cells in the evolutionary origin of the neocortex. Keywords: neocortex, chick, pallium, ventral pallium, evo-devo, evolution, Dbx1, telencephalon

  7. Brain glutamine synthesis requires neuronal-born aspartate as amino donor for glial glutamate formation.

    Pardo, Beatriz; Rodrigues, Tiago B; Contreras, Laura; Garzón, Miguel; Llorente-Folch, Irene; Kobayashi, Keiko; Saheki, Takeyori; Cerdan, Sebastian; Satrústegui, Jorgina

    2011-01-01

    The glutamate-glutamine cycle faces a drain of glutamate by oxidation, which is balanced by the anaplerotic synthesis of glutamate and glutamine in astrocytes. De novo synthesis of glutamate by astrocytes requires an amino group whose origin is unknown. The deficiency in Aralar/AGC1, the main mitochondrial carrier for aspartate-glutamate expressed in brain, results in a drastic fall in brain glutamine production but a modest decrease in brain glutamate levels, which is not due to decreases in neuronal or synaptosomal glutamate content. In vivo (13)C nuclear magnetic resonance labeling with (13)C(2)acetate or (1-(13)C) glucose showed that the drop in brain glutamine is due to a failure in glial glutamate synthesis. Aralar deficiency induces a decrease in aspartate content, an increase in lactate production, and lactate-to-pyruvate ratio in cultured neurons but not in cultured astrocytes, indicating that Aralar is only functional in neurons. We find that aspartate, but not other amino acids, increases glutamate synthesis in both control and aralar-deficient astrocytes, mainly by serving as amino donor. These findings suggest the existence of a neuron-to-astrocyte aspartate transcellular pathway required for astrocyte glutamate synthesis and subsequent glutamine formation. This pathway may provide a mechanism to transfer neuronal-born redox equivalents to mitochondria in astrocytes.

  8. Dissecting mechanisms of brain aging by studying the intrinsic excitability of neurons

    Valerio eRizzo

    2015-01-01

    Full Text Available Several studies using vertebrate and invertebrate animal models have shown aging associated changes in brain function. Importantly, changes in soma size, loss or regression of dendrites and dendritic spines and alterations in the expression of neurotransmitter receptors in specific neurons were described. Despite this understanding, how aging impacts intrinsic properties of individual neurons or circuits that govern a defined behavior is yet to be determined. Here we discuss current understanding of specific electrophysiological changes in individual neurons and circuits during aging.

  9. Effect of ketamine on aquaporin-4 expression and neuronal apoptosis in brain tissues following brain injury in rats

    Zangong Zhou; Xiangyu Ji; Li Song; Jianfang Song; Shiduan Wang; Yanwei Yin

    2006-01-01

    BACKGROUND: Aquaporin-4 (AQP-4) is closely related to the formation of brain edema. Neuronal apoptosis plays an important part in the conversion of swelled neuron following traumatic brain injury. At present, the studies on the protective effect of ketamine on brain have involved in its effect on aquaporin-4 expression and neuronal apoptosis in the brain tissues following brain injury in rats.OBJECTIVE: To observe the effect of ketamine on AQP-4 expression and neuronal apoptosis in the brain tissue following rat brain injury, and analyze the time-dependence of ketamine in the treatment of brain injury.DESIGN: Randomized grouping design, controlled animal trial.SETTING: Department of Anesthesiology, the Medical School Hospital of Qingdao University.MATERIALS: Totally 150 rats of clean grade, aged 3 months, were involved and randomized into control group and ketamine-treated group, with 75 rats in each. Each group was divided into 5 subgroups separately at 6,12, 24, 48 and 72 hours after injury, with 15 rats at each time point. Main instruments and reagents:homemade beat machine, ketamine hydrochloride (Hengrui Pharmaceutical Factory, Jiangsu), rabbit anti-rat AQP-4 polyclonal antibody, SABC immunohistochemical reagent kit and TUNEL reagent kit (Boster Co.,Ltd.,Wuhan).METHODS: This trial was carried out in the Institute of Cerebrovascular Disease, Medical College of Qingdao University during March 2005 to February 2006. A weight-dropping rat model of brain injury was created with Feeney method. The rats in the ketamine-treated group were intraperitoneally administered with 50 g/L ketamine (120 mg/kg) one hour after injury, but ketamine was replaced by normal saline in the control group. In each subgroup, the water content of cerebral hemisphere was measured in 5 rats chosen randomly. The left 10 rats in each subgroup were transcardiacally perfused with ketamine, then the brain tissue was made into paraffin sections and stained by haematoxylin and eosin. Neuronal

  10. Neuronal substrates of sensory gating within the human brain.

    Grunwald, T.; Boutros, N.N.; Pezer, N.; Oertzen, J. von; Fernandez, G.S.E.; Schaller, C.; Elger, C.E.

    2003-01-01

    BACKGROUND: For the human brain, habituation to irrelevant sensory input is an important function whose failure is associated with behavioral disturbances. Sensory gating can be studied by recording the brain's electrical responses to repeated clicks: the P50 potential is normally reduced to the

  11. Whole-Brain Mapping of Neuronal Activity in the Learned Helplessness Model of Depression.

    Kim, Yongsoo; Perova, Zinaida; Mirrione, Martine M; Pradhan, Kith; Henn, Fritz A; Shea, Stephen; Osten, Pavel; Li, Bo

    2016-01-01

    Some individuals are resilient, whereas others succumb to despair in repeated stressful situations. The neurobiological mechanisms underlying such divergent behavioral responses remain unclear. Here, we employed an automated method for mapping neuronal activity in search of signatures of stress responses in the entire mouse brain. We used serial two-photon tomography to detect expression of c-FosGFP - a marker of neuronal activation - in c-fosGFP transgenic mice subjected to the learned helplessness (LH) procedure, a widely used model of stress-induced depression-like phenotype in laboratory animals. We found that mice showing "helpless" behavior had an overall brain-wide reduction in the level of neuronal activation compared with mice showing "resilient" behavior, with the exception of a few brain areas, including the locus coeruleus, that were more activated in the helpless mice. In addition, the helpless mice showed a strong trend of having higher similarity in whole-brain activity profile among individuals, suggesting that helplessness is represented by a more stereotypic brain-wide activation pattern. This latter effect was confirmed in rats subjected to the LH procedure, using 2-deoxy-2[18F]fluoro-D-glucose positron emission tomography to assess neural activity. Our findings reveal distinct brain activity markings that correlate with adaptive and maladaptive behavioral responses to stress, and provide a framework for further studies investigating the contribution of specific brain regions to maladaptive stress responses.

  12. Whole-brain mapping of neuronal activity in the learned helplessness model of depression

    Yongsoo eKim

    2016-02-01

    Full Text Available Some individuals are resilient, whereas others succumb to despair in repeated stressful situations. The neurobiological mechanisms underlying such divergent behavioral responses remain unclear. Here, we employed an automated method for mapping neuronal activity in search of signatures of stress responses in the entire mouse brain. We used serial two-photon tomography to detect expression of c-FosGFP – a marker of neuronal activation – in c-fosGFP transgenic mice subjected to the learned helplessness (LH procedure, a widely used model of stress-induced depression-like phenotype in laboratory animals. We found that mice showing helpless behavior had an overall brain-wide reduction in the level of neuronal activation compared with mice showing resilient behavior, with the exception of a few brain areas, including the locus coeruleus, that were more activated in the helpless mice. In addition, the helpless mice showed a strong trend of having higher similarity in whole brain activity profile among individuals, suggesting that helplessness is represented by a more stereotypic brain-wide activation pattern. This latter effect was confirmed in rats subjected to the LH procedure, using 2-deoxy-2[18F]fluoro-D-glucose positron emission tomography to assess neural activity. Our findings reveal distinct brain activity markings that correlate with adaptive and maladaptive behavioral responses to stress, and provide a framework for further studies investigating the contribution of specific brain regions to maladaptive stress responses.

  13. Leaping from brain to mind: a critique of mirror neuron explanations of countertransference.

    Vivona, Jeanine M

    2009-06-01

    In the current vigorous debate over the value of neuroscience to psychoanalysis, the epistemological status of the links between the data of brain research and the constructs of interest to psychoanalysts has rarely been examined. An inspection of recent discussions of mirror neuron research, particularly regarding countertransference, reveals gaps between psychoanalytic processes and the available brain activation data, and allows the evaluation of evidence for three implicit assumptions frequently made to bridge these gaps: (1) there is a straightforward correspondence between observed brain activity and mental activity; (2) similarity of localized brain activity across individuals signifies a shared interpersonal experience; (3) an automatic brain mechanism enables direct interpersonal sharing of experiences in the absence of inference and language. Examination of mirror neuron research findings reveals that these assumptions are either untested or questionable. Moreover, within neuroscience there are competing interpretations of mirror neuron findings, with diverse implications for psychoanalysis. The present state of mirror neuron research may offer us new hypotheses or metaphors, but does not provide empirical validation of the proposed models. More generally, as we attempt to learn from research findings generated outside psychoanalysis, we must strive to think scientifically, by minding the difference between data and interpretation.

  14. Peroxiredoxin distribution in the mouse brain with emphasis on neuronal populations affected in neurodegenerative disorders.

    Goemaere, Julie; Knoops, Bernard

    2012-02-01

    Redox changes are observed in neurodegenerative diseases, ranging from increased levels of reactive oxygen/nitrogen species and disturbance of antioxidant systems, to nitro-oxidative damage. By reducing hydrogen peroxide, peroxynitrite, and organic hydroperoxides, peroxiredoxins (Prdxs) represent a major potential protective barrier against nitro-oxidative insults in the brain. While recent works have investigated the putative role of Prdxs in neurodegenerative disorders, less is known about their expression in the healthy brain. Here we used immunohistochemistry to map basal expression of Prdxs throughout C57BL/6 mouse brain. We first confirmed the neuronal localization of Prdx2-5 and the glial expression of Prdx1, Prdx4, and Prdx6. Then we performed an in-depth analysis of neuronal Prdx distribution in the brain. Our results show that Prdx2-5 are widely detected in the different neuronal populations, and especially well expressed in the olfactory bulb, in the cerebral cortex, in pons nuclei, in the red nucleus, in all cranial nerve nuclei, in the cerebellum, and in motor neurons of the spinal cord. In contrast, Prdx expression is very low in the dopaminergic neurons of substantia nigra pars compacta and in the CA1/2 pyramidal cells of hippocampus. This low basal expression may contribute to the vulnerability of these neurons to nitro-oxidative attacks occurring in Parkinson's disease and Alzheimer's disease. In addition, we found that Prdx expression levels are unevenly distributed among neurons of a determined region and that distinct regional patterns of expression are observed between isoforms, reinforcing the hypothesis of the nonredundant function of Prdxs. Copyright © 2011 Wiley-Liss, Inc.

  15. Physiological basis and image processing in functional magnetic resonance imaging: Neuronal and motor activity in brain

    Sharma Rakesh

    2004-05-01

    Full Text Available Abstract Functional magnetic resonance imaging (fMRI is recently developing as imaging modality used for mapping hemodynamics of neuronal and motor event related tissue blood oxygen level dependence (BOLD in terms of brain activation. Image processing is performed by segmentation and registration methods. Segmentation algorithms provide brain surface-based analysis, automated anatomical labeling of cortical fields in magnetic resonance data sets based on oxygen metabolic state. Registration algorithms provide geometric features using two or more imaging modalities to assure clinically useful neuronal and motor information of brain activation. This review article summarizes the physiological basis of fMRI signal, its origin, contrast enhancement, physical factors, anatomical labeling by segmentation, registration approaches with examples of visual and motor activity in brain. Latest developments are reviewed for clinical applications of fMRI along with other different neurophysiological and imaging modalities.

  16. TDP-43 causes differential pathology in neuronal versus glial cells in the mouse brain.

    Yan, Sen; Wang, Chuan-En; Wei, Wenjie; Gaertig, Marta A; Lai, Liangxue; Li, Shihua; Li, Xiao-Jiang

    2014-05-15

    Mutations in TAR DNA-binding protein 43 (TDP-43) are associated with familial forms of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Although recent studies have revealed that mutant TDP-43 in neuronal and glial cells is toxic, how mutant TDP-43 causes primarily neuronal degeneration in an age-dependent manner remains unclear. Using adeno-associated virus (AAV) that expresses mutant TDP-43 (M337V) ubiquitously, we found that mutant TDP-43 accumulates preferentially in neuronal cells in the postnatal mouse brain. We then ubiquitously or selectively expressed mutant TDP-43 in neuronal and glial cells in the striatum of adult mouse brains via stereotaxic injection of AAV vectors and found that it also preferentially accumulates in neuronal cells. Expression of mutant TDP-43 in neurons in the striatum causes more severe degeneration, earlier death and more robust symptoms in mice than expression of mutant TDP-43 in glial cells; however, aging increases the expression of mutant TDP-43 in glial cells, and expression of mutant TDP-43 in older mice caused earlier onset of phenotypes and more severe neuropathology than that in younger mice. Although expression of mutant TDP-43 in glial cells via stereotaxic injection does not lead to robust neurological phenotypes, systemic inhibition of the proteasome activity via MG132 in postnatal mice could exacerbate glial TDP-43-mediated toxicity and cause mice to die earlier. Consistently, this inhibition increases the expression of mutant TDP-43 in glial cells in mouse brains. Thus, the differential accumulation of mutant TDP-43 in neuronal versus glial cells contributes to the preferential toxicity of mutant TDP-43 in neuronal cells and age-dependent pathology.

  17. Optogenetic stimulation of cholinergic projection neurons as an alternative for deep brain stimulation for Alzheimer's treatment

    Mancuso, James; Chen, Yuanxin; Zhao, Zhen; Li, Xuping; Xue, Zhong; Wong, Stephen T. C.

    2013-03-01

    Deep brain stimulation (DBS) of the cholinergic nuclei has emerged as a powerful potential treatment for neurodegenerative disease and is currently in a clinical trial for Alzheimer's therapy. While effective in treatment for a number of conditions from depression to epilepsy, DBS remains somewhat unpredictable due to the heterogeneity of the projection neurons that are activated, including glutamatergic, GABAergic, and cholinergic neurons, leading to unacceptable side effects ranging from apathy to depression or even suicidal behavior. It would be highly advantageous to confine stimulation to specific populations of neurons, particularly in brain diseases involving complex network interactions such as Alzheimer's. Optogenetics, now firmly established as an effective approach to render genetically-defined populations of cells sensitive to light activation including mice expressing Channelrhodopsin-2 specifically in cholinergic neurons, provides just this opportunity. Here we characterize the light activation properties and cell density of cholinergic neurons in healthy mice and mouse models of Alzheimer's disease in order to evaluate the feasibility of using optogenetic modulation of cholinergic synaptic activity to slow or reverse neurodegeneration. This paper is one of the very first reports to suggest that, despite the anatomical depth of their cell bodies, cholinergic projection neurons provide a better target for systems level optogenetic modulation than cholinergic interneurons found in various brain regions including striatum and the cerebral cortex. Additionally, basal forebrain channelrhodopsin-expressing cholinergic neurons are shown to exhibit normal distribution at 60 days and normal light activation at 40 days, the latest timepoints observed. The data collected form the basis of ongoing computational modeling of light stimulation of entire populations of cholinergic neurons.

  18. Three Types of Cortical L5 Neurons that Differ in Brain-Wide Connectivity and Function

    Kim, Euiseok J.; Juavinett, Ashley L.; Kyubwa, Espoir M.; Jacobs, Matthew W.; Callaway, Edward M.

    2015-01-01

    SUMMARY Cortical layer 5 (L5) pyramidal neurons integrate inputs from many sources and distribute outputs to cortical and subcortical structures. Previous studies demonstrate two L5 pyramid types: cortico-cortical (CC) and cortico-subcortical (CS). We characterize connectivity and function of these cell types in mouse primary visual cortex and reveal a new subtype. Unlike previously described L5 CC and CS neurons, this new subtype does not project to striatum [cortico-cortical, non-striatal (CC-NS)] and has distinct morphology, physiology and visual responses. Monosynaptic rabies tracing reveals that CC neurons preferentially receive input from higher visual areas, while CS neurons receive more input from structures implicated in top-down modulation of brain states. CS neurons are also more direction-selective and prefer faster stimuli than CC neurons. These differences suggest distinct roles as specialized output channels, with CS neurons integrating information and generating responses more relevant to movement control and CC neurons being more important in visual perception. PMID:26671462

  19. Three Types of Cortical Layer 5 Neurons That Differ in Brain-wide Connectivity and Function.

    Kim, Euiseok J; Juavinett, Ashley L; Kyubwa, Espoir M; Jacobs, Matthew W; Callaway, Edward M

    2015-12-16

    Cortical layer 5 (L5) pyramidal neurons integrate inputs from many sources and distribute outputs to cortical and subcortical structures. Previous studies demonstrate two L5 pyramid types: cortico-cortical (CC) and cortico-subcortical (CS). We characterize connectivity and function of these cell types in mouse primary visual cortex and reveal a new subtype. Unlike previously described L5 CC and CS neurons, this new subtype does not project to striatum [cortico-cortical, non-striatal (CC-NS)] and has distinct morphology, physiology, and visual responses. Monosynaptic rabies tracing reveals that CC neurons preferentially receive input from higher visual areas, while CS neurons receive more input from structures implicated in top-down modulation of brain states. CS neurons are also more direction-selective and prefer faster stimuli than CC neurons. These differences suggest distinct roles as specialized output channels, with CS neurons integrating information and generating responses more relevant to movement control and CC neurons being more important in visual perception. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Interleukin 6 modulates acetylcholinesterase activity of brain neurons

    Clarencon, D.; Multon, E.; Galonnier, M.; Estrade, M.; Fournier, C.; Mathieu, J.; Mestries, J.C.; Testylier, G.; Fatome, M.

    1995-01-01

    Classically, radiation injuries results in a peripheral inflammatory process, and we have previously observed an early systemic interleukin 6 (IL-6) release following whole-body irradiation. Besides, we have demonstrated an early decrease of rat or primate brain acetylcholinesterase (AChE) activity a gamma exposure. The object of the present study is to find possible IL-6 systemic effects on the brain AChE activity. We show that, though intravenous (i.v.) or intra-cerebro-ventricular (ICV) injection of IL-6 can induce a drop in rat brain AChE activity, this cytokine induces only a slight decrease of the AChE release in cultured brain cells. (author)

  1. Tracking Neuronal Connectivity from Electric Brain Signals to Predict Performance.

    Vecchio, Fabrizio; Miraglia, Francesca; Rossini, Paolo Maria

    2018-05-01

    The human brain is a complex container of interconnected networks. Network neuroscience is a recent venture aiming to explore the connection matrix built from the human brain or human "Connectome." Network-based algorithms provide parameters that define global organization of the brain; when they are applied to electroencephalographic (EEG) signals network, configuration and excitability can be monitored in millisecond time frames, providing remarkable information on their instantaneous efficacy also for a given task's performance via online evaluation of the underlying instantaneous networks before, during, and after the task. Here we provide an updated summary on the connectome analysis for the prediction of performance via the study of task-related dynamics of brain network organization from EEG signals.

  2. Brain-specific transcriptional regulator T-brain-1 controls brain wiring and neuronal activity in autism spectrum disorders

    Tzyy-Nan eHuang

    2015-11-01

    Full Text Available T-brain-1 (TBR1 is a brain-specific T-box transcription factor. In 1995, Tbr1 was first identified from a subtractive hybridization that compared mouse embryonic and adult telencephalons. Previous studies of Tbr1–/– mice have indicated critical roles for TBR1 in the development of the cerebral cortex, amygdala and olfactory bulb. Neuronal migration and axonal projection are two important developmental features controlled by TBR1. Recently, recurrent de novo disruptive mutations in the TBR1 gene have been found in patients with autism spectrum disorders (ASDs. Human genetic studies have identified TBR1 as a high-confidence risk factor for ASDs. Because only one allele of the TBR1 gene is mutated in these patients, Tbr1+/– mice serve as a good genetic mouse model to explore the mechanism by which de novo TBR1 mutation leads to ASDs. Although neuronal migration and axonal projection defects of cerebral cortex are the most prominent phenotypes in Tbr1–/– mice, these features are not found in Tbr1+/– mice. Instead, inter- and intra-amygdalar axonal projections and NMDAR expression and activity in amygdala are particularly susceptible to Tbr1 haploinsufficiency. The studies indicated that both abnormal brain wiring (abnormal amygdalar connections and excitation/inhibition imbalance (NMDAR hypoactivity, two prominent models for ASD etiology, are present in Tbr1+/– mice. Moreover, calcium/calmodulin-dependent serine protein kinase (CASK was found to interact with TBR1. The CASK-TBR1 complex had been shown to directly bind the promoter of the Grin2b gene, which is also known as Nmdar2b, and upregulate Grin2b expression. This molecular function of TBR1 provides an explanation for NMDAR hypoactivity in Tbr1+/– mice. In addition to Grin2b, cell adhesion molecules-including Ntng1, Cdh8 and Cntn2-are also regulated by TBR1 to control axonal projections of amygdala. Taken together, the studies of Tbr1 provide an integrated picture of ASD

  3. Guest editorial: Brain/neuronal computer games interfaces and interaction

    Coyle, D.; Principe, J.; Lotte, F.; Nijholt, Antinus

    2013-01-01

    Nowadays brainwave or electroencephalogram (EEG) controlled games controllers are adding new options to satisfy the continual demand for new ways to interact with games, following trends such as the Nintendo® Wii, Microsoft® Kinect and Playstation® Move which are based on accelerometers and motion capture. EEG-based brain-computer games interaction are controlled through brain-computer interface (BCI) technology which requires sophisticated signal processing to produce a low communication ban...

  4. Deep-brain electrical microstimulation is an effective tool to explore functional characteristics of somatosensory neurons in the rat brain.

    Han-Jia Jiang

    Full Text Available In neurophysiology researches, peripheral stimulation is used along with recordings of neural activities to study the processing of somatosensory signals in the brain. However, limited precision of peripheral stimulation makes it difficult to activate the neuron with millisecond resolution and study its functional properties in this scale. Also, tissue/receptor damage that could occur in some experiments often limits the amount of responses that can be recorded and hence reduces data reproducibility. To overcome these limitations, electrical microstimulation (ES of the brain could be used to directly and more precisely evoke neural responses. For this purpose, a deep-brain ES protocol for rat somatosensory relay neurons was developed in this study. Three male Wistar rats were used in the experiment. The ES was applied to the thalamic region responsive to hindpaw tactile stimulation (TS via a theta glass microelectrode. The resulting ES-evoked cortical responses showed action potentials and thalamocortical relay latencies very similar to those evoked by TS. This result shows that the developed deep-brain ES protocol is an effective tool to bypass peripheral tissue for in vivo functional analysis of specific types of somatosensory neurons. This protocol could be readily applied in researches of nociception and other somatosensory systems to allow more extensive exploration of the neural functional networks.

  5. Administration of Protocatechuic Acid Reduces Traumatic Brain Injury-Induced Neuronal Death

    Sang Hwon Lee

    2017-11-01

    Full Text Available Protocatechuic acid (PCA was first purified from green tea and has shown numerous biological activities, including anti-apoptotic, anti-inflammatory, and anti-atherosclerotic effects. The effect of PCA on traumatic brain injury (TBI-induced neuronal death has not previously been evaluated. TBI is defined as damage to the brain resulting from external mechanical force, such as rapid acceleration or deceleration, impact, blast waves, or penetration by a projectile. TBI causes neuronal death in the hippocampus and cerebral cortex. The present study aimed to evaluate the therapeutic potential of PCA on TBI-induced neuronal death. Here, TBI was induced by a controlled cortical impact model using rats. PCA (30 mg/kg was injected into the intraperitoneal (ip space immediately after TBI. Neuronal death was evaluated with Fluoro Jade-B (FJB staining at 24 h after TBI. Oxidative injury was detected by 4-hydroxy-2-nonenal (4HNE, glutathione (GSH concentration was analyzed by glutathione adduct with N-ethylmaleimide (GS-NEM staining at 24 h after TBI, and microglial activation in the hippocampus was detected by CD11b immunohistochemistry at one week after TBI. We found that the proportion of degenerating neurons, oxidative injury, GSH depletion, and microglia activation in the hippocampus and cortex were all reduced by PCA treatment following TBI. Therefore, our study suggests that PCA may have therapeutic potential in preventing TBI-induced neuronal death.

  6. A Statistically Representative Atlas for Mapping Neuronal Circuits in the Drosophila Adult Brain.

    Arganda-Carreras, Ignacio; Manoliu, Tudor; Mazuras, Nicolas; Schulze, Florian; Iglesias, Juan E; Bühler, Katja; Jenett, Arnim; Rouyer, François; Andrey, Philippe

    2018-01-01

    Imaging the expression patterns of reporter constructs is a powerful tool to dissect the neuronal circuits of perception and behavior in the adult brain of Drosophila , one of the major models for studying brain functions. To date, several Drosophila brain templates and digital atlases have been built to automatically analyze and compare collections of expression pattern images. However, there has been no systematic comparison of performances between alternative atlasing strategies and registration algorithms. Here, we objectively evaluated the performance of different strategies for building adult Drosophila brain templates and atlases. In addition, we used state-of-the-art registration algorithms to generate a new group-wise inter-sex atlas. Our results highlight the benefit of statistical atlases over individual ones and show that the newly proposed inter-sex atlas outperformed existing solutions for automated registration and annotation of expression patterns. Over 3,000 images from the Janelia Farm FlyLight collection were registered using the proposed strategy. These registered expression patterns can be searched and compared with a new version of the BrainBaseWeb system and BrainGazer software. We illustrate the validity of our methodology and brain atlas with registration-based predictions of expression patterns in a subset of clock neurons. The described registration framework should benefit to brain studies in Drosophila and other insect species.

  7. A Statistically Representative Atlas for Mapping Neuronal Circuits in the Drosophila Adult Brain

    Ignacio Arganda-Carreras

    2018-03-01

    Full Text Available Imaging the expression patterns of reporter constructs is a powerful tool to dissect the neuronal circuits of perception and behavior in the adult brain of Drosophila, one of the major models for studying brain functions. To date, several Drosophila brain templates and digital atlases have been built to automatically analyze and compare collections of expression pattern images. However, there has been no systematic comparison of performances between alternative atlasing strategies and registration algorithms. Here, we objectively evaluated the performance of different strategies for building adult Drosophila brain templates and atlases. In addition, we used state-of-the-art registration algorithms to generate a new group-wise inter-sex atlas. Our results highlight the benefit of statistical atlases over individual ones and show that the newly proposed inter-sex atlas outperformed existing solutions for automated registration and annotation of expression patterns. Over 3,000 images from the Janelia Farm FlyLight collection were registered using the proposed strategy. These registered expression patterns can be searched and compared with a new version of the BrainBaseWeb system and BrainGazer software. We illustrate the validity of our methodology and brain atlas with registration-based predictions of expression patterns in a subset of clock neurons. The described registration framework should benefit to brain studies in Drosophila and other insect species.

  8. Neural stem cells improve neuronal survival in cultured postmortem brain tissue from aged and Alzheimer patients

    Wu, L.; Sluiter, A.A.; Guo, Ho Fu; Balesar, R. A.; Swaab, D. F.; Zhou, Jiang Ning; Verwer, R. W H

    Neurodegenerative diseases are progressive and incurable and are becoming ever more prevalent. To study whether neural stem cell can reactivate or rescue functions of impaired neurons in the human aging and neurodegenerating brain, we co-cultured postmortem slices from Alzheimer patients and control

  9. Molecular fingerprint of neuropeptide S-producing neurons in the mouse brain

    Liu, Xiaobin; Zeng, Joanne; Zhou, Anni

    2011-01-01

    /EGFP-transgenic mice show anatomically correct and overlapping expression of both NPS and EGFP. A total number of ~500 NPS/EGFP-positive neurons are present in the mouse brain, located in the pericoerulear region and the Kölliker-Fuse nucleus. NPS and transgene expression is first detectable around E14, indicating...

  10. Imaging separation of neuronal from vascular effects of cocaine on rat cortical brain in vivo

    Yuan, Z.; Du, C.; Luo, Z.; Volkow, N.D.; Pan, Y.

    2011-01-01

    MRI techniques to study brain function assume coupling between neuronal activity, metabolism and flow. However, recent evidence of physiological uncoupling between neuronal and cerebrovascular events highlights the need for methods to simultaneously measure these three properties. We report a multimodality optical approach that integrates dual-wavelength laser speckle imaging (measures changes in blood flow, blood volume and hemoglobin oxygenation), digital-frequency-ramping optical coherence tomography (images quantitative 3D vascular network) and Rhod2 fluorescence (images intracellular calcium for measure of neuronal activity) at high spatiotemporal resolutions (30 (micro)m, 10 Hz) and over a large field of view (3 x 5 mm 2 ). We apply it to assess cocaine's effects in rat cortical brain and show an immediate decrease 3.5 ± 0.9 min, phase (1) in the oxygen content of hemoglobin and the cerebral blood flow followed by an overshoot 7.1 ± 0.2 min, phase (2) lasting over 20 min whereas Ca 2+ increased immediately (peaked at t = 4.1 ± 0.4 min) and remained elevated. This enabled us to identify a delay (2.9 ± 0.5 min) between peak neuronal and vascular responses in phase 2. The ability of this multimodality optical approach for simultaneous imaging at high spatiotemporal resolutions permits us to distinguish the vascular versus cellular changes of the brain, thus complimenting other neuroimaging modalities for brain functional studies (e. g., PET, fMRI).

  11. Imaging separation of neuronal from vascular effects of cocaine on rat cortical brain in vivo

    Yuan, Z.; Du, C.; Yuan, Z.; Luo, Z.; Volkow, N.D.; Pan, Y.; Du, C.

    2010-09-08

    MRI techniques to study brain function assume coupling between neuronal activity, metabolism and flow. However, recent evidence of physiological uncoupling between neuronal and cerebrovascular events highlights the need for methods to simultaneously measure these three properties. We report a multimodality optical approach that integrates dual-wavelength laser speckle imaging (measures changes in blood flow, blood volume and hemoglobin oxygenation), digital-frequency-ramping optical coherence tomography (images quantitative 3D vascular network) and Rhod2 fluorescence (images intracellular calcium for measure of neuronal activity) at high spatiotemporal resolutions (30 {micro}m, 10 Hz) and over a large field of view (3 x 5 mm{sup 2}). We apply it to assess cocaine's effects in rat cortical brain and show an immediate decrease 3.5 {+-} 0.9 min, phase (1) in the oxygen content of hemoglobin and the cerebral blood flow followed by an overshoot 7.1 {+-} 0.2 min, phase (2) lasting over 20 min whereas Ca{sup 2+} increased immediately (peaked at t = 4.1 {+-} 0.4 min) and remained elevated. This enabled us to identify a delay (2.9 {+-} 0.5 min) between peak neuronal and vascular responses in phase 2. The ability of this multimodality optical approach for simultaneous imaging at high spatiotemporal resolutions permits us to distinguish the vascular versus cellular changes of the brain, thus complimenting other neuroimaging modalities for brain functional studies (e. g., PET, fMRI).

  12. Postresuscitative Changes of Brain-Derived Neurotrophic Factor (BDNF Protein Expression: Association With Neuronal Death

    M. Sh. Avrushchenko

    2017-01-01

    Full Text Available Aim of the study: to evaluate expression level of BDNF and its association with the postresuscitative neuronal death in highly hypoxia-sensitive brain regions.Materials and methods. Cardiac arrest in adult albino male rats was evoked by intrathoracic clamping of supracardiac bundle of vessels for 10 min. Pyramidal neurons of the hippocampus and Purkinje cells of the cerebellum were analyzed at various time points after resuscitation (days 1, 4, 7, 14. Shame-operated rats served as controls. The expression of BDNF protein was immunohistochemically determined. The BDNF expression level was determined by evalution on the base of the average optical density. The number of neurons with different BDNF expression levels and the total number of neurons per 1 mm of the layer length were computed. Image analysis systems (Intel personal computer, Olympus BX-41 microscope, ImageScopeM, ImageJ 1,48v and MS Excel 2007 software packages were used in the study. Data statistical processing was performed with the aid of Statistica 7.0 program and Kolmogorov-Smirnov λ-test, Mann-Whitney U-test and Student's t-test.Results. The dynamics of postresuscitative shifts of BDNF immunoreactivity in neuronal populations of hippocampal pyramidal cells and cerebellar Purkinje cells was established. It was shown that the level of BDNF expression within the two neuronal populations decreased, that was accompanied by neuronal death. In the Purkinje cell population the neuronal death occurred by the 4th day after resuscitation, while in the hippocampus, it occurs only by the 7th day. Notably, only BDNF-negative neurons or neurons with low level of BDNF expression died in both neuronal populations.Conclusion. The results of the study indicate the existence of an interrelation between the shifts in BDNF expression and the postresuscitative neuronal death. It was shown that only the cells with none or poor BDNF expression underwent death in highly hypoxia-sensitive neuronal

  13. Local-learning-based neuron selection for grasping gesture prediction in motor brain machine interfaces

    Xu, Kai; Wang, Yiwen; Wang, Yueming; Wang, Fang; Hao, Yaoyao; Zhang, Shaomin; Zhang, Qiaosheng; Chen, Weidong; Zheng, Xiaoxiang

    2013-04-01

    Objective. The high-dimensional neural recordings bring computational challenges to movement decoding in motor brain machine interfaces (mBMI), especially for portable applications. However, not all recorded neural activities relate to the execution of a certain movement task. This paper proposes to use a local-learning-based method to perform neuron selection for the gesture prediction in a reaching and grasping task. Approach. Nonlinear neural activities are decomposed into a set of linear ones in a weighted feature space. A margin is defined to measure the distance between inter-class and intra-class neural patterns. The weights, reflecting the importance of neurons, are obtained by minimizing a margin-based exponential error function. To find the most dominant neurons in the task, 1-norm regularization is introduced to the objective function for sparse weights, where near-zero weights indicate irrelevant neurons. Main results. The signals of only 10 neurons out of 70 selected by the proposed method could achieve over 95% of the full recording's decoding accuracy of gesture predictions, no matter which different decoding methods are used (support vector machine and K-nearest neighbor). The temporal activities of the selected neurons show visually distinguishable patterns associated with various hand states. Compared with other algorithms, the proposed method can better eliminate the irrelevant neurons with near-zero weights and provides the important neuron subset with the best decoding performance in statistics. The weights of important neurons converge usually within 10-20 iterations. In addition, we study the temporal and spatial variation of neuron importance along a period of one and a half months in the same task. A high decoding performance can be maintained by updating the neuron subset. Significance. The proposed algorithm effectively ascertains the neuronal importance without assuming any coding model and provides a high performance with different

  14. Brain-specific Crmp2 deletion leads to neuronal development deficits and behavioural impairments in mice.

    Zhang, Hongsheng; Kang, Eunchai; Wang, Yaqing; Yang, Chaojuan; Yu, Hui; Wang, Qin; Chen, Zheyu; Zhang, Chen; Christian, Kimberly M; Song, Hongjun; Ming, Guo-Li; Xu, Zhiheng

    2016-06-01

    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.

  15. Optimal staining methods for delineation of cortical areas and neuron counts in human brains.

    Uylings, H B; Zilles, K; Rajkowska, G

    1999-04-01

    For cytoarchitectonic delineation of cortical areas in human brain, the Gallyas staining for somata with its sharp contrast between cell bodies and neuropil is preferable to the classical Nissl staining, the more so when an image analysis system is used. This Gallyas staining, however, does not appear to be appropriate for counting neuron numbers in pertinent brain areas, due to the lack of distinct cytological features between small neurons and glial cells. For cell counting Nissl is preferable. In an optimal design for cell counting at least both the Gallyas and the Nissl staining must be applied, the former staining for cytoarchitectural delineaton of cortical areas and the latter for counting the number of neurons in the pertinent cortical areas. Copyright 1999 Academic Press.

  16. Brain stimulation used as biofeedback in neuronal activation of the temporal lobe area in autistic children

    Vernon Furtado da Silva

    2016-08-01

    Full Text Available ABSTRACT This study focused upon the functional capacity of mirror neurons in autistic children. 30 individuals, 10 carriers of the autistic syndrome (GCA, 10 with intellectual impairments (GDI, and 10 non-autistics (GCN had registered eletroencephalogram from the brain area theoretically related to mirror neurons. Data collection procedure occurred prior to brain stimulation and after the stimulation session. During the second session, participants had to alternately process figures evoking neutral, happy, and/or sorrowful feelings. Results proved that, for all groups, the stimulation process in fact produced additional activation in the neural area under study. The level of activation was related to the format of emotional stimuli and the likelihood of boosting such stimuli. Since the increase of activation occurred in a model similar to the one observed for the control group, we may suggest that the difficulty people with autism have at expressing emotions is not due to nonexistence of mirror neurons.

