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Sample records for neonatal brain growth

  1. Intranasal epidermal growth factor treatment rescues neonatal brain injury

    Science.gov (United States)

    Scafidi, Joseph; Hammond, Timothy R.; Scafidi, Susanna; Ritter, Jonathan; Jablonska, Beata; Roncal, Maria; Szigeti-Buck, Klara; Coman, Daniel; Huang, Yuegao; McCarter, Robert J.; Hyder, Fahmeed; Horvath, Tamas L.; Gallo, Vittorio

    2014-02-01

    There are no clinically relevant treatments available that improve function in the growing population of very preterm infants (less than 32 weeks' gestation) with neonatal brain injury. Diffuse white matter injury (DWMI) is a common finding in these children and results in chronic neurodevelopmental impairments. As shown recently, failure in oligodendrocyte progenitor cell maturation contributes to DWMI. We demonstrated previously that the epidermal growth factor receptor (EGFR) has an important role in oligodendrocyte development. Here we examine whether enhanced EGFR signalling stimulates the endogenous response of EGFR-expressing progenitor cells during a critical period after brain injury, and promotes cellular and behavioural recovery in the developing brain. Using an established mouse model of very preterm brain injury, we demonstrate that selective overexpression of human EGFR in oligodendrocyte lineage cells or the administration of intranasal heparin-binding EGF immediately after injury decreases oligodendroglia death, enhances generation of new oligodendrocytes from progenitor cells and promotes functional recovery. Furthermore, these interventions diminish ultrastructural abnormalities and alleviate behavioural deficits on white-matter-specific paradigms. Inhibition of EGFR signalling with a molecularly targeted agent used for cancer therapy demonstrates that EGFR activation is an important contributor to oligodendrocyte regeneration and functional recovery after DWMI. Thus, our study provides direct evidence that targeting EGFR in oligodendrocyte progenitor cells at a specific time after injury is clinically feasible and potentially applicable to the treatment of premature children with white matter injury.

  2. Altered resting-state whole-brain functional networks of neonates with intrauterine growth restriction.

    Science.gov (United States)

    Batalle, Dafnis; Muñoz-Moreno, Emma; Tornador, Cristian; Bargallo, Nuria; Deco, Gustavo; Eixarch, Elisenda; Gratacos, Eduard

    2016-04-01

    The feasibility to use functional MRI (fMRI) during natural sleep to assess low-frequency basal brain activity fluctuations in human neonates has been demonstrated, although its potential to characterise pathologies of prenatal origin has not yet been exploited. In the present study, we used intrauterine growth restriction (IUGR) as a model of altered neurodevelopment due to prenatal condition to show the suitability of brain networks to characterise functional brain organisation at neonatal age. Particularly, we analysed resting-state fMRI signal of 20 neonates with IUGR and 13 controls, obtaining whole-brain functional networks based on correlations of blood oxygen level-dependent (BOLD) signal in 90 grey matter regions of an anatomical atlas (AAL). Characterisation of the networks obtained with graph theoretical features showed increased network infrastructure and raw efficiencies but reduced efficiency after normalisation, demonstrating hyper-connected but sub-optimally organised IUGR functional brain networks. Significant association of network features with neurobehavioral scores was also found. Further assessment of spatiotemporal dynamics displayed alterations into features associated to frontal, cingulate and lingual cortices. These findings show the capacity of functional brain networks to characterise brain reorganisation from an early age, and their potential to develop biomarkers of altered neurodevelopment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. The neonatal brain

    International Nuclear Information System (INIS)

    Flodmark, O.