  17. Brain stimulation used as biofeedback in neuronal activation of the temporal lobe area in autistic children.

    Silva, Vernon Furtado da; Calomeni, Mauricio Rocha; Nunes, Rodolfo Alkmim Moreira; Pimentel, Carlos Elias; Martins, Gabriela Paes; Oliveira, Patrícia da Cruz Araruna; Silva, Patrícia Bagno; Silva, Alair Pedro Ribeiro de Souza E

    2016-08-01

    This study focused upon the functional capacity of mirror neurons in autistic children. 30 individuals, 10 carriers of the autistic syndrome (GCA), 10 with intellectual impairments (GDI), and 10 non-autistics (GCN) had registered eletroencephalogram from the brain area theoretically related to mirror neurons. Data collection procedure occurred prior to brain stimulation and after the stimulation session. During the second session, participants had to alternately process figures evoking neutral, happy, and/or sorrowful feelings. Results proved that, for all groups, the stimulation process in fact produced additional activation in the neural area under study. The level of activation was related to the format of emotional stimuli and the likelihood of boosting such stimuli. Since the increase of activation occurred in a model similar to the one observed for the control group, we may suggest that the difficulty people with autism have at expressing emotions is not due to nonexistence of mirror neurons.

  18. Neuronal nitric oxide synthase inhibition prevents cerebral palsy following hypoxia-ischemia in fetal rabbits: comparison between JI-8 and 7-nitroindazole.

    Yu, Lei; Derrick, Matthew; Ji, Haitao; Silverman, Richard B; Whitsett, Jennifer; Vásquez-Vivar, Jeannette; Tan, Sidhartha

    2011-01-01

    Cerebral palsy and death are serious consequences of perinatal hypoxia-ischemia (HI). Important concepts can now be tested using an animal model of cerebral palsy. We have previously shown that reactive oxygen and nitrogen species are produced in antenatal HI. A novel class of neuronal nitric oxide synthase (nNOS) inhibitors have been designed, and they ameliorate postnatal motor deficits when administered prior to the hypoxic-ischemic insult. This study asks how the new class of inhibitors, using JI-8 (K(i) for nNOS: 0.014 μM) as a representative, compare with the frequently used nNOS inhibitor 7-nitroindazole (7-NI; K(i): 0.09 ± 0.024 μM). A theoretical dose equivalent to 75 K(i) of JI-8 or equimolar 7-NI was administered to pregnant rabbit dams 30 min prior to and immediately after 40 min of uterine ischemia at 22 days gestation (70% term). JI-8 treatment resulted in a significant decrease in NOS activity (39%) in fetal brain homogenates acutely after HI, without affecting maternal blood pressure and heart rate. JI-8 treatment resulted in 33 normal kits, 2 moderately and 13 severely affected kits and 5 stillbirths, compared with 8 normal, 3 moderately affected and 5 severely affected kits and 10 stillbirths in the 7-NI group. In terms of neurobehavioral outcome, 7-NI was not different from saline treatment, while JI-8 was superior to saline and 7-NI in its protective effect (p JI-8 significantly improved the locomotion score over both saline and 7-NI scores. JI-8 was also significantly superior to saline in preserving smell, muscle tone and righting reflex function, but 7-NI did not show significant improvement. Furthermore, a 100-fold increase in the dose (15.75 μmol/kg) of 7-NI significantly decreased systolic blood pressure in the dam, while JI-8 did not. The new class of inhibitors such as JI-8 shows promise in the prevention of cerebral palsy and is superior to the previously more commonly used nNOS inhibitor. Copyright © 2011 S. Karger AG, Basel.

  19. Multielectrode recordings from auditory neurons in the brain of a small grasshopper.

    Bhavsar, Mit Balvantray; Heinrich, Ralf; Stumpner, Andreas

    2015-12-30

    Grasshoppers have been used as a model system to study the neuronal basis of insect acoustic behavior. Auditory neurons have been described from intracellular recordings. The growing interest to study population activity of neurons has been satisfied so far with artificially combining data from different individuals. We for the first time used multielectrode recordings from a small grasshopper brain. We used three 12μm tungsten wires (combined in a multielectrode) to record from local brain neurons and from a population of auditory neurons entering the brain from the thorax. Spikes of the recorded units were separated by sorting algorithms and spike collision analysis. The tungsten wires enabled stable recordings with high signal to noise ratio. Due to the tight temporal coupling of auditory activity to the stimulus spike collisions were frequent and collision analysis retrieved 10-15% of additional spikes. Marking the electrode position was possible using a fluorescent dye or electrocoagulation with high current. Physiological identification of units described from intracellular recordings was hard to achieve. 12μm tungsten wires gave a better signal to noise ratio than 15μm copper wires previously used in recordings from bees' brains. Recording the population activity of auditory neurons in one individual prevents interindividual and trial-to-trial variability which otherwise reduce the validity of the analysis. Double intracellular recordings have quite low success rate and therefore are rarely achieved and their stability is much lower than that of multielectrode recordings which allows sampling of data for 30min or more. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Neuronal DNA Methylation Profiling of Blast-Related Traumatic Brain Injury.

    Haghighi, Fatemeh; Ge, Yongchao; Chen, Sean; Xin, Yurong; Umali, Michelle U; De Gasperi, Rita; Gama Sosa, Miguel A; Ahlers, Stephen T; Elder, Gregory A

    2015-08-15

    Long-term molecular changes in the brain resulting from blast exposure may be mediated by epigenetic changes, such as deoxyribonucleic acid (DNA) methylation, that regulate gene expression. Aberrant regulation of gene expression is associated with behavioral abnormalities, where DNA methylation bridges environmental signals to sustained changes in gene expression. We assessed DNA methylation changes in the brains of rats exposed to three 74.5 kPa blast overpressure events, conditions that have been associated with long-term anxiogenic manifestations weeks or months following the initial exposures. Rat frontal cortex eight months post-exposure was used for cell sorting of whole brain tissue into neurons and glia. We interrogated DNA methylation profiles in these cells using Expanded Reduced Representation Bisulfite Sequencing. We obtained data for millions of cytosines, showing distinct methylation profiles for neurons and glia and an increase in global methylation in neuronal versus glial cells (pDNA methylation perturbations in blast overpressure-exposed animals, compared with sham blast controls, within 458 and 379 genes in neurons and glia, respectively. Differentially methylated neuronal genes showed enrichment in cell death and survival and nervous system development and function, including genes involved in transforming growth factor β and nitric oxide signaling. Functional validation via gene expression analysis of 30 differentially methylated neuronal and glial genes showed a 1.2 fold change in gene expression of the serotonin N-acetyltransferase gene (Aanat) in blast animals (pDNA methylation induced in response to multiple blast overpressure exposures. In particular, increased methylation and decreased gene expression were observed in the Aanat gene, which is involved in converting serotonin to the circadian hormone melatonin and is implicated in sleep disturbance and depression associated with traumatic brain injury.

  1. D22S15 - a fetal brain cDNA with BanII and SacI RFLP

    Rouleau, G A; Kurnit, D M; Neve, R L; Bazanowsky, A; Patterson, D; Gusella, J F

    1988-02-25

    A .58 kb single copy EcoRI fragment was isolated from a human fetal brain cDNA library and cloned into pBR322. This fragment recognizes a two allele polymorphism when used to probe human genomic DNA digested with SacI. There are no constant bands. Additional polymorphisms recognized by BanII and Bsp1286 are in disequilibrium with the BanII polymorphism. It has been localized to chromosome 22 by somatic cell hybrid analysis and linkage analysis. Co-dominant segregation has been observed in 15 informative families.

  2. Development of normal fetal brain by MRI with a half-Fourier rapid acquisition with relaxation enhancement sequence

    Li Meilan; Liu Xuejun; Wang Jianhong; Zhao Cheng; Li Xiang

    2006-01-01

    Objective: To evaluate normal maturation of the fetal brain with half-Fourier rapid acquisition with relaxation enhancement (RARE) MRI. Methods: The normal brains of 25 fetuses of 12-38 weeks gestational age were examined in utero with half-Fourier RARE imaging. Gyrus maturation, gray and white matter differentiation, ventricle-to-brain diameter ratio, and subarachnoid space size were evaluated with respect to gestational age. Results: At 12-23 weeks, the brain had a smooth surface, and two or three layers were differentiated in the cerebral cortex. At 24-26 weeks, only a few shallow grooves were seen in the central sulcus, and three layers, including the immature cortex, intermediate zone, and germinal matrix, were differentiated in all fetuses. At 27-29 weeks, sulcus formation was observed in various regions of the brain parenchyma, and the germinal matrix became invisible. Sulcation was seen in the whole cerebral cortex from 30 weeks on. However, the cortex did not undergo infolding, and opercular formation was not seen before 33 weeks. At 23 weeks and earlier, the cerebral ventricles were large; thereafter, they gradually became smaller. The subarachnoid space overlying the cortical convexities was slightly dilated at all gestational ages, most markedly at 21-26 weeks. Conclusion: Changes in brain maturation proceed through stages in an orderly and predictable fashion and can be evaluated reliably with half-Fourier RARE MRI. (authors)

  3. FTO is expressed in neurones throughout the brain and its expression is unaltered by fasting.

    McTaggart, James S; Lee, Sheena; Iberl, Michaela; Church, Chris; Cox, Roger D; Ashcroft, Frances M

    2011-01-01

    Single-nucleotide polymorphisms in the first intron of the ubiquitously expressed FTO gene are associated with obesity. Although the physiological functions of FTO remain unclear, food intake is often altered when Fto expression levels are manipulated. Furthermore, deletion of FTO from neurones alone has a similar effect on food intake to deletion of FTO in all tissues. These results indicate that FTO expression in the brain is particularly important. Considerable focus has been placed on the dynamic regulation of Fto mRNA expression in the hypothalamus after short-term (16-48 hour) fasting, but results have been controversial. There are no studies that quantify FTO protein levels across the brain, and assess its alteration following short-term fasting. Using immunohistochemistry, we found that FTO protein is widely expressed in mouse brain, and present in the majority of neurones. Using quantitative Western blotting and RT-qPCR we show that FTO protein and mRNA levels in the hypothalamus, cerebellum and rostral brain are relatively uniform, and levels in the brain are higher than in skeletal muscles of the lower limbs. Fasting for 18 hours does not alter the expression pattern, or levels, of FTO protein and mRNA. We further show that the majority of POMC neurones, which are critically involved in food intake regulation, also express FTO, but that the percentage of FTO-positive POMC neurones is not altered by fasting. In summary, we find no evidence that Fto/FTO expression is regulated by short-term (18-hour) fasting. Thus, it is unlikely that the hunger and increased post-fasting food intake caused by such food deprivation is driven by alterations in Fto/FTO expression. The widespread expression of FTO in neurones also suggests that physiological studies of this protein should not be limited to the hypothalamus.

  4. FTO is expressed in neurones throughout the brain and its expression is unaltered by fasting.

    James S McTaggart

    Full Text Available Single-nucleotide polymorphisms in the first intron of the ubiquitously expressed FTO gene are associated with obesity. Although the physiological functions of FTO remain unclear, food intake is often altered when Fto expression levels are manipulated. Furthermore, deletion of FTO from neurones alone has a similar effect on food intake to deletion of FTO in all tissues. These results indicate that FTO expression in the brain is particularly important. Considerable focus has been placed on the dynamic regulation of Fto mRNA expression in the hypothalamus after short-term (16-48 hour fasting, but results have been controversial. There are no studies that quantify FTO protein levels across the brain, and assess its alteration following short-term fasting. Using immunohistochemistry, we found that FTO protein is widely expressed in mouse brain, and present in the majority of neurones. Using quantitative Western blotting and RT-qPCR we show that FTO protein and mRNA levels in the hypothalamus, cerebellum and rostral brain are relatively uniform, and levels in the brain are higher than in skeletal muscles of the lower limbs. Fasting for 18 hours does not alter the expression pattern, or levels, of FTO protein and mRNA. We further show that the majority of POMC neurones, which are critically involved in food intake regulation, also express FTO, but that the percentage of FTO-positive POMC neurones is not altered by fasting. In summary, we find no evidence that Fto/FTO expression is regulated by short-term (18-hour fasting. Thus, it is unlikely that the hunger and increased post-fasting food intake caused by such food deprivation is driven by alterations in Fto/FTO expression. The widespread expression of FTO in neurones also suggests that physiological studies of this protein should not be limited to the hypothalamus.

  5. Pigment-Dispersing Factor-expressing neurons convey circadian information in the honey bee brain

    Beer, Katharina; Kolbe, Esther; Kahana, Noa B.; Yayon, Nadav; Weiss, Ron; Menegazzi, Pamela; Bloch, Guy

    2018-01-01

    Pigment-Dispersing Factor (PDF) is an important neuropeptide in the brain circadian network of Drosophila and other insects, but its role in bees in which the circadian clock influences complex behaviour is not well understood. We combined high-resolution neuroanatomical characterizations, quantification of PDF levels over the day and brain injections of synthetic PDF peptide to study the role of PDF in the honey bee Apis mellifera. We show that PDF co-localizes with the clock protein Period (PER) in a cluster of laterally located neurons and that the widespread arborizations of these PER/PDF neurons are in close vicinity to other PER-positive cells (neurons and glia). PDF-immunostaining intensity oscillates in a diurnal and circadian manner with possible influences for age or worker task on synchrony of oscillations in different brain areas. Finally, PDF injection into the area between optic lobes and the central brain at the end of the subjective day produced a consistent trend of phase-delayed circadian rhythms in locomotor activity. Altogether, these results are consistent with the hypothesis that PDF is a neuromodulator that conveys circadian information from pacemaker cells to brain centres involved in diverse functions including locomotion, time memory and sun-compass orientation. PMID:29321240

  6. Antenatal antioxidant treatment with melatonin to decrease newborn neurodevelopmental deficits and brain injury caused by fetal growth restriction.

    Miller, Suzanne L; Yawno, Tamara; Alers, Nicole O; Castillo-Melendez, Margie; Supramaniam, Veena G; VanZyl, Niel; Sabaretnam, Tharani; Loose, Jan M; Drummond, Grant R; Walker, David W; Jenkin, Graham; Wallace, Euan M

    2014-04-01

    Fetal intrauterine growth restriction (IUGR) is a serious pregnancy complication associated with increased rates of perinatal morbidity and mortality, and ultimately with long-term neurodevelopmental impairments. No intervention currently exists that can improve the structure and function of the IUGR brain before birth. Here, we investigated whether maternal antenatal melatonin administration reduced brain injury in ovine IUGR. IUGR was induced in pregnant sheep at 0.7 gestation and a subset of ewes received melatonin via intravenous infusion until term. IUGR, IUGR + melatonin (IUGR + MLT) and control lambs were born naturally, neonatal behavioral assessment was used to examine neurological function and at 24 hr after birth the brain was collected for the examination of neuropathology. Compared to control lambs, IUGR lambs took significantly longer to achieve normal neonatal lamb behaviors, such as standing and suckling. IUGR brains showed widespread cellular and axonal lipid peroxidation, and white matter hypomyelination and axonal damage. Maternal melatonin administration ameliorated oxidative stress, normalized myelination and rescued axonopathy within IUGR lamb brains, and IUGR + MLT lambs demonstrated significant functional improvements including a reduced time taken to attach to and suckle at the udder after birth. Based on these observations, we began a pilot clinical trial of oral melatonin administration to women with an IUGR fetus. Maternal melatonin was not associated with adverse maternal or fetal effects and it significantly reduced oxidative stress, as evidenced by reduced malondialdehyde levels, in the IUGR + MLT placenta compared to IUGR alone. Melatonin should be considered for antenatal neuroprotective therapy in human IUGR. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Volitional enhancement of firing synchrony and oscillation by neuronal operant conditioning: interaction with neurorehabilitation and brain-machine interface.

    Sakurai, Yoshio; Song, Kichan; Tachibana, Shota; Takahashi, Susumu

    2014-01-01

    In this review, we focus on neuronal operant conditioning in which increments in neuronal activities are directly rewarded without behaviors. We discuss the potential of this approach to elucidate neuronal plasticity for enhancing specific brain functions and its interaction with the progress in neurorehabilitation and brain-machine interfaces. The key to-be-conditioned activities that this paper emphasizes are synchronous and oscillatory firings of multiple neurons that reflect activities of cell assemblies. First, we introduce certain well-known studies on neuronal operant conditioning in which conditioned enhancements of neuronal firing were reported in animals and humans. These studies demonstrated the feasibility of volitional control over neuronal activity. Second, we refer to the recent studies on operant conditioning of synchrony and oscillation of neuronal activities. In particular, we introduce a recent study showing volitional enhancement of oscillatory activity in monkey motor cortex and our study showing selective enhancement of firing synchrony of neighboring neurons in rat hippocampus. Third, we discuss the reasons for emphasizing firing synchrony and oscillation in neuronal operant conditioning, the main reason being that they reflect the activities of cell assemblies, which have been suggested to be basic neuronal codes representing information in the brain. Finally, we discuss the interaction of neuronal operant conditioning with neurorehabilitation and brain-machine interface (BMI). We argue that synchrony and oscillation of neuronal firing are the key activities required for developing both reliable neurorehabilitation and high-performance BMI. Further, we conclude that research of neuronal operant conditioning, neurorehabilitation, BMI, and system neuroscience will produce findings applicable to these interrelated fields, and neuronal synchrony and oscillation can be a common important bridge among all of them.

  8. Multichannel optical brain imaging to separate cerebral vascular, tissue metabolic, and neuronal effects of cocaine

    Ren, Hugang; Luo, Zhongchi; Yuan, Zhijia; Pan, Yingtian; Du, Congwu

    2012-02-01

    Characterization of cerebral hemodynamic and oxygenation metabolic changes, as well neuronal function is of great importance to study of brain functions and the relevant brain disorders such as drug addiction. Compared with other neuroimaging modalities, optical imaging techniques have the potential for high spatiotemporal resolution and dissection of the changes in cerebral blood flow (CBF), blood volume (CBV), and hemoglobing oxygenation and intracellular Ca ([Ca2+]i), which serves as markers of vascular function, tissue metabolism and neuronal activity, respectively. Recently, we developed a multiwavelength imaging system and integrated it into a surgical microscope. Three LEDs of λ1=530nm, λ2=570nm and λ3=630nm were used for exciting [Ca2+]i fluorescence labeled by Rhod2 (AM) and sensitizing total hemoglobin (i.e., CBV), and deoxygenated-hemoglobin, whereas one LD of λ1=830nm was used for laser speckle imaging to form a CBF mapping of the brain. These light sources were time-sharing for illumination on the brain and synchronized with the exposure of CCD camera for multichannel images of the brain. Our animal studies indicated that this optical approach enabled simultaneous mapping of cocaine-induced changes in CBF, CBV and oxygenated- and deoxygenated hemoglobin as well as [Ca2+]i in the cortical brain. Its high spatiotemporal resolution (30μm, 10Hz) and large field of view (4x5 mm2) are advanced as a neuroimaging tool for brain functional study.

  9. Loss of aPKCλ in differentiated neurons disrupts the polarity complex but does not induce obvious neuronal loss or disorientation in mouse brains.

    Tomoyuki Yamanaka

    Full Text Available Cell polarity plays a critical role in neuronal differentiation during development of the central nervous system (CNS. Recent studies have established the significance of atypical protein kinase C (aPKC and its interacting partners, which include PAR-3, PAR-6 and Lgl, in regulating cell polarization during neuronal differentiation. However, their roles in neuronal maintenance after CNS development remain unclear. Here we performed conditional deletion of aPKCλ, a major aPKC isoform in the brain, in differentiated neurons of mice by camk2a-cre or synapsinI-cre mediated gene targeting. We found significant reduction of aPKCλ and total aPKCs in the adult mouse brains. The aPKCλ deletion also reduced PAR-6β, possibly by its destabilization, whereas expression of other related proteins such as PAR-3 and Lgl-1 was unaffected. Biochemical analyses suggested that a significant fraction of aPKCλ formed a protein complex with PAR-6β and Lgl-1 in the brain lysates, which was disrupted by the aPKCλ deletion. Notably, the aPKCλ deletion mice did not show apparent cell loss/degeneration in the brain. In addition, neuronal orientation/distribution seemed to be unaffected. Thus, despite the polarity complex disruption, neuronal deletion of aPKCλ does not induce obvious cell loss or disorientation in mouse brains after cell differentiation.

  10. Neuron-astrocyte interactions, pyruvate carboxylation and the pentose phosphate pathway in the neonatal rat brain.

    Morken, Tora Sund; Brekke, Eva; Håberg, Asta; Widerøe, Marius; Brubakk, Ann-Mari; Sonnewald, Ursula

    2014-01-01

    Glucose and acetate metabolism and the synthesis of amino acid neurotransmitters, anaplerosis, glutamate-glutamine cycling and the pentose phosphate pathway (PPP) have been extensively investigated in the adult, but not the neonatal rat brain. To do this, 7 day postnatal (P7) rats were injected with [1-(13)C]glucose and [1,2-(13)C]acetate and sacrificed 5, 10, 15, 30 and 45 min later. Adult rats were injected and sacrificed after 15 min. To analyse pyruvate carboxylation and PPP activity during development, P7 rats received [1,2-(13)C]glucose and were sacrificed 30 min later. Brain extracts were analysed using (1)H- and (13)C-NMR spectroscopy. Numerous differences in metabolism were found between the neonatal and adult brain. The neonatal brain contained lower levels of glutamate, aspartate and N-acetylaspartate but similar levels of GABA and glutamine per mg tissue. Metabolism of [1-(13)C]glucose at the acetyl CoA stage was reduced much more than that of [1,2-(13)C]acetate. The transfer of glutamate from neurons to astrocytes was much lower while transfer of glutamine from astrocytes to glutamatergic neurons was relatively higher. However, transport of glutamine from astrocytes to GABAergic neurons was lower. Using [1,2-(13)C]glucose it could be shown that despite much lower pyruvate carboxylation, relatively more pyruvate from glycolysis was directed towards anaplerosis than pyruvate dehydrogenation in astrocytes. Moreover, the ratio of PPP/glucose-metabolism was higher. These findings indicate that only the part of the glutamate-glutamine cycle that transfers glutamine from astrocytes to neurons is operating in the neonatal brain and that compared to adults, relatively more glucose is prioritised to PPP and pyruvate carboxylation. Our results may have implications for the capacity to protect the neonatal brain against excitotoxicity and oxidative stress.

  11. Multiregional Age-Associated Reduction of Brain Neuronal Reserve Without Association With Neurofibrillary Degeneration or β-Amyloidosis.

    Wegiel, Jerzy; Flory, Michael; Kuchna, Izabela; Nowicki, Krzysztof; Yong Ma, Shuang; Wegiel, Jarek; Badmaev, Eulalia; Silverman, Wayne P; de Leon, Mony; Reisberg, Barry; Wisniewski, Thomas

    2017-06-01

    Increase in human life expectancy has resulted in the rapid growth of the elderly population with minimal or no intellectual deterioration. The aim of this stereological study of 10 structures and 5 subdivisions with and without neurofibrillary degeneration in the brains of 28 individuals 25-102-years-old was to establish the pattern of age-associated neurodegeneration and neuronal loss in the brains of nondemented adults and elderly. The study revealed the absence of significant neuronal loss in 7 regions and topographically selective reduction of neuronal reserve over 77 years in 8 brain structures including the entorhinal cortex (EC) (-33.3%), the second layer of the EC (-54%), cornu Ammonis sector 1 (CA1) (-28.5%), amygdala, (-45.8%), thalamus (-40.5%), caudate nucleus (-35%), Purkinje cells (-48.3%), and neurons in the dentate nucleus (40.1%). A similar rate of neuronal loss in adults and elderly, without signs of accelerating neuronal loss in agers or super-agers, appears to indicate age-associated brain remodeling with significant reduction of neuronal reserve in 8 brain regions. Multivariate analysis demonstrates the absence of a significant association between neuronal loss and the severity of neurofibrillary degeneration and β-amyloidosis, and a similar rate of age-associated neuronal loss in structures with and without neurofibrillary degeneration. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

  12. Measurements using 7.0 T post-mortem magnetic resonance imaging of the scalar dimensions of the fetal brain between 12 and 20 weeks gestational age.

    Lin, Xiangtao; Zhang, Zhonghe; Teng, Gaojun; Meng, Haiwei; Yu, Taifei; Hou, Zhongyu; Fang, Fang; Zang, Fengchao; Liu, Shuwei

    2011-12-01

    In this study, scalar values for the fetal brain from 12 to 20 weeks gestational age were obtained. Fifty-two fetal specimens of 12-20 weeks gestational age with an anatomically normal and developmentally appropriate central nervous system (CNS) were scanned using a 7.0 T magnetic resonance imaging (MRI) scanner. The linear biometric measurements of the brain were then determined. All the measurements (except for the interhemispheric distance) were found to increase linearly with gestational age, although each increased at a different growth rates. The 95% confidence interval for each value was obtained. These data may be considered to be a valuable reference for the assessment of normal fetal brain development in clinical settings and as a supplement to post-mortem MRI or anatomical investigations. Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

  13. Are dragon-king neuronal avalanches dungeons for self-organized brain activity?

    de Arcangelis, L.

    2012-05-01

    Recent experiments have detected a novel form of spontaneous neuronal activity both in vitro and in vivo: neuronal avalanches. The statistical properties of this activity are typical of critical phenomena, with power laws characterizing the distributions of avalanche size and duration. A critical behaviour for the spontaneous brain activity has important consequences on stimulated activity and learning. Very interestingly, these statistical properties can be altered in significant ways in epilepsy and by pharmacological manipulations. In particular, there can be an increase in the number of large events anticipated by the power law, referred to herein as dragon-king avalanches. This behaviour, as verified by numerical models, can originate from a number of different mechanisms. For instance, it is observed experimentally that the emergence of a critical behaviour depends on the subtle balance between excitatory and inhibitory mechanisms acting in the system. Perturbing this balance, by increasing either synaptic excitation or the incidence of depolarized neuronal up-states causes frequent dragon-king avalanches. Conversely, an unbalanced GABAergic inhibition or long periods of low activity in the network give rise to sub-critical behaviour. Moreover, the existence of power laws, common to other stochastic processes, like earthquakes or solar flares, suggests that correlations are relevant in these phenomena. The dragon-king avalanches may then also be the expression of pathological correlations leading to frequent avalanches encompassing all neurons. We will review the statistics of neuronal avalanches in experimental systems. We then present numerical simulations of a neuronal network model introducing within the self-organized criticality framework ingredients from the physiology of real neurons, as the refractory period, synaptic plasticity and inhibitory synapses. The avalanche critical behaviour and the role of dragon-king avalanches will be discussed in

  14. Regulation of neurogenesis: factors affecting of new neurons formation in adult mammals brain

    Michalina Respondek

    2015-12-01

    Full Text Available Neurogenesis is a complex and multi-step process of generating completely functional neurons. This process in adult brain is based on pluripotentional neuronal stem cells (NSC, which are able to proliferation and differentiation into mature neurons or glial cells. NSC are located in subgranular zone inside hippocampus and in subventricular zone. The new neurons formation depends on many endo- and exogenous factors which modulate each step of neurogenesis. This article describes the most important regulators of adult neurogenesis, mainly: neurotrophins, growth factors, hormones, neurotransmitters and microenvironment of NSC. Some drugs, especially antipsychotics, antidepressants and normothymics may affect the neurogenic properties of adult brain. Moreover pathological processes such as neuroinflammation, stroke or epilepsy are able to induce proliferation of NSC. The proneurogenic effects of psychotropic drugs and pathological processes are associated with their ability to increase some hormones and neurotrophins level, as well as with rising the expression of antiapoptotic Bcl-2 protein and metalloproteinase MMP-2. Additionaly, some drugs, for example haloperidol, are able to block prolactin and dopaminergic neuroblasts receptors. Down-regulation of adult neurogenesis is associated with alcohol abuse and high stress level. Negative effect of many drugs, such as cytostatics, COX-2 inhibitors and opioides was also observed. The proneurogenic effect of described factors suggest their broad therapeutic potential and gives a new perspective on an effective and modern treatment of many neuropsychiatric disorders. This effect can also help to clarify the pathogenesis of disorders associated with proliferation and degeneration of adult brain cells.

  15. An Evolutionarily Conserved Role of Presenilin in Neuronal Protection in the Aging Drosophila Brain.

    Kang, Jongkyun; Shin, Sarah; Perrimon, Norbert; Shen, Jie

    2017-07-01

    Mutations in the Presenilin genes are the major genetic cause of Alzheimer's disease. Presenilin and Nicastrin are essential components of γ-secretase, a multi-subunit protease that cleaves Type I transmembrane proteins. Genetic studies in mice previously demonstrated that conditional inactivation of Presenilin or Nicastrin in excitatory neurons of the postnatal forebrain results in memory deficits, synaptic impairment, and age-dependent neurodegeneration. The roles of Drosophila Presenilin ( Psn ) and Nicastrin ( Nct ) in the adult fly brain, however, are unknown. To knockdown (KD) Psn or Nct selectively in neurons of the adult brain, we generated multiple shRNA lines. Using a ubiquitous driver, these shRNA lines resulted in 80-90% reduction of mRNA and pupal lethality-a phenotype that is shared with Psn and Nct mutants carrying nonsense mutations. Furthermore, expression of these shRNAs in the wing disc caused notching wing phenotypes, which are also shared with Psn and Nct mutants. Similar to Nct , neuron-specific Psn KD using two independent shRNA lines led to early mortality and rough eye phenotypes, which were rescued by a fly Psn transgene. Interestingly, conditional KD (cKD) of Psn or Nct in adult neurons using the elav-Gal4 and tubulin-Gal80 ts system caused shortened lifespan, climbing defects, increases in apoptosis, and age-dependent neurodegeneration. Together, these findings demonstrate that, similar to their mammalian counterparts, Drosophila Psn and Nct are required for neuronal survival during aging and normal lifespan, highlighting an evolutionarily conserved role of Presenilin in neuronal protection in the aging brain. Copyright © 2017 by the Genetics Society of America.

  16. Extrasynaptic neurotransmission in the modulation of brain function. Focus on the striatal neuronal-glial networks

    Kjell eFuxe

    2012-06-01

    Full Text Available Extrasynaptic neurotransmission is an important short distance form of volume transmission (VT and describes the extracellular diffusion of transmitters and modulators after synaptic spillover or extrasynaptic release in the local circuit regions binding to and activating mainly extrasynaptic neuronal and glial receptors in the neuroglial networks of the brain. Receptor-receptor interactions in G protein-coupled receptor (GPCR heteromers play a major role, on dendritic spines and nerve terminals including glutamate synapses, in the integrative processes of the extrasynaptic signaling. Heteromeric complexes between GPCR and ion-channel receptors play a special role in the integration of the synaptic and extrasynaptic signals. Changes in extracellular concentrations of the classical synaptic neurotransmitters glutamate and GABA found with microdialysis is likely an expression of the activity of the neuron-astrocyte unit of the brain and can be used as an index of VT-mediated actions of these two neurotransmitters in the brain. Thus, the activity of neurons may be functionally linked to the activity of astrocytes, which may release glutamate and GABA to the extracellular space where extrasynaptic glutamate and GABA receptors do exist. Wiring transmission (WT and VT are fundamental properties of all neurons of the CNS but the balance between WT and VT varies from one nerve cell population to the other. The focus is on the striatal cellular networks, and the WT and VT and their integration via receptor heteromers are described in the GABA projection neurons, the glutamate, dopamine, 5-hydroxytryptamine (5-HT and histamine striatal afferents, the cholinergic interneurons and different types of GABA interneurons. In addition, the role in these networks of VT signaling of the energy-dependent modulator adenosine and of endocannabinoids mainly formed in the striatal projection neurons will be underlined to understand the communication in the striatal

  17. Impact of prenatal antimicrobial treatment on fetal brain damage due to autogenous fecal peritonitis in Wistar rats: A Histomorphometric Study

    Neylane Gadelha

    2017-10-01

    Full Text Available Purpose: To investigate brain neuronal density in newborn rats whose mothers were subjected to fecal peritonitis and compare findings between rats born to mothers treated and not treated with antimicrobials. Methods: Peritonitis was induced with a 10% fecal suspension (4mL/kg in 2 pregnant rats. Of these, 1 received antimicrobial treatment 24 hours after peritonitis induction: moxifloxacin and dexamethasone plus 2 mL of the inner bark of the Schinus terebinthifolius raddi extract. One pregnant rat underwent no intervention and served as a control. Results: The newborn brains of rats born to mothers with fecal peritonitis were significantly smaller and of less firm consistency. Brain neuronal density was lower in the untreated group than in the control and treated groups (P<0.01. Conclusions: Untreated peritonitis caused brain damage in the offspring, which was averted by effective early antimicrobial treatment. This approach may provide an early avenue for translation of such therapy in humans. Keywords: peritonitis, brain injuries, rats

  18. Conversion of brain cytosol profile from fetal to adult type during the perinatal period: Taurine-NAA exchange

    NAKADA, Tsutomu

    2010-01-01

    Mammals face drastic environmental changes at birth. Appropriate adjustments of various systems must take place rapidly to accommodate this once in a life time event. The brain undergoes significant adjustments as well, the most obvious of which is in its need to meet the drastic increase in energy consumption at the neuronal cell membrane due to the explosive increase in neural activities after birth. Actual changes were found to be taken place in two systems, namely, acid base balance contr...

  19. Cerebellins are differentially expressed in selective subsets of neurons throughout the brain.

    Seigneur, Erica; Südhof, Thomas C

    2017-10-15

    Cerebellins are secreted hexameric proteins that form tripartite complexes with the presynaptic cell-adhesion molecules neurexins or 'deleted-in-colorectal-cancer', and the postsynaptic glutamate-receptor-related proteins GluD1 and GluD2. These tripartite complexes are thought to regulate synapses. However, cerebellins are expressed in multiple isoforms whose relative distributions and overall functions are not understood. Three of the four cerebellins, Cbln1, Cbln2, and Cbln4, autonomously assemble into homohexamers, whereas the Cbln3 requires Cbln1 for assembly and secretion. Here, we show that Cbln1, Cbln2, and Cbln4 are abundantly expressed in nearly all brain regions, but exhibit strikingly different expression patterns and developmental dynamics. Using newly generated knockin reporter mice for Cbln2 and Cbln4, we find that Cbln2 and Cbln4 are not universally expressed in all neurons, but only in specific subsets of neurons. For example, Cbln2 and Cbln4 are broadly expressed in largely non-overlapping subpopulations of excitatory cortical neurons, but only sparse expression was observed in excitatory hippocampal neurons of the CA1- or CA3-region. Similarly, Cbln2 and Cbln4 are selectively expressed, respectively, in inhibitory interneurons and excitatory mitral projection neurons of the main olfactory bulb; here, these two classes of neurons form dendrodendritic reciprocal synapses with each other. A few brain regions, such as the nucleus of the lateral olfactory tract, exhibit astoundingly high Cbln2 expression levels. Viewed together, our data show that cerebellins are abundantly expressed in relatively small subsets of neurons, suggesting specific roles restricted to subsets of synapses. © 2017 Wiley Periodicals, Inc.

  20. Molecular Mechanisms Responsible for Neuron-Derived Conditioned Medium (NCM-Mediated Protection of Ischemic Brain.

    Chi-Hsin Lin

    Full Text Available The protective value of neuron-derived conditioned medium (NCM in cerebral ischemia and the underlying mechanism(s responsible for NCM-mediated brain protection against cerebral ischemia were investigated in the study. NCM was first collected from the neuronal culture growing under the in vitro ischemic condition (glucose-, oxygen- and serum-deprivation or GOSD for 2, 4 or 6 h. Through the focal cerebral ischemia (bilateral CCAO/unilateral MCAO animal model, we discovered that ischemia/reperfusion (I/R-induced brain infarction was significantly reduced by NCM, given directly into the cistern magna at the end of 90 min of CCAO/MCAO. Immunoblocking and chemical blocking strategies were applied in the in vitro ischemic studies to show that NCM supplement could protect microglia, astrocytes and neurons from GOSD-induced cell death, in a growth factor (TGFβ1, NT-3 and GDNF and p-ERK dependent manner. Brain injection with TGFβ1, NT3, GDNF and ERK agonist (DADS alone or in combination, therefore also significantly decreased the infarct volume of ischemic brain. Moreover, NCM could inhibit ROS but stimulate IL-1β release from GOSD-treated microglia and limit the infiltration of IL-β-positive microglia into the core area of ischemic brain, revealing the anti-oxidant and anti-inflammatory activities of NCM. In overall, NCM-mediated brain protection against cerebral ischemia has been demonstrated for the first time in S.D. rats, due to its anti-apoptotic, anti-oxidant and potentially anti-glutamate activities (NCM-induced IL-1β can inhibit the glutamate-mediated neurotoxicity and restriction upon the infiltration of inflammatory microglia into the core area of ischemic brain. The therapeutic potentials of NCM, TGFβ1, GDNF, NT-3 and DADS in the control of cerebral ischemia in human therefore have been suggested and require further investigation.

  1. N-3 fatty acids, neuronal activity and energy metabolism in the brain

    Harbeby Emilie

    2012-07-01

    Full Text Available The content of docosahexaenoic acid (DHA in brain membranes is of crucial importance for the optimum development of brain functions. A lack of DHA accretion in the brain is accompanied by deficits in learning behavior linked to impairments in neurotransmission processes, which might result from alteration of brain fuel supply and hence energy metabolism. Experimental data we published support the hypothesis that n-3 fatty acids may modulate brain glucose utilization and metabolism. Indeed rats made deficient in DHA by severe depletion of total n-3 fatty acid intake have 1 a lower brain glucose utilization, 2 a decrease of the glucose transporter protein content GLUT1 both in endothelial cells and in astrocytes, 3 a repression of GLUT1 gene expression in basal state as well as upon neuronal activation. This could be due to the specific action of DHA on the regulation of GLUT1 expression since rat brain endothelial cells cultured with physiological doses of DHA had an increased GLUT1 protein content and glucose transport when compared to non-supplemented cells. These experimental data highlight the impact of n-3 fatty acids on the use of brain glucose, thereby constituting a key factor in the control of synaptic activity. This emerging role suggests that dietary intake of n-3 fatty acids can help to reduce the cognitive deficits in the elderly and possibly symptomatic cerebral metabolic alterations in Alzheimer disease by promoting brain glucose metabolism.

  2. Brain-derived neurotrophic factor mediates estradiol-induced dendritic spine formation in hippocampal neurons

    Murphy, Diane D.; Cole, Nelson B.; Segal, Menahem

    1998-01-01

    Dendritic spines are of major importance in information processing and memory formation in central neurons. Estradiol has been shown to induce an increase of dendritic spine density on hippocampal neurons in vivo and in vitro. The neurotrophin brain-derived neurotrophic factor (BDNF) recently has been implicated in neuronal maturation, plasticity, and regulation of GABAergic interneurons. We now demonstrate that estradiol down-regulates BDNF in cultured hippocampal neurons to 40% of control values within 24 hr of exposure. This, in turn, decreases inhibition and increases excitatory tone in pyramidal neurons, leading to a 2-fold increase in dendritic spine density. Exogenous BDNF blocks the effects of estradiol on spine formation, and BDNF depletion with a selective antisense oligonucleotide mimics the effects of estradiol. Addition of BDNF antibodies also increases spine density, and diazepam, which facilitates GABAergic neurotransmission, blocks estradiol-induced spine formation. These observations demonstrate a functional link between estradiol, BDNF as a potent regulator of GABAergic interneurons, and activity-dependent formation of dendritic spines in hippocampal neurons. PMID:9736750

  3. Central Artery Stiffness, Baroreflex Sensitivity, and Brain White Matter Neuronal Fiber Integrity in Older Adults

    Tarumi, Takashi; de Jong, Daan L.K.; Zhu, David C.; Tseng, Benjamin Y.; Liu, Jie; Hill, Candace; Riley, Jonathan; Womack, Kyle B.; Kerwin, Diana R.; Lu, Hanzhang; Cullum, C. Munro; Zhang, Rong

    2015-01-01

    Cerebral hypoperfusion elevates the risk of brain white matter (WM) lesions and cognitive impairment. Central artery stiffness impairs baroreflex, which controls systemic arterial perfusion, and may deteriorate neuronal fiber integrity of brain WM. The purpose of this study was to examine the associations among brain WM neuronal fiber integrity, baroreflex sensitivity (BRS), and central artery stiffness in older adults. Fifty-four adults (65±6 years) with normal cognitive function or mild cognitive impairment (MCI) were tested. The neuronal fiber integrity of brain WM was assessed from diffusion metrics acquired by diffusion tensor imaging. BRS was measured in response to acute changes in blood pressure induced by bolus injections of vasoactive drugs. Central artery stiffness was measured by carotid-femoral pulse wave velocity (cfPWV). The WM diffusion metrics including fractional anisotropy (FA) and radial (RD) and axial (AD) diffusivities, BRS, and cfPWV were not different between the control and MCI groups. Thus, the data from both groups were combined for subsequent analyses. Across WM, fiber tracts with decreased FA and increased RD were associated with lower BRS and higher cfPWV, with many of the areas presenting spatial overlap. In particular, the BRS assessed during hypotension was strongly correlated with FA and RD when compared with hypertension. Executive function performance was associated with FA and RD in the areas that correlated with cfPWV and BRS. These findings suggest that baroreflex-mediated control of systemic arterial perfusion, especially during hypotension, may play a crucial role in maintaining neuronal fiber integrity of brain WM in older adults. PMID:25623500

  4. Role of phosphatidylinositol 3-kinase in angiotensin II regulation of norepinephrine neuromodulation in brain neurons of the spontaneously hypertensive rat.

    Yang, H; Raizada, M K

    1999-04-01

    Chronic stimulation of norepinephrine (NE) neuromodulation by angiotensin II (Ang II) involves activation of the Ras-Raf-MAP kinase signal transduction pathway in Wistar Kyoto (WKY) rat brain neurons. This pathway is only partially responsible for this heightened action of Ang II in the spontaneously hypertensive rat (SHR) brain neurons. In this study, we demonstrate that the MAP kinase-independent signaling pathway in the SHR neuron involves activation of PI3-kinase and protein kinase B (PKB/Akt). Ang II stimulated PI3-kinase activity in both WKY and SHR brain neurons and was accompanied by its translocation from the cytoplasmic to the nuclear compartment. Although the magnitude of stimulation by Ang II was comparable, the stimulation was more persistent in the SHR neuron compared with the WKY rat neuron. Inhibition of PI3-kinase had no significant effect in the WKY rat neuron. However, it caused a 40-50% attenuation of the Ang II-induced increase in norepinephrine transporter (NET) and tyrosine hydroxylase (TH) mRNAs and [3H]-NE uptake in the SHR neuron. In contrast, inhibition of MAP kinase completely attenuated Ang II stimulation of NET and TH mRNA levels in the WKY rat neuron, whereas it caused only a 45% decrease in the SHR neuron. However, an additive attenuation was observed when both kinases of the SHR neurons were inhibited. Ang II also stimulated PKB/Akt activity in both WKY and SHR neurons. This stimulation was 30% higher and lasted longer in the SHR neuron compared with the WKY rat neuron. In conclusion, these observations demonstrate an exclusive involvement of PI3-kinase-PKB-dependent signaling pathway in a heightened NE neuromodulatory action of Ang II in the SHR neuron. Thus, this study offers an excellent potential for the development of new therapies for the treatment of centrally mediated hypertension.

  5. Neuronal replacement therapy: previous achievements and challenges ahead

    Grade, Sofia; Götz, Magdalena

    2017-10-01

    Lifelong neurogenesis and incorporation of newborn neurons into mature neuronal circuits operates in specialized niches of the mammalian brain and serves as role model for neuronal replacement strategies. However, to which extent can the remaining brain parenchyma, which never incorporates new neurons during the adulthood, be as plastic and readily accommodate neurons in networks that suffered neuronal loss due to injury or neurological disease? Which microenvironment is permissive for neuronal replacement and synaptic integration and which cells perform best? Can lost function be restored and how adequate is the participation in the pre-existing circuitry? Could aberrant connections cause malfunction especially in networks dominated by excitatory neurons, such as the cerebral cortex? These questions show how important connectivity and circuitry aspects are for regenerative medicine, which is the focus of this review. We will discuss the impressive advances in neuronal replacement strategies and success from exogenous as well as endogenous cell sources. Both have seen key novel technologies, like the groundbreaking discovery of induced pluripotent stem cells and direct neuronal reprogramming, offering alternatives to the transplantation of fetal neurons, and both herald great expectations. For these to become reality, neuronal circuitry analysis is key now. As our understanding of neuronal circuits increases, neuronal replacement therapy should fulfill those prerequisites in network structure and function, in brain-wide input and output. Now is the time to incorporate neural circuitry research into regenerative medicine if we ever want to truly repair brain injury.

  6. The assessment of fetal brain function in fetuses with ventrikulomegaly: the role of the KANET test.

    Talic, Amira; Kurjak, Asim; Stanojevic, Milan; Honemeyer, Ulrich; Badreldeen, Ahmed; DiRenzo, Gian Carlo

    2012-08-01

    To assess differences in fetal behavior in both normal fetuses and fetuses with cerebral ventriculomegaly (VM). In a period of eighteen months, in a longitudinal prospective cohort study, Kurjak Antenatal NeuorogicalTest (KANET) was applied to assess fetal behavior in both normal pregnancies and pregnancies with cerebral VM using four-dimensional ultrasound (4D US). According to the degree of enlargement of the ventricles, VM was divided into three groups: mild, moderate and severe. Moreover fetuses with isolated VM were separated from those with additional abnormalities. According to the KANET, fetuses with scores ≥ 14 were considered normal, those with scores 6-13 borderline and abnormal if the score was ≤ 5. Differences between two groups were examined by Fisher's exact test. Differences within the subgroups were examined by Kruskal-Wallis test and contingency table test. KANET scores in normal pregnancies and pregnancies with VM showed statistically significant differences. Most of the abnormal KANET scores as well as most of the borderline-scores were found among the fetuses with severe VM associated with additional abnormalities. There were no statistically significant differences between the control group and the groups with isolated and mild and /or moderate VM. Evaluation of the fetal behavior in fetuses with cerebral VM using KANET test has the potential to detect fetuses with abnormal behavior, and to add the dimension of CNS function to the morphological criteria of VM. Long-term postnatal neurodevelopmental follow-up should confirm the data from prenatal investigation of fetal behavior.

  7. Dogs Have the Most Neurons, Though Not the Largest Brain: Trade-Off between Body Mass and Number of Neurons in the Cerebral Cortex of Large Carnivoran Species

    Débora Jardim-Messeder

    2017-12-01

    Full Text Available Carnivorans are a diverse group of mammals that includes carnivorous, omnivorous and herbivorous, domesticated and wild species, with a large range of brain sizes. Carnivory is one of several factors expected to be cognitively demanding for carnivorans due to a requirement to outsmart larger prey. On the other hand, large carnivoran species have high hunting costs and unreliable feeding patterns, which, given the high metabolic cost of brain neurons, might put them at risk of metabolic constraints regarding how many brain neurons they can afford, especially in the cerebral cortex. For a given cortical size, do carnivoran species have more cortical neurons than the herbivorous species they prey upon? We find they do not; carnivorans (cat, mongoose, dog, hyena, lion share with non-primates, including artiodactyls (the typical prey of large carnivorans, roughly the same relationship between cortical mass and number of neurons, which suggests that carnivorans are subject to the same evolutionary scaling rules as other non-primate clades. However, there are a few important exceptions. Carnivorans stand out in that the usual relationship between larger body, larger cortical mass and larger number of cortical neurons only applies to small and medium-sized species, and not beyond dogs: we find that the golden retriever dog has more cortical neurons than the striped hyena, African lion and even brown bear, even though the latter species have up to three times larger cortices than dogs. Remarkably, the brown bear cerebral cortex, the largest examined, only has as many neurons as the ten times smaller cat cerebral cortex, although it does have the expected ten times as many non-neuronal cells in the cerebral cortex compared to the cat. We also find that raccoons have dog-like numbers of neurons in their cat-sized brain, which makes them comparable to primates in neuronal density. Comparison of domestic and wild species suggests that the neuronal

  8. Neuraminidases 3 and 4 regulate neuronal function by catabolizing brain gangliosides.

    Pan, Xuefang; De Aragão, Camila De Britto Pará; Velasco-Martin, Juan P; Priestman, David A; Wu, Harry Y; Takahashi, Kohta; Yamaguchi, Kazunori; Sturiale, Luisella; Garozzo, Domenico; Platt, Frances M; Lamarche-Vane, Nathalie; Morales, Carlos R; Miyagi, Taeko; Pshezhetsky, Alexey V

    2017-08-01

    Gangliosides (sialylated glycolipids) play an essential role in the CNS by regulating recognition and signaling in neurons. Metabolic blocks in processing and catabolism of gangliosides result in the development of severe neurologic disorders, including gangliosidoses manifesting with neurodegeneration and neuroinflammation. We demonstrate that 2 mammalian enzymes, neuraminidases 3 and 4, play important roles in catabolic processing of brain gangliosides by cleaving terminal sialic acid residues in their glycan chains. In neuraminidase 3 and 4 double-knockout mice, G M3 ganglioside is stored in microglia, vascular pericytes, and neurons, causing micro- and astrogliosis, neuroinflammation, accumulation of lipofuscin bodies, and memory loss, whereas their cortical and hippocampal neurons have lower rate of neuritogenesis in vitro Double-knockout mice also have reduced levels of G M1 ganglioside and myelin in neuronal axons. Furthermore, neuraminidase 3 deficiency drastically increased storage of G M2 in the brain tissues of an asymptomatic mouse model of Tay-Sachs disease, a severe human gangliosidosis, indicating that this enzyme is responsible for the metabolic bypass of β-hexosaminidase A deficiency. Together, our results provide the first in vivo evidence that neuraminidases 3 and 4 have important roles in CNS function by catabolizing gangliosides and preventing their storage in lipofuscin bodies.-Pan, X., De Britto Pará De Aragão, C., Velasco-Martin, J. P., Priestman, D. A., Wu, H. Y., Takahashi, K., Yamaguchi, K., Sturiale, L., Garozzo, D., Platt, F. M., Lamarche-Vane, N., Morales, C. R., Miyagi, T., Pshezhetsky, A. V. Neuraminidases 3 and 4 regulate neuronal function by catabolizing brain gangliosides. © FASEB.

  9. A signaling network for patterning of neuronal connectivity in the Drosophila brain.

    Mohammed Srahna

    2006-10-01

    Full Text Available The precise number and pattern of axonal connections generated during brain development regulates animal behavior. Therefore, understanding how developmental signals interact to regulate axonal extension and retraction to achieve precise neuronal connectivity is a fundamental goal of neurobiology. We investigated this question in the developing adult brain of Drosophila and find that it is regulated by crosstalk between Wnt, fibroblast growth factor (FGF receptor, and Jun N-terminal kinase (JNK signaling, but independent of neuronal activity. The Rac1 GTPase integrates a Wnt-Frizzled-Disheveled axon-stabilizing signal and a Branchless (FGF-Breathless (FGF receptor axon-retracting signal to modulate JNK activity. JNK activity is necessary and sufficient for axon extension, whereas the antagonistic Wnt and FGF signals act to balance the extension and retraction required for the generation of the precise wiring pattern.

  10. The perinatal effects of maternal caffeine intake on fetal and neonatal brain levels of testosterone, estradiol, and dihydrotestosterone in rats.

    Karaismailoglu, S; Tuncer, M; Bayrak, S; Erdogan, G; Ergun, E L; Erdem, A

    2017-08-01

    Testosterone, estradiol, and dihydrotestosterone are the main sex steroid hormones responsible for the organization and sexual differentiation of brain structures during early development. The hypothalamo-pituitary-adrenocortical axis, adrenal cells, and gonads play a key role in the production of sex steroids and express adenosine receptors. Caffeine is a non-selective adenosine antagonist; therefore, it can modulate metabolic pathways in these tissues. Besides, the proportion of pregnant women that consume caffeine is ∼60%. That is why the relationship between maternal caffeine consumption and fetal development is important. Therefore, we aimed to investigate this modulatory effect of maternal caffeine consumption on sex steroids in the fetal and neonatal brain tissues. Pregnant rats were treated with a low (0.3 g/L) or high (0.8 g/L) dose of caffeine in their drinking water during pregnancy and lactation. The testosterone, estradiol, and dihydrotestosterone levels in the frontal cortex and hypothalamus were measured using radioimmunoassay at embryonic day 19 (E19), birth (PN0), and postnatal day 4 (PN4). The administration of low-dose caffeine increased the body weight in PN4 male and female rats and anogenital index in PN4 males. The administration of high-dose caffeine decreased the adrenal weight in E19 male rats and increased testosterone levels in the frontal cortex of E19 female rats and the hypothalamus of PN0 male rats. Maternal caffeine intake during pregnancy affects sex steroid levels in the frontal cortex and hypothalamus of the offspring. This concentration changes of the sex steroids in the brain may influence behavioral and neuroendocrine functions at some point in adult life.

  11. Cerebellar cytokine expression in a rat model for fetal asphyctic preconditioning and perinatal asphyxia

    Vlassaks, Evi; Brudek, Tomasz; Pakkenberg, Bente

    2014-01-01

    the effects of perinatal asphyxia and fetal asphyctic preconditioning on the inflammatory cytokine response in the cerebellum. Fetal asphyxia was induced at embryonic day 17 by clamping the uterine vasculature for 30 min. At term birth, global perinatal asphyxia was induced by placing the uterine horns...... was decreased 96 h postfetal asphyxia. When applied as preconditioning stimulus, fetal asphyxia attenuates the cerebellar cytokine response. These results indicate that sublethal fetal asphyxia may protect the cerebellum from perinatal asphyxia-induced damage via inhibition of inflammation.......Asphyctic brain injury is a major cause of neuronal inflammation in the perinatal period. Fetal asphyctic preconditioning has been shown to modulate the cerebral inflammatory cytokine response, hereby protecting the brain against asphyctic injury at birth. This study was designated to examine...

  12. Brain region specific mitophagy capacity could contribute to selective neuronal vulnerability in Parkinson's disease

    Zabel Claus

    2011-09-01

    Full Text Available Abstract Parkinson's disease (PD is histologically well defined by its characteristic degeneration of dopaminergic neurons in the substantia nigra pars compacta. Remarkably, divergent PD-related mutations can generate comparable brain region specific pathologies. This indicates that some intrinsic region-specificity respecting differential neuron vulnerability exists, which codetermines the disease progression. To gain insight into the pathomechanism of PD, we investigated protein expression and protein oxidation patterns of three different brain regions in a PD mouse model, the PINK1 knockout mice (PINK1-KO, in comparison to wild type control mice. The dysfunction of PINK1 presumably affects mitochondrial turnover by disturbing mitochondrial autophagic pathways. The three brain regions investigated are the midbrain, which is the location of substantia nigra; striatum, the major efferent region of substantia nigra; and cerebral cortex, which is more distal to PD pathology. In all three regions, mitochondrial proteins responsible for energy metabolism and membrane potential were significantly altered in the PINK1-KO mice, but with very different region specific accents in terms of up/down-regulations. This suggests that disturbed mitophagy presumably induced by PINK1 knockout has heterogeneous impacts on different brain regions. Specifically, the midbrain tissue seems to be most severely hit by defective mitochondrial turnover, whereas cortex and striatum could compensate for mitophagy nonfunction by feedback stimulation of other catabolic programs. In addition, cerebral cortex tissues showed the mildest level of protein oxidation in both PINK1-KO and wild type mice, indicating either a better oxidative protection or less reactive oxygen species (ROS pressure in this brain region. Ultra-structural histological examination in normal mouse brain revealed higher incidences of mitophagy vacuoles in cerebral cortex than in striatum and substantia

  13. Accumulation of neuronal DNA damage as an early covariate of determinant of death after whole-brain irradiaton

    Wheeler, K.T.; Weinstein, R.E.

    1979-01-01

    The state of the DNA from cerebellar neurons of male Sprague-Dawley rats after whole-brain irradiation with 2000 rad of x rays was determined at various times by obtaining DNA sedimentation profiles using alkaline sucrose gradients in slow reorienting zonal rotors. It took more than 4 weeks after irradiation for the neuronal DNA distributions to return to those obtained from the unirradiated controls. At 7 weeks, the DNA from irradiated neurons sedimented more rapidly than that from unirradiated neurons. Accumulation of the neuronal DNA damage (degradation.) which led to slower sedimenting DNA species began by Week 10 and continued until the majority of the irradiated rats began to die at Week 20. We propose as a working hypothesis that the accumulation of neuronal DNA damage initially observed 10 weeks after 2000 rad of whole-brain irradiation may reflect or cause changes in the central nervous system that later result in the death of the animal

  14. Mapping directionality specific volume changes using tensor based morphometry: an application to the study of gyrogenesis and lateralization of the human fetal brain.

    Rajagopalan, Vidya; Scott, Julia; Habas, Piotr A; Kim, Kio; Rousseau, Francois; Glenn, Orit A; Barkovich, A James; Studholme, Colin

    2012-11-01

    Tensor based morphometry (TBM) is a powerful approach to analyze local structural changes in brain anatomy. However, conventional scalar TBM methods do not completely capture all direction specific volume changes required to model complex changes such as those during brain growth. In this paper, we describe novel TBM descriptors for studying direction-specific changes in a subject population which can be used in conjunction with scalar TBM to analyze local patterns in directionality of volume change during brain development. We also extend the methodology to provide a new approach to mapping directional asymmetry in deformation tensors associated with the emergence of structural asymmetry in the developing brain. We illustrate the use of these methods by studying developmental patterns in the human fetal brain, in vivo. Results show that fetal brain development exhibits a distinct spatial pattern of anisotropic growth. The most significant changes in the directionality of growth occur in the cortical plate at major sulci. Our analysis also detected directional growth asymmetry in the peri-Sylvian region and the medial frontal lobe of the fetal brain. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Olfactory map formation in the Drosophila brain: genetic specificity and neuronal variability.

    Brochtrup, Anna; Hummel, Thomas

    2011-02-01

    The development of the Drosophila olfactory system is a striking example of how genetic programs specify a large number of different neuron types and assemble them into functional circuits. To ensure precise odorant perception, each sensory neuron has to not only select a single olfactory receptor (OR) type out of a large genomic repertoire but also segregate its synaptic connections in the brain according to the OR class identity. Specification and patterning of second-order interneurons in the olfactory brain center occur largely independent of sensory input, followed by a precise point-to-point matching of sensory and relay neurons. Here we describe recent progress in the understanding of how cell-intrinsic differentiation programs and context-dependent cellular interactions generate a stereotyped sensory map in the Drosophila brain. Recent findings revealed an astonishing morphological diversity among members of the same interneuron class, suggesting an unexpected variability in local microcircuits involved in insect sensory processing. Copyright © 2010 Elsevier Ltd. All rights reserved.

  16. From Blood to Brain: Adult-Born Neurons in the Crayfish Brain Are the Progeny of Cells Generated by the Immune System

    Barbara S. Beltz

    2017-12-01

    Full Text Available New neurons continue to be born and integrated into the brains of adult decapod crustaceans. Evidence in crayfish indicates that the 1st-generation neural precursors that generate these adult-born neurons originate in the immune system and travel to the neurogenic niche via the circulatory system. These precursors are attracted to the niche, become integrated amongst niche cells, and undergo mitosis within a few days; both daughters of this division migrate away from the niche toward the brain clusters where they will divide again and differentiate into neurons. In the crustacean brain, the rate of neuronal production is highly sensitive to serotonin (5-hydroxytryptamine, 5-HT levels. These effects are lineage-dependent, as serotonin's influence is limited to late 2nd-generation neural precursors and their progeny. Experiments indicate that serotonin regulates adult neurogenesis in the crustacean brain by multiple mechanisms: via direct effects of serotonin released from brain neurons into the hemolymph or by local release onto target cells, or by indirect influences via a serotonin-mediated release of agents from other regions, such as hormones from the sinus gland and cytokines from hematopoietic tissues. Evidence in crayfish also indicates that serotonin mediates the attraction of neural precursors generated by the immune system to the neurogenic niche. Thus, studies in the crustacean brain have revealed multiple roles for this monoamine in adult neurogenesis, and identified several pathways by which serotonin influences the generation of new neurons.

  17. I-123 iomazenil single photon emission computed tomography for detecting loss of neuronal integrity in patients with traumatic brain injury

    Abiko, Kagari; Ikoma, Katsunori; Shiga, Tohru; Katoh, Chietsugu; Hirata, Kenji; Kuge, Yuji; Kobayashi, Kentaro; Tamaki, Nagara

    2017-01-01

    Background Traumatic brain injury (TBI) causes brain dysfunction in many patients. Using C-11 flumazenil (FMZ) positron emission tomography (PET), we have detected and reported the loss of neuronal integrity, leading to brain dysfunction in TBI patients. Similarly to FMZ PET, I-123 iomazenil (IMZ) single photon emission computed tomography (SPECT) is widely used to determine the distribution of the benzodiazepine receptor (BZR) in the brain cortex. The purpose of this study is to examine whet...

  18. Role of CB1 cannabinoid receptors on GABAergic neurons in brain aging.

    Albayram, Onder; Alferink, Judith; Pitsch, Julika; Piyanova, Anastasia; Neitzert, Kim; Poppensieker, Karola; Mauer, Daniela; Michel, Kerstin; Legler, Anne; Becker, Albert; Monory, Krisztina; Lutz, Beat; Zimmer, Andreas; Bilkei-Gorzo, Andras

    2011-07-05

    Brain aging is associated with cognitive decline that is accompanied by progressive neuroinflammatory changes. The endocannabinoid system (ECS) is involved in the regulation of glial activity and influences the progression of age-related learning and memory deficits. Mice lacking the Cnr1 gene (Cnr1(-/-)), which encodes the cannabinoid receptor 1 (CB1), showed an accelerated age-dependent deficit in spatial learning accompanied by a loss of principal neurons in the hippocampus. The age-dependent decrease in neuronal numbers in Cnr1(-/-) mice was not related to decreased neurogenesis or to epileptic seizures. However, enhanced neuroinflammation characterized by an increased density of astrocytes and activated microglia as well as an enhanced expression of the inflammatory cytokine IL-6 during aging was present in the hippocampus of Cnr1(-/-) mice. The ongoing process of pyramidal cell degeneration and neuroinflammation can exacerbate each other and both contribute to the cognitive deficits. Deletion of CB1 receptors from the forebrain GABAergic, but not from the glutamatergic neurons, led to a similar neuronal loss and increased neuroinflammation in the hippocampus as observed in animals lacking CB1 receptors in all cells. Our results suggest that CB1 receptor activity on hippocampal GABAergic neurons protects against age-dependent cognitive decline by reducing pyramidal cell degeneration and neuroinflammation.

  19. β1 integrin signaling promotes neuronal migration along vascular scaffolds in the post-stroke brain

    Teppei Fujioka

    2017-02-01

    Full Text Available Cerebral ischemic stroke is a main cause of chronic disability. However, there is currently no effective treatment to promote recovery from stroke-induced neurological symptoms. Recent studies suggest that after stroke, immature neurons, referred to as neuroblasts, generated in a neurogenic niche, the ventricular-subventricular zone, migrate toward the injured area, where they differentiate into mature neurons. Interventions that increase the number of neuroblasts distributed at and around the lesion facilitate neuronal repair in rodent models for ischemic stroke, suggesting that promoting neuroblast migration in the post-stroke brain could improve efficient neuronal regeneration. To move toward the lesion, neuroblasts form chain-like aggregates and migrate along blood vessels, which are thought to increase their migration efficiency. However, the molecular mechanisms regulating these migration processes are largely unknown. Here we studied the role of β1-class integrins, transmembrane receptors for extracellular matrix proteins, in these migrating neuroblasts. We found that the neuroblast chain formation and blood vessel-guided migration critically depend on β1 integrin signaling. β1 integrin facilitated the adhesion of neuroblasts to laminin and the efficient translocation of their soma during migration. Moreover, artificial laminin-containing scaffolds promoted neuroblast chain formation and migration toward the injured area. These data suggest that laminin signaling via β1 integrin supports vasculature-guided neuronal migration to efficiently supply neuroblasts to injured areas. This study also highlights the importance of vascular scaffolds for cell migration in development and regeneration.

  20. Increased histone H3 phosphorylation in neurons in specific brain structures after induction of status epilepticus in mice.

    Tetsuji Mori

    Full Text Available Status epilepticus (SE induces pathological and morphological changes in the brain. Recently, it has become clear that excessive neuronal excitation, stress and drug abuse induce chromatin remodeling in neurons, thereby altering gene expression. Chromatin remodeling is a key mechanism of epigenetic gene regulation. Histone H3 phosphorylation is frequently used as a marker of chromatin remodeling and is closely related to the upregulation of mRNA transcription. In the present study, we analyzed H3 phosphorylation levels in vivo using immunohistochemistry in the brains of mice with pilocarpine-induced SE. A substantial increase in H3 phosphorylation was detected in neurons in specific brain structures. Increased H3 phosphorylation was dependent on neuronal excitation. In particular, a robust upregulation of H3 phosphorylation was detected in the caudate putamen, and there was a gradient of phosphorylated H3(+ (PH3(+ neurons along the medio-lateral axis. After unilateral ablation of dopaminergic neurons in the substantia nigra by injection of 6-hydroxydopamine, the distribution of PH3(+ neurons changed in the caudate putamen. Moreover, our histological analysis suggested that, in addition to the well-known MSK1 (mitogen and stress-activated kinase/H3 phosphorylation/c-fos pathway, other signaling pathways were also activated. Together, our findings suggest that a number of genes involved in the pathology of epileptogenesis are upregulated in PH3(+ brain regions, and that H3 phosphorylation is a suitable indicator of strong neuronal excitation.

  1. Neuroserpin and brain-derived neurotrophic factor in neuroendocrine and neuronal plasticity. Functional studies in (transgenic) Xenopus intermediate pituitary cells

    Rotteveel-de Groot, D.M. de

    2007-01-01

    The molecular mechanisms underlying neuronal plasticity, i.e. the capacity of the brain to continuously adapt its structural organization to new situations, remain largely unknown. In this thesis, we explored functional aspects of two proteins that presumably play a role in neuronal plasticity,

  2. Maternal and fetal brain contents of docosahexaenoic acid (DHA) and arachidonic acid (AA) at various essential fatty acid (EFA), DHA and AA dietary intakes during pregnancy in mice

    van Goor, Saskia A; Dijck-Brouwer, D A Janneke; Fokkema, M Rebecca; van der Iest, Theo Hans; Muskiet, Frits A J

    We investigated essential fatty acids (EFA) and long-chain polyunsaturated fatty acids (LCP) in maternal and fetal brain as a function of EFA/LCP availability to the feto-maternal unit in mice. Diets varying in parent EFA, arachidonic acid (AA), and docosahexaenoic acid (DHA) were administered from

  3. Validation of functional fetal autonomic brain age score fABAS in 5 min short recordings

    Hoyer, Dirk; Kowalski, Eva-Maria; Schmidt, Alexander; Witte, Otto W; Schneider, Uwe; Schleußner, Ekkehard; Hatzmann, Wolfgang; Grönemeyer, Dietrich HW; Van Leeuwen, Peter

    2015-01-01

    With the objective of evaluating the functional maturation age and developmental disturbances we have previously introduced the fetal autonomic brain age score (fABAS) using 30 min fetal magnetocardiographic recordings (fMCG, Jena). The score is based on heart rate pattern indices that are related to universal principles of developmental biology. The present work aims at the validation of the fABAS methodology on 5 min recordings from an independent database (fMCG, Bochum).We found high agreement of fABAS obtained from Jena normal fetuses (5 min subsets, n  =  364) and Bochum recordings (n  =  322, normal fetuses). fABAS of 48 recordings from fetuses with intra-uterine growth restriction (IUGR, Bochum) was reduced in most of the cases, a result consistent with IUGR fetuses from Jena previously reported. fABAS calculated from 5 min snapshots only partly covers the accuracy when compared to fABAS from 30 min recordings. More precise diagnosis requires longer recordings.fABAS obtained from fMCG recordings is a strong candidate for standardized assessment of functional maturation age and developmental disturbances. Even 5 min recordings seem to be valuable for screening for maturation problems. (paper)

  4. Non-iterative relative bias correction for 3D reconstruction of in utero fetal brain MR imaging.

    Kim, Kio; Habas, Piotr; Rajagopalan, Vidya; Scott, Julia; Corbett-Detig, James; Rousseau, Francois; Glenn, Orit; Barkovich, James; Studholme, Colin

    2010-01-01

    The slice intersection motion correction (SIMC) method is a powerful tool to compensate for motion that occurs during in utero acquisition of the multislice magnetic resonance (MR) images of the human fetal brain. The SIMC method makes use of the slice intersection intensity profiles of orthogonally planned slice pairs to simultaneously correct for the relative motion occurring between all the acquired slices. This approach is based on the assumption that the bias field is consistent between slices. However, for some clinical studies where there is a strong bias field combined with significant fetal motion relative to the coils, this assumption is broken and the resulting motion estimate and the reconstruction to a 3D volume can both contain errors. In this work, we propose a method to correct for the relative differences in bias field between all slice pairs. For this, we define the energy function as the mean square difference of the intersection profiles, that is then minimized with respect to the bias field parameters of the slices. A non iterative method which considers the relative bias between each slice simultaneously is used to efficiently remove inconsistencies. The method, when tested on synthetic simulations and actual clinical imaging studies where bias was an issue, brought a significant improvement to the final reconstructed image.

  5. Cortical neurons and networks are dormant but fully responsive during isoelectric brain state.

    Altwegg-Boussac, Tristan; Schramm, Adrien E; Ballestero, Jimena; Grosselin, Fanny; Chavez, Mario; Lecas, Sarah; Baulac, Michel; Naccache, Lionel; Demeret, Sophie; Navarro, Vincent; Mahon, Séverine; Charpier, Stéphane

    2017-09-01

    A continuous isoelectric electroencephalogram reflects an interruption of endogenously-generated activity in cortical networks and systematically results in a complete dissolution of conscious processes. This electro-cerebral inactivity occurs during various brain disorders, including hypothermia, drug intoxication, long-lasting anoxia and brain trauma. It can also be induced in a therapeutic context, following the administration of high doses of barbiturate-derived compounds, to interrupt a hyper-refractory status epilepticus. Although altered sensory responses can be occasionally observed on an isoelectric electroencephalogram, the electrical membrane properties and synaptic responses of individual neurons during this cerebral state remain largely unknown. The aim of the present study was to characterize the intracellular correlates of a barbiturate-induced isoelectric electroencephalogram and to analyse the sensory-evoked synaptic responses that can emerge from a brain deprived of spontaneous electrical activity. We first examined the sensory responsiveness from patients suffering from intractable status epilepticus and treated by administration of thiopental. Multimodal sensory responses could be evoked on the flat electroencephalogram, including visually-evoked potentials that were significantly amplified and delayed, with a high trial-to-trial reproducibility compared to awake healthy subjects. Using an analogous pharmacological procedure to induce prolonged electro-cerebral inactivity in the rat, we could describe its cortical and subcortical intracellular counterparts. Neocortical, hippocampal and thalamo-cortical neurons were all silent during the isoelectric state and displayed a flat membrane potential significantly hyperpolarized compared with spontaneously active control states. Nonetheless, all recorded neurons could fire action potentials in response to intracellularly injected depolarizing current pulses and their specific intrinsic

  6. An algorithm based on OmniView technology to reconstruct sagittal and coronal planes of the fetal brain from volume datasets acquired by three-dimensional ultrasound.

    Rizzo, G; Capponi, A; Pietrolucci, M E; Capece, A; Aiello, E; Mammarella, S; Arduini, D

    2011-08-01

    To describe a novel algorithm, based on the new display technology 'OmniView', developed to visualize diagnostic sagittal and coronal planes of the fetal brain from volumes obtained by three-dimensional (3D) ultrasonography. We developed an algorithm to image standard neurosonographic planes by drawing dissecting lines through the axial transventricular view of 3D volume datasets acquired transabdominally. The algorithm was tested on 106 normal fetuses at 18-24 weeks of gestation and the visualization rates of brain diagnostic planes were evaluated by two independent reviewers. The algorithm was also applied to nine cases with proven brain defects. The two reviewers, using the algorithm on normal fetuses, found satisfactory images with visualization rates ranging between 71.7% and 96.2% for sagittal planes and between 76.4% and 90.6% for coronal planes. The agreement rate between the two reviewers, as expressed by Cohen's kappa coefficient, was > 0.93 for sagittal planes and > 0.89 for coronal planes. All nine abnormal volumes were identified by a single observer from among a series including normal brains, and eight of these nine cases were diagnosed correctly. This novel algorithm can be used to visualize standard sagittal and coronal planes in the fetal brain. This approach may simplify the examination of the fetal brain and reduce dependency of success on operator skill. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

  7. Sleep deprivation does not affect neuronal susceptibility to mild traumatic brain injury in the rat

    Caron AM

    2015-06-01

    Full Text Available Aimee M Caron, Richard Stephenson Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada Abstract: Mild and moderate traumatic brain injuries (TBIs (and concussion occur frequently as a result of falls, automobile accidents, and sporting activities, and are a major cause of acute and chronic disability. Fatigue and excessive sleepiness are associated with increased risk of accidents, but it is unknown whether prior sleep debt also affects the pathophysiological outcome of concussive injury. Using the “dark neuron” (DN as a marker of reversible neuronal damage, we tested the hypothesis that acute (48 hours total sleep deprivation (TSD and chronic sleep restriction (CSR; 10 days, 6-hour sleep/day affect DN formation following mild TBI in the rat. TSD and CSR were administered using a walking wheel apparatus. Mild TBI was administered under anesthesia using a weight-drop impact model, and the acute neuronal response was observed without recovery. DNs were detected using standard bright-field microscopy with toluidine blue stain following appropriate tissue fixation. DN density was low under home cage and sleep deprivation control conditions (respective median DN densities, 0.14% and 0.22% of neurons, and this was unaffected by TSD alone (0.1%. Mild TBI caused significantly higher DN densities (0.76%, and this was unchanged by preexisting acute or chronic sleep debt (TSD, 0.23%; CSR, 0.7%. Thus, although sleep debt may be predicted to increase the incidence of concussive injury, the present data suggest that sleep debt does not exacerbate the resulting neuronal damage. Keywords: sleep deprivation, concussion, traumatic brain injury, dark neuron, neurodegeneration, rat cortex

  8. Prenatal Exposure to Autism-Specific Maternal Autoantibodies Alters Proliferation of Cortical Neural Precursor Cells, Enlarges Brain, and Increases Neuronal Size in Adult Animals.