    1987-01-01

    The clinical examination of the CNS in the neonate is often difficult in cases of complex pathology. Diagnostic imaging of the neonatal brain has become extremely useful and in the last decade has developed in two main directions: CT and US. MR imaging has been used recently with varying success in the diagnosis of pathology in the neonatal brain. Despite technical difficulties, this imaging method is likely to become increasingly important in the neonate. The paper examines the normal neonatal brain anatomy as seen with the different modalities, followed by pathologic conditions. Attention is directed to the common pathology, in asphyxiated newborns, the patholphysiology of intraventicular hemorrhage and periventricular leukomalacia in the preterm neonate, and hypoxic-ischemic brain injury in the term neonate. Pitfalls, artifacts, and problems in image interpretation are illustrated. Finally, the subsequent appearance of neonatal pathology later in infancy and childhood is discussed

  4. Regional gray matter growth, sexual dimorphism, and cerebral asymmetry in the neonatal brain.

    Science.gov (United States)

    Gilmore, John H; Lin, Weili; Prastawa, Marcel W; Looney, Christopher B; Vetsa, Y Sampath K; Knickmeyer, Rebecca C; Evans, Dianne D; Smith, J Keith; Hamer, Robert M; Lieberman, Jeffrey A; Gerig, Guido

    2007-02-07

    Although there has been recent interest in the study of childhood and adolescent brain development, very little is known about normal brain development in the first few months of life. In older children, there are regional differences in cortical gray matter development, whereas cortical gray and white matter growth after birth has not been studied to a great extent. The adult human brain is also characterized by cerebral asymmetries and sexual dimorphisms, although very little is known about how these asymmetries and dimorphisms develop. We used magnetic resonance imaging and an automatic segmentation methodology to study brain structure in 74 neonates in the first few weeks after birth. We found robust cortical gray matter growth compared with white matter growth, with occipital regions growing much faster than prefrontal regions. Sexual dimorphism is present at birth, with males having larger total brain cortical gray and white matter volumes than females. In contrast to adults and older children, the left hemisphere is larger than the right hemisphere, and the normal pattern of fronto-occipital asymmetry described in older children and adults is not present. Regional differences in cortical gray matter growth are likely related to differential maturation of sensory and motor systems compared with prefrontal executive function after birth. These findings also indicate that whereas some adult patterns of sexual dimorphism and cerebral asymmetries are present at birth, others develop after birth.

  5. Basic fibroblast growth factor enhances cell proliferation in the dentate gyrus of neonatal rats following hypoxic-ischemic brain damage.

    Science.gov (United States)

    Zhu, Huan; Qiao, Lixing; Sun, Yao; Yin, Liping; Huang, Li; Jiang, Li; Li, Jiaqing

    2018-04-23

    Perinatal hypoxic-ischemic insult is considered a major contributor to child mortality and morbidity and leads to neurological deficits in newborn infants. There has been a lack of promising neurotherapeutic interventions for hypoxic-ischemic brain damage (HIBD) for clinical application in infants. The present study aimed to investigate the correlation between neurogenesis and basic fibroblast growth factor (bFGF) in the hippocampal dentate gyrus (DG) region in neonatal rats following HIBD. Cell proliferation was examined by detecting BrdU signals, and the role of bFGF in cell proliferation in the DG region following neonatal HIBD was investigated. Cell proliferation was induced by HIBD in the hippocampal DG of neonatal rats. Furthermore, bFGF gene expression was upregulated in the hippocampus in neonatal rats, particularly between 7 and 14 days after HIBD. Moreover, intraperitoneal injection of exogenous bFGF enhanced cell proliferation in the hippocampal DG following neonatal HIBD. Taken together, these data indicate that cell proliferation in the DG could be induced by neonatal HIBD, and bFGF promotes proliferation following neonatal HIBD. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Neonate brain disorders

    International Nuclear Information System (INIS)

    Xydis, V.