    Martínez-Cerdeño, Verónica; Camacho, Jasmin; Fox, Elizabeth; Miller, Elaine; Ariza, Jeanelle; Kienzle, Devon; Plank, Kaela; Noctor, Stephen C; Van de Water, Judy

    2016-01-01

    Autism spectrum disorders (ASDs) affect up to 1 in 68 children. Autism-specific autoantibodies directed against fetal brain proteins have been found exclusively in a subpopulation of mothers whose children were diagnosed with ASD or maternal autoantibody-related autism. We tested the impact of autoantibodies on brain development in mice by transferring human antigen-specific IgG directly into the cerebral ventricles of embryonic mice during cortical neurogenesis. We show that autoantibodies recognize radial glial cells during development. We also show that prenatal exposure to autism-specific maternal autoantibodies increased stem cell proliferation in the subventricular zone (SVZ) of the embryonic neocortex, increased adult brain size and weight, and increased the size of adult cortical neurons. We propose that prenatal exposure to autism-specific maternal autoantibodies directly affects radial glial cell development and presents a viable pathologic mechanism for the maternal autoantibody-related prenatal ASD risk factor. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Intersection Based Motion Correction of Multi-Slice MRI for 3D in utero Fetal Brain Image Formation

    Kim, Kio; Habas, Piotr A.; Rousseau, Francois; Glenn, Orit A.; Barkovich, Anthony J.; Studholme, Colin

    2012-01-01

    In recent years post-processing of fast multi-slice MR imaging to correct fetal motion has provided the first true 3D MR images of the developing human brain in utero. Early approaches have used reconstruction based algorithms, employing a two step iterative process, where slices from the acquired data are re-aligned to an approximate 3D reconstruction of the fetal brain, which is then refined further using the improved slice alignment. This two step slice-to-volume process, although powerful, is computationally expensive in needing a 3D reconstruction, and is limited in its ability to recover sub-voxel alignment. Here, we describe an alternative approach which we term slice intersection motion correction (SIMC), that seeks to directly co-align multiple slice stacks by considering the matching structure along all intersecting slice pairs in all orthogonally planned slices that are acquired in clinical imaging studies. A collective update scheme for all slices is then derived, to simultaneously drive slices into a consistent match along their lines of intersection. We then describe a 3D reconstruction algorithm that, using the final motion corrected slice locations, suppresses through-plane partial volume effects to provide a single high isotropic resolution 3D image. The method is tested on simulated data with known motions and is applied to retrospectively reconstruct 3D images from a range of clinically acquired imaging studies. The quantitative evaluation of the registration accuracy for the simulated data sets demonstrated a significant improvement over previous approaches. An initial application of the technique to studying clinical pathology is included, where the proposed method recovered up to 15 mm of translation and 30 degrees of rotation for individual slices, and produced full 3D reconstructions containing clinically useful additional information not visible in the original 2D slices. PMID:19744911

  10. Fetal MRI and ultrasound of congenital CNS anomalies

    Pogledic, I.; Reith, W.; Meyberg-Solomayer, G.

    2013-01-01

    In the last decade the newest technologies, fetal magnetic resonance imaging (MRI) and 3D ultrasound, have given an insight into the minute structures of the fetal brain. However, without knowledge of the basic developmental processes the imaging is futile. Knowledge of fetal neuroanatomy corresponding to the gestational week is necessary in order to recognize pathological structures. Furthermore, a modern neuroradiologist should be acquainted with the three steps in the formation of the cerebral cortex: proliferation, migration and differentiation of neurons in order to be in a position to suspect that there is a pathology and start recognizing and discovering the abnormalities. The fetal MRI has become an important complementary method to ultrasound especially in cortical malformations when confirmation of the prenatal diagnosis is needed and additional pathologies need to be diagnosed. In this manner these two methods help in parental counseling and treatment planning. (orig.) [de

  11. Gonadotropin-releasing hormone immunoreactivity in the adult and fetal human olfactory system.

    Kim, K H; Patel, L; Tobet, S A; King, J C; Rubin, B S; Stopa, E G

    1999-05-01

    Studies in fetal brain tissue of rodents, nonhuman primates and birds have demonstrated that cells containing gonadotropin-releasing hormone (GnRH) migrate from the olfactory placode across the nasal septum into the forebrain. The purpose of this study was to examine GnRH neurons in components of the adult and fetal human olfactory system. In the adult human brain (n=4), immunoreactive GnRH was evident within diffusely scattered cell bodies and processes in the olfactory bulb, olfactory nerve, olfactory cortex, and nervus terminalis located on the anterior surface of the gyrus rectus. GnRH-immunoreactive structures showed a similar distribution in 20-week human fetal brains (n=2), indicating that the migration of GnRH neurons is complete at this time. In 10-11-week fetal brains (n=2), more cells were noted in the nasal cavity than in the brain. Our data are consistent with observations made in other species, confirming olfactory derivation and migration of GnRH neurons into the brain from the olfactory placode. Copyright 1999 Elsevier Science B.V.

  12. Delivery of circulating lipoproteins to specific neurons in the Drosophila brain regulates systemic insulin signaling.

    Brankatschk, Marko; Dunst, Sebastian; Nemetschke, Linda; Eaton, Suzanne

    2014-10-02

    The Insulin signaling pathway couples growth, development and lifespan to nutritional conditions. Here, we demonstrate a function for the Drosophila lipoprotein LTP in conveying information about dietary lipid composition to the brain to regulate Insulin signaling. When yeast lipids are present in the diet, free calcium levels rise in Blood Brain Barrier glial cells. This induces transport of LTP across the Blood Brain Barrier by two LDL receptor-related proteins: LRP1 and Megalin. LTP accumulates on specific neurons that connect to cells that produce Insulin-like peptides, and induces their release into the circulation. This increases systemic Insulin signaling and the rate of larval development on yeast-containing food compared with a plant-based food of similar nutritional content.

  13. Fetal alcohol exposure disrupts metabolic signaling in hypothalamic proopiomelanocortin neurons via a circadian mechanism in male mice.

    Agapito, Maria A; Zhang, Changqing; Murugan, Sengottuvelan; Sarkar, Dipak K

    2014-07-01

    Early-life ethanol feeding (ELAF) alters the metabolic function of proopiomelanocortin (POMC)-producing neurons and the circadian expression of clock regulatory genes in the hypothalamus. We investigated whether the circadian mechanisms control the action of ELAF on metabolic signaling genes in POMC neurons. Gene expression measurements of Pomc and a selected group of metabolic signaling genes, Stat3, Sirt1, Pgc1-α, and Asb4 in laser-captured microdissected POMC neurons in the hypothalamus of POMC-enhanced green fluorescent protein mice showed circadian oscillations under light/dark and constant darkness conditions. Ethanol programmed these neurons such that the adult expression of Pomc, Stat3, Sirt, and Asb4 gene transcripts became arrhythmic. In addition, ELAF dampened the circadian peak of gene expression of Bmal1, Per1, and Per2 in POMC neurons. We crossed Per2 mutant mice with transgenic POMC-enhanced green fluorescent protein mice to determine the role of circadian mechanism in ELAF-altered metabolic signaling in POMC neurons. We found that ELAF failed to alter arrhythmic expression of most circadian genes, with the exception of the Bmal1 gene and metabolic signaling regulating genes in Per2 mutant mice. Comparison of the ELAF effects on the circadian blood glucose in wild-type and Per2 mutant mice revealed that ELAF dampened the circadian peak of glucose, whereas the Per2 mutation shifted the circadian cycle and prevented the ELAF dampening of the glucose peak. These data suggest the possibility that the Per2 gene mutation may regulate the ethanol actions on Pomc and the metabolic signaling genes in POMC neurons in the hypothalamus by blocking circadian mechanisms.

  14. Neuron-specific caveolin-1 overexpression improves motor function and preserves memory in mice subjected to brain trauma.

    Egawa, Junji; Schilling, Jan M; Cui, Weihua; Posadas, Edmund; Sawada, Atsushi; Alas, Basheer; Zemljic-Harpf, Alice E; Fannon-Pavlich, McKenzie J; Mandyam, Chitra D; Roth, David M; Patel, Hemal H; Patel, Piyush M; Head, Brian P

    2017-08-01

    Studies in vitro and in vivo demonstrate that membrane/lipid rafts and caveolin (Cav) organize progrowth receptors, and, when overexpressed specifically in neurons, Cav-1 augments neuronal signaling and growth and improves cognitive function in adult and aged mice; however, whether neuronal Cav-1 overexpression can preserve motor and cognitive function in the brain trauma setting is unknown. Here, we generated a neuron-targeted Cav-1-overexpressing transgenic (Tg) mouse [synapsin-driven Cav-1 (SynCav1 Tg)] and subjected it to a controlled cortical impact model of brain trauma and measured biochemical, anatomic, and behavioral changes. SynCav1 Tg mice exhibited increased hippocampal expression of Cav-1 and membrane/lipid raft localization of postsynaptic density protein 95, NMDA receptor, and tropomyosin receptor kinase B. When subjected to a controlled cortical impact, SynCav1 Tg mice demonstrated preserved hippocampus-dependent fear learning and memory, improved motor function recovery, and decreased brain lesion volume compared with wild-type controls. Neuron-targeted overexpression of Cav-1 in the adult brain prevents hippocampus-dependent learning and memory deficits, restores motor function after brain trauma, and decreases brain lesion size induced by trauma. Our findings demonstrate that neuron-targeted Cav-1 can be used as a novel therapeutic strategy to restore brain function and prevent trauma-associated maladaptive plasticity.-Egawa, J., Schilling, J. M., Cui, W., Posadas, E., Sawada, A., Alas, B., Zemljic-Harpf, A. E., Fannon-Pavlich, M. J., Mandyam, C. D., Roth, D. M., Patel, H. H., Patel, P. M., Head, B. P. Neuron-specific caveolin-1 overexpression improves motor function and preserves memory in mice subjected to brain trauma. © FASEB.

  15. Autoradiographic localization of putative nicotinic receptors in the rat brain using 125I-neuronal bungarotoxin

    Schulz, D.W.; Loring, R.H.; Aizenman, E.; Zigmond, R.E.

    1991-01-01

    Neuronal bungarotoxin (NBT), a snake venom neurotoxin, selectively blocks nicotinic receptors in many peripheral and central neuronal preparations. alpha-Bungarotoxin (alpha BT), on the other hand, a second toxin isolated from the venom of the same snake, is an ineffective nicotinic antagonist in most vertebrate neuronal preparations studied thus far. To examine central nicotinic receptors recognized by NBT, we have characterized the binding of 125I-labeled NBT (125I-NBT) to rat brain membranes and have mapped the distribution of 125I-NBT binding in brain sections using quantitative light microscopic autoradiography. The binding of 125I-NBT was found to be saturable, of high affinity, and heterogeneously distributed in the brain. Pharmacological studies suggested that more than one population of sites is labeled by 125I-NBT. For example, one component of 125I-NBT binding was also recognized by alpha BT, while a second component, not recognized by alpha BT, was recognized by the nicotinic agonist nicotine. The highest densities of these alpha BT-insensitive, nicotine-sensitive sites were found in the fasciculus retroflexus, the lateral geniculate nucleus, the medial terminal nucleus of the accessory optic tract, and the olivary pretectal nucleus. alpha BT-sensitive NBT binding sites were found in highest density in the lateral geniculate nucleus, the subthalamic nucleus, the dorsal tegmental nucleus, and the medial mammillary nucleus (lateral part). The number of brain regions with a high density of 125I-NBT binding sites, blocked either by alpha BT or by nicotine, is low when compared with results obtained using other approaches to studying the central distribution of nicotinic receptors, such as labeling with 3H-nicotine or labeling with cDNA probes to mRNAs coding for putative receptor subunits

  16. Mitochondrial targeted neuron focused genes in hippocampus of rats with traumatic brain injury.

    Sharma, Pushpa; Su, Yan A; Barry, Erin S; Grunberg, Neil E; Lei, Zhang

    2012-09-01

    Mild traumatic brain injury (mTBI) represents a major health problem in civilian populations as well as among the military service members due to (1) lack of effective treatments, and (2) our incomplete understanding about the progression of secondary cell injury cascades resulting in neuronal cell death due to deficient cellular energy metabolism and damaged mitochondria. The aim of this study was to identify and delineate the mitochondrial targeted genes responsible for altered brain energy metabolism in the injured brain. Rats were either grouped into naïve controls or received lateral fluid percussion brain injury (2-2.5 atm) and followed up for 7 days. Rats were either grouped into naïve controls or received lateral fluid percussion brain injury (2-2.5 atm) and followed for 7 days. The severity of brain injury was evaluated by the neurological severity scale-revised (NSS-R) at 3 and 5 days post TBI and immunohistochemical analyses at 7 days post TBI. The expression profiles of mitochondrial-targeted genes across the hippocampus from TBI and naïe rats were also examined by oligo-DNA microarrays. NSS-R scores of TBI rats (5.4 ± 0.5) in comparison to naïe rats (3.9 ± 0.5) and H and E staining of brain sections suggested a mild brain injury. Bioinformatics and systems biology analyses showed 31 dysregulated genes, 10 affected canonical molecular pathways including a number of genes involved in mitochondrial enzymes for oxidative phosphorylation, mitogen-activated protein Kinase (MAP), peroxisome proliferator-activated protein (PPAP), apoptosis signaling, and genes responsible for long-term potentiation of Alzheimer's and Parkinson's diseases. Our results suggest that dysregulated mitochondrial-focused genes in injured brains may have a clinical utility for the development of future therapeutic strategies aimed at the treatment of TBI.

  17. Brain Aromatase Modulates Serotonergic Neuron by Regulating Serotonin Levels in Zebrafish Embryos and Larvae

    Zulvikar Syambani Ulhaq

    2018-05-01

    Full Text Available Teleost fish are known to express two isoforms of P450 aromatase, a key enzyme for estrogen synthesis. One of the isoforms, brain aromatase (AroB, cyp19a1b, is highly expressed during early development of zebrafish, thereby suggesting its role in brain development. On the other hand, early development of serotonergic neuron, one of the major monoamine neurons, is considered to play an important role in neurogenesis. Therefore, in this study, we investigated the role of AroB in development of serotonergic neuron by testing the effects of (1 estradiol (E2 exposure and (2 morpholino (MO-mediated AroB knockdown. When embryos were exposed to E2, the effects were biphasic. The low dose of E2 (0.005 µM significantly increased serotonin (5-HT positive area at 48 hour post-fertilization (hpf detected by immunohistochemistry and relative mRNA levels of tryptophan hydroxylase isoforms (tph1a, tph1b, and tph2 at 96 hpf measured by semi-quantitative PCR. To test the effects on serotonin transmission, heart rate and thigmotaxis, an indicator of anxiety, were analyzed. The low dose also significantly increased heart rate at 48 hpf and decreased thigmotaxis. The high dose of E2 (1 µM exhibited opposite effects in all parameters. The effects of both low and high doses were reversed by addition of estrogen receptor (ER blocker, ICI 182,780, thereby suggesting that the effects were mediated through ER. When AroB MO was injected to fertilized eggs, 5-HT-positive area was significantly decreased, while the significant decrease in relative tph mRNA levels was found only with tph2 but not with two other isoforms. AroB MO also decreased heart rate and increased thigmotaxis. All the effects were rescued by co-injection with AroB mRNA and by exposure to E2. Taken together, this study demonstrates the role of brain aromatase in development of serotonergic neuron in zebrafish embryos and larvae, implying that brain-formed estrogen is an important factor to

  18. A Tyrosine-Hydroxylase Characterization of Dopaminergic Neurons in the Honey Bee Brain

    Stevanus R. Tedjakumala

    2017-07-01

    Full Text Available Dopamine (DA plays a fundamental role in insect behavior as it acts both as a general modulator of behavior and as a value system in associative learning where it mediates the reinforcing properties of unconditioned stimuli (US. Here we aimed at characterizing the dopaminergic neurons in the central nervous system of the honey bee, an insect that serves as an established model for the study of learning and memory. We used tyrosine hydroxylase (TH immunoreactivity (ir to ensure that the neurons detected synthesize DA endogenously. We found three main dopaminergic clusters, C1–C3, which had been previously described; the C1 cluster is located in a small region adjacent to the esophagus (ES and the antennal lobe (AL; the C2 cluster is situated above the C1 cluster, between the AL and the vertical lobe (VL of the mushroom body (MB; the C3 cluster is located below the calyces (CA of the MB. In addition, we found a novel dopaminergic cluster, C4, located above the dorsomedial border of the lobula, which innervates the visual neuropils of the bee brain. Additional smaller processes and clusters were found and are described. The profuse dopaminergic innervation of the entire bee brain and the specific connectivity of DA neurons, with visual, olfactory and gustatory circuits, provide a foundation for a deeper understanding of how these sensory modules are modulated by DA, and the DA-dependent value-based associations that occur during associative learning.

  19. The Brain-to-Pancreatic Islet Neuronal Map Reveals Differential Glucose Regulation From Distinct Hypothalamic Regions.

    Rosario, Wilfredo; Singh, Inderroop; Wautlet, Arnaud; Patterson, Christa; Flak, Jonathan; Becker, Thomas C; Ali, Almas; Tamarina, Natalia; Philipson, Louis H; Enquist, Lynn W; Myers, Martin G; Rhodes, Christopher J

    2016-09-01

    The brain influences glucose homeostasis, partly by supplemental control over insulin and glucagon secretion. Without this central regulation, diabetes and its complications can ensue. Yet, the neuronal network linking to pancreatic islets has never been fully mapped. Here, we refine this map using pseudorabies virus (PRV) retrograde tracing, indicating that the pancreatic islets are innervated by efferent circuits that emanate from the hypothalamus. We found that the hypothalamic arcuate nucleus (ARC), ventromedial nucleus (VMN), and lateral hypothalamic area (LHA) significantly overlap PRV and the physiological glucose-sensing enzyme glucokinase. Then, experimentally lowering glucose sensing, specifically in the ARC, resulted in glucose intolerance due to deficient insulin secretion and no significant effect in the VMN, but in the LHA it resulted in a lowering of the glucose threshold that improved glucose tolerance and/or improved insulin sensitivity, with an exaggerated counter-regulatory response for glucagon secretion. No significant effect on insulin sensitivity or metabolic homeostasis was noted. Thus, these data reveal novel direct neuronal effects on pancreatic islets and also render a functional validation of the brain-to-islet neuronal map. They also demonstrate that distinct regions of the hypothalamus differentially control insulin and glucagon secretion, potentially in partnership to help maintain glucose homeostasis and guard against hypoglycemia. © 2016 by the American Diabetes Association.

  20. Structural alterations of the DNA in cerebellar neurons after whole-brain irradiation

    Wheeler, K.T.; Winstein, R.E.; Kaufman, K.; Ritter, P.

    1981-01-01

    Male Sprague-Dawley rats weighing 260 to 280 g were whole-brain-irradiated with x-ray doses of 433, 867, 1083, 1300, 1516, and 1713 rad. Over the next 2.25 years rats were killed at various times, and the state of the DNA in their cerebellar neurons was examined by sedimentation through alkaline sucrose gradients in reorienting zonal rotors. The data were analyzed as the percentage of the sedimenting DNA with sedimentation coefficients greater than 300 S, an arbitrarily selected category of no defined molecular significance. The general pattern at all doses consisted first of a slow return to the unirradiated DNA state that was relatively dose dependent. This was followed by an increase in the amount of DNA sedimenting >300 S; both the extent and time course of this increase appeared to be dose dependent. Finally, the DNA degraded at a relatively dose independent rate. There was little change in the neuronal DNA from unirradiated rats during this study. The data suggest that increases in the amount of fast-sedimenting DNA observed 30 to 80 weeks after low to moderate doses of whole-brain irradiation represent a type of DNA damage rather than repair and that this damage ultimately results in degradation of the neuronal DNA and death of the rat

  1. The energy demand of fast neuronal network oscillations: insights from brain slice preparations

    Oliver eKann

    2012-01-01

    Full Text Available Fast neuronal network oscillations in the gamma range (30-100 Hz in the cerebral cortex have been implicated in higher cognitive functions such as sensual perception, working memory, and, perhaps, consciousness. However, little is known about the energy demand of gamma oscillations. This is mainly caused by technical limitations that are associated with simultaneous recordings of neuronal activity and energy metabolism in small neuronal networks and at the level of mitochondria in vivo. Thus recent studies have focused on brain slice preparations to address the energy demand of gamma oscillations in vitro. Here, reports will be summarized and discussed that combined electrophysiological recordings, oxygen sensor microelectrodes and live-cell fluorescence imaging in acutely prepared slices and organotypic slice cultures of the hippocampus from both, mouse and rat. These reports consistently show that gamma oscillations can be reliably induced in hippocampal slice preparations by different pharmacological tools. They suggest that gamma oscillations are associated with high energy demand, requiring both rapid adaptation of oxidative energy metabolism and sufficient supply with oxygen and nutrients. These findings might help to explain the exceptional vulnerability of higher cognitive functions during pathological processes of the brain, such as circulatory disturbances, genetic mitochondrial diseases, and neurodegeneration.

  2. The 5-HT1A serotonin receptor is located on calbindin- and parvalbumin-containing neurons in the rat brain

    Aznar, Susana; Qian, Zhaoxia; Shah, Reshma

    2003-01-01

    distributed in the rat brain, with a particularly high density in the limbic system. The receptor's localization in the different neuronal subtypes, which may be of importance for understanding its role in neuronal circuitries, is, however, unknown. In this study we show by immunocytochemical double......-labeling techniques, that the 5-HT(1A) receptor is present on both pyramidal and principal cells, and calbindin- and parvalbumin-containing neurons, which generally define two different subtypes of interneurons. Moreover, semiquantitative analysis showed that the receptor's distribution in the different neuronal...... types varies between brain areas. In cortex, hippocampus, hypothalamus, and amygdala the receptor was located on both principal cells and calbindin- and parvalbumin-containing neurons. In septum and thalamus, the receptor was mostly present on calbindin- and parvalbumin-containing cells. Especially...

  3. Chemotherapy Agents and the Inhibition of Neuronal Birthing in the Brain - The Cause of "Chemo Brain"

    Gross, Robert A

    2005-01-01

    .... We further hypothesize that agents that do not cross the blood-brain barrier will not show reduced rates of neurogenesis, in contrast to agents that readily cross into the central nervous system (CNS...

  4. Chemotherapy Agents and the Inhibition of Neuronal Birthing in the Brain- The Cause of "Chemo Brain"

    Gross, Robert A

    2004-01-01

    .... We further hypothesize that agents that do not cross the blood-brain barrier will not show reduced rates of neurogenesis, in contrast to agents that readily cross into the central nervous system (CNS...

  5. Chemotherapy Agents and the Inhibition of Neuronal Birthing in the Brain - The Cause of Chemo Brain

    Gross, Robert A

    2006-01-01

    .... We further hypothesize that agents that do not cross the blood-brain barrier will not show reduced rates of neurogenesis, in contrast to agents that readily cross into the central nervous system (CNS...

  6. Analyzing topological characteristics of neuronal functional networks in the rat brain

    Lu, Hu [School of Computer Science and Communication Engineering, Jiangsu University, Jiangsu 212003 (China); School of Computer Science, Fudan University, Shanghai 200433 (China); Yang, Shengtao [Institutes of Brain Science, Fudan University, Shanghai 200433 (China); Song, Yuqing [School of Computer Science and Communication Engineering, Jiangsu University, Jiangsu 212003 (China); Wei, Hui [School of Computer Science, Fudan University, Shanghai 200433 (China)

    2014-08-28

    In this study, we recorded spike trains from brain cortical neurons of several behavioral rats in vivo by using multi-electrode recordings. An NFN was constructed in each trial, obtaining a total of 150 NFNs in this study. The topological characteristics of NFNs were analyzed by using the two most important characteristics of complex networks, namely, small-world structure and community structure. We found that the small-world properties exist in different NFNs constructed in this study. Modular function Q was used to determine the existence of community structure in NFNs, through which we found that community-structure characteristics, which are related to recorded spike train data sets, are more evident in the Y-maze task than in the DM-GM task. Our results can also be used to analyze further the relationship between small-world characteristics and the cognitive behavioral responses of rats. - Highlights: • We constructed the neuronal function networks based on the recorded neurons. • We analyzed the two main complex network characteristics, namely, small-world structure and community structure. • NFNs which were constructed based on the recorded neurons in this study exhibit small-world properties. • Some NFNs have community structure characteristics.

  7. Analyzing topological characteristics of neuronal functional networks in the rat brain

    Lu, Hu; Yang, Shengtao; Song, Yuqing; Wei, Hui

    2014-01-01

    In this study, we recorded spike trains from brain cortical neurons of several behavioral rats in vivo by using multi-electrode recordings. An NFN was constructed in each trial, obtaining a total of 150 NFNs in this study. The topological characteristics of NFNs were analyzed by using the two most important characteristics of complex networks, namely, small-world structure and community structure. We found that the small-world properties exist in different NFNs constructed in this study. Modular function Q was used to determine the existence of community structure in NFNs, through which we found that community-structure characteristics, which are related to recorded spike train data sets, are more evident in the Y-maze task than in the DM-GM task. Our results can also be used to analyze further the relationship between small-world characteristics and the cognitive behavioral responses of rats. - Highlights: • We constructed the neuronal function networks based on the recorded neurons. • We analyzed the two main complex network characteristics, namely, small-world structure and community structure. • NFNs which were constructed based on the recorded neurons in this study exhibit small-world properties. • Some NFNs have community structure characteristics

  8. DCC Expression by Neurons Regulates Synaptic Plasticity in the Adult Brain

    Katherine E. Horn

    2013-01-01

    Full Text Available The transmembrane protein deleted in colorectal cancer (DCC and its ligand, netrin-1, regulate synaptogenesis during development, but their function in the mature central nervous system is unknown. Given that DCC promotes cell-cell adhesion, is expressed by neurons, and activates proteins that signal at synapses, we hypothesized that DCC expression by neurons regulates synaptic function and plasticity in the adult brain. We report that DCC is enriched in dendritic spines of pyramidal neurons in wild-type mice, and we demonstrate that selective deletion of DCC from neurons in the adult forebrain results in the loss of long-term potentiation (LTP, intact long-term depression, shorter dendritic spines, and impaired spatial and recognition memory. LTP induction requires Src activation of NMDA receptor (NMDAR function. DCC deletion severely reduced Src activation. We demonstrate that enhancing NMDAR function or activating Src rescues LTP in the absence of DCC. We conclude that DCC activation of Src is required for NMDAR-dependent LTP and certain forms of learning and memory.

  9. The role of glycogen, glucose and lactate in neuronal activity during hypoxia in the hooded seal (Cystophora cristata) brain.

    Czech-Damal, N U; Geiseler, S J; Hoff, M L M; Schliep, R; Ramirez, J-M; Folkow, L P; Burmester, T

    2014-09-05

    The brains of diving mammals are repeatedly exposed to hypoxic conditions during diving. Brain neurons of the hooded seal (Cystophora cristata) have been shown to be more hypoxia tolerant than those of mice, but the underlying mechanisms are not clear. Here we investigated the roles of different metabolic substrates for maintenance of neuronal activity and integrity, by comparing the in vitro spontaneous neuronal activity of brain slices from layer V of the visual cortex of hooded seals with those in mice (Mus musculus). Studies were conducted by manipulating the composition of the artificial cerebrospinal fluid (aCSF), containing either 10 mM glucose, or 20 mM lactate, or no external carbohydrate supply (aglycemia). Normoxic, hypoxic and ischemic conditions were applied. The lack of glucose or the application of lactate in the aCSF containing no glucose had little effect on the neuronal activity of seal neurons in either normoxia or hypoxia, while neurons from mice survived in hypoxia only few minutes regardless of the composition of the aCSF. We propose that seal neurons have higher intrinsic energy stores. Indeed, we found about three times higher glycogen stores in the seal brain (∼4.1 ng per μg total protein in the seal cerebrum) than in the mouse brain. Notably, in aCSF containing no glucose, seal neurons can tolerate 20 mM lactate while in mouse neuronal activity vanished after few minutes even in normoxia. This can be considered as an adaptation to long dives, during which lactate accumulates in the blood. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. Effects of an overload of animal protein on the rat: brain DNA alterations and tissue morphological modifications during fetal and post-natal stage.

    Greco, A M; Sticchi, R; Boschi, G; Vetrani, A; Salvatore, G

    1985-01-01

    On account of many literature reports about the definite correlation between high animal protein intake and cardiovascular diseases, we have studied the effect of a hyperproteic purified diet (casein 40%, lactalbumin 20%) on fetal and post-natal (not further than 40th day) stage of the rat, when cell subdivision process is faster and therefore damage by nutritional imbalance is certainly more serious. Litters of rats were grouped according to mother's (either hyperproteic or common basic) and rat's (after lactation) diet. Brain DNA and histology of various organs were studied. Hyperproteic diet during fetal stage and lactation would inhibit brain cell subdivision since overall content of brain DNA would be decreased on autoptic finding. Structural changes were also shown in liver, heart, kidney and adrenal cortex, especially when hyperproteic diet was continued even after lactation.

  11. Lipopolysaccharide (LPS Accumulates in Neocortical Neurons of Alzheimer’s Disease (AD Brain and Impairs Transcription in Human Neuronal-Glial Primary Co-cultures

    Yuhai Zhao

    2017-12-01

    Full Text Available Several independent laboratories have recently reported the detection of bacterial nucleic acid sequences or bacterial-derived neurotoxins, such as highly inflammatory lipopolysaccharide (LPS, within Alzheimer’s disease (AD affected brain tissues. Whether these bacterial neurotoxins originate from the gastrointestinal (GI tract microbiome, a possible brain microbiome or some dormant pathological microbiome is currently not well understood. Previous studies indicate that the co-localization of pro-inflammatory LPS with AD-affected brain cell nuclei suggests that there may be a contribution of this neurotoxin to genotoxic events that support inflammatory neurodegeneration and failure in homeostatic gene expression. In this report we provide evidence that in sporadic AD, LPS progressively accumulates in neuronal parenchyma and appears to preferentially associate with the periphery of neuronal nuclei. Run-on transcription studies utilizing [α-32P]-uridine triphosphate incorporation into newly synthesized total RNA further indicates that human neuronal-glial (HNG cells in primary co-culture incubated with LPS exhibit significantly reduced output of DNA transcription products. These studies suggest that in AD LPS may impair the efficient readout of neuronal genetic information normally required for the homeostatic operation of brain cell function and may contribute to a progressive disruption in the read-out of genetic information.

  12. Detectability of Neuronal Currents in Human Brain with Magnetic Resonance Spectroscopy.

    Jones, Howland D. T. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Thomas, Edward V. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Harper, Jason C. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Mayer, Andrew R. [Mind Research Network, Albuquerque, NM (United States); Univ. of New Mexico, Albuquerque, NM (United States); Caprihan, Arvind [Mind Research Network, Albuquerque, NM (United States); Gasparovic, Charles [Mind Research Network, Albuquerque, NM (United States); Univ. of New Mexico, Albuquerque, NM (United States); Blagoev, Krastan B. [Mind Research Network, Albuquerque, NM (United States); Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Haaland, David M. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2012-09-01

    Magnetic resonance spectroscopy has been used in a high-risk, high-payoff search for neuronal current (NC) signals in the free induction decay (FID) data from the visual cortex of human subjects during visual stimulation. If successful, this approach could make possible the detection of neuronal currents in the brain at high spatial and temporal resolution. Our initial experiments indicated the presence of a statistically significant change in the FID containing the NC relative to FIDs with the NC absent, and this signal was consistent with the presence of NC. Unfortunately, two follow-on experiments were not able to confirm or replicate the positive findings of the first experiment. However, even if the result from the first experiment were evidence of NC in the FID, it is clear that its effect is so small, that a true NC imaging experiment would not be possible with the current instrumentation and experimental protocol used here.

  13. IMAGING DIAGNOSIS-MAGNETIC RESONANCE IMAGING OF A NEURONAL HETEROTOPIA IN THE BRAIN OF A CAT.

    DeJesus, Antonia; Turek, Bradley J; Galban, Evelyn; Suran, Jantra Ngosuwan

    2018-03-01

    A domestic shorthair kitten was presented for evaluation and further treatment of seizures. Magnetic resonance imaging of the brain revealed a large multilobulated mass in the third ventricle extending into the right lateral ventricle with secondary obstructive hydrocephalus. The mass was homogeneously isointense to gray matter on T2W, T2-FLAIR, T2 * W, T1W, and ADC images, and hyperintense on DW-EPI. There was no appreciable contrast enhancement. Seizures were managed medically and with subsequent ventriculoperitoneal shunt placement. Clinical status later deteriorated and the cat was euthanized. Histopathology confirmed that the mass was the result of neuronal heterotopia. To the authors' knowledge this is the first report of neuronal heterotopia in a cat. © 2016 American College of Veterinary Radiology.

  14. Melanin-concentrating hormone: unique peptide neuronal systems in the rat brain and pituitary gland

    Zamir, N.; Skofitsch, G.; Bannon, M.J.; Jacobowitz, D.M.

    1986-01-01

    A unique neuronal system was detected in the rat central nervous system by immunohistochemistry and radioimmunoassay with antibodies to salmon melanin-concentrating hormone (MCH). MCH-like immunoreactive (MCH-LI) cell bodies were confined to the hypothalamus. MCH-LI fibers were found throughout the brain but were most prevalent in hypothalamus, mesencephalon, and pons-medulla regions. High concentrations of MCH-LI were measured in the hypothalamic medial forebrain bundle (MFB), posterior hypothalamic nucleus, and nucleus of the diagonal band. Reversed-phase high-performance liquid chromatography of MFB extracts from rat brain indicate that MCH-like peptide from the rat has a different retention time than that of the salmon MCH. An osmotic stimuls (2% NaCl as drinking water for 120 hr) caused a marked increase in MCH-LI concentrations in the lateral hypothalamus and neurointermediate lobe. The present studies establish the presence of MCH-like peptide in the rat brain. The MCH-LI neuronal system is well situated to coordinate complex functions such as regulation of water intake

  15. Optimal and Local Connectivity Between Neuron and Synapse Array in the Quantum Dot/Silicon Brain

    Duong, Tuan A.; Assad, Christopher; Thakoor, Anikumar P.

    2010-01-01

    This innovation is used to connect between synapse and neuron arrays using nanowire in quantum dot and metal in CMOS (complementary metal oxide semiconductor) technology to enable the density of a brain-like connection in hardware. The hardware implementation combines three technologies: 1. Quantum dot and nanowire-based compact synaptic cell (50x50 sq nm) with inherently low parasitic capacitance (hence, low dynamic power approx.l0(exp -11) watts/synapse), 2. Neuron and learning circuits implemented in 50-nm CMOS technology, to be integrated with quantum dot and nanowire synapse, and 3. 3D stacking approach to achieve the overall numbers of high density O(10(exp 12)) synapses and O(10(exp 8)) neurons in the overall system. In a 1-sq cm of quantum dot layer sitting on a 50-nm CMOS layer, innovators were able to pack a 10(exp 6)-neuron and 10(exp 10)-synapse array; however, the constraint for the connection scheme is that each neuron will receive a non-identical 10(exp 4)-synapse set, including itself, via its efficacy of the connection. This is not a fully connected system where the 100x100 synapse array only has a 100-input data bus and 100-output data bus. Due to the data bus sharing, it poses a great challenge to have a complete connected system, and its constraint within the quantum dot and silicon wafer layer. For an effective connection scheme, there are three conditions to be met: 1. Local connection. 2. The nanowire should be connected locally, not globally from which it helps to maximize the data flow by sharing the same wire space location. 3. Each synapse can have an alternate summation line if needed (this option is doable based on the simple mask creation). The 10(exp 3)x10(exp 3)-neuron array was partitioned into a 10-block, 10(exp 2)x10(exp 3)-neuron array. This building block can be completely mapped within itself (10,000 synapses to a neuron).

  16. Developmental Profile and Sexually Dimorphic Expression of Kiss1 and Kiss1r in the Fetal Mouse Brain

    John Gabriel Knoll

    2013-10-01

    Full Text Available The hypothalamic-pituitary-gonadal axis (HPG is a complex neuroendocrine circuit involving multiple levels of regulation. Kisspeptin neurons play essential roles in controlling the HPG axis from the perspectives of puberty onset, oscillations of gonadotropin releasing hormone (GnRH neuron activity and the pre-ovulatory LH surge. The current studies focus on the expression of kisspeptin during murine fetal development using in situ hybridization (ISH, quantitative reverse transcription real-time PCR (QPCR and immunocytochemistry. Expression of mRNA coding for kisspeptin (KISS1 and its receptor KISS1R was observed at embryonic (E day 13 by ISH. At E13 and other later ages examined, Kiss1 signal in individual cells within the arcuate nucleus (ARC appeared stronger in females than males. ISH examination of agonadal steroidogenic factor-1 (Sf1 knockout mice revealed that E17 XY knockouts resembled wild-type XX females. These findings raise the possibility that gonadal hormones modulate the expression of Kiss1 in the ARC prior to birth. The sex and genotype differences were tested quantitatively by QPCR experiments in dissected hypothalami from mice at E17 and adulthood. Females had significantly more Kiss1 than males at both ages, even though the number of cells detected by ISH was similar. In addition, QPCR revealed a significant difference in the amount of Kiss1 mRNA in Sf1 mice with wild-type (WT XY mice expressing less than XY knockouts (KO and XX mice of both genotypes. The detection of immunoreactive KISS1 in perikarya of the ARC at E17 indicates that early mRNA is translated to peptide. The functional significance of this early expression of Kiss1 awaits elucidation.

  17. The IGFBP7 homolog Imp-L2 promotes insulin signaling in distinct neurons of the Drosophila brain.

    Bader, R; Sarraf-Zadeh, L; Peters, M; Moderau, N; Stocker, H; Köhler, K; Pankratz, M J; Hafen, E

    2013-06-15

    In Drosophila, Insulin-like peptide 2 (Dilp-2) is expressed by insulin-producing cells in the brain, and is secreted into the hemolymph to activate insulin signaling systemically. Within the brain, however, a more local activation of insulin signaling may be required to couple behavioral and physiological traits to nutritional inputs. We show that a small subset of neurons in the larval brain has high Dilp-2-mediated insulin signaling activity. This local insulin signaling activation is accompanied by selective Dilp-2 uptake and depends on the expression of the Imaginal morphogenesis protein-late 2 (Imp-L2) in the target neurons. We suggest that Imp-L2 acts as a licensing factor for neuronal IIS activation through Dilp-2 to further increase the precision of insulin activity in the brain.

  18. Simultaneous Transplantation of Fetal Ventral Mesencephalic Tissue and Encapsulated Genetically Modified Cells Releasing GDNF in a Hemi-Parkinsonian Rat Model of Parkinson’s Disease

    Perez-Bouza, Alberto; Di Santo, Stefano; Seiler, Stefanie

    2017-01-01

    Transplantation of fetal ventral mesencephalic (VM) neurons for Parkinson's disease (PD) is limited by poor survival and suboptimal integration of grafted tissue into the host brain. In a 6-OHDA rat model of PD we investigated the feasibility of simultaneous transplantation of rat fetal VM tissue...... between groups were observed for the number of surviving TH-ir neurons or graft volume. In conclusion, our findings demonstrate that simultaneous transplantation of fetal VM tissue and encapsulated GDNF-releasing cells is feasible and support the graft survival and function. Pre-treatment of donor tissue...

  19. Normal and abnormal fetal brain development during the third trimester as demonstrated by neurosonography

    Malinger, G.; Lev, D.; Lerman-Sagie, T.

    2006-01-01

    The multiplanar neurosonographic examination of the fetus enables superb visualization of brain anatomy during pregnancy. The examination may be performed using a transvaginal or a transfundal approach and it is indicated in patients at high risk for CNS anomalies or in those with a suspicious finding during a routine examination. The purpose of this paper is to present a description of the normal brain and of abnormal findings usually diagnosed late in pregnancy, including malformations of cortical development, infratentorial anomalies, and prenatal insults

  20. BIG1 is required for the survival of deep layer neurons, neuronal polarity, and the formation of axonal tracts between the thalamus and neocortex in developing brain.

    Jia-Jie Teoh

    Full Text Available BIG1, an activator protein of the small GTPase, Arf, and encoded by the Arfgef1 gene, is one of candidate genes for epileptic encephalopathy. To know the involvement of BIG1 in epileptic encephalopathy, we analyzed BIG1-deficient mice and found that BIG1 regulates neurite outgrowth and brain development in vitro and in vivo. The loss of BIG1 decreased the size of the neocortex and hippocampus. In BIG1-deficient mice, the neuronal progenitor cells (NPCs and the interneurons were unaffected. However, Tbr1+ and Ctip2+ deep layer (DL neurons showed spatial-temporal dependent apoptosis. This apoptosis gradually progressed from the piriform cortex (PIR, peaked in the neocortex, and then progressed into the hippocampus from embryonic day 13.5 (E13.5 to E17.5. The upper layer (UL and DL order in the neocortex was maintained in BIG1-deficient mice, but the excitatory neurons tended to accumulate before their destination layers. Further pulse-chase migration assay showed that the migration defect was non-cell autonomous and secondary to the progression of apoptosis into the BIG1-deficient neocortex after E15.5. In BIG1-deficient mice, we observed an ectopic projection of corticothalamic axons from the primary somatosensory cortex (S1 into the dorsal lateral geniculate nucleus (dLGN. The thalamocortical axons were unable to cross the diencephalon-telencephalon boundary (DTB. In vitro, BIG1-deficient neurons showed a delay in neuronal polarization. BIG1-deficient neurons were also hypersensitive to low dose glutamate (5 μM, and died via apoptosis. This study showed the role of BIG1 in the survival of DL neurons in developing embryonic brain and in the generation of neuronal polarity.

  1. Preliminary Findings that a Targeted Intervention Leads to Altered Brain Function in Children with Fetal Alcohol Spectrum Disorder

    Kelly Nash

    2017-12-01

    Full Text Available Children with fetal alcohol spectrum disorder (FASD exhibit behavioral dysregulation, executive dysfunction, and atypical function in associated brain regions. Previous research shows early intervention mitigates these outcomes but corresponding brain changes were not studied. Given the Alert® Program for Self-Regulation improves behavioral regulation and executive function in children with FASD, we asked if this therapy also improves their neural functioning in associated regions. Twenty-one children with FASD aged 8–12 years were randomized to the Alert®-treatment (TXT; n = 10 or waitlist-control (WL; n = 11 conditions. They were assessed with a Go-NoGo functional magnetic resonance imaging (fMRI paradigm before and after training or the wait-out period. Groups initially performed equivalently and showed no fMRI differences. At post-test, TXT outperformed WL on NoGo trials while fMRI in uncorrected results with a small-volume correction showed less activation in prefrontal, temporal, and cingulate regions. Groups also demonstrated different patterns of change over time reflecting reduced signal at post-test in selective prefrontal and parietal regions in TXT and increased in WL. In light of previous evidence indicating TXT at post-test perform similar to non-exposed children on the Go-NoGo fMRI paradigm, our findings suggest Alert® does improve functional integrity in the neural circuitry for behavioral regulation in children with FASD.

  2. On the Photonic Cellular Interaction and the Electric Activity of Neurons in the Human Brain

    Salari, V; Tuszynski, J; Bokkon, I; Rahnama, M; Cifra, M

    2011-01-01

    The subject of Ultraweak Photon Emission (UPE) by biological systems is very fascinating, and both evidence of its effects and applications are growing rapidly due to improvements in experimental techniques. Since the relevant equipment should be ultrasensitive with high quantum efficiencies and very low noise levels, the subject of UPE is still hotly debated and some of the interpretations need stronger empirical evidence to be accepted at face value. In this paper we first review different types of interactions between light and living systems based on recent publications. We then discuss the feasibility of UPE production in the human brain. The subject of UPE in the brain is still in early stages of development and needs more accurate experimental methods for proper analysis. In this work we also discuss a possible role of mitochondria in the production of UPE in the neurons of the brain and the plausibility of their effects on microtubules (MTs). MTs have been implicated as playing an important role in the signal and information processing taking place in the mammalian (especially human) brain. Finally, we provide a short discussion about the feasible effects of MTs on electric neural activity in the human brain.

  3. The dynamic brain: from spiking neurons to neural masses and cortical fields.

    Gustavo Deco

    2008-08-01

    Full Text Available The cortex is a complex system, characterized by its dynamics and architecture, which underlie many functions such as action, perception, learning, language, and cognition. Its structural architecture has been studied for more than a hundred years; however, its dynamics have been addressed much less thoroughly. In this paper, we review and integrate, in a unifying framework, a variety of computational approaches that have been used to characterize the dynamics of the cortex, as evidenced at different levels of measurement. Computational models at different space-time scales help us understand the fundamental mechanisms that underpin neural processes and relate these processes to neuroscience data. Modeling at the single neuron level is necessary because this is the level at which information is exchanged between the computing elements of the brain; the neurons. Mesoscopic models tell us how neural elements interact to yield emergent behavior at the level of microcolumns and cortical columns. Macroscopic models can inform us about whole brain dynamics and interactions between large-scale neural systems such as cortical regions, the thalamus, and brain stem. Each level of description relates uniquely to neuroscience data, from single-unit recordings, through local field potentials to functional magnetic resonance imaging (fMRI, electroencephalogram (EEG, and magnetoencephalogram (MEG. Models of the cortex can establish which types of large-scale neuronal networks can perform computations and characterize their emergent properties. Mean-field and related formulations of dynamics also play an essential and complementary role as forward models that can be inverted given empirical data. This makes dynamic models critical in integrating theory and experiments. We argue that elaborating principled and informed models is a prerequisite for grounding empirical neuroscience in a cogent theoretical framework, commensurate with the achievements in the

  4. When larger brains do not have more neurons: Increased numbers of cells are compensated by decreased average cell size across mouse individuals

    Suzana eHerculano-Houzel

    2015-06-01

    Full Text Available There is a strong trend toward increased brain size in mammalian evolution, with larger brains composed of more and larger neurons than smaller brains across species within each mammalian order. Does the evolution of increased numbers of brain neurons, and thus larger brain size, occur simply through the selection of individuals with more and larger neurons, and thus larger brains, within a population? That is, do individuals with larger brains also have more, and larger, neurons than individuals with smaller brains, such that allometric relationships across species are simply an extension of intraspecific scaling? Here we show that this is not the case across adult male mice of a similar age. Rather, increased numbers of neurons across individuals are accompanied by increased numbers of other cells and smaller average cell size of both types, in a trade-off that explains how increased brain mass does not necessarily ensue. Fundamental regulatory mechanisms thus must exist that tie numbers of neurons to numbers of other cells and to average cell size within individual brains. Finally, our results indicate that changes in brain size in evolution are not an extension of individual variation in numbers of neurons, but rather occur through step changes that must simultaneously increase numbers of neurons and cause cell size to increase, rather than decrease.

  5. Localization of [18F]fluorodeoxyglucose in mouse brain neurons with micro-autoradiography

    Yamada, Susumu; Kubota, Roko; Kubota, Kazuo; Ishiwata, Kiichi; Ido, Tatsuo

    1990-01-01

    This is the first study of micro-autoradiography (micro-ARG) for [ 18 F]2-fluoro-2-deoxy-D-glucose ([ 18 F]FDG). The localization of [ 18 F]FDG was demonstrated in dendrites of neuron and also in the myelinated axon in mouse normal brain in vivo. The nucleolus was relatively free of label. The counted silver grain numbers in autoradiogram were linearly correlated to the 18 F radioactivities in the specimen. The micro-ARG using positron emitting 18 F is a very time-saving technique with 4 hours exposure compared with the conventional method using 3 H- or 14 C-labelled tracers. (author)

  6. Augmenting brain metabolism to increase macro- and chaperone-mediated autophagy for decreasing neuronal proteotoxicity and aging.

    Loos, Ben; Klionsky, Daniel J; Wong, Esther

    2017-09-01

    Accumulation of toxic protein aggregates in the nerve cells is a hallmark of neuronal diseases and brain aging. Mechanisms to enhance neuronal surveillance to improve neuronal proteostasis have a direct impact on promoting neuronal health and forestalling age-related decline in brain function. Autophagy is a lysosomal degradative pathway pivotal for neuronal protein quality control. Different types of autophagic mechanisms participate in protein handling in neurons. Macroautophagy targets misfolded and aggregated proteins in autophagic vesicles to the lysosomes for destruction, while chaperone-mediated autophagy (CMA) degrades specific soluble cytosolic proteins delivered to the lysosomes by chaperones. Dysfunctions in macroautophagy and CMA contribute to proteo- and neuro-toxicity associated with neurodegeneration and aging. Thus, augmenting or preserving both autophagic mechanisms pose significant benefits in delaying physiological and pathological neuronal demises. Recently, life-style interventions that modulate metabolite ketone bodies, energy intake by caloric restriction and energy expenditure by exercise have shown to enhance both autophagy and brain health. However, to what extent these interventions affect neuronal autophagy to promote brain fitness remains largely unclear. Here, we review the functional connections of how macroautophagy and CMA are affected by ketone bodies, caloric restriction and exercise in the context of neurodegeneration. A concomitant assessment of yeast Saccharomyces cerevisiae is performed to reveal the conserved nature of such autophagic responses to substrate perturbations. In doing so, we provide novel insights and integrated evidence for a potential adjuvant therapeutic strategy to intervene in the neuronal decline in neurodegenerative diseases by controlling both macroautophagy and CMA fluxes favorably. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Brain Distribution and Modulation of Neuronal Excitability by Indicaxanthin From Opuntia Ficus Indica Administered at Nutritionally-Relevant Amounts

    Giuditta Gambino

    2018-05-01

    Full Text Available Several studies have recently investigated the role of nutraceuticals in complex pathophysiological processes such as oxidative damages, inflammatory conditions and excitotoxicity. In this regard, the effects of nutraceuticals on basic functions of neuronal cells, such as excitability, are still poorly investigated. For this reason, the possible modulation of neuronal excitability by phytochemicals (PhC could represent an interesting field of research given that excitotoxicity phenomena are involved in neurodegenerative alterations leading, for example, to Alzheimer’s disease. The present study was focused on indicaxanthin from Opuntia ficus indica, a bioactive betalain pigment, with a proven antioxidant and anti-inflammatory potential, previously found to cross blood-brain barrier (BBB and to modulate the bioelectric activity of hippocampal neurons. On this basis, we aimed at detecting the specific brain areas where indicaxanthin localizes after oral administration at dietary-achievable amounts and highlighting eventual local effects on the excitability of single neuronal units. HPLC analysis of brain tissue 1 h after ingestion of 2 μmol/kg indicaxanthin indicated that the phytochemical accumulates in cortex, hippocampus, diencephalon, brainstem and cerebellum, but not in the striato-pallidal complex. Then, electrophysiological recordings, applying the microiontophoretic technique, were carried out with different amounts of indicaxanthin (0.34, 0.17, 0.085 ng/neuron to assess whether indicaxanthin influenced the neuronal firing rate. The data showed that the bioelectric activity of neurons belonging to different brain areas was modulated after local injection of indicaxanthin, mainly with dose-related responses. A predominating inhibitory effect was observed, suggesting a possible novel beneficial effect of indicaxanthin in reducing cell excitability. These findings can constitute a new rationale for exploring biological mechanisms through

  8. Brain Distribution and Modulation of Neuronal Excitability by Indicaxanthin From Opuntia Ficus Indica Administered at Nutritionally-Relevant Amounts

    Gambino, Giuditta; Allegra, Mario; Sardo, Pierangelo; Attanzio, Alessandro; Tesoriere, Luisa; Livrea, Maria A.; Ferraro, Giuseppe; Carletti, Fabio

    2018-01-01

    Several studies have recently investigated the role of nutraceuticals in complex pathophysiological processes such as oxidative damages, inflammatory conditions and excitotoxicity. In this regard, the effects of nutraceuticals on basic functions of neuronal cells, such as excitability, are still poorly investigated. For this reason, the possible modulation of neuronal excitability by phytochemicals (PhC) could represent an interesting field of research given that excitotoxicity phenomena are involved in neurodegenerative alterations leading, for example, to Alzheimer’s disease. The present study was focused on indicaxanthin from Opuntia ficus indica, a bioactive betalain pigment, with a proven antioxidant and anti-inflammatory potential, previously found to cross blood-brain barrier (BBB) and to modulate the bioelectric activity of hippocampal neurons. On this basis, we aimed at detecting the specific brain areas where indicaxanthin localizes after oral administration at dietary-achievable amounts and highlighting eventual local effects on the excitability of single neuronal units. HPLC analysis of brain tissue 1 h after ingestion of 2 μmol/kg indicaxanthin indicated that the phytochemical accumulates in cortex, hippocampus, diencephalon, brainstem and cerebellum, but not in the striato-pallidal complex. Then, electrophysiological recordings, applying the microiontophoretic technique, were carried out with different amounts of indicaxanthin (0.34, 0.17, 0.085 ng/neuron) to assess whether indicaxanthin influenced the neuronal firing rate. The data showed that the bioelectric activity of neurons belonging to different brain areas was modulated after local injection of indicaxanthin, mainly with dose-related responses. A predominating inhibitory effect was observed, suggesting a possible novel beneficial effect of indicaxanthin in reducing cell excitability. These findings can constitute a new rationale for exploring biological mechanisms through which PhC could

  9. Lipopolysaccharide Associates with Amyloid Plaques, Neurons and Oligodendrocytes in Alzheimer’s Disease Brain: A Review

    Xinhua Zhan

    2018-02-01

    Full Text Available This review proposes that lipopolysaccharide (LPS, found in the wall of all Gram-negative bacteria could play a role in causing sporadic Alzheimer’s disease (AD. This is based in part upon recent studies showing that: Gram-negative E. coli bacteria can form extracellular amyloid; bacterial-encoded 16S rRNA is present in all human brains with over 70% being Gram-negative bacteria; ultrastructural analyses have shown microbes in erythrocytes of AD patients; blood LPS levels in AD patients are 3-fold the levels in control; LPS combined with focal cerebral ischemia and hypoxia produced amyloid-like plaques and myelin injury in adult rat cortex. Moreover, Gram-negative bacterial LPS was found in aging control and AD brains, though LPS levels were much higher in AD brains. In addition, LPS co-localized with amyloid plaques, peri-vascular amyloid, neurons, and oligodendrocytes in AD brains. Based upon the postulate LPS caused oligodendrocyte injury, degraded Myelin Basic Protein (dMBP levels were found to be much higher in AD compared to control brains. Immunofluorescence showed that the dMBP co-localized with β amyloid (Aβ and LPS in amyloid plaques in AD brain, and dMBP and other myelin molecules were found in the walls of vesicles in periventricular White Matter (WM. These data led to the hypothesis that LPS acts on leukocyte and microglial TLR4-CD14/TLR2 receptors to produce NFkB mediated increases of cytokines which increase Aβ levels, damage oligodendrocytes and produce myelin injury found in AD brain. Since Aβ1–42 is also an agonist for TLR4 receptors, this could produce a vicious cycle that accounts for the relentless progression of AD. Thus, LPS, the TLR4 receptor complex, and Gram-negative bacteria might be treatment or prevention targets for sporadic AD.

  10. Brain neuronal CB2 cannabinoid receptors in drug abuse and depression: from mice to human subjects.

    Emmanuel S Onaivi

    Full Text Available BACKGROUND: Addiction and major depression are mental health problems associated with stressful events in life with high relapse and reoccurrence even after treatment. Many laboratories were not able to detect the presence of cannabinoid CB2 receptors (CB2-Rs in healthy brains, but there has been demonstration of CB2-R expression in rat microglial cells and other brain associated cells during inflammation. Therefore, neuronal expression of CB2-Rs had been ambiguous and controversial and its role in depression and substance abuse is unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study we tested the hypothesis that genetic variants of CB2 gene might be associated with depression in a human population and that alteration in CB2 gene expression may be involved in the effects of abused substances including opiates, cocaine and ethanol in rodents. Here we demonstrate that a high incidence of (Q63R but not (H316Y polymorphism in the CB2 gene was found in Japanese depressed subjects. CB2-Rs and their gene transcripts are expressed in the brains of naïve mice and are modulated following exposure to stressors and administration of abused drugs. Mice that developed alcohol preference had reduced CB2 gene expression and chronic treatment with JWH015 a putative CB2-R agonist, enhanced alcohol consumption in stressed but not in control mice. The direct intracerebroventricular microinjection of CB2 anti-sense oligonucleotide into the mouse brain reduced mouse aversions in the plus-maze test, indicating the functional presence of CB2-Rs in the brain that modifies behavior. We report for the using electron microscopy the sub cellular localization of CB2-Rs that are mainly on post-synaptic elements in rodent brain. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate the functional expression of CB2-Rs in brain that may provide novel targets for the effects of cannabinoids in depression and substance abuse disorders beyond neuro-immunocannabinoid activity.

  11. Glycogen metabolism in brain and neurons - astrocytes metabolic cooperation can be altered by pre- and neonatal lead (Pb) exposure.

    Baranowska-Bosiacka, Irena; Falkowska, Anna; Gutowska, Izabela; Gąssowska, Magdalena; Kolasa-Wołosiuk, Agnieszka; Tarnowski, Maciej; Chibowska, Karina; Goschorska, Marta; Lubkowska, Anna; Chlubek, Dariusz

    2017-09-01

    Lead (Pb) is an environmental neurotoxin which particularly affects the developing brain but the molecular mechanism of its neurotoxicity still needs clarification. The aim of this paper was to examine whether pre- and neonatal exposure to Pb (concentration of Pb in rat offspring blood below the "threshold level") may affect the brain's energy metabolism in neurons and astrocytes via the amount of available glycogen. We investigated the glycogen concentration in the brain, as well as the expression of the key enzymes involved in glycogen metabolism in brain: glycogen synthase 1 (Gys1), glycogen phosphorylase (PYGM, an isoform active in astrocytes; and PYGB, an isoform active in neurons) and phosphorylase kinase β (PHKB). Moreover, the expression of connexin 43 (Cx43) was evaluated to analyze whether Pb poisoning during the early phase of life may affect the neuron-astrocytes' metabolic cooperation. This work shows for the first time that exposure to Pb in early life can impair brain energy metabolism by reducing the amount of glycogen and decreasing the rate of its metabolism. This reduction in brain glycogen level was accompanied by a decrease in Gys1 expression. We noted a reduction in the immunoreactivity and the gene expression of both PYGB and PYGM isoform, as well as an increase in the expression of PHKB in Pb-treated rats. Moreover, exposure to Pb induced decrease in connexin 43 immunoexpression in all the brain structures analyzed, both in astrocytes as well as in neurons. Our data suggests that exposure to Pb in the pre- and neonatal periods results in a decrease in the level of brain glycogen and a reduction in the rate of its metabolism, thereby reducing glucose availability, which as a further consequence may lead to the impairment of brain energy metabolism and the metabolic cooperation between neurons and astrocytes. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. EAAC1 Gene Deletion Increases Neuronal Death and Blood Brain Barrier Disruption after Transient Cerebral Ischemia in Female Mice

    Bo Young Choi

    2014-10-01

    Full Text Available EAAC1 is important in modulating brain ischemic tolerance. Mice lacking EAAC1 exhibit increased susceptibility to neuronal oxidative stress in mice after transient cerebral ischemia. EAAC1 was first described as a glutamate transporter but later recognized to also function as a cysteine transporter in neurons. EAAC1-mediated transport of cysteine into neurons contributes to neuronal antioxidant function by providing cysteine substrates for glutathione synthesis. Here we evaluated the effects of EAAC1 gene deletion on hippocampal blood vessel disorganization after transient cerebral ischemia. EAAC1−/− female mice subjected to transient cerebral ischemia by common carotid artery occlusion for 30 min exhibited twice as much hippocampal neuronal death compared to wild-type female mice as well as increased reduction of neuronal glutathione, blood–brain barrier (BBB disruption and vessel disorganization. Pre-treatment of N-acetyl cysteine, a membrane-permeant cysteine prodrug, increased basal glutathione levels in the EAAC1−/− female mice and reduced ischemic neuronal death, BBB disruption and vessel disorganization. These findings suggest that cysteine uptake by EAAC1 is important for neuronal antioxidant function under ischemic conditions.

  13. How does transcranial magnetic stimulation modify neuronal activity in the brain? Implications for studies of cognition

    Siebner, Hartwig R; Hartwigsen, Gesa; Kassuba, Tanja

    2009-01-01

    Transcranial magnetic stimulation (TMS) uses a magnetic field to "carry" a short lasting electrical current pulse into the brain where it stimulates neurones, particularly in superficial regions of cerebral cortex. TMS can interfere with cognitive functions in two ways. A high intensity TMS pulse...... in the human brain. This transient neurodisruption has been termed a "virtual lesion". Smaller intensities of stimulation produce less activity; in such cases, cognitive operations can probably continue but are disrupted because of the added noisy input from the TMS pulse. It is usually argued that if a TMS...... pulse affects performance, then the area stimulated must provide an essential contribution to behaviour being studied. However, there is one exception to this: the pulse could be applied to an area that is not involved in the task but which has projections to the critical site. Activation of outputs...

  14. 14-3-3 Proteins in Brain Development: Neurogenesis, Neuronal Migration and Neuromorphogenesis

    Brett Cornell

    2017-10-01

    Full Text Available The 14-3-3 proteins are a family of highly conserved, multifunctional proteins that are highly expressed in the brain during development. Cumulatively, the seven 14-3-3 isoforms make up approximately 1% of total soluble brain protein. Over the last decade, evidence has accumulated implicating the importance of the 14-3-3 protein family in the development of the nervous system, in particular cortical development, and have more recently been recognized as key regulators in a number of neurodevelopmental processes. In this review we will discuss the known roles of each 14-3-3 isoform in the development of the cortex, their relation to human neurodevelopmental disorders, as well as the challenges and questions that are left to be answered. In particular, we focus on the 14-3-3 isoforms and their involvement in the three key stages of cortical development; neurogenesis and differentiation, neuronal migration and neuromorphogenesis and synaptogenesis.

  15. Sex differences in the brain, behavior, and neuropsychiatric disorders

    Bao, Ai-Min; Swaab, Dick F.

    2010-01-01

    Sex differences in the brain are reflected in behavior and in the risk for neuropsychiatric disorders. The fetal brain develops in the male direction due to a direct effect of testosterone on the developing neurons, or in the female direction due to the absence of such a testosterone surge. Because

  16. Corrigendum to “Long-term valproic acid exposure increases the number of neocortical neurons in the developing rat brain" [Neurosci.Lett. 580 (2014) 12–16] A possible new animal model of autism

    Sabers, Anne; Bertelsen, Freja C B; Scheel-Krüger, Jørgen

    2015-01-01

    The aim of this study was to test the hypothesis that long-term fetal valproic acid (VPA) exposure at doses relevant to the human clinic interferes with normal brain development. Pregnant rats were given intraperitoneal injections of VPA (20 mg/kg or 100 mg/kg) continuously during the last 9......–12 days of pregnancy and during the lactation period until sacrifice on the 23rd postnatal day. Total number of neocortical neurons was estimated using the optical fraction at or and frontal cortical thicknesses were sampled in VPA exposed pups compared with an unexposed control group. We found that pups....... Pups exposed to 100 mg/kg, but not to 20 mg/kg VPA displayed a significant (p brain development by disturbing neocortical organization...

  17. Responsiveness of fetal rat brain cells to glia maturation factor during neoplastic transformation in cell culture

    Haugen, A; Laerum, O D; Bock, E

    1981-01-01

    of gestation. The brains of the treated fetuses were transferred to cell culture and underwent neoplastic transformation with a characteristic sequence of phenotypic alterations which could be divided into five different stages. During the first 40 days after explantation (stage I & II) BE induced...

  18. Abnormal neuronal activity in Tourette syndrome and its modulation using deep brain stimulation

    Israelashvili, Michal; Loewenstern, Yocheved

    2015-01-01

    Tourette syndrome (TS) is a common childhood-onset disorder characterized by motor and vocal tics that are typically accompanied by a multitude of comorbid symptoms. Pharmacological treatment options are limited, which has led to the exploration of deep brain stimulation (DBS) as a possible treatment for severe cases. Multiple lines of evidence have linked TS with abnormalities in the motor and limbic cortico-basal ganglia (CBG) pathways. Neurophysiological data have only recently started to slowly accumulate from multiple sources: noninvasive imaging and electrophysiological techniques, invasive electrophysiological recordings in TS patients undergoing DBS implantation surgery, and animal models of the disorder. These converging sources point to system-level physiological changes throughout the CBG pathway, including both general altered baseline neuronal activity patterns and specific tic-related activity. DBS has been applied to different regions along the motor and limbic pathways, primarily to the globus pallidus internus, thalamic nuclei, and nucleus accumbens. In line with the findings that also draw on the more abundant application of DBS to Parkinson's disease, this stimulation is assumed to result in changes in the neuronal firing patterns and the passage of information through the stimulated nuclei. We present an overview of recent experimental findings on abnormal neuronal activity associated with TS and the changes in this activity following DBS. These findings are then discussed in the context of current models of CBG function in the normal state, during TS, and finally in the wider context of DBS in CBG-related disorders. PMID:25925326

  19. A portable telemetry system for brain stimulation and neuronal activity recording in freely behaving small animals.

    Ye, Xuesong; Wang, Peng; Liu, Jun; Zhang, Shaomin; Jiang, Jun; Wang, Qingbo; Chen, Weidong; Zheng, Xiaoxiang

    2008-09-30

    A portable multi-channel telemetry system which can be used for brain stimulation and neuronal activity recording in freely behaving small animals is described here. This system consists of three major components of headstage, backpack and portable Personal Digital Assistant (PDA). The headstage contains high precision instrument amplifiers with high input impedance. The backpack is comprised of two parts: (1) a main board (size: 36 mm x 22 mm x 3.5 mm and weight: 40 g with batteries, 20 g without), with current/voltage stimulator and special circuit suitable for neuronal activity recording and (2) and a bluetooth transceiver, with a high data transmission rate up to 70 kb/s, suitable for downloading stimulation commands and uploading acquired data. We recorded neuronal activities of the primary motor area of a freely behaving rat with 12-bit resolution at 12 k samples/s. The recorded data and analysis results showed that the system was successful by comparing with the commercial equipment Cerebus 128-Channel Data Acquisition System (Cyberkinetics Inc.). Using the PDA, we can control stimulation and recording. It provides a flexible method to do some research work in the circumstances where other approaches would be difficult or impossible.

  20. Ventral medullary neurones excited from the hypothalamic and mid-brain defence areas.

    Hilton, S M; Smith, P R

    1984-07-01

    In cats anaesthetised with chloralose, the ventral medulla was explored in and around the strip previously identified as the location of the efferent pathway from the hypothalamic and mid-brain defence areas to the spinal cord, in a search for neurones excited by electrical stimulation of the defence areas. Such units were found mostly in the caudal part of this strip, at a depth of not more than 500 microns from the surface. Nearly all were located in the ventral part of nucleus paragigantocellularis lateralis (PGL) at the level of the rostral pole of the inferior olive. There was evidence of temporal and spatial facilitation, indicating a convergent excitatory input from the defence areas onto neurones in PGL. This is consistent with earlier evidence of a synaptic relay in the efferent pathway at this site. When the pathway is blocked at this site, arterial blood pressure falls profoundly, so activity in these neurones may be essential for the normal level of sympathetic nerve activity.

  1. Time- and dose-dependent changes in neuronal activity produced by X radiation in brain slices

    Pellmar, T.C.; Schauer, D.A.; Zeman, G.H.

    1990-01-01

    A new method of exposing tissues to X rays in a lead Faraday cage has made it possible to examine directly radiation damage to isolated neuronal tissue. Thin slices of hippocampus from brains of euthanized guinea pigs were exposed to 17.4 ke V X radiation. Electrophysiological recordings were made before, during, and after exposure to doses between 5 and 65 Gy at a dose rate of 1.54 Gy/min. Following exposure to doses of 40 Gy and greater, the synaptic potential was enhanced, reaching a steady level soon after exposure. The ability of the synaptic potential to generate a spike was reduced and damage progressed after termination of the radiation exposure. Recovery was not observed following termination of exposure. These results demonstrate that an isolated neuronal network can show complex changes in electrophysiological properties following moderate doses of ionizing radiation. An investigation of radiation damage directly to neurons in vitro will contribute to the understanding of the underlying mechanisms of radiation-induced nervous system dysfunction

  2. Combined autoradiographic-immunocytochemical analysis of opioid receptors and opioid peptide neuronal systems in brain

    Lewis, M.E.; Khachaturian, H.; Watson, S.J.

    1985-01-01

    Using adjacent section autoradiography-immunocytochemistry, the distribution of (TH)naloxone binding sites was studied in relation to neuronal systems containing (Leu)enkephalin, dynorphin A, or beta-endorphin immunoreactivity in rat brain. Brain sections from formaldehyde-perfused rats show robust specific binding of (TH)naloxone, the pharmacological (mu-like) properties of which appear unaltered. In contrast, specific binding of the delta ligand (TH)D-Ala2,D-Leu5-enkephalin was virtually totally eliminated as a result of formaldehyde perfusion. Using adjacent section analysis, the authors have noted associations between (TH)naloxone binding sites and one, two, or all three opioid systems in different brain regions; however, in some areas, no apparent relationship could be observed. Within regions, the relationship was complex. The complexity of the association between (TH)naloxone binding sites and the multiple opioid systems, and previous reports of co-localization of mu and kappa receptors in rat brain, are inconsistent with a simple-one-to-one relationship between a given opioid precursor and opioid receptor subtype. Instead, since differential processing of the three precursors gives rise to peptides of varying receptor subtype potencies and selectivities, the multiple peptide-receptor relationships may point to a key role of post-translational processing in determining the physiological consequences of opioid neurotransmission.

  3. Visualization of migration of human cortical neurons generated from induced pluripotent stem cells.

    Bamba, Yohei; Kanemura, Yonehiro; Okano, Hideyuki; Yamasaki, Mami

    2017-09-01

    Neuronal migration is considered a key process in human brain development. However, direct observation of migrating human cortical neurons in the fetal brain is accompanied by ethical concerns and is a major obstacle in investigating human cortical neuronal migration. We established a novel system that enables direct visualization of migrating cortical neurons generated from human induced pluripotent stem cells (hiPSCs). We observed the migration of cortical neurons generated from hiPSCs derived from a control and from a patient with lissencephaly. Our system needs no viable brain tissue, which is usually used in slice culture. Migratory behavior of human cortical neuron can be observed more easily and more vividly by its fluorescence and glial scaffold than that by earlier methods. Our in vitro experimental system provides a new platform for investigating development of the human central nervous system and brain malformation. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Brain-derived neurotrophic factor/neurotrophin 3 regulate axon initial segment location and affect neuronal excitability in cultured hippocampal neurons.

    Guo, Yu; Su, Zi-Jun; Chen, Yi-Kun; Chai, Zhen

    2017-07-01

    Plasticity of the axon initial segment (AIS) has aroused great interest in recent years because it regulates action potential initiation and neuronal excitability. AIS plasticity manifests as modulation of ion channels or variation in AIS structure. However, the mechanisms underlying structural plasticity of the AIS are not well understood. Here, we combined immunofluorescence, patch-clamp recordings, and pharmacological methods in cultured hippocampal neurons to investigate the factors participating in AIS structural plasticity during development. With lowered neuronal density, the distance between the AIS and the soma increased, while neuronal excitability decreased, as shown by the increased action potential threshold and current threshold for firing an action potential. This variation in the location of the AIS was associated with cellular secretory substances, including brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3). Indeed, blocking BDNF and NT3 with TrkB-Fc eliminated the effect of conditioned medium collected from high-density cultures on AIS relocation. Elevating the extracellular concentration of BDNF or NT3 promoted movement of the AIS proximally to the soma and increased neuronal excitability. Furthermore, knockdown of neurotrophin receptors TrkB and TrkC caused distal movement of the AIS. Our results demonstrate that BDNF and NT3 regulate AIS location and neuronal excitability. These regulatory functions of neurotrophic factors provide insight into the molecular mechanisms underlying AIS biology. © 2017 International Society for Neurochemistry.