    2012-01-01

    Full text: Hypoxic-Ischemic insults in the brain of neonates constitute major cause of morbidity and mortality. A wide range of motor, sensory, and cognitive disabilities are observed in this population spanning from slight motor deficits, school difficulties and behavioral problems up to cerebral palsy and mental retardation. Pathologically involved areas characterized by high metabolic demands and therefore with enhanced vulnerability to any reduction or cessation of energy and oxygen supply. Watershed areas of the brain (vascular end zones and vascular border zones) are predominately affected in any adverse event. Radiologic and pathologic appearance of these lesions depends both on the severity of the insult and the maturity of the brain. The dominant pathology observed in preterm neonates is white matter lesions. There are three basic patterns of brain destruction in this population. Periventricular leukomalacia (PVL focal fPVL, diffuse dPVL), germinal matrix haemorrhage (GMH) associated with intraventricular haemorrhage (IVH), and parenchymal haemorrhage (PH). fPVL is characterized by focal necrosis of all cellular elements in the periventricular white matter, resulting in the formation of cysts, and dPVL is characterized by diffuse destruction of the premyelinating oligodendrocytes (pre-OLs) the precursors of mature oligodendroglia cells responsible for the formation of myelin in a later stage. GMH is located beneath germinal matrix layer surrounding the lateral ventricles and can extend into the ventricular system resulting thus to IVH. Finally, PH is located within the parenchyma adjacent to the ventricles and is believed to represent haemorrhagic infarcts following venous drainage compromise. In term or near-term neonates, the top-ographic pattern of injuries involves mainly gray matter structures. Most frequent predilection sites include the cerebral cortex (paracentral lobule, Rolandic area, visual cortex and hippocampus), basal ganglia, thalamus, and

  7. Effects of induced placental and fetal growth restriction, size at birth and early neonatal growth on behavioural and brain structural lateralization in sheep.

    Science.gov (United States)

    Hunter, Damien Seth; Hazel, Susan J; Kind, Karen L; Liu, Hong; Marini, Danila; Giles, Lynne C; De Blasio, Miles J; Owens, Julie A; Pitcher, Julia B; Gatford, Kathryn L

    2017-09-01

    Poor perinatal growth in humans results in asymmetrical grey matter loss in fetuses and infants and increased functional and behavioural asymmetry, but specific contributions of pre- and postnatal growth are unclear. We therefore compared strength and direction of lateralization in obstacle avoidance and maze exit preference tasks in offspring of placentally restricted (PR: 10M, 13F) and control (CON: 23M, 17F) sheep pregnancies at 18 and 40 weeks of age, and examined gross brain structure of the prefrontal cortex at 52 weeks of age (PR: 14M, 18F; CON: 23M, 25F). PR did not affect lateralization direction, but 40-week-old PR females had greater lateralization strength than CON (P = .021). Behavioural lateralization measures were not correlated with perinatal growth. PR did not alter brain morphology. In males, cross-sectional areas of the prefrontal cortex and left hemisphere correlated positively with skull width at birth, and white matter area correlated positively with neonatal growth rate of the skull (all P programming, and suggest that restricting in utero growth has relatively mild effects on gross brain structural or behavioural lateralization in sheep.

  8. Diffusion Weighted Imaging of the Neonatal Brain

    NARCIS (Netherlands)

    J. Dudink (Jeroen)

    2010-01-01

    textabstractAlthough in the last decades advances in fetal and neonatal medicine have reduced mortality in neonatal intensive care units in the Western world, the morbidity due to brain injury remains high. Patterns of neonatal brain injury can be roughly divided in (1) term and (2) preterm

  9. Effects of hyperbaric oxygen and nerve growth factor on the long-term neural behavior of neonatal rats with hypoxic ischemic brain damage.

    Science.gov (United States)

    Wei, Lixia; Ren, Qing; Zhang, Yongjun; Wang, Jiwen

    2017-04-01

    To evaluate the effects of HBO (Hyperbaric oxygen) and NGF (Nerve growth factor) on the long-term neural behavior of neonatal rats with HIBD (Neonatal hypoxic ischemic brain damage). The HIBD model was produced by ligating the right common carotid artery of 7 days old SD (Sprague-Dawley) rats followed by 8% O2 + 92% N2 for 2h. Totally 40 rats were randomly divided into 5 groups including sham-operated group, HIBD control group, HBO treated group, NGF treated group and NGF + HBO treated group. The learning and memory ability of these rats was evaluated by Morris water maze at 30 days after birth, and sensory motor function was assessed by experiments of foot error and limb placement at 42 days after birth. The escape latency of HBO treated group, NGF treated group and NGF + HBO treated group was shorter than that of HIBD control group (pmemory ability and sensory motor function in neonatal rats after hypoxic ischemic brain damage.