  5. Increased Sleep Need and Reduction of Tuberomammillary Histamine Neurons after Rodent Traumatic Brain Injury.

    Noain, Daniela; Büchele, Fabian; Schreglmann, Sebastian R; Valko, Philipp O; Gavrilov, Yuri V; Morawska, Marta M; Imbach, Lukas L; Baumann, Christian R

    2018-01-01

    Although sleep-wake disturbances are prevalent and well described after traumatic brain injury, their pathophysiology remains unclear, most likely because human traumatic brain injury is a highly heterogeneous entity that makes the systematic study of sleep-wake disturbances in relation to trauma-induced histological changes a challenging task. Despite increasing interest, specific and effective treatment strategies for post-traumatic sleep-wake disturbances are still missing. With the present work, therefore, we aimed at studying acute and chronic sleep-wake disturbances by electrophysiological means, and at assessing their histological correlates after closed diffuse traumatic brain injury in rats with the ultimate goal of generating a model of post-traumatic sleep-wake disturbances and associated histopathological findings that accurately represents the human condition. We assessed sleep-wake behavior by means of standard electrophysiological recordings before and 1, 7, and 28 days after sham or traumatic brain injury procedures. Sleep-wake findings were then correlated to immunohistochemically labeled and stereologically quantified neuronal arousal systems. Compared with control animals, we found that closed diffuse traumatic brain injury caused increased sleep need one month after trauma, and sleep was more consolidated. As histological correlate, we found a reduced number of histamine immunoreactive cells in the tuberomammillary nucleus, potentially related to increased neuroinflammation. Monoaminergic and hypocretinergic neurotransmitter systems in the hypothalamus and rostral brainstem were not affected, however. These results suggest that our rat traumatic brain injury model reflects human post-traumatic sleep-wake disturbances and associated histopathological findings very accurately, thus providing a study platform for novel treatment strategies for affected patients.

  6. Energy Metabolism of the Brain, Including the Cooperation between Astrocytes and Neurons, Especially in the Context of Glycogen Metabolism

    Falkowska, Anna; Gutowska, Izabela; Goschorska, Marta; Nowacki, Przemys?aw; Chlubek, Dariusz; Baranowska-Bosiacka, Irena

    2015-01-01

    Glycogen metabolism has important implications for the functioning of the brain, especially the cooperation between astrocytes and neurons. According to various research data, in a glycogen deficiency (for example during hypoglycemia) glycogen supplies are used to generate lactate, which is then transported to neighboring neurons. Likewise, during periods of intense activity of the nervous system, when the energy demand exceeds supply, astrocyte glycogen is immediately converted to lactate, s...

  7. Contribution of Histologic Chorioamnionitis and Fetal Inflammatory Response Syndrome to Increased Risk of Brain Injury in Infants With Preterm Premature Rupture of Membranes.

    Lu, Hong-Yan; Zhang, Qiang; Wang, Qiu-Xia; Lu, Jun-Ying

    2016-08-01

    To determine the association of histologic chorioamnionitis (HCA) and fetal inflammatory response syndrome (FIRS) with brain injuries in infants born to mothers with preterm premature rupture of membranes. A total of 103 singleton infants born to mothers with preterm premature rupture of membranes were enrolled. The placental inflammation was confirmed by HCA, and FIRS was defined in fetuses with preterm labor and an elevation of the fetal plasma interleukin-6 concentration. Examination of brain images was conducted to confirm the existence of brain injuries. Based on placental HCA and umbilical cord blood interleukin-6 level, all patients were divided into three groups: HCA(-)FIRS(+), HCA(+)FIRS(-), and HCA(+)FIRS(+). Among all infants with preterm premature rupture of membranes, 53.40% were exposed to HCA, 20.38% experienced FIRS, and the overall incidence of brain injuries was 38.83%. The incidence of brain injury in HCA(-)FIRS(+), HCA(+)FIRS(-), and HCA(+)FIRS(+) groups were 20.83%, 41.18%, and 76.19%, respectively. HCA at the advanced grades and stages was associated with increased risk of brain injury. Umbilical cord blood levels of interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-α), and granulocyte-colony stimulating factor (G-CSF) in premature infants with brain injuries were significantly higher than in those without brain injuries. Infants diagnosed with both HCA and FIRS showed significantly higher levels of IL-8, TNF-α, and G-CSF than those with HCA alone. Preterm infants exposed to severe chorioamnionitis had an increased risk of brain injury. IL-6, IL-8, TNF-α, and G-CSF in cord blood were associated with brain injuries in preterm infants and may be used as extradiagnostic criteria. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Human Brain Networks: Spiking Neuron Models, Multistability, Synchronization, Thermodynamics, Maximum Entropy Production, and Anesthetic Cascade Mechanisms

    Wassim M. Haddad

    2014-07-01

    theoretical foundation for general anesthesia using the network properties of the brain. Finally, we present some key emergent properties from the fields of thermodynamics and electromagnetic field theory to qualitatively explain the underlying neuronal mechanisms of action for anesthesia and consciousness.

  9. Energy Metabolism of the Brain, Including the Cooperation between Astrocytes and Neurons, Especially in the Context of Glycogen Metabolism.

    Falkowska, Anna; Gutowska, Izabela; Goschorska, Marta; Nowacki, Przemysław; Chlubek, Dariusz; Baranowska-Bosiacka, Irena

    2015-10-29

    Glycogen metabolism has important implications for the functioning of the brain, especially the cooperation between astrocytes and neurons. According to various research data, in a glycogen deficiency (for example during hypoglycemia) glycogen supplies are used to generate lactate, which is then transported to neighboring neurons. Likewise, during periods of intense activity of the nervous system, when the energy demand exceeds supply, astrocyte glycogen is immediately converted to lactate, some of which is transported to the neurons. Thus, glycogen from astrocytes functions as a kind of protection against hypoglycemia, ensuring preservation of neuronal function. The neuroprotective effect of lactate during hypoglycemia or cerebral ischemia has been reported in literature. This review goes on to emphasize that while neurons and astrocytes differ in metabolic profile, they interact to form a common metabolic cooperation.

  10. Neural correlates of olfactory learning paradigms in an identified neuron in the honeybee brain.

    Mauelshagen, J

    1993-02-01

    1. Sensitization and classical odor conditioning of the proboscis extension reflex were functionally analyzed by repeated intracellular recordings from a single identified neuron (PE1-neuron) in the central bee brain. This neuron belongs to the class of "extrinsic cells" arising from the pedunculus of the mushroom bodies and has extensive arborizations in the median and lateral protocerebrum. The recordings were performed on isolated bee heads. 2. Two different series of physiological experiments were carried out with the use of a similar temporal succession of stimuli as in previous behavioral experiments. In the first series, one group of animals was used for a single conditioning trial [conditioned stimulus (CS), carnation; unconditioned stimulus (US), sucrose solution to the antennae and proboscis), a second group was used for sensitization (sensitizing stimulus, sucrose solution to the antennae and/or proboscis), and the third group served as control (no sucrose stimulation). In the second series, a differential conditioning paradigm (paired odor CS+, carnation; unpaired odor CS-, orange blossom) was applied to test the associative nature of the conditioning effect. 3. The PE1-neuron showed a characteristic burstlike odor response before the training procedures. The treatments resulted in different spike-frequency modulations of this response, which were specific for the nonassociative and associative stimulus paradigms applied. During differential conditioning, there are dynamic up and down modulations of spike frequencies and of the DC potentials underlying the responses to the CS+. Overall, only transient changes in the minute range were observed. 4. The results of the sensitization procedures suggest two qualitatively different US pathways. The comparison between sensitization and one-trial conditioning shows differential effects of nonassociative and associative stimulus paradigms on the response behavior of the PE1-neuron. The results of the differential

  11. Fetal functional imaging portrays heterogeneous development of emerging human brain networks

    Schwartz, Ernst; Kasprian, Gregor; Gruber, Gerlinde M.; Prayer, Daniela; Langs, Georg; Jakab, András; Schöpf, Veronika

    2014-01-01

    The functional connectivity architecture of the adult human brain enables complex cognitive processes, and exhibits a remarkably complex structure shared across individuals. We are only beginning to understand its heterogeneous structure, ranging from a strongly hierarchical organization in sensorimotor areas to widely distributed networks in areas such as the parieto-frontal cortex. Our study relied on the functional magnetic resonance imaging (fMRI) data of 32 fetuses with no detectable mor...

  12. Electroresponsive properties and membrane potential trajectories of three types of inspiratory neurons in the newborn mouse brain stem in vitro

    Rekling, J C; Champagnat, J; Denavit-Saubié, M

    1996-01-01

    with the aim of extending the classification of inspiratory neurons to include analysis of active membrane properties. 2. The slice generated a regular rhythmic motor output recorded as burst of action potentials on a XII nerve root with a peak to peak time of 11.5 +/- 3.4 s and a duration of 483 +/- 54 ms......1. The electrophysiological properties of inspiratory neurons were studied in a rhythmically active thick-slice preparation of the newborn mouse brain stem maintained in vitro. Whole cell patch recordings were performed from 60 inspiratory neurons within the rostral ventrolateral part of the slice...

  13. Divergent projections of catecholaminergic neurons in the nucleus of the solitary tract to limbic forebrain and medullary autonomic brain regions.

    Reyes, Beverly A S; Van Bockstaele, Elisabeth J

    2006-10-30

    The nucleus of the solitary tract (NTS) is a critical structure involved in coordinating autonomic and visceral activities. Previous independent studies have demonstrated efferent projections from the NTS to the nucleus paragigantocellularis (PGi) and the central nucleus of the amygdala (CNA) in rat brain. To further characterize the neural circuitry originating from the NTS with postsynaptic targets in the amygdala and medullary autonomic targets, distinct green or red fluorescent latex microspheres were injected into the PGi and the CNA, respectively, of the same rat. Thirty-micron thick tissue sections through the lower brainstem and forebrain were collected. Every fourth section through the NTS region was processed for immunocytochemical detection of tyrosine hydroxylase (TH), a marker of catecholaminergic neurons. Retrogradely labeled neurons from the PGi or CNA were distributed throughout the rostro-caudal segments of the NTS. However, the majority of neurons containing both retrograde tracers were distributed within the caudal third of the NTS. Cell counts revealed that approximately 27% of neurons projecting to the CNA in the NTS sent collateralized projections to the PGi while approximately 16% of neurons projecting to the PGi sent collateralized projections to the CNA. Interestingly, more than half of the PGi and CNA-projecting neurons in the NTS expressed TH immunoreactivity. These data indicate that catecholaminergic neurons in the NTS are poised to simultaneously coordinate activities in limbic and medullary autonomic brain regions.

  14. Region specific regulation of glutamic acid decarboxylase mRNA expression by dopamine neurons in rat brain.

    Lindefors, N; Brene, S; Herrera-Marschitz, M; Persson, H

    1989-01-01

    In situ hybridization histochemistry and RNA blots were used to study the expression of glutamic acid decarboxylase (GAD) mRNA in rats with or without a unilateral lesion of midbrain dopamine neurons. Two populations of GAD mRNA positive neurons were found in the intact caudate-putamen, substantia nigra and fronto-parietal cortex. In caudate-putamen, only one out of ten of the GAD mRNA positive neurons expressed high levels, while in substantia nigra every second of the positive neurons expressed high levels of GAD mRNA. Relatively few, but intensively labelled neurons were found in the intact fronto-parietal cerebral cortex. In addition, one out of six of the GAD mRNA positive neurons in the fronto-parietal cortex showed a low labeling. On the ipsilateral side, the forebrain dopamine deafferentation induced an increase in the number of neurons expressing high levels of GAD mRNA in caudate-putamen, and a decrease in fronto-parietal cortex. A smaller decrease was also seen in substantia nigra. However, the total number of GAD mRNA positive neurons were not significantly changed in any of these brain regions. The changes in the levels of GAD mRNA after the dopamine lesion were confirmed by RNA blot analysis. Hence, midbrain dopamine neurons appear to control neuronal expression of GAD mRNA by a tonic down-regulation in a fraction of GAD mRNA positive neurons in caudate-putamen, and a tonic up-regulation in a fraction of GAD mRNA positive neurons in fronto-parietal cortex and substantia nigra.

  15. Mesenchymal stem cells support neuronal fiber growth in an organotypic brain slice co-culture model.

    Sygnecka, Katja; Heider, Andreas; Scherf, Nico; Alt, Rüdiger; Franke, Heike; Heine, Claudia

    2015-04-01

    Mesenchymal stem cells (MSCs) have been identified as promising candidates for neuroregenerative cell therapies. However, the impact of different isolation procedures on the functional and regenerative characteristics of MSC populations has not been studied thoroughly. To quantify these differences, we directly compared classically isolated bulk bone marrow-derived MSCs (bulk BM-MSCs) to the subpopulation Sca-1(+)Lin(-)CD45(-)-derived MSCs(-) (SL45-MSCs), isolated by fluorescence-activated cell sorting from bulk BM-cell suspensions. Both populations were analyzed with respect to functional readouts, that are, frequency of fibroblast colony forming units (CFU-f), general morphology, and expression of stem cell markers. The SL45-MSC population is characterized by greater morphological homogeneity, higher CFU-f frequency, and significantly increased nestin expression compared with bulk BM-MSCs. We further quantified the potential of both cell populations to enhance neuronal fiber growth, using an ex vivo model of organotypic brain slice co-cultures of the mesocortical dopaminergic projection system. The MSC populations were cultivated underneath the slice co-cultures without direct contact using a transwell system. After cultivation, the fiber density in the border region between the two brain slices was quantified. While both populations significantly enhanced fiber outgrowth as compared with controls, purified SL45-MSCs stimulated fiber growth to a larger degree. Subsequently, we analyzed the expression of different growth factors in both cell populations. The results show a significantly higher expression of brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor in the SL45-MSCs population. Altogether, we conclude that MSC preparations enriched for primary MSCs promote neuronal regeneration and axonal regrowth, more effectively than bulk BM-MSCs, an effect that may be mediated by a higher BDNF secretion.

  16. CRMP5 regulates generation and survival of newborn neurons in olfactory and hippocampal neurogenic areas of the adult mouse brain.

    Alexandra Veyrac

    Full Text Available The Collapsin Response Mediator Proteins (CRMPS are highly expressed in the developing brain, and in adult brain areas that retain neurogenesis, ie: the olfactory bulb (OB and the dentate gyrus (DG. During brain development, CRMPs are essentially involved in signaling of axon guidance and neurite outgrowth, but their functions in the adult brain remain largely unknown. CRMP5 has been initially identified as the target of auto-antibodies involved in paraneoplasic neurological diseases and further implicated in a neurite outgrowth inhibition mediated by tubulin binding. Interestingly, CRMP5 is also highly expressed in adult brain neurogenic areas where its functions have not yet been elucidated. Here we observed in both neurogenic areas of the adult mouse brain that CRMP5 was present in proliferating and post-mitotic neuroblasts, while they migrate and differentiate into mature neurons. In CRMP5(-/- mice, the lack of CRMP5 resulted in a significant increase of proliferation and neurogenesis, but also in an excess of apoptotic death of granule cells in the OB and DG. These findings provide the first evidence that CRMP5 is involved in the generation and survival of newly generated neurons in areas of the adult brain with a high level of activity-dependent neuronal plasticity.

  17. Housekeeping gene expression during fetal brain development in the rat-validation by semi-quantitative RT-PCR.

    Al-Bader, Maie Dawoud; Al-Sarraf, Hameed Ali

    2005-04-21

    Mammalian gene expression is usually carried out at the level of mRNA where the amount of mRNA of interest is measured under different conditions such as growth and development. It is therefore important to use a "housekeeping gene", that does not change in relative abundance during the experimental conditions, as a standard or internal control. However, recent data suggest that expression of some housekeeping genes may vary with the extent of cell proliferation, differentiation and under various experimental conditions. In this study, the expression of various housekeeping genes (18S rRNA [18S], glyceraldehydes-3-phosphate dehydrogenase [G3PDH], beta-glucuronidase [BGLU], histone H4 [HH4], ribosomal protein L19 [RPL19] and cyclophilin [CY]) was investigated during fetal rat brain development using semi-quantitative RT-PCR at 16, 19 and 21 days gestation. It was found that all genes studied, with exception to G3PDH, did not show any change in their expression levels during development. G3PDH, on the other hand, showed increased expression with development. These results suggest that the choice of a housekeeping gene is critical to the interpretation of experimental results and should be modified according to the nature of the study.

  18. Low fetal hemoglobin percentage is associated with silent brain lesions in adults with homozygous sickle cell disease.

    Calvet, David; Tuilier, Titien; Mélé, Nicolas; Turc, Guillaume; Habibi, Anoosha; Abdallah, Nassim Ait; Majhadi, Loubna; Hemery, François; Edjlali, Myriam; Galacteros, Frédéric; Bartolucci, Pablo

    2017-12-12

    Silent white matter changes (WMCs) on brain imaging are common in individuals with sickle cell disease (SCD) and are associated with cognitive deficits in children. We investigated the factors predictive of WMCs in adults with homozygous SCD and no history of neurological conditions. Patients were recruited from a cohort of adults with homozygous SCD followed up at an adult sickle cell referral center for which steady-state measurements of biological parameters and magnetic resonance imaging scans of the brain were available. WMCs were rated by consensus, on a validated age-related WMC scale. The prevalence of WMCs was 49% (95% confidence interval [CI], 39%-60%) in the 83 patients without vasculopathy included. In univariable analysis, the patients who had WMCs were more likely to be older ( P = .003) and to have hypertension ( P = .02), a lower mean corpuscular volume ( P = .005), a lower corpuscular hemoglobin concentration ( P = .008), and a lower fetal hemoglobin percentage (%HbF) ( P = .003). In multivariable analysis, only a lower %HbF remained associated with the presence of WMCs (odds ratio [OR] per 1% increase in %HbF, 0.84; 95% CI, 0.72-0.97; P = .021). %HbF was also associated with WMC burden ( P for trend = .007). Multivariable ordinal logistic regression showed an inverse relationship between WMC burden (age-related WMC score divided into 4 strata) and HbF level (OR for 1% increase in %HbF, 0.89; 95% CI, 0.79-0.99; P = .039). Our study suggests that HbF may protect against silent WMCs, decreasing the likelihood of WMCs being present and their severity. It may therefore be beneficial to increase HbF levels in patients with WMCs.

  19. Upper motor neuron and extra-motor neuron involvement in amyotrophic lateral sclerosis: A clinical and brain imaging review

    van der Graaff, M. M.; de Jong, J. M. B. V.; Baas, F.; de Visser, M.

    2009-01-01

    There is an ongoing discussion whether ALS is primarily a disease of upper motor neurons or lower motor neurons. We undertook a review to assess how new insights have contributed to solve this controversy. For this purpose we selected relevant publications from 1995 onwards focussing on (1) primary

  20. Neuronal LRP1 regulates glucose metabolism and insulin signaling in the brain.

    Liu, Chia-Chen; Hu, Jin; Tsai, Chih-Wei; Yue, Mei; Melrose, Heather L; Kanekiyo, Takahisa; Bu, Guojun

    2015-04-08

    Alzheimer's disease (AD) is a neurological disorder characterized by profound memory loss and progressive dementia. Accumulating evidence suggests that Type 2 diabetes mellitus, a metabolic disorder characterized by insulin resistance and glucose intolerance, significantly increases the risk for developing AD. Whereas amyloid-β (Aβ) deposition and neurofibrillary tangles are major histological hallmarks of AD, impairment of cerebral glucose metabolism precedes these pathological changes during the early stage of AD and likely triggers or exacerbates AD pathology. However, the mechanisms linking disturbed insulin signaling/glucose metabolism and AD pathogenesis remain unclear. The low-density lipoprotein receptor-related protein 1 (LRP1), a major apolipoprotein E receptor, plays critical roles in lipoprotein metabolism, synaptic maintenance, and clearance of Aβ in the brain. Here, we demonstrate that LRP1 interacts with the insulin receptor β in the brain and regulates insulin signaling and glucose uptake. LRP1 deficiency in neurons leads to impaired insulin signaling as well as reduced levels of glucose transporters GLUT3 and GLUT4. Consequently, glucose uptake is reduced. By using an in vivo microdialysis technique sampling brain glucose concentration in freely moving mice, we further show that LRP1 deficiency in conditional knock-out mice resulted in glucose intolerance in the brain. We also found that hyperglycemia suppresses LRP1 expression, which further exacerbates insulin resistance, glucose intolerance, and AD pathology. As loss of LRP1 expression is seen in AD brains, our study provides novel insights into insulin resistance in AD. Our work also establishes new targets that can be explored for AD prevention or therapy. Copyright © 2015 the authors 0270-6474/15/355851-09$15.00/0.

  1. Physiological neuronal decline in healthy aging human brain - An in vivo study with MRI and short echo-time whole-brain (1)H MR spectroscopic imaging.

    Ding, Xiao-Qi; Maudsley, Andrew A; Sabati, Mohammad; Sheriff, Sulaiman; Schmitz, Birte; Schütze, Martin; Bronzlik, Paul; Kahl, Kai G; Lanfermann, Heinrich

    2016-08-15

    Knowledge of physiological aging in healthy human brain is increasingly important for neuroscientific research and clinical diagnosis. To investigate neuronal decline in normal aging brain eighty-one healthy subjects aged between 20 and 70years were studied with MRI and whole-brain (1)H MR spectroscopic imaging. Concentrations of brain metabolites N-acetyl-aspartate (NAA), choline (Cho), total creatine (tCr), myo-inositol (mI), and glutamine+glutamate (Glx) in ratios to internal water, and the fractional volumes of brain tissue were estimated simultaneously in eight cerebral lobes and in cerebellum. Results demonstrated that an age-related decrease in gray matter volume was the largest contribution to changes in brain volume. Both lobar NAA and the fractional volume of gray matter (FVGM) decreased with age in all cerebral lobes, indicating that the decreased NAA was predominantly associated with decreased gray matter volume and neuronal density or metabolic activity. In cerebral white matter Cho, tCr, and mI increased with age in association with increased fractional volume, showing altered cellular membrane turn-over, energy metabolism, and glial activity in human aging white matter. In cerebellum tCr increased while brain tissue volume decreased with age, showing difference to cerebral aging. The observed age-related metabolic and microstructural variations suggest that physiological neuronal decline in aging human brain is associated with a reduction of gray matter volume and neuronal density, in combination with cellular aging in white matter indicated by microstructural alterations and altered energy metabolism in the cerebellum. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. BrainFrame: a node-level heterogeneous accelerator platform for neuron simulations

    Smaragdos, Georgios; Chatzikonstantis, Georgios; Kukreja, Rahul; Sidiropoulos, Harry; Rodopoulos, Dimitrios; Sourdis, Ioannis; Al-Ars, Zaid; Kachris, Christoforos; Soudris, Dimitrios; De Zeeuw, Chris I.; Strydis, Christos

    2017-12-01

    Objective. The advent of high-performance computing (HPC) in recent years has led to its increasing use in brain studies through computational models. The scale and complexity of such models are constantly increasing, leading to challenging computational requirements. Even though modern HPC platforms can often deal with such challenges, the vast diversity of the modeling field does not permit for a homogeneous acceleration platform to effectively address the complete array of modeling requirements. Approach. In this paper we propose and build BrainFrame, a heterogeneous acceleration platform that incorporates three distinct acceleration technologies, an Intel Xeon-Phi CPU, a NVidia GP-GPU and a Maxeler Dataflow Engine. The PyNN software framework is also integrated into the platform. As a challenging proof of concept, we analyze the performance of BrainFrame on different experiment instances of a state-of-the-art neuron model, representing the inferior-olivary nucleus using a biophysically-meaningful, extended Hodgkin-Huxley representation. The model instances take into account not only the neuronal-network dimensions but also different network-connectivity densities, which can drastically affect the workload’s performance characteristics. Main results. The combined use of different HPC technologies demonstrates that BrainFrame is better able to cope with the modeling diversity encountered in realistic experiments while at the same time running on significantly lower energy budgets. Our performance analysis clearly shows that the model directly affects performance and all three technologies are required to cope with all the model use cases. Significance. The BrainFrame framework is designed to transparently configure and select the appropriate back-end accelerator technology for use per simulation run. The PyNN integration provides a familiar bridge to the vast number of models already available. Additionally, it gives a clear roadmap for extending the platform

  3. Optimal control of directional deep brain stimulation in the parkinsonian neuronal network

    Fan, Denggui; Wang, Zhihui; Wang, Qingyun

    2016-07-01

    The effect of conventional deep brain stimulation (DBS) on debilitating symptoms of Parkinson's disease can be limited because it can only yield the spherical field. And, some side effects are clearly induced with influencing their adjacent ganglia. Recent experimental evidence for patients with Parkinson's disease has shown that a novel DBS electrode with 32 independent stimulation source contacts can effectively optimize the clinical therapy by enlarging the therapeutic windows, when it is applied on the subthalamic nucleus (STN). This is due to the selective activation in clusters of various stimulation contacts which can be steered directionally and accurately on the targeted regions of interest. In addition, because of the serious damage to the neural tissues, the charge-unbalanced stimulation is not typically indicated and the real DBS utilizes charge-balanced bi-phasic (CBBP) pulses. Inspired by this, we computationally investigate the optimal control of directional CBBP-DBS from the proposed parkinsonian neuronal network of basal ganglia-thalamocortical circuit. By appropriately tuning stimulation for different neuronal populations, it can be found that directional steering CBBP-DBS paradigms are superior to the spherical case in improving parkinsonian dynamical properties including the synchronization of neuronal populations and the reliability of thalamus relaying the information from cortex, which is in a good agreement with the physiological experiments. Furthermore, it can be found that directional steering stimulations can increase the optimal stimulation intensity of desynchronization by more than 1 mA compared to the spherical case. This is consistent with the experimental result with showing that there exists at least one steering direction that can allow increasing the threshold of side effects by 1 mA. In addition, we also simulate the local field potential (LFP) and dominant frequency (DF) of the STN neuronal population induced by the activation

  4. Inflammatory responses are not sufficient to cause delayed neuronal death in ATP-induced acute brain injury.

    Hey-Kyeong Jeong

    Full Text Available BACKGROUND: Brain inflammation is accompanied by brain injury. However, it is controversial whether inflammatory responses are harmful or beneficial to neurons. Because many studies have been performed using cultured microglia and neurons, it has not been possible to assess the influence of multiple cell types and diverse factors that dynamically and continuously change in vivo. Furthermore, behavior of microglia and other inflammatory cells could have been overlooked since most studies have focused on neuronal death. Therefore, it is essential to analyze the precise roles of microglia and brain inflammation in the injured brain, and determine their contribution to neuronal damage in vivo from the onset of injury. METHODS AND FINDINGS: Acute neuronal damage was induced by stereotaxic injection of ATP into the substantia nigra pars compacta (SNpc and the cortex of the rat brain. Inflammatory responses and their effects on neuronal damage were investigated by immunohistochemistry, electron microscopy, quantitative RT-PCR, and stereological counting, etc. ATP acutely caused death of microglia as well as neurons in a similar area within 3 h. We defined as the core region the area where both TH(+ and Iba-1(+ cells acutely died, and as the penumbra the area surrounding the core where Iba-1(+ cells showed activated morphology. In the penumbra region, morphologically activated microglia arranged around the injury sites. Monocytes filled the damaged core after neurons and microglia died. Interestingly, neither activated microglia nor monocytes expressed iNOS, a major neurotoxic inflammatory mediator. Monocytes rather expressed CD68, a marker of phagocytic activity. Importantly, the total number of dopaminergic neurons in the SNpc at 3 h (∼80% of that in the contralateral side did not decrease further at 7 d. Similarly, in the cortex, ATP-induced neuron-damage area detected at 3 h did not increase for up to 7 d. CONCLUSIONS: Different cellular

  5. Organotins in Neuronal Damage, Brain Function, and Behavior: A Short Review

    Igor Ferraz da Silva

    2018-01-01

    Full Text Available The consequences of exposure to environmental contaminants have shown significant effects on brain function and behavior in different experimental models. The endocrine-disrupting chemicals (EDC present various classes of pollutants with potential neurotoxic actions, such as organotins (OTs. OTs have received special attention due to their toxic effects on the central nervous system, leading to abnormal mammalian neuroendocrine axis function. OTs are organometallic pollutants with a tin atom bound to one or more carbon atoms. OT exposure may occur through the food chain and/or contaminated water, since they have multiple applications in industry and agriculture. In addition, OTs have been used with few legal restrictions in the last decades, despite being highly toxic. In addition to their action as EDC, OTs can also cross the blood–brain barrier and show relevant neurotoxic effects, as observed in several animal model studies specifically involving the development of neurodegenerative processes, neuroinflammation, and oxidative stress. Thus, the aim of this short review is to summarize the toxic effects of the most common OT compounds, such as trimethyltin, tributyltin, triethyltin, and triphenyltin, on the brain with a focus on neuronal damage as a result of oxidative stress and neuroinflammation. We also aim to present evidence for the disruption of behavioral functions, neurotransmitters, and neuroendocrine pathways caused by OTs.

  6. Characterization of cortical neuronal and glial alterations during culture of organotypic whole brain slices from neonatal and mature mice.

    Staal, Jerome A; Alexander, Samuel R; Liu, Yao; Dickson, Tracey D; Vickers, James C

    2011-01-01

    Organotypic brain slice culturing techniques are extensively used in a wide range of experimental procedures and are particularly useful in providing mechanistic insights into neurological disorders or injury. The cellular and morphological alterations associated with hippocampal brain slice cultures has been well established, however, the neuronal response of mouse cortical neurons to culture is not well documented. In the current study, we compared the cell viability, as well as phenotypic and protein expression changes in cortical neurons, in whole brain slice cultures from mouse neonates (P4-6), adolescent animals (P25-28) and mature adults (P50+). Cultures were prepared using the membrane interface method. Propidium iodide labeling of nuclei (due to compromised cell membrane) and AlamarBlue™ (cell respiration) analysis demonstrated that neonatal tissue was significantly less vulnerable to long-term culture in comparison to the more mature brain tissues. Cultures from P6 animals showed a significant increase in the expression of synaptic markers and a decrease in growth-associated proteins over the entire culture period. However, morphological analysis of organotypic brain slices cultured from neonatal tissue demonstrated that there were substantial changes to neuronal and glial organization within the neocortex, with a distinct loss of cytoarchitectural stratification and increased GFAP expression (pglial limitans and, after 14 DIV, displayed substantial cellular protrusions from slice edges, including cells that expressed both glial and neuronal markers. In summary, we present a substantial evaluation of the viability and morphological changes that occur in the neocortex of whole brain tissue cultures, from different ages, over an extended period of culture.

  7. Lack of appropriate stoichiometry: Strong evidence against an energetically important astrocyte-neuron lactate shuttle in brain.

    Dienel, Gerald A

    2017-11-01

    Glutamate-stimulated aerobic glycolysis in astrocytes coupled with lactate shuttling to neurons where it can be oxidized was proposed as a mechanism to couple excitatory neuronal activity with glucose utilization (CMR glc ) during brain activation. From the outset, this model was not viable because it did not fulfill critical stoichiometric requirements: (i) Calculated glycolytic rates and measured lactate release rates were discordant in cultured astrocytes. (ii) Lactate oxidation requires oxygen consumption, but the oxygen-glucose index (OGI, calculated as CMR O2 /CMR glc ) fell during activation in human brain, and the small rise in CMR O2 could not fully support oxidation of lactate produced by disproportionate increases in CMR glc . (iii) Labeled products of glucose metabolism are not retained in activated rat brain, indicating rapid release of a highly labeled, diffusible metabolite identified as lactate, thereby explaining the CMR glc -CMR O2 mismatch. Additional independent lines of evidence against lactate shuttling include the following: astrocytic oxidation of glutamate after its uptake can help "pay" for its uptake without stimulating glycolysis; blockade of glutamate receptors during activation in vivo prevents upregulation of metabolism and lactate release without impairing glutamate uptake; blockade of β-adrenergic receptors prevents the fall in OGI in activated human and rat brain while allowing glutamate uptake; and neurons upregulate glucose utilization in vivo and in vitro under many stimulatory conditions. Studies in immature cultured cells are not appropriate models for lactate shuttling in adult brain because of their incomplete development of metabolic capability and astrocyte-neuron interactions. Astrocyte-neuron lactate shuttling does not make large, metabolically significant contributions to energetics of brain activation. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  8. Maternal allopurinol during fetal hypoxia lowers cord blood levels of the brain injury marker S-100B

    Torrance, Helen L.; Benders, Manon J.; Derks, Jan B.; Rademaker, Carin M. A.; Bos, Arie F.; Van Den Berg, Paul; Longini, Mariangela; Buonocore, Giuseppe; Venegas, MariaElena; Baquero, Hernando; Visser, Gerard H. A.; Van Bel, Frank

    BACKGROUND: Fetal hypoxia is an important determinant of neonatal encephalopathy caused by birth asphyxia, in which hypoxia-induced free radical formation plays an important role. HYPOTHESIS: Maternal treatment with allopurinol, will cross the placenta during fetal hypoxia (rimary outcome) and

  9. Localization of ( sup 18 F)fluorodeoxyglucose in mouse brain neurons with micro-autoradiography

    Yamada, Susumu; Kubota, Roko; Kubota, Kazuo [Department of Radiology and Nuclear Medicine, The Research Institute for Tuberculosis and Cancer (Japan); Ishiwata, Kiichi; Ido, Tatsuo [Tohoku Univ., Sendai (Japan). Cyclotron and Radioisotope Center

    1990-12-11

    This is the first study of micro-autoradiography (micro-ARG) for ({sup 18}F)2-fluoro-2-deoxy-D-glucose (({sup 18}F)FDG). The localization of ({sup 18}F)FDG was demonstrated in dendrites of neuron and also in the myelinated axon in mouse normal brain in vivo. The nucleolus was relatively free of label. The counted silver grain numbers in autoradiogram were linearly correlated to the {sup 18}F radioactivities in the specimen. The micro-ARG using positron emitting {sup 18}F is a very time-saving technique with 4 hours exposure compared with the conventional method using {sup 3}H- or {sup 14}C-labelled tracers. (author).

  10. Coexistence of intermittencies in the neuronal network of the epileptic brain.

    Koronovskii, Alexey A; Hramov, Alexander E; Grubov, Vadim V; Moskalenko, Olga I; Sitnikova, Evgenia; Pavlov, Alexey N

    2016-03-01

    Intermittent behavior occurs widely in nature. At present, several types of intermittencies are known and well-studied. However, consideration of intermittency has usually been limited to the analysis of cases when only one certain type of intermittency takes place. In this paper, we report on the temporal behavior of the complex neuronal network in the epileptic brain, when two types of intermittent behavior coexist and alternate with each other. We prove the presence of this phenomenon in physiological experiments with WAG/Rij rats being the model living system of absence epilepsy. In our paper, the deduced theoretical law for distributions of the lengths of laminar phases prescribing the power law with a degree of -2 agrees well with the experimental neurophysiological data.

  11. Artificial brains. A million spiking-neuron integrated circuit with a scalable communication network and interface.

    Merolla, Paul A; Arthur, John V; Alvarez-Icaza, Rodrigo; Cassidy, Andrew S; Sawada, Jun; Akopyan, Filipp; Jackson, Bryan L; Imam, Nabil; Guo, Chen; Nakamura, Yutaka; Brezzo, Bernard; Vo, Ivan; Esser, Steven K; Appuswamy, Rathinakumar; Taba, Brian; Amir, Arnon; Flickner, Myron D; Risk, William P; Manohar, Rajit; Modha, Dharmendra S

    2014-08-08

    Inspired by the brain's structure, we have developed an efficient, scalable, and flexible non-von Neumann architecture that leverages contemporary silicon technology. To demonstrate, we built a 5.4-billion-transistor chip with 4096 neurosynaptic cores interconnected via an intrachip network that integrates 1 million programmable spiking neurons and 256 million configurable synapses. Chips can be tiled in two dimensions via an interchip communication interface, seamlessly scaling the architecture to a cortexlike sheet of arbitrary size. The architecture is well suited to many applications that use complex neural networks in real time, for example, multiobject detection and classification. With 400-pixel-by-240-pixel video input at 30 frames per second, the chip consumes 63 milliwatts. Copyright © 2014, American Association for the Advancement of Science.

  12. Repeated mild traumatic brain injury in female rats increases lipid peroxidation in neurons.

    Yates, Nathanael J; Lydiard, Stephen; Fehily, Brooke; Weir, Gillian; Chin, Aaron; Bartlett, Carole A; Alderson, Jacqueline; Fitzgerald, Melinda

    2017-07-01

    Negative outcomes of mild traumatic brain injury (mTBI) can be exacerbated by repeated insult. Animal models of repeated closed-head mTBI provide the opportunity to define acute pathological mechanisms as the number of mTBI increases. Furthermore, little is known about the effects of mTBI impact site, and how this may affect brain function. We use a closed head, weight drop model of mTBI that allows head movement following impact, in adult female rats to determine the role of the number and location of mTBI on brain pathology and behaviour. Biomechanical assessment of two anatomically well-defined mTBI impact sites were used, anterior (bregma) and posterior (lambda). Location of the impact had no significant effect on impact forces (450 N), and the weight impact locations were on average 5.4 mm from the desired impact site. No between location vertical linear head kinematic differences were observed immediately following impact, however, in the 300 ms post-impact, significantly higher mean vertical head displacement and velocity were observed in the mTBI lambda trials. Breaches of the blood brain barrier were observed with three mTBI over bregma, associated with immunohistochemical indicators of damage. However, an increased incidence of hairline fractures of the skull and macroscopic haemorrhaging made bregma an unsuitable impact location to model repeated mTBI. Repeated mTBI over lambda did not cause skull fractures and were examined more comprehensively, with outcomes following one, two or three mTBI or sham, delivered at 1 day intervals, assessed on days 1-4. We observe a mild behavioural phenotype, with subtle deficits in cognitive function, associated with no identifiable neuroanatomical or inflammatory changes. However, an increase in lipid peroxidation in a subset of cortical neurons following two mTBI indicates increasing oxidative damage with repeated injury in female rats, supported by increased amyloid precursor protein immunoreactivity with three m

  13. Receptive fields of locust brain neurons are matched to polarization patterns of the sky.

    Bech, Miklós; Homberg, Uwe; Pfeiffer, Keram

    2014-09-22

    Many animals, including insects, are able to use celestial cues as a reference for spatial orientation and long-distance navigation [1]. In addition to direct sunlight, the chromatic gradient of the sky and its polarization pattern are suited to serve as orientation cues [2-5]. Atmospheric scattering of sunlight causes a regular pattern of E vectors in the sky, which are arranged along concentric circles around the sun [5, 6]. Although certain insects rely predominantly on sky polarization for spatial orientation [7], it has been argued that detection of celestial E vector orientation may not suffice to differentiate between solar and antisolar directions [8, 9]. We show here that polarization-sensitive (POL) neurons in the brain of the desert locust Schistocerca gregaria can overcome this ambiguity. Extracellular recordings from POL units in the central complex and lateral accessory lobes revealed E vector tunings arranged in concentric circles within large receptive fields, matching the sky polarization pattern at certain solar positions. Modeling of neuronal responses under an idealized sky polarization pattern (Rayleigh sky) suggests that these "matched filter" properties allow locusts to unambiguously determine the solar azimuth by relying solely on the sky polarization pattern for compass navigation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Brain-specific Foxp1 deletion impairs neuronal development and causes autistic-like behaviour.

    Bacon, C; Schneider, M; Le Magueresse, C; Froehlich, H; Sticht, C; Gluch, C; Monyer, H; Rappold, G A

    2015-05-01

    Neurodevelopmental disorders are multi-faceted and can lead to intellectual disability, autism spectrum disorder and language impairment. Mutations in the Forkhead box FOXP1 gene have been linked to all these disorders, suggesting that it may play a central role in various cognitive and social processes. To understand the role of Foxp1 in the context of neurodevelopment leading to alterations in cognition and behaviour, we generated mice with a brain-specific Foxp1 deletion (Nestin-Cre(Foxp1-/-)mice). The mutant mice were viable and allowed for the first time the analysis of pre- and postnatal neurodevelopmental phenotypes, which included a pronounced disruption of the developing striatum and more subtle alterations in the hippocampus. More detailed analysis in the CA1 region revealed abnormal neuronal morphogenesis that was associated with reduced excitability and an imbalance of excitatory to inhibitory input in CA1 hippocampal neurons in Nestin-Cre(Foxp1-/-) mice. Foxp1 ablation was also associated with various cognitive and social deficits, providing new insights into its behavioural importance.

  15. Operant behavior to obtain palatable food modifies neuronal plasticity in the brain reward circuit.

    Guegan, Thomas; Cutando, Laura; Ayuso, Eduard; Santini, Emanuela; Fisone, Gilberto; Bosch, Fatima; Martinez, Albert; Valjent, Emmanuel; Maldonado, Rafael; Martin, Miquel

    2013-02-01

    Palatability enhances food intake by hedonic mechanisms that prevail over caloric necessities. Different studies have demonstrated the role of endogenous cannabinoids in the mesocorticolimbic system in controlling food hedonic value and consumption. We hypothesize that the endogenous cannabinoid system could also be involved in the development of food-induced behavioral alterations, such as food-seeking and binge-eating, by a mechanism that requires neuroplastic changes in the brain reward pathway. For this purpose, we evaluated the role of the CB1 cannabinoid receptor (CB1-R) in the behavioral and neuroplastic changes induced by operant training for standard, highly caloric or highly palatable isocaloric food using different genetics, viral and pharmacological approaches. Neuroplasticity was evaluated by measuring changes in dendritic spine density in neurons previously labeled with the dye DiI. Only operant training to obtain highly palatable isocaloric food induced neuroplastic changes in neurons of the nucleus accumbens shell and prefrontal cortex that were associated to changes in food-seeking behavior. These behavioral and neuroplastic modifications induced by highly palatable isocaloric food were dependent on the activity of the CB1-R. Neuroplastic changes induced by highly palatable isocaloric food are similar to those produced by some drugs of abuse and may be crucial in the alteration of food-seeking behavior leading to overweight and obesity. Copyright © 2012 Elsevier B.V. and ECNP. All rights reserved.

  16. Critical role of NADPH oxidase in neuronal oxidative damage and microglia activation following traumatic brain injury.

    Quan-Guang Zhang

    Full Text Available BACKGROUND: Oxidative stress is known to play an important role in the pathology of traumatic brain injury. Mitochondria are thought to be the major source of the damaging reactive oxygen species (ROS following TBI. However, recent work has revealed that the membrane, via the enzyme NADPH oxidase can also generate the superoxide radical (O(2(-, and thereby potentially contribute to the oxidative stress following TBI. The current study thus addressed the potential role of NADPH oxidase in TBI. METHODOLOGY/PRINCIPAL FINDINGS: The results revealed that NADPH oxidase activity in the cerebral cortex and hippocampal CA1 region increases rapidly following controlled cortical impact in male mice, with an early peak at 1 h, followed by a secondary peak from 24-96 h after TBI. In situ localization using oxidized hydroethidine and the neuronal marker, NeuN, revealed that the O(2(- induction occurred in neurons at 1 h after TBI. Pre- or post-treatment with the NADPH oxidase inhibitor, apocynin markedly inhibited microglial activation and oxidative stress damage. Apocynin also attenuated TBI-induction of the Alzheimer's disease proteins β-amyloid and amyloid precursor protein. Finally, both pre- and post-treatment of apocynin was also shown to induce significant neuroprotection against TBI. In addition, a NOX2-specific inhibitor, gp91ds-tat was also shown to exert neuroprotection against TBI. CONCLUSIONS/SIGNIFICANCE: As a whole, the study demonstrates that NADPH oxidase activity and superoxide production exhibit a biphasic elevation in the hippocampus and cortex following TBI, which contributes significantly to the pathology of TBI via mediation of oxidative stress damage, microglial activation, and AD protein induction in the brain following TBI.

  17. A role for neuronal cAMP responsive-element binding (CREB)-1 in brain responses to calorie restriction

    Fusco, Salvatore; Ripoli, Cristian; Podda, Maria Vittoria; Ranieri, Sofia Chiatamone; Leone, Lucia; Toietta, Gabriele; McBurney, Michael W.; Schütz, Günther; Riccio, Antonella; Grassi, Claudio; Galeotti, Tommaso; Pani, Giovambattista

    2012-01-01

    Calorie restriction delays brain senescence and prevents neurodegeneration, but critical regulators of these beneficial responses other than the NAD+-dependent histone deacetylase Sirtuin-1 (Sirt-1) are unknown. We report that effects of calorie restriction on neuronal plasticity, memory and social behavior are abolished in mice lacking cAMP responsive-element binding (CREB)-1 in the forebrain. Moreover, CREB deficiency drastically reduces the expression of Sirt-1 and the induction of genes relevant to neuronal metabolism and survival in the cortex and hippocampus of dietary-restricted animals. Biochemical studies reveal a complex interplay between CREB and Sirt-1: CREB directly regulates the transcription of the sirtuin in neuronal cells by binding to Sirt-1 chromatin; Sirt-1, in turn, is recruited by CREB to DNA and promotes CREB-dependent expression of target gene peroxisome proliferator-activated receptor-γ coactivator-1α and neuronal NO Synthase. Accordingly, expression of these CREB targets is markedly reduced in the brain of Sirt KO mice that are, like CREB-deficient mice, poorly responsive to calorie restriction. Thus, the above circuitry, modulated by nutrient availability, links energy metabolism with neurotrophin signaling, participates in brain adaptation to nutrient restriction, and is potentially relevant to accelerated brain aging by overnutrition and diabetes. PMID:22190495

  18. High-Content Screening in hPSC-Neural Progenitors Identifies Drug Candidates that Inhibit Zika Virus Infection in Fetal-like Organoids and Adult Brain.

    Zhou, Ting; Tan, Lei; Cederquist, Gustav Y; Fan, Yujie; Hartley, Brigham J; Mukherjee, Suranjit; Tomishima, Mark; Brennand, Kristen J; Zhang, Qisheng; Schwartz, Robert E; Evans, Todd; Studer, Lorenz; Chen, Shuibing

    2017-08-03

    Zika virus (ZIKV) infects fetal and adult human brain and is associated with serious neurological complications. To date, no therapeutic treatment is available to treat ZIKV-infected patients. We performed a high-content chemical screen using human pluripotent stem cell-derived cortical neural progenitor cells (hNPCs) and found that hippeastrine hydrobromide (HH) and amodiaquine dihydrochloride dihydrate (AQ) can inhibit ZIKV infection in hNPCs. Further validation showed that HH also rescues ZIKV-induced growth and differentiation defects in hNPCs and human fetal-like forebrain organoids. Finally, HH and AQ inhibit ZIKV infection in adult mouse brain in vivo. Strikingly, HH suppresses viral propagation when administered to adult mice with active ZIKV infection, highlighting its therapeutic potential. Our approach highlights the power of stem cell-based screens and validation in human forebrain organoids and mouse models in identifying drug candidates for treating ZIKV infection and related neurological complications in fetal and adult patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Parameter set for computer-assisted texture analysis of fetal brain.

    Gentillon, Hugues; Stefańczyk, Ludomir; Strzelecki, Michał; Respondek-Liberska, Maria

    2016-11-25

    Magnetic resonance data were collected from a diverse population of gravid women to objectively compare the quality of 1.5-tesla (1.5 T) versus 3-T magnetic resonance imaging of the developing human brain. MaZda and B11 computational-visual cognition tools were used to process 2D images. We proposed a wavelet-based parameter and two novel histogram-based parameters for Fisher texture analysis in three-dimensional space. Wavenhl, focus index, and dispersion index revealed better quality for 3 T. Though both 1.5 and 3 T images were 16-bit DICOM encoded, nearly 16 and 12 usable bits were measured in 3 and 1.5 T images, respectively. The four-bit padding observed in 1.5 T K-space encoding mimics noise by adding illusionistic details, which are not really part of the image. In contrast, zero-bit padding in 3 T provides space for storing more details and increases the likelihood of noise but as well as edges, which in turn are very crucial for differentiation of closely related anatomical structures. Both encoding modes are possible with both units, but higher 3 T resolution is the main difference. It contributes to higher perceived and available dynamic range. Apart from surprisingly larger Fisher coefficient, no significant difference was observed when testing was conducted with down-converted 8-bit BMP images.

  20. The brain-specific factor FEZ1 is a determinant of neuronal susceptibility to HIV-1 infection.

    Haedicke, Juliane

    2009-08-18

    Neurons are one of the few cell types in the human body that do not support HIV type-1 (HIV-1) replication. Although the lack of key receptors is a major obstacle to infection, studies suggest that additional functions inhibit virus replication to explain the exquisite resistance of neurons to HIV-1. However, specific neuronal factors that may explain this resistance remain to be discovered. In a screen for antiviral factors using a fibroblast line chemically mutagenized and selected for resistance to retroviral infection, we recently identified induction of rat FEZ1 (fasciculation and elongation protein zeta-1), a brain-specific protein, as the cause of this resistance. When exogenously expressed in nonneuronal cell lines rat FEZ1 blocked nuclear entry of retroviral DNA. Here, we demonstrate that among human brain cells, neurons naturally express high levels of FEZ1 compared to astrocytes or microglia cells and are correspondingly less susceptible to infection with pseudotyped HIV-1 that bypasses receptor-mediated viral entry. Demonstrating that endogenous FEZ1 was functionally important in the resistance of neurons to HIV-1 infection, siRNA-mediated knockdown of endogenous FEZ1 increased the infectivity of neurons while sensitive brain cell types like microglia became more resistant upon FEZ1 overexpression. In addition, FEZ1 expression was not induced in response to IFN treatment. As such, in contrast to other widely expressed, IFN-inducible antiviral factors, FEZ1 appears to represent a unique neuron-specific determinant of cellular susceptibility to infection in a cell type that is naturally resistant to HIV-1.

  1. [Ultrastructural changes in the MP3 neuron of the mollusk Lymnaea stagnalis after cryopreservation of the isolated brain].

    Dmitrieva, E V; Moshkov, D A; Gakhova, E N

    2006-01-01

    Investigation of a possibility of long-term storage of frozen (-196 degrees C) viable neurons and nervous tissue is one of the central present day problems. In this study ultrastructural changes in neurons of frozen-thawed snail brain were examined as a function of time. We studied the influence of cryopreservation, cryoprotectant (Me2SO), cooling to 4-6 degrees C, and a prolonged incubation in physiological solution at 4-6 degrees C on dictyosomes of Golgi apparatus, endoplasmic reticulum (ER) cisternae and mitochondria. It has been found that responses of these intracellular structures of cryopreserved neurons to the above influences are similar: dissociation of Golgi dictyosomes, swelling of endoplasmic reticulum cisternae and mitochondrial cristae. Both freezing-thawing and cryoprotectant were seen to cause an increase in the number of lysosomes, liposomes, myelin-like structures, and to form large vacuoles. The structural changes in molluscan neurons caused by cryopreservation with Me2SO (2 M) were reversible.

  2. UV-laser microdissection and mRNA expression analysis of individual neurons from postmortem Parkinson's disease brains.

    Gründemann, Jan; Schlaudraff, Falk; Liss, Birgit

    2011-01-01

    Cell specificity of gene expression analysis is essential to avoid tissue sample related artifacts, in particular when the relative number of target cells present in the compared tissues varies dramatically, e.g., when comparing dopamine neurons in midbrain tissues from control subjects with those from Parkinson's disease (PD) cases. Here, we describe a detailed protocol that combines contact-free UV-laser microdissection and quantitative PCR of reverse-transcribed RNA of individual neurons from postmortem human midbrain tissue from PD patients and unaffected controls. Among expression changes in a variety of dopamine neuron marker, maintenance, and cell-metabolism genes, we found that α-synuclein mRNA levels were significantly elevated in individual neuromelanin-positive dopamine midbrain neurons from PD brains when compared to those from matched controls.

  3. GLIA AND NEURODEVELOPMENT: FOCUS ON FETAL ALCOHOL SPECTRUM DISORDERS

    Marina eGuizzetti

    2014-11-01

    Full Text Available During the last 20 years new and exciting roles for glial cells in brain development have been described. Moreover, several recent studies implicated glial cells in the pathogenesis of neurodevelopmental disorders including Down syndrome, Fragile X syndrome, Rett Syndrome, Autism Spectrum Disorders, and Fetal Alcohol Spectrum Disorders (FASD.Abnormalities in glial cell development and proliferation and increased glial cell apoptosis contribute to the adverse effects of ethanol on the developing brain and it is becoming apparent that the effects of fetal alcohol are due, at least in part, to effects on glial cells affecting their ability to modulate neuronal development and function. The three major classes of glial cells, astrocytes, oligodendrocytes, and microglia as well as their precursors are affected by ethanol during brain development. Alterations in glial cell functions by ethanol dramatically affect neuronal development, survival, and function and ultimately impair the development of the proper brain architecture and connectivity. For instance, ethanol inhibits astrocyte-mediated neuritogenesis and oligodendrocyte development, survival and myelination; furthermore, ethanol induces microglia activation and oxidative stress leading to the exacerbation of ethanol-induced neuronal cell death.This review article describes the most significant recent findings pertaining the effects of ethanol on glial cells and their significance in the pathophysiology of FASD and other neurodevelopmental disorders.

  4. NOX4-dependent neuronal autotoxicity and BBB breakdown explain the superior sensitivity of the brain to ischemic damage.

    Casas, Ana I; Geuss, Eva; Kleikers, Pamela W M; Mencl, Stine; Herrmann, Alexander M; Buendia, Izaskun; Egea, Javier; Meuth, Sven G; Lopez, Manuela G; Kleinschnitz, Christoph; Schmidt, Harald H H W

    2017-11-14

    Ischemic injury represents the most frequent cause of death and disability, and it remains unclear why, of all body organs, the brain is most sensitive to hypoxia. In many tissues, type 4 NADPH oxidase is induced upon ischemia or hypoxia, converting oxygen to reactive oxygen species. Here, we show in mouse models of ischemia in the heart, brain, and hindlimb that only in the brain does NADPH oxidase 4 (NOX4) lead to ischemic damage. We explain this distinct cellular distribution pattern through cell-specific knockouts. Endothelial NOX4 breaks down the BBB, while neuronal NOX4 leads to neuronal autotoxicity. Vascular smooth muscle NOX4, the common denominator of ischemia within all ischemic organs, played no apparent role. The direct neuroprotective potential of pharmacological NOX4 inhibition was confirmed in an ex vivo model, free of vascular and BBB components. Our results demonstrate that the heightened sensitivity of the brain to ischemic damage is due to an organ-specific role of NOX4 in blood-brain-barrier endothelial cells and neurons. This mechanism is conserved in at least two rodents and humans, making NOX4 a prime target for a first-in-class mechanism-based, cytoprotective therapy in the unmet high medical need indication of ischemic stroke. Copyright © 2017 the Author(s). Published by PNAS.

  5. Average fetal depth in utero: data for estimation of fetal absorbed radiation dose

    Ragozzino, M.W.; Breckle, R.; Hill, L.M.; Gray, J.E.

    1986-01-01

    To estimate fetal absorbed dose from radiographic examinations, the depth from the anterior maternal surface to the midline of the fetal skull and abdomen was measured by ultrasound in 97 pregnant women. The relationships between fetal depth, fetal presentation, and maternal parameters of height, weight, anteroposterior (AP) thickness, gestational age, placental location, and bladder volume were analyzed. Maternal AP thickness (MAP) can be estimated from gestational age, maternal height, and maternal weight. Fetal midskull and abdominal depths were nearly equal. Fetal depth normalized to MAP was independent or nearly independent of maternal parameters and fetal presentation. These data enable a reasonable estimation of absorbed dose to fetal brain, abdomen, and whole body

  6. Cadherin-13 Deficiency Increases Dorsal Raphe 5-HT Neuron Density and Prefrontal Cortex Innervation in the Mouse Brain

    Andrea Forero

    2017-09-01

    Full Text Available Background: During early prenatal stages of brain development, serotonin (5-HT-specific neurons migrate through somal translocation to form the raphe nuclei and subsequently begin to project to their target regions. The rostral cluster of cells, comprising the median and dorsal raphe (DR, innervates anterior regions of the brain, including the prefrontal cortex. Differential analysis of the mouse 5-HT system transcriptome identified enrichment of cell adhesion molecules in 5-HT neurons of the DR. One of these molecules, cadherin-13 (Cdh13 has been shown to play a role in cell migration, axon pathfinding, and synaptogenesis. This study aimed to investigate the contribution of Cdh13 to the development of the murine brain 5-HT system.Methods: For detection of Cdh13 and components of the 5-HT system at different embryonic developmental stages of the mouse brain, we employed immunofluorescence protocols and imaging techniques, including epifluorescence, confocal and structured illumination microscopy. The consequence of CDH13 loss-of-function mutations on brain 5-HT system development was explored in a mouse model of Cdh13 deficiency.Results: Our data show that in murine embryonic brain Cdh13 is strongly expressed on 5-HT specific neurons of the DR and in radial glial cells (RGCs, which are critically involved in regulation of neuronal migration. We observed that 5-HT neurons are intertwined with these RGCs, suggesting that these neurons undergo RGC-guided migration. Cdh13 is present at points of intersection between these two cell types. Compared to wildtype controls, Cdh13-deficient mice display increased cell densities in the DR at embryonic stages E13.5, E17.5, and adulthood, and higher serotonergic innervation of the prefrontal cortex at E17.5.Conclusion: Our findings provide evidence for a role of CDH13 in the development of the serotonergic system in early embryonic stages. Specifically, we indicate that Cdh13 deficiency affects the cell

  7. Brains are not just neurons. Comment on “Toward a computational framework for cognitive biology: Unifying approaches from cognitive neuroscience and comparative cognition” by Fitch

    Huber, Ludwig

    2014-09-01

    This comment addresses the first component of Fitch's framework: the computational power of single neurons [3]. Although I agree that traditional models of neural computation have vastly underestimated the computational power of single neurons, I am hesitant to follow him completely. The exclusive focus on neurons is likely to underestimate the importance of other cells in the brain. In the last years, two such cell types have received appropriate attention by neuroscientists: interneurons and glia. Interneurons are small, tightly packed cells involved in the control of information processing in learning and memory. Rather than transmitting externally (like motor or sensory neurons), these neurons process information within internal circuits of the brain (therefore also called 'relay neurons'). Some specialized interneuron subtypes temporally regulate the flow of information in a given cortical circuit during relevant behavioral events [4]. In the human brain approx. 100 billion interneurons control information processing and are implicated in disorders such as epilepsy and Parkinson's.

  8. Activity-based anorexia activates nesfatin-1 immunoreactive neurons in distinct brain nuclei of female rats.

    Scharner, Sophie; Prinz, Philip; Goebel-Stengel, Miriam; Lommel, Reinhard; Kobelt, Peter; Hofmann, Tobias; Rose, Matthias; Stengel, Andreas

    2017-12-15

    Activity-based anorexia (ABA) is an established animal model for the eating disorder anorexia nervosa (AN). The pathophysiology of AN and the involvement of food intake-regulatory peptides is still poorly understood. Nesfatin-1, an anorexigenic peptide also involved in the mediation of stress, anxiety and depression might be a likely candidate involved in the pathogenesis of AN. Therefore, activation of nesfatin-1 immunoreactive (ir) brain nuclei was investigated under conditions of ABA. Female Sprague-Dawley rats were used and divided into four groups (n=6/group): activity-based anorexia (ABA), restricted feeding (RF), activity (AC) and ad libitum fed (AL). After the 21-day experimental period and development of ABA, brains were processed for c-Fos/nesfatin-1 double labeling immunohistochemistry. ABA increased the number of nesfatin-1 immunopositive neurons in the paraventricular nucleus, arcuate nucleus, dorsomedial hypothalamic nucleus, locus coeruleus and in the rostral part of the nucleus of the solitary tract compared to AL and AC groups (p0.05). Moreover, we observed significantly more c-Fos and nesfatin-1 ir double-labeled cells in ABA rats compared to RF, AL and AC in the supraoptic nucleus (p<0.05) and compared to AL and AC in the paraventricular nucleus, arcuate nucleus, dorsomedial hypothalamic nucleus, dorsal raphe nucleus and the rostral raphe pallidus (p<0.05). Since nesfatin-1 plays a role in the inhibition of food intake and the response to stress, we hypothesize that the observed changes of brain nesfatin-1 might play a role in the pathophysiology and symptomatology under conditions of ABA and potentially also in patients with AN. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Riding the glial monorail: a common mechanism for glial-guided neuronal migration in different regions of the developing mammalian brain.

    Hatten, M E

    1990-05-01

    In vitro studies from our laboratory indicate that granule neurons, purified from early postnatal mouse cerebellum, migrate on astroglial fibers by forming a 'migration junction' with the glial fiber along the length of the neuronal soma and extending a motile 'leading process' in the direction of migration. Similar dynamics are seen for hippocampal neurons migrating along hippocampal astroglial fibers in vitro. In heterotypic recombinations of neurons and glia from mouse cerebellum and rat hippocampus, neurons migrate on astroglial processes with a cytology and neuron-glia relationship identical to that of homotypic neuronal migration in vitro. In all four cases, the migrating neuron presents a stereotyped posture, speed and mode of movement, suggesting that glial fibers provide a generic pathway for neuronal migration in developing brain. Studies on the molecular basis of glial-guided migration suggest that astrotactin, a neuronal antigen that functions as a neuron-glia ligand, is likely to play a crucial role in the locomotion of the neuron along glial fibers. The navigation of neurons from glial fibers into cortical layers, in turn, is likely to involve neuron-neuron adhesion ligands.

  10. Flow Cytometric Detection of PrPSc in Neurons and Glial Cells from Prion-Infected Mouse Brains.

    Yamasaki, Takeshi; Suzuki, Akio; Hasebe, Rie; Horiuchi, Motohiro

    2018-01-01

    In prion diseases, an abnormal isoform of prion protein (PrP Sc ) accumulates in neurons, astrocytes, and microglia in the brains of animals affected by prions. Detailed analyses of PrP Sc -positive neurons and glial cells are required to clarify their pathophysiological roles in the disease. Here, we report a novel method for the detection of PrP Sc in neurons and glial cells from the brains of prion-infected mice by flow cytometry using PrP Sc -specific staining with monoclonal antibody (MAb) 132. The combination of PrP Sc staining and immunolabeling of neural cell markers clearly distinguished neurons, astrocytes, and microglia that were positive for PrP Sc from those that were PrP Sc negative. The flow cytometric analysis of PrP Sc revealed the appearance of PrP Sc -positive neurons, astrocytes, and microglia at 60 days after intracerebral prion inoculation, suggesting the presence of PrP Sc in the glial cells, as well as in neurons, from an early stage of infection. Moreover, the kinetic analysis of PrP Sc revealed a continuous increase in the proportion of PrP Sc -positive cells for all cell types with disease progression. Finally, we applied this method to isolate neurons, astrocytes, and microglia positive for PrP Sc from a prion-infected mouse brain by florescence-activated cell sorting. The method described here enables comprehensive analyses specific to PrP Sc -positive neurons, astrocytes, and microglia that will contribute to the understanding of the pathophysiological roles of neurons and glial cells in PrP Sc -associated pathogenesis. IMPORTANCE Although formation of PrP Sc in neurons is associated closely with neurodegeneration in prion diseases, the mechanism of neurodegeneration is not understood completely. On the other hand, recent studies proposed the important roles of glial cells in PrP Sc -associated pathogenesis, such as the intracerebral spread of PrP Sc and clearance of PrP Sc from the brain. Despite the great need for detailed analyses

  11. An AAV promoter-driven neuropeptide Y gene delivery system using Sendai virosomes for neurons and rat brain.

    Wu, P; de Fiebre, C M; Millard, W J; King, M A; Wang, S; Bryant, S O; Gao, Y P; Martin, E J; Meyer, E M

    1996-03-01

    An adeno-associated virus (AAV)-derived construct (pJDT95npy) containing rat neuropeptide Y (NPY) cDNA inserted downstream of endogenous AAV promoters was used to investigate AAV-driven NPY expression in postmitotic neurons in vitro and in the brain. NPY mRNA was expressed in NT2/N and rat brain primary neuronal cultures after transfection. There was a corresponding increase in the number of neurons staining for NPY-like immunoreactivity and an increase in NPY release during depolarization in the primary cultures. Injections of Sendai-virosome encapsulated pJDT95npy into neocortex increased NPY-like immunoreactivity in neurons but not glia indicating that the latter cell type did not have the translational, post-translational or storage capacity to accumulate the peptide. Injections into the rat hypothalamic para-ventricular nucleus increased body weight and food intake for 21 days, though NPY-like immunoreactivity remained elevated for at least 50 days. These studies demonstrate that AAV-derived constructs may be useful for delivering genes into post-mitotic neurons, and that Sendai virosomes are effective for delivering these constructs in vivo.

  12. Self-other relations in social development and autism: multiple roles for mirror neurons and other brain bases.

    Williams, Justin H G

    2008-04-01

    Mirror neuron system dysfunction may underlie a self-other matching impairment, which has previously been suggested to account for autism. Embodied Cognition Theory, which proposes that action provides a foundation for cognition has lent further credence to these ideas. The hypotheses of a self-other matching deficit and impaired mirror neuron function in autism have now been well supported by studies employing a range of methodologies. However, underlying mechanisms require further exploration to explain how mirror neurons may be involved in attentional and mentalizing processes. Impairments in self-other matching and mirror neuron function are not necessarily inextricably linked and it seems possible that different sub-populations of mirror neurons, located in several regions, contribute differentially to social cognitive functions. It is hypothesized that mirror neuron coding for action-direction may be required for developing attentional sensitivity to self-directed actions, and consequently for person-oriented, stimulus-driven attention. Mirror neuron networks may vary for different types of social learning such as "automatic" imitation and imitation learning. Imitation learning may be more reliant on self-other comparison processes (based on mirror neurons) that identify differences as well as similarities between actions. Differential connectivity with the amygdala-orbitofrontal system may also be important. This could have implications for developing "theory of mind," with intentional self-other comparison being relevant to meta-representational abilities, and "automatic" imitation being more relevant to empathy. While it seems clear that autism is associated with impaired development of embodied aspects of cognition, the ways that mirror neurons contribute to these brain-behavior links are likely to be complex.

  13. Friends and foes from an ant brain's point of view--neuronal correlates of colony odors in a social insect.

    Brandstaetter, Andreas Simon; Rössler, Wolfgang; Kleineidam, Christoph Johannes

    2011-01-01

    Successful cooperation depends on reliable identification of friends and foes. Social insects discriminate colony members (nestmates/friends) from foreign workers (non-nestmates/foes) by colony-specific, multi-component colony odors. Traditionally, complex processing in the brain has been regarded as crucial for colony recognition. Odor information is represented as spatial patterns of activity and processed in the primary olfactory neuropile, the antennal lobe (AL) of insects, which is analogous to the vertebrate olfactory bulb. Correlative evidence indicates that the spatial activity patterns reflect odor-quality, i.e., how an odor is perceived. For colony odors, alternatively, a sensory filter in the peripheral nervous system was suggested, causing specific anosmia to nestmate colony odors. Here, we investigate neuronal correlates of colony odors in the brain of a social insect to directly test whether they are anosmic to nestmate colony odors and whether spatial activity patterns in the AL can predict how odor qualities like "friend" and "foe" are attributed to colony odors. Using ant dummies that mimic natural conditions, we presented colony odors and investigated their neuronal representation in the ant Camponotus floridanus. Nestmate and non-nestmate colony odors elicited neuronal activity: In the periphery, we recorded sensory responses of olfactory receptor neurons (electroantennography), and in the brain, we measured colony odor specific spatial activity patterns in the AL (calcium imaging). Surprisingly, upon repeated stimulation with the same colony odor, spatial activity patterns were variable, and as variable as activity patterns elicited by different colony odors. Ants are not anosmic to nestmate colony odors. However, spatial activity patterns in the AL alone do not provide sufficient information for colony odor discrimination and this finding challenges the current notion of how odor quality is coded. Our result illustrates the enormous challenge

  14. Catalpol ameliorates beta amyloid-induced degeneration of cholinergic neurons by elevating brain-derived neurotrophic factors.

    Wang, Z; Liu, Q; Zhang, R; Liu, S; Xia, Z; Hu, Y

    2009-11-10

    The purpose of this work is to study the effect of catalpol, an iridoid from Rehmannia glutinosa on neurodegenerative changes induced by beta-amyloid peptide Abeta(25-35) or Abeta(25-35)+ibotenic acid and the underlying mechanism. Results showed that catalpol significantly improved the memory deficits in the neurodegenerative mouse model produced by injection of Abeta(25-35)+ibotenic acid to the nucleus magnocellularis basalis, yet it is neither a cholinesterase inhibitor nor a muscarinic (M) receptor agonist. Instead, the choline acetyl transferase (ChAT) activity and the M receptor density in brain were significantly decreased in the model mice and catalpol could significantly elevate their levels. Furthermore, the brain-derived neurotrophic factor (BDNF) content in brain was significantly decreased in the model mice and catalpol elevated it to normal level (83%+/-3% and 102%+/-2% of normal respectively). There is a significant positive correlation between BDNF content and memory. Primary culture of forebrain neurons revealed that aggregated Abeta(25-35) induced significant decrease of ChAT positive neuron number, neurite outgrowth length, and M receptor density, while catalpol added to the culture medium 2 h prior to Abeta addition showed significant dose dependent protective effect. Notably, 24 h and 48 h after the addition of Abeta to the cultured cells, the BDNF mRNA level in the neurons decreased to 76%+/-7% and 66%+/-3% of control without catalpol treatment, but became 128%+/-17% and 131%+/-23% of control with catalpol treatment. When the action of BDNF was inhibited by k252a in the cultured neurons, the protective effect of catalpol was completely (neurite outgrowth length) or partially (ChAT positive neuron number and the M receptor density) abolished. Taken together, catalpol improves memory and protects the forebrain neurons from neurodegeneration through increasing BDNF expression. Whether catalpol could reverse the neurodegenerative changes already

  15. Expression of Brain-Derived Neurotrophic Factor (BDNF Increases the Resistance of Neurons to Death in the Postresuscitation Period

    I. V. Ostrova

    2015-01-01

    Full Text Available A search for substances that are able to protect brain cells from the damaging effect of hypoxia remains one of the most relevant issues in modern neurobiology and medicine. Whether neurotrophic factors, brain-derived neurotrophic factor (BDNF protein in particular, can be used to treat neurological diseases is the subject of wide speculation in the literature now. However, how the expression of this protein in the brain neurons changes after systemic circulatory arrest in the postresuscitation period remains uncertain.Objective: to estimate the level of BDNF expression in the highly ischemia-sensitive neuronal population of cerebellar Purkinje cells and the value of BDNF in the resistance of neurons to ischemia-reperfusion.Materials and methods. In mature outbred male albino rats (n=11, the heart was stopped under ether anesthesia at 12 minutes via intrathoracic ligation of the vascular fascicle, followed by revivification. A control group included pseudo-operated animals (n=11. On days 7 after revivification, a morphometric analysis of Nissl-stained paraffin sections 5—6 μm thick was used to determine the total number of Purkinje cells per 1 mm of their layer length. The expression of BDNF protein in the Purkinje cells was immunohistochemically examined by an indirect peroxidase-antiperoxidase test using primary polyclonal antibodies against BDNF. The count of Purkinje cells with different immune responses to BDNF protein was calculated. The intensity of BDNF expression was estimated from the mean optical density. Results. 12-minute systemic circulatory arrest in the rats resulted in a 12.5% reduction in the number of Purkinje cells. The immunohistochemical examination revealed a lower numbers of BDNF– neurons in the resuscitated rats. In this case, the count of BDNF+ and BDNF++ neurons corresponded to their reference level. Consequently, only BDNF-negative neurons, i.e. those that failed to express BDNF protein, died. Analysis of the

  16. Calcium-dependent plateau potentials in rostral ambiguus neurons in the newborn mouse brain stem in vitro

    Rekling, J C; Feldman, J L

    1997-01-01

    Calcium-dependent plateau potentials in rostral ambiguus neurons in the newborn mouse brain stem in vitro. J. Neurophysiol. 78: 2483-2492, 1997. The nucleus ambiguus contains vagal and glossopharyngeal motoneurons and preganglionic neurons involved in respiration, swallowing, vocalization......-stimulus orthodromic activation, using an electrode placed in the dorsomedial slice near the nucleus tractus solitarius, evoked single excitatory postsynaptic potentials (EPSPs) or short trains of EPSPs (500 ms to 1 s). However, tetanic stimulation (5 pulses, 10 Hz) induced voltage-dependent afterdepolarizations...

  17. Human fetal anatomy: MR imaging.

    Weinreb, J C; Lowe, T; Cohen, J M; Kutler, M

    1985-12-01

    Twenty-four pregnant women carrying 26 fetuses (two sets of twins) were imaged with magnetic resonance (MR) imaging at 0.35 T following sonographic evaluation. Each study was retrospectively evaluated to determine which of 33 normal fetal structures were visible on the images and which imaging parameters were most useful for depicting fetal anatomy. Fetal motion degraded fetal images in all but two cases, both with oligohydramnios and in the third trimester of gestation. Nevertheless, many fetal structures were identifiable, particularly in the third trimester. Visualization of fetal anatomy improved with intravenous maternal sedation in five cases. Relatively T1-weighted images occasionally offered the advantage of less image degradation owing to fetal motion and improved contrast between different fetal structures. More T2 weighting was believed to be advantageous in one case for outlining the fetal head and in one case for delineation of the brain. In many cases, structures were similarly identifiable (though with different signal intensities) regardless of the parameters selected. The authors conclude that MR imaging of many fetal structures is currently unsatisfactory and is probably of limited value, particularly in the first and second trimesters. However, the relative frequency and detail with which the fetal head and liver can be depicted indicate that these may be areas for further investigation, and the potential utility of imaging fetal fat warrants further investigation.