  10. Structural Connectivity Asymmetry in the Neonatal Brain

    OpenAIRE

    Ratnarajah, Nagulan; Rifkin-Graboi, Anne; Fortier, Marielle V.; Chong, Yap Seng; Kwek, Kenneth; Saw, Seang-Mei; Godfrey, Keith M; Gluckman, Peter D.; Meaney, Michael J.; Qiu, Anqi

    2013-01-01

    Asymmetry of the neonatal brain is not yet understood at the level of structural connectivity. We utilized DTI deterministic tractography and structural network analysis based on graph theory to determine the pattern of structural connectivity asymmetry in 124 normal neonates. We tracted white matter axonal pathways characterizing interregional connections among brain regions and inferred asymmetry in left and right anatomical network properties. Our findings revealed that in neonates, small-...

  11. Brain Tissues Oxidative Damage as a Possible Mechanism of Deleterious Effects of Propylthiouracil- Induced Hypothyroidism on Learning and Memory in Neonatal and Juvenile Growth in Rats

    Directory of Open Access Journals (Sweden)

    Esmeil Farrokhi

    2014-11-01

    randomly selected and tested in the Morris water maze (MWM. Then, samples of blood were collected to measure thyroxine. Finally, the brains were removed and total thiol groups and molondialdehyde (MDA concentrations were determined. Results: Compared to the control group’s offspring, serum thyroxine levels in the PTU group’s off spring were significantly low (P<0.001. In MWM, the escape latency and traveled path in the PTU group were significantly higher than that in the control group (P<0.01- P<0.001. In PTU group, the total thiol concentrations in both cortical and hippocampal tissues were significantly lower and MDA concentrations were higher than control group (P<0.001. Discussion: It seems that deleterious effect of hypothyroidism during neonatal and juvenile growth on learning and memory is at least in part due to brain tissues oxidative damage.

  12. Susceptibility weighted imaging of the neonatal brain

    International Nuclear Information System (INIS)

    Meoded, A.; Poretti, A.; Northington, F.J.; Tekes, A.; Intrapiromkul, J.; Huisman, T.A.G.M.

    2012-01-01

    Susceptibility weighted imaging (SWI) is a well-established magnetic resonance technique, which is highly sensitive for blood, iron, and calcium depositions in the brain and has been implemented in the routine clinical use in both children and neonates. SWI in neonates might provide valuable additional diagnostic and prognostic information for a wide spectrum of neonatal neurological disorders. To date, there are few articles available on the application of SWI in neonatal neurological disorders. The purpose of this article is to illustrate and describe the characteristic SWI findings in various typical neonatal neurological disorders.

  13. Susceptibility weighted imaging of the neonatal brain

    Energy Technology Data Exchange (ETDEWEB)

    Meoded, A.; Poretti, A. [Division of Pediatric Radiology and Division of Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Northington, F.J. [Division of Neonatology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Tekes, A.; Intrapiromkul, J. [Division of Pediatric Radiology and Division of Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Huisman, T.A.G.M., E-mail: thuisma1@jhmi.edu [Division of Pediatric Radiology and Division of Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD (United States)

    2012-08-15

    Susceptibility weighted imaging (SWI) is a well-established magnetic resonance technique, which is highly sensitive for blood, iron, and calcium depositions in the brain and has been implemented in the routine clinical use in both children and neonates. SWI in neonates might provide valuable additional diagnostic and prognostic information for a wide spectrum of neonatal neurological disorders. To date, there are few articles available on the application of SWI in neonatal neurological disorders. The purpose of this article is to illustrate and describe the characteristic SWI findings in various typical neonatal neurological disorders.

  14. Structural connectivity asymmetry in the neonatal brain.

    Science.gov (United States)

    Ratnarajah, Nagulan; Rifkin-Graboi, Anne; Fortier, Marielle V; Chong, Yap Seng; Kwek, Kenneth; Saw, Seang-Mei; Godfrey, Keith M; Gluckman, Peter D; Meaney, Michael J; Qiu, Anqi

    2013-07-15

    Asymmetry of the neonatal brain is not yet understood at the level of structural connectivity. We utilized DTI deterministic tractography and structural network analysis based on graph theory to determine the pattern of structural connectivity asymmetry in 124 normal neonates. We tracted white matter axonal pathways characterizing interregional connections among brain regions and inferred asymmetry in left and right anatomical network properties. Our findings revealed that in neonates, small-world characteristics were exhibited, but did not differ between the two hemispheres, suggesting that neighboring brain regions connect tightly with each other, and that one region is only a few paths away from any other region within each hemisphere. Moreover, the neonatal brain showed greater structural efficiency in the left hemisphere than that in the right. In neonates, brain regions involved in motor, language, and memory functions play crucial roles in efficient communication in the left hemisphere, while brain regions involved in emotional processes play crucial roles in efficient communication in the right hemisphere. These findings suggest that even at birth, the topology of each cerebral hemisphere is organized in an efficient and compact manner that maps onto asymmetric functional specializations seen in adults, implying lateralized brain functions in infancy. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Practical MRI atlas of neonatal brain development

    International Nuclear Information System (INIS)

    Barkovich, A.J.; Truwit, C.L.

    1990-01-01

    This book is an anatomical reference for cranial magnetic resonance imaging (MRI) studies in neonates and infants. It contains 122 clear, sharp MRI scans and drawings showing changes in the normal appearance of the brain and skull during development. Sections of the atlas depict the major processes of maturation: brain myelination, development of the corpus callosum, development of the cranial bone marrow, and iron deposition in the brain. High-quality scans illustrate how these changes appear on magnetic resonance images during various stages of development

  16. Molecular Mechanisms of Neonatal Brain Injury

    Directory of Open Access Journals (Sweden)

    Claire Thornton

    2012-01-01

    Full Text Available Fetal/neonatal brain injury is an important cause of neurological disability. Hypoxia-ischemia and excitotoxicity are considered important insults, and, in spite of their acute nature, brain injury develops over a protracted time period during the primary, secondary, and tertiary phases. The concept that most of the injury develops with a delay after the insult makes it possible to provide effective neuroprotective treatment after the insult. Indeed, hypothermia applied within 6 hours after birth in neonatal encephalopathy reduces neurological disability in clinical trials. In order to develop the next generation of treatment, we need to know more about the pathophysiological mechanism during the secondary and tertiary phases of injury. We review some of the critical molecular events related to mitochondrial dysfunction and apoptosis during the secondary phase and report some recent evidence that intervention may be feasible also days-weeks after the insult.

  17. Patterns of neonatal hypoxic-ischaemic brain injury

    International Nuclear Information System (INIS)

    Vries, Linda S. de; Groenendaal, Floris

    2010-01-01

    Enormous progress has been made in assessing the neonatal brain, using magnetic resonance imaging (MRI). In this review, we will describe the use of MRI and proton magnetic resonance spectroscopy in detecting different patterns of brain injury in (full-term) human neonates following hypoxic-ischaemic brain injury and indicate the relevance of these findings in predicting neurodevelopmental outcome. (orig.)

  18. Patterns of neonatal hypoxic-ischaemic brain injury

    Energy Technology Data Exchange (ETDEWEB)

    Vries, Linda S. de [University Medical Centre, Department of Neonatology, Wilhelmina Children' s Hospital, Utrecht (Netherlands); Wilhelmina Children' s Hospital, University Medical Centre, Department of Neonatology, KE 04.123.1, P.O. Box 85090, Utrecht (Netherlands); Groenendaal, Floris [University Medical Centre, Department of Neonatology, Wilhelmina Children' s Hospital, Utrecht (Netherlands)

    2010-06-15

    Enormous progress has been made in assessing the neonatal brain, using magnetic resonance imaging (MRI). In this review, we will describe the use of MRI and proton magnetic resonance spectroscopy in detecting different patterns of brain injury in (full-term) human neonates following hypoxic-ischaemic brain injury and indicate the relevance of these findings in predicting neurodevelopmental outcome. (orig.)

  19. Brain death in neonates: a case report

    Directory of Open Access Journals (Sweden)

    Georgios Mitsiakos

    2014-06-01

    Full Text Available Brain death (BD is the permanent and complete loss of cerebral and brainstem function. It is relatively uncommon in newborns with its percentage among deaths being 1-6.3%. BD leads to debate for medical, ethical and philosophical issues. It is a challenging condition in neonatal intensive care units (NICUs since difficulties for BD diagnosis in neonates and ever more so in preterm neonates do arise. Revised guidelines for BD diagnosis definition include history with known etiology, clinical examination, apnea testing and neurological evaluation often assisted by ancillary tests. We present the case of a near term female baby that was born with brain death due to hypoxic ischemic encephalopathy. We conclude that BD in newborns is a challenge to NICUs and there is a need for establishing and implementing new guidelines and checklists on national basis. Proceedings of the 10th International Workshop on Neonatology · Cagliari (Italy · October 22nd-25th, 2014 · The last ten years, the next ten years in Neonatology Guest Editors: Vassilios Fanos, Michele Mussap, Gavino Faa, Apostolos Papageorgiou

  20. Fetal trauma: brain imaging in four neonates

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  1. Fetal trauma: brain imaging in four neonates

    International Nuclear Information System (INIS)

    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.)

  2. Prenatal methadone exposure is associated with altered neonatal brain development

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    Victoria J. Monnelly

    Full Text Available Methadone is used for medication-assisted treatment of heroin addiction during pregnancy. The neurodevelopmental outcome of children with prenatal methadone exposure can be sub-optimal. We tested the hypothesis that brain development is altered among newborn infants whose mothers were prescribed methadone.20 methadone-exposed neonates born after 37weeks' postmenstrual age (PMA and 20 non-exposed controls underwent diffusion MRI at mean PMA of 39+2 and 41+1weeks, respectively. An age-optimized Tract-based Spatial Statistics (TBSS pipeline was used to perform voxel-wise statistical comparison of fractional anisotropy (FA data between exposed and non-exposed neonates.Methadone-exposed neonates had decreased FA within the centrum semiovale, inferior longitudinal fasciculi (ILF and the internal and external capsules after adjustment for GA at MRI (p<0.05, TFCE corrected. Median FA across the white matter skeleton was 12% lower among methadone-exposed infants. Mean head circumference (HC z-scores were lower in the methadone-exposed group (−0.52 (0.99 vs 1.15 (0.84, p<0.001; after adjustment for HC z-scores, differences in FA remained in the anterior and posterior limbs of the internal capsule and the ILF. Polydrug use among cases was common.Prenatal methadone exposure is associated with microstructural alteration in major white matter tracts, which is present at birth and is independent of head growth. Although the findings cannot be attributed to methadone per se, the data indicate that further research to determine optimal management of opioid use disorder during pregnancy is required. Future studies should evaluate childhood outcomes including infant brain development and long-term neurocognitive function. Keywords: Prenatal, Methadone, Brain, Neonate, MRI, Opioid

  3. Neonatal ischemic brain injury: what every radiologist needs to know

    International Nuclear Information System (INIS)

    Badve, Chaitra A.; Khanna, Paritosh C.; Ishak, Gisele E.

    2012-01-01

    We present a pictorial review of neonatal ischemic brain injury and look at its pathophysiology, imaging features and differential diagnoses from a radiologist's perspective. The concept of perinatal stroke is defined and its distinction from hypoxic-ischemic injury is emphasized. A brief review of recent imaging advances is included and a diagnostic approach to neonatal ischemic brain injury is suggested. (orig.)

  4. General anaesthetics do not impair developmental expression