  18. Glucose administration after traumatic brain injury improves cerebral metabolism and reduces secondary neuronal injury.

    Moro, Nobuhiro; Ghavim, Sima; Harris, Neil G; Hovda, David A; Sutton, Richard L

    2013-10-16

    Clinical studies have indicated an association between acute hyperglycemia and poor outcomes in patients with traumatic brain injury (TBI), although optimal blood glucose levels needed to maximize outcomes for these patients' remain under investigation. Previous results from experimental animal models suggest that post-TBI hyperglycemia may be harmful, neutral, or beneficial. The current studies determined the effects of single or multiple episodes of acute hyperglycemia on cerebral glucose metabolism and neuronal injury in a rodent model of unilateral controlled cortical impact (CCI) injury. In Experiment 1, a single episode of hyperglycemia (50% glucose at 2 g/kg, i.p.) initiated immediately after CCI was found to significantly attenuate a TBI-induced depression of glucose metabolism in cerebral cortex (4 of 6 regions) and subcortical regions (2 of 7) as well as to significantly reduce the number of dead/dying neurons in cortex and hippocampus at 24 h post-CCI. Experiment 2 examined effects of more prolonged and intermittent hyperglycemia induced by glucose administrations (2 g/kg, i.p.) at 0, 1, 3 and 6h post-CCI. The latter study also found significantly improved cerebral metabolism (in 3 of 6 cortical and 3 of 7 subcortical regions) and significant neuroprotection in cortex and hippocampus 1 day after CCI and glucose administration. These results indicate that acute episodes of post-TBI hyperglycemia can be beneficial and are consistent with other recent studies showing benefits of providing exogenous energy substrates during periods of increased cerebral metabolic demand. © 2013 Elsevier B.V. All rights reserved.

  19. Rosiglitazone attenuates inflammation and CA3 neuronal loss following traumatic brain injury in rats

    Liu, Hao; Rose, Marie E. [Geriatric Research Educational and Clinical Center, V.A. Pittsburgh Healthcare System, PA (United States); Department of Neurology, University of Pittsburgh School of Medicine, PA (United States); Culver, Sherman; Ma, Xiecheng; Dixon, C. Edward [Geriatric Research Educational and Clinical Center, V.A. Pittsburgh Healthcare System, PA (United States); Department of Neurosurgery, University of Pittsburgh, PA 15216 (United States); Department of Critical Care Medicine, University of Pittsburgh, PA 15216 (United States); Graham, Steven H., E-mail: Steven.Graham@va.gov [Geriatric Research Educational and Clinical Center, V.A. Pittsburgh Healthcare System, PA (United States); Department of Neurology, University of Pittsburgh School of Medicine, PA (United States)

    2016-04-15

    Rosiglitazone, a potent peroxisome proliferator-activated receptor (PPAR)-γ agonist, has been shown to confer neuroprotective effects in stroke and spinal cord injury, but its role in the traumatic brain injury (TBI) is still controversial. Using a controlled cortical impact model in rats, the current study was designed to determine the effects of rosiglitazone treatment (6 mg/kg at 5 min, 6 h and 24 h post injury) upon inflammation and histological outcome at 21 d after TBI. In addition, the effects of rosiglitazone upon inflammatory cytokine transcription, vestibulomotor behavior and spatial memory function were determined at earlier time points (24 h, 1–5 d, 14–20 d post injury, respectively). Compared with the vehicle-treated group, rosiglitazone treatment suppressed production of TNFα at 24 h after TBI, attenuated activation of microglia/macrophages and increased survival of CA3 neurons but had no effect on lesion volume at 21 d after TBI. Rosiglitazone-treated animals had improved performance on beam balance testing, but there was no difference in spatial memory function as determined by Morris water maze. In summary, this study indicates that rosiglitazone treatment in the first 24 h after TBI has limited anti-inflammatory and neuroprotective effects in rat traumatic injury. Further study using an alternative dosage paradigm and more sensitive behavioral testing may be warranted. - Highlights: • Effects of rosiglitazone after CCI were evaluated using a rat TBI model. • Rosiglitazone suppressed production of TNFα at 24 h after CCI. • Rosiglitazone inhibited microglial activation at 21 d after CCI. • Rosiglitazone increased survival of CA3 neurons at 21 d after CCI. • Rosiglitazone-treated animals had improved performance in beam balance testing.

  20. Rosiglitazone attenuates inflammation and CA3 neuronal loss following traumatic brain injury in rats

    Liu, Hao; Rose, Marie E.; Culver, Sherman; Ma, Xiecheng; Dixon, C. Edward; Graham, Steven H.

    2016-01-01

    Rosiglitazone, a potent peroxisome proliferator-activated receptor (PPAR)-γ agonist, has been shown to confer neuroprotective effects in stroke and spinal cord injury, but its role in the traumatic brain injury (TBI) is still controversial. Using a controlled cortical impact model in rats, the current study was designed to determine the effects of rosiglitazone treatment (6 mg/kg at 5 min, 6 h and 24 h post injury) upon inflammation and histological outcome at 21 d after TBI. In addition, the effects of rosiglitazone upon inflammatory cytokine transcription, vestibulomotor behavior and spatial memory function were determined at earlier time points (24 h, 1–5 d, 14–20 d post injury, respectively). Compared with the vehicle-treated group, rosiglitazone treatment suppressed production of TNFα at 24 h after TBI, attenuated activation of microglia/macrophages and increased survival of CA3 neurons but had no effect on lesion volume at 21 d after TBI. Rosiglitazone-treated animals had improved performance on beam balance testing, but there was no difference in spatial memory function as determined by Morris water maze. In summary, this study indicates that rosiglitazone treatment in the first 24 h after TBI has limited anti-inflammatory and neuroprotective effects in rat traumatic injury. Further study using an alternative dosage paradigm and more sensitive behavioral testing may be warranted. - Highlights: • Effects of rosiglitazone after CCI were evaluated using a rat TBI model. • Rosiglitazone suppressed production of TNFα at 24 h after CCI. • Rosiglitazone inhibited microglial activation at 21 d after CCI. • Rosiglitazone increased survival of CA3 neurons at 21 d after CCI. • Rosiglitazone-treated animals had improved performance in beam balance testing.

  1. Bmi1 is down-regulated in the aging brain and displays antioxidant and protective activities in neurons.

    Mohamed Abdouh

    Full Text Available Aging increases the risk to develop several neurodegenerative diseases, although the underlying mechanisms are poorly understood. Inactivation of the Polycomb group gene Bmi1 in mice results in growth retardation, cerebellar degeneration, and development of a premature aging-like phenotype. This progeroid phenotype is characterized by formation of lens cataracts, apoptosis of cortical neurons, and increase of reactive oxygen species (ROS concentrations, owing to p53-mediated repression of antioxidant response (AOR genes. Herein we report that Bmi1 expression progressively declines in the neurons of aging mouse and human brains. In old brains, p53 accumulates at the promoter of AOR genes, correlating with a repressed chromatin state, down-regulation of AOR genes, and increased oxidative damages to lipids and DNA. Comparative gene expression analysis further revealed that aging brains display an up-regulation of the senescence-associated genes IL-6, p19(Arf and p16(Ink4a, along with the pro-apoptotic gene Noxa, as seen in Bmi1-null mice. Increasing Bmi1 expression in cortical neurons conferred robust protection against DNA damage-induced cell death or mitochondrial poisoning, and resulted in suppression of ROS through activation of AOR genes. These observations unveil that Bmi1 genetic deficiency recapitulates aspects of physiological brain aging and that Bmi1 over-expression is a potential therapeutic modality against neurodegeneration.

  2. Study on cognition disorder and morphologic change of neurons in hippocampus area following traumatic brain injury in rats

    洪军; 崔建忠; 周云涛; 高俊玲

    2002-01-01

    Objective: To explore the correlation between cognition disorder and morphologic change of hippocampal neurons after traumatic brain injury (TBI).   Methods: Wistar rat models with severe TBI were made by Marmarous method. The histopathological change of the neurons in the hippocampus area were studied with hematoxylin-eosin (HE) staining and terminal deoxynucleotidyl transferase-mediated X-dUPT nick end labeling (TUNEL), respectively. The cognitive function was evaluated with the Morris water maze test.   Results: The comprehensive neuronal degeneration and necrosis could be observed in CA2-3 regions of hippocampus at 3 days after injury. Apoptotic positive neurons in CA2-4 regions of hippocampus and dentate gyrus increased in the injured group at 24 hours following TBI. They peaked at 7 days and then declined. Significant impairment of spatial learning and memory was observed after injury in the rats.   Conclusions: The rats have obvious disorders in spatial learning and memory after severe TBI. Meanwhile, delayed neuronal necrosis and apoptosis can be observed in the neurons in the hippocampus area. It suggests that delayed hippocampal cell death may contribute to the functional deficit.

  3. Attenuation of hypoxic current by intracellular applications of ATP regenerating agents in hippocampal CA1 neurons of rat brain slices.

    Chung, I; Zhang, Y; Eubanks, J H; Zhang, L

    1998-10-01

    Hypoxia-induced outward currents (hyperpolarization) were examined in hippocampal CA1 neurons of rat brain slices, using the whole-cell recording technique. Hypoxic episodes were induced by perfusing slices with an artificial cerebrospinal fluid aerated with 5% CO2/95% N2 rather than 5% CO2/95% O2, for about 3 min. The hypoxic current was consistently and reproducibly induced in CA1 neurons dialysed with an ATP-free patch pipette solution. This current manifested as an outward shift in the holding current in association with increased conductance, and it reversed at -78 +/- 2.5 mV, with a linear I-V relation in the range of -100 to -40 mV. To provide extra energy resources to individual neurons recorded, agents were added to the patch pipette solution, including MgATP alone, MgATP + phosphocreatine + creatine kinase, or MgATP + creatine. In CA1 neurons dialysed with patch solutions including these agents, hypoxia produced small outward currents in comparison with those observed in CA1 neurons dialysed with the ATP-free solution. Among the above agents examined, whole-cell dialysis with MgATP + creatine was the most effective at decreasing the hypoxic outward currents. We suggest that the hypoxic hyperpolarization is closely related to energy metabolism in individual CA1 neurons, and that the energy supply provided by phosphocreatine metabolism may play a critical role during transient metabolic stress.

  4. Protective effect of green tea polyphenol EGCG against neuronal damage and brain edema after unilateral cerebral ischemia in gerbils.

    Lee, Hyung; Bae, Jae Hoon; Lee, Seong-Ryong

    2004-09-15

    Previous studies have demonstrated that a green tea polyphenol, (-)-epigallocatechine gallate (EGCG), has a potent free radical scavenging and antioxidant effect. Glutamate leads to excitotoxicity and oxidative stress, which are important pathophysiologic responses to cerebral ischemia resulting in brain edema and neuronal damage. We investigated the effect of EGCG on excitotoxic neuronal damage in a culture system and the effect on brain edema formation and lesion after unilateral cerebral ischemia in gerbils. In vitro, excitotoxicity was induced by 24-hr incubation with N-methyl-D-aspartate (NMDA; 10 microM), AMPA (10 microM), or kainate (20 microM). EGCG (5 microM) was added to the culture media alone or with excitotoxins. We examined malondialdehyde (MDA) level and neuronal viability to evaluate the effect of EGCG. In vivo, unilateral cerebral ischemia was induced by occlusion of the right common carotid artery for 30, 60, or 90 min and followed by reperfusion of 24 hr. Brain edema, MDA, and infarction were examined to evaluate the protective effect of EGCG. EGCG (25 or 50 mg/kg, intraperitoneally) was administered twice, at 30 min before and immediately after ischemia. EGCG reduced excitotoxin-induced MDA production and neuronal damage in the culture system. In the in vivo study, treatment of gerbils with the lower EGCG dose failed to show neuroprotective effects; however, the higher EGCG dose attenuated the increase in MDA level caused by cerebral ischemia. EGCG also reduced the formation of postischemic brain edema and infarct volume. These results demonstrate EGCG may have future possibilities as a neuroprotective agent against excitotoxicity-related neurologic disorders such as brain ischemia.

  5. Different populations of prostaglandin EP3 receptor-expressing preoptic neurons project to two fever-mediating sympathoexcitatory brain regions.

    Nakamura, Y; Nakamura, K; Morrison, S F

    2009-06-30

    The central mechanism of fever induction is triggered by an action of prostaglandin E(2) (PGE(2)) on neurons in the preoptic area (POA) through the EP3 subtype of prostaglandin E receptor. EP3 receptor (EP3R)-expressing POA neurons project directly to the dorsomedial hypothalamus (DMH) and to the rostral raphe pallidus nucleus (rRPa), key sites for the control of thermoregulatory effectors. Based on physiological findings, we hypothesize that the febrile responses in brown adipose tissue (BAT) and those in cutaneous vasoconstrictors are controlled independently by separate neuronal pathways: PGE(2) pyrogenic signaling is transmitted from EP3R-expressing POA neurons via a projection to the DMH to activate BAT thermogenesis and via another projection to the rRPa to increase cutaneous vasoconstriction. In this case, DMH-projecting and rRPa-projecting neurons would constitute segregated populations within the EP3R-expressing neuronal group in the POA. Here, we sought direct anatomical evidence to test this hypothesis with a double-tracing experiment in which two types of the retrograde tracer, cholera toxin b-subunit (CTb), conjugated with different fluorophores were injected into the DMH and the rRPa of rats and the resulting retrogradely labeled populations of EP3R-immunoreactive neurons in the POA were identified with confocal microscopy. We found substantial numbers of EP3R-immunoreactive neurons in both the DMH-projecting and the rRPa-projecting populations. However, very few EP3R-immunoreactive POA neurons were labeled with both the CTb from the DMH and that from the rRPa, although a substantial number of neurons that were not immunoreactive for EP3R were double-labeled with both CTbs. The paucity of the EP3R-expressing neurons that send collaterals to both the DMH and the rRPa suggests that pyrogenic signals are sent independently to these caudal brain regions from the POA and that such pyrogenic outputs from the POA reflect different control mechanisms for BAT

  6. Fetal echocardiography

    Chaubal, Nitin G.; Chaubal, Jyoti

    2009-01-01

    USG performed with a high-end machine, using a good cine-loop facility is extremely helpful in the diagnosis of fetal cardiac anomalies. In fetal echocardiography, the four-chamber view and the outflow-tract view are used to diagnose cardiac anomalies. The most important objective during a targeted anomaly scan is to identify those cases that need a dedicated fetal echocardiogram. Associated truncal and chromosomal anomalies need to be identified. This review shows how fetal echocardiography, apart from identifying structural defects in the fetal heart, can be used to look at rhythm abnormalities and other functional aspects of the fetal heart

  7. Rescue of axotomized rubrospinal neurons by brain-derived neurotrophic factor (BDNF) in the developing opossum, Didelphis virginiana.

    Wang, X M; Terman, J R; Martin, G F

    1999-12-10

    Many rubrospinal neurons die in developing opossums when their axon is cut at thoracic levels of the spinal cord and in the present study we asked whether they can be rescued by brain-derived neurotrophic factor (BDNF). Bilateral injections of Fast Blue (FB) were made into the rostral lumbar cord to prelabel rubrospinal neurons and 5 days later the rubrospinal tract was cut unilaterally by hemisecting the thoracic cord. Immediately after hemisection, BDNF-soaked gelfoam was placed into the lesion cavity. Since pilot data indicated that one application of BDNF was not sufficient to produce a rescue effect, a second application was made 7 days later. Seven days after the second application the pups were killed by an overdose of anesthetic so that the red nucleus contralateral and ipsilateral to the lesion site could be examined for labeled neurons. The rubrospinal tract is almost entirely crossed, so the red nucleus contralateral to the lesion contained many axotomized neurons, whereas the red nucleus ipsilateral to it did not. Age-matched controls were subjected to the same procedures, but the gelfoam applied to the lesion site in the experimental animals was soaked only in the vehicle used to deliver BDNF. In all cases, labeled neurons were fewer in number in the red nucleus contralateral to the lesion than ipsilateral to it. It was of particular interest, however, that labeled neurons contralateral to the lesion were more numerous in the animals treated with BDNF than in the controls. We conclude that BDNF rescues at least some rubrospinal neurons from axotomy-induced cell death in developing opossums suggesting that loss of access to BDNF, and perhaps other neurotrophins, contributes to failure of rubrospinal neurons to survive axotomy.

  8. Comparative immunocytochemical study of FMRFamide neuronal system in the brain of Danio rerio and Acipenser ruthenus during development.

    Pinelli, C; D'Aniello, B; Sordino, P; Meyer, D L; Fiorentino, M; Rastogi, R K

    2000-02-07

    The distribution of FMRFamide-like immunoreactive (ir) neurons and fibers was investigated in the central nervous system of developing zebrafish and juvenile sturgeon (sterlet). Adult zebrafish was also studied. In zebrafish embryos FMRFamide-ir elements first appeared 30 h post-fertilization (PF). Ir somata were located in the olfactory placode and in the ventral diencephalon. FMRFamide-ir fibers originating from diencephalic neurons were found in the ventral telencephalon and in ventral portions of the brainstem. At 48 h PF, the ir perikarya in the olfactory placode displayed increased immunoreactivity and stained fibers emerged from the somata. At 60 h PF, bilaterally, clusters of FMRFamide-ir neurons were found along the rostro-caudal axis of the brain, from the olfactory placode to rostral regions of the ventro-lateral telencephalon. At 60 h PF, numerous ir fibers appeared in the dorsal telencephalon, optic lobes, optic nerves, and retina. Except for ir fibers in the hypophysis at the age of 72 h PF, and a few ir cells in the nucleus olfacto-retinalis (NOR) at the age of 2 months PF, no major re-organization was noted in subsequent ontogenetic stages. The number of stained NOR neurons increased markedly in sexually mature zebrafish. In adult zebrafish, other ir neurons were located in the dorsal zones of the periventricular hypothalamus and in components of the nervus terminalis. We are inclined to believe that neurons expressing FMRFamide originate in the olfactory placode and in the ventricular ependyma in the hypothalamus. On the same grounds, a dual origin of FMRFamide-ir neurons is inferred in the sturgeon, an ancestral bony fish: prior to the observation of ir cells in the nasal area and in the telencephalon stained neurons were noted in circumventricular hypothalamic regions.

  9. Expression of TRPM8 in the distal cerebrospinal fluid-contacting neurons in the brain mesencephalon of rats

    Zhang Licai

    2009-03-01

    Full Text Available Abstract Background It has been shown that distal cerebrospinal fluid-contacting neurons (dCSF-CNs exist near the ventral midline of the midbrain aqueduct and also in the grey matter of the inferior third ventricle and the fourth ventricle floor in the superior segment of the pons. The dCSF-CNs communicate between the cerebrospinal fluid (CSF and the brain parenchyma and may participate in the transduction and regulation of pain signals. The cold sensation receptor channel, TRPM8 is involved in analgesia for neuropathic pain, but whether the TRPM8 receptor exists on dCSF-CNs remains unknown. However, there is preliminary evidence that TRPM8 is expressed in dCSF-CNs and may participate in the transmission and regulation of sensory information between brain parenchyma and cerebrospinal fluid (CSF in rats. Methods Retrograde tracing of the cholera toxin subunit B labeled with horseradish peroxidase (CB-HRP injected into the lateral ventricle was used to identify dCSF-CNs. A double-labeled immunofluorescent technique and laser scanning confocal microscopy were used to identify the expression of TRPM8 in dCSF-CNs. Software Image-Pro Plus was used to count the number of neurons in three sections where CB-HRP positive neurons were located in the mesencephalon of six rats. Results The cell bodies of CB-HRP-positive dCSF-CNs were found in the brain parenchyma near the midline of the ventral Aq, also in the grey of the 3V, and the 4V floor in the superior segment of the pons. In the mesencephalon their processes extended into the CSF. TRPM8 labeled neurons were also found in the same area as were CB-HRP/TRPM8 double-labeled neurons. CB-HRP/TRPM8 double-labeled neurons were found in 42.9 ± 2.3% of neurons labeled by TRPM8, and all CB-HRP-labeled neurons were also labeled with TPRM8. Conclusion This study has demonstrated that the cold sensation receptor channel, TRPM8, is localised within the dCSF-CNs of the mesencephalon. TRPM8 acts as receptor of d

  10. Drosophila Clock Is Required in Brain Pacemaker Neurons to Prevent Premature Locomotor Aging Independently of Its Circadian Function.

    Alexandra Vaccaro

    2017-01-01

    Full Text Available Circadian clocks control many self-sustained rhythms in physiology and behavior with approximately 24-hour periodicity. In many organisms, oxidative stress and aging negatively impact the circadian system and sleep. Conversely, loss of the clock decreases resistance to oxidative stress, and may reduce lifespan and speed up brain aging and neurodegeneration. Here we examined the effects of clock disruptions on locomotor aging and longevity in Drosophila. We found that lifespan was similarly reduced in three arrhythmic mutants (ClkAR, cyc0 and tim0 and in wild-type flies under constant light, which stops the clock. In contrast, ClkAR mutants showed significantly faster age-related locomotor deficits (as monitored by startle-induced climbing than cyc0 and tim0, or than control flies under constant light. Reactive oxygen species accumulated more with age in ClkAR mutant brains, but this did not appear to contribute to the accelerated locomotor decline of the mutant. Clk, but not Cyc, inactivation by RNA interference in the pigment-dispersing factor (PDF-expressing central pacemaker neurons led to similar loss of climbing performance as ClkAR. Conversely, restoring Clk function in these cells was sufficient to rescue the ClkAR locomotor phenotype, independently of behavioral rhythmicity. Accelerated locomotor decline of the ClkAR mutant required expression of the PDF receptor and correlated to an apparent loss of dopaminergic neurons in the posterior protocerebral lateral 1 (PPL1 clusters. This neuronal loss was rescued when the ClkAR mutation was placed in an apoptosis-deficient background. Impairing dopamine synthesis in a single pair of PPL1 neurons that innervate the mushroom bodies accelerated locomotor decline in otherwise wild-type flies. Our results therefore reveal a novel circadian-independent requirement for Clk in brain circadian neurons to maintain a subset of dopaminergic cells and avoid premature locomotor aging in Drosophila.

  11. Decoding the non-stationary neuron spike trains by dual Monte Carlo point process estimation in motor Brain Machine Interfaces.

    Liao, Yuxi; Li, Hongbao; Zhang, Qiaosheng; Fan, Gong; Wang, Yiwen; Zheng, Xiaoxiang

    2014-01-01

    Decoding algorithm in motor Brain Machine Interfaces translates the neural signals to movement parameters. They usually assume the connection between the neural firings and movements to be stationary, which is not true according to the recent studies that observe the time-varying neuron tuning property. This property results from the neural plasticity and motor learning etc., which leads to the degeneration of the decoding performance when the model is fixed. To track the non-stationary neuron tuning during decoding, we propose a dual model approach based on Monte Carlo point process filtering method that enables the estimation also on the dynamic tuning parameters. When applied on both simulated neural signal and in vivo BMI data, the proposed adaptive method performs better than the one with static tuning parameters, which raises a promising way to design a long-term-performing model for Brain Machine Interfaces decoder.

  12. Electrical and chemical transmission between striatal GABAergic output neurones in rat brain slices

    Venance, Laurent; Glowinski, Jacques; Giaume, Christian

    2004-01-01

    Basal ganglia are interconnected subcortical nuclei, connected to the thalamus and all cortical areas involved in sensory motor control, limbic functions and cognition. The striatal output neurones (SONs), the major striatal population, are believed to act as detectors and integrators of distributed patterns of cerebral cortex inputs. Despite the key role of SONs in cortico-striatal information processing, little is known about their local interactions. Here, we report the existence and characterization of electrical and GABAergic transmission between SONs in rat brain slices. Tracer coupling (biocytin) incidence was high during the first two postnatal weeks and then decreased (postnatal days (P) 5–25, 60%; P25–30, 29%; n = 61). Electrical coupling was observed between 27% of SON pairs (coupling coefficient: 3.1 ± 0.3%, n = 89 at P15) and as shown by single-cell RT-PCR, several connexin (Cx) mRNAs were found to be expressed (Cx31.1, Cx32, Cx36 and Cx47). GABAergic synaptic transmission (abolished by bicuculline, a GABAA receptor antagonist) observed in 19% of SON pairs (n = 62) was reliable (mean failure rate of 6 ± 3%), precise (variation coefficient of latency, 0.06), strong (IPSC amplitudes of 38 ± 12 pA) and unidirectional. Interestingly, electrical and chemical transmission were mutually exclusive. These results suggest that preferential networks of electrically and chemically connected SONs, might be involved in the channelling of cortico-basal ganglia information processing. PMID:15235091

  13. Structural and functional brain signatures of C9orf72 in motor neuron disease.

    Agosta, Federica; Ferraro, Pilar M; Riva, Nilo; Spinelli, Edoardo Gioele; Domi, Teuta; Carrera, Paola; Copetti, Massimiliano; Falzone, Yuri; Ferrari, Maurizio; Lunetta, Christian; Comi, Giancarlo; Falini, Andrea; Quattrini, Angelo; Filippi, Massimo

    2017-09-01

    This study investigated structural and functional magnetic resonance imaging abnormalities in hexanucleotide repeat expansion in chromosome 9 open reading frame 72 (C9orf72) motor neuron disease (MND) relative to disease severity-matched sporadic MND cases. We enrolled 19 C9orf72 and 67 disease severity-matched sporadic MND patients, and 22 controls. Sporadic cases were grouped in patients with: no cognitive/behavioral deficits (sporadic-motor); same patterns of cognitive/behavioral impairment as C9orf72 cases (sporadic-cognitive); shorter disease duration versus other sporadic groups (sporadic-early). C9orf72 patients showed cerebellar and thalamic atrophy versus all sporadic cases. All MND patients showed motor, frontal, and temporoparietal cortical thinning and motor and extramotor white matter damage versus controls, independent of genotype and presence of cognitive impairment. Compared with sporadic-early, C9orf72 patients revealed an occipital cortical thinning. C9orf72 patients had enhanced visual network functional connectivity versus sporadic-motor and sporadic-early cases. Structural cerebellar and thalamic damage and posterior cortical alterations are the brain magnetic resonance imaging signatures of C9orf72 MND. Frontotemporal cortical and widespread white matter involvement are likely to be an effect of the disease evolution rather than a C9orf72 marker. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Recovered neuronal viability revealed by Iodine-123-iomazenil SPECT following traumatic brain injury.

    Koizumi, Hiroyasu; Fujisawa, Hirosuke; Kurokawa, Tetsu; Suehiro, Eiichi; Iwanaga, Hideyuki; Nakagawara, Jyoji; Suzuki, Michiyasu

    2010-10-01

    We evaluated cortical damages following traumatic brain injury (TBI) in the acute phase with [(123)I] iomazenil (IMZ) single photon emission computed tomography (SPECT). In all, 12 patients with cerebral contusion following TBI were recruited. All patients underwent IMZ SPECT within 1 week after TBI. To investigate the changes in distribution of IMZ in the cortex in the chronic phase, after conventional treatment, patients underwent IMZ SPECT again. A decrease in the accumulation of radioligand for the central benzodiazepine receptor in the cortex corresponding to the contusion revealed with computed tomography (CT) scans and magnetic resonance imaging (MRI) were shown on IMZ SPECT in the acute phase in all patients. In 9 of 12 patients (75%), images of IMZ SPECT obtained in the chronic phase of TBI showed that areas with a decreased distribution of IMZ were remarkably reduced in comparison with those obtained in the acute phase. Both CT scans and MRI showed a normal appearance of the cortex morphologically, where the binding potential of IMZ recovered in the chronic phase. Reduced binding potential of radioligand for the central benzodiazepine receptor is considered to be an irreversible reaction; however, in this study, IMZ accumulation in the cortex following TBI was recovered in the chronic phase in several patients. [(123)I] iomazenil SPECT may have a potential to disclose a reversible vulnerability of neurons following TBI.

  15. Biofuel Cell Based on Microscale Nanostructured Electrodes with Inductive Coupling to Rat Brain Neurons

    Andoralov, Viktor; Falk, Magnus; Suyatin, Dmitry B.; Granmo, Marcus; Sotres, Javier; Ludwig, Roland; Popov, Vladimir O.; Schouenborg, Jens; Blum, Zoltan; Shleev, Sergey

    2013-11-01

    Miniature, self-contained biodevices powered by biofuel cells may enable a new generation of implantable, wireless, minimally invasive neural interfaces for neurophysiological in vivo studies and for clinical applications. Here we report on the fabrication of a direct electron transfer based glucose/oxygen enzymatic fuel cell (EFC) from genuinely three-dimensional (3D) nanostructured microscale gold electrodes, modified with suitable biocatalysts. We show that the process underlying the simple fabrication method of 3D nanostructured electrodes is based on an electrochemically driven transformation of physically deposited gold nanoparticles. We experimentally demonstrate that mediator-, cofactor-, and membrane-less EFCs do operate in cerebrospinal fluid and in the brain of a rat, producing amounts of electrical power sufficient to drive a self-contained biodevice, viz. 7 μW cm-2 in vitro and 2 μW cm-2 in vivo at an operating voltage of 0.4 V. Last but not least, we also demonstrate an inductive coupling between 3D nanobioelectrodes and living neurons.

  16. Fetal echocardiography

    ... page: //medlineplus.gov/ency/article/007340.htm Fetal echocardiography To use the sharing features on this page, please enable JavaScript. Fetal echocardiography is a test that uses sound waves ( ultrasound ) ...

  17. Edaravone attenuates neuronal apoptosis in hypoxic-ischemic brain damage rat model via suppression of TRAIL signaling pathway.

    Li, Chunyi; Mo, Zhihuai; Lei, Junjie; Li, Huiqing; Fu, Ruying; Huang, Yanxia; Luo, Shijian; Zhang, Lei

    2018-06-01

    Edaravone is a new type of oxygen free radical scavenger and able to attenuate various brain damage including hypoxic-ischemic brain damage (HIBD). This study was aimed at investigating the neuroprotective mechanism of edaravone in rat hypoxic-ischemic brain damage model and its correlation with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) signaling pathway. 75 seven-day-old Sprague-Dawley neonatal rats were equally divided into three groups: sham-operated group (sham), HIBD group and HIBD rats injected with edaravone (HIBD + EDA) group. Neurological severity and space cognitive ability of rats in each group were evaluated using Longa neurological severity score and Morris water maze testing. TUNEL assay and flow cytometry were used to determine brain cell apoptosis. Western blot was used to estimate the expression level of death receptor-5 (DR5), Fas-associated protein with death domain (FADD), caspase 8, B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax). In addition, immunofluorescence was performed to detect caspase 3. Edaravone reduced neurofunctional damage caused by HIBD and improved the cognitive capability of rats. The above experiment results suggested that edaravone could down-regulate the expression of active caspase 3 protein, thereby relieving neuronal apoptosis. Taken together, edaravone could attenuate neuronal apoptosis in rat hypoxic-ischemic brain damage model via suppression of TRAIL signaling pathway, which also suggested that edaravone might be an effective therapeutic strategy for HIBD clinical treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. (3H)-dihydrotestosterone in catecholamine neurons of rat brain stem: combined localization by autoradiography and formaldehyde-induced fluorescence

    Heritage, A.S.; Stumpf, W.E.; Sar, M.; Grant, L.D.

    1981-01-01

    A combined formaldehyde-induced fluorescence (FIF)-autoradiography procedure was used to determine how and where the androgen, dihydrotestosterone (DHT), is associated with catecholamine systems in the rat brain. With this dual localization method, ( 3 H)-DHT target sites can be visualized in relation to catecholamine perikarya and terminals. In the hindbrain, catecholamine neurons adjacent to the fourth ventricle (group A4), the nucleus (n.) olivaris superior (group A5), the n. parabranchialis medialis (group A7), and in the locus coeruleus (group A6) and subcoeruleal regions, as well as in the substantia grisea centralis, concentrate ( 3 H)-DHT in their nuclei. ( 3 H)-DHT target neurons appear to be innervated by numerous catecholamine terminals in the following hindbrain regions: n. motorius dorsalis nervi vagi, n. tractus solitarii, n. commissuralis, n. raphe pallidus, n. olivaris inferior, the ventrolateral portion of the substantia grisea centralis, n. cuneiformis, and the ventrolateral reticular formation in the caudal mesencephalon. In the forebrain, ( 3 H)-DHT concentrates in nuclei of catecholamine neurons located in the n. arcuatus and n. periventricularis (group A12). In addition, ( 3 H)-DHT target neurons appear to be innervated by numerous catecholamine terminals in the following forebrain regions: n. periventricularis rotundocellularis, n. paraventricularis, n. dorsomedialis, n. periventricularis, area retrochiasmatica, n. interstititalis striae terminalis (ventral portion), and n. amygdaloideus centralis. The disclosure of a morphologic association between ( 3 H)-DHT target sites and certain brain catecholamine systems suggests a close functional interdependence between androgens and catecholamines

  19. Comparative studies on mitochondria isolated from neuron-enriched and glia-enriched fractions of rabbit and beef brain.

    Hamberger, A; Blomstrand, C; Lehninger, A L

    1970-05-01

    Fractions enriched in neuronal and glial cells were obtained from dispersions of whole beef brain and rabbit cerebral cortex by large-scale density gradient centrifugation procedures. The fractions were characterized by appropriate microscopic observation. Mitochondria were then isolated from these fractions by differential centrifugation of their homogenates. The two different types of mitochondria were characterized with respect to certain enzyme activities, respiratory rate, rate of protein synthesis, and their buoyant density in sucrose gradients. The mitochondria from the neuron-enriched fraction were distinguished by a higher rate of incorporation of amino acids into protein, higher cytochrome oxidase activity, and a higher buoyant density in sucrose density gradients. Mitochondria from the glia-enriched fraction showed relatively high monoamine oxidase and Na(+)- and K(+)-stimulated ATPase activities. The rates of oxidation of various substrates and the acceptor control ratios did not differ appreciably between the two types of mitochondria. The difference in the buoyant density of mitochondria isolated from the neuron-enriched and glia-enriched cell fractions was utilized in attempts to separate neuronal and glial mitochondria from the mixed mitochondria obtained from whole brain homogenates in shallow sucrose gradients. The appearance of two peaks of cytochrome oxidase, monoamine oxidase, and protein concentration in such gradients shows the potential feasibility of such an approach.

  20. I-123 iomazenil single photon emission computed tomography for detecting loss of neuronal integrity in patients with traumatic brain injury.

    Abiko, Kagari; Ikoma, Katsunori; Shiga, Tohru; Katoh, Chietsugu; Hirata, Kenji; Kuge, Yuji; Kobayashi, Kentaro; Tamaki, Nagara

    2017-12-01

    Traumatic brain injury (TBI) causes brain dysfunction in many patients. Using C-11 flumazenil (FMZ) positron emission tomography (PET), we have detected and reported the loss of neuronal integrity, leading to brain dysfunction in TBI patients. Similarly to FMZ PET, I-123 iomazenil (IMZ) single photon emission computed tomography (SPECT) is widely used to determine the distribution of the benzodiazepine receptor (BZR) in the brain cortex. The purpose of this study is to examine whether IMZ SPECT is as useful as FMZ PET for evaluating the loss of neuronal integrity in TBI patients. The subjects of this study were seven patients who suffered from neurobehavioral disability. They underwent IMZ SPECT and FMZ PET. Nondisplaceable binding potential (BP ND ) was calculated from FMZ PET images. The uptake of IMZ was evaluated on the basis of lesion-to-pons ratio (LPR). The locations of low uptake levels were visually evaluated both in IMZ SPECT and FMZ PET images. We compared FMZ BP ND and (LPR-1) of IMZ SPECT. In the visual assessment, FMZ BP ND decreased in 11 regions. In IMZ SPECT, low uptake levels were observed in eight of the 11 regions. The rate of concordance between FMZ PET and IMZ SPECT was 72.7%. The mean values IMZ (LPR-1) (1.95 ± 1.01) was significantly lower than that of FMZ BP ND (2.95 ± 0.80 mL/mL). There was good correlation between FMZ BP ND and IMZ (LPR-1) (r = 0.80). IMZ SPECT findings were almost the same as FMZ PET findings in TBI patients. The results indicated that IMZ SPECT is useful for evaluating the loss of neuronal integrity. Because IMZ SPECT can be performed in various facilities, IMZ SPECT may become widely adopted for evaluating the loss of neuronal integrity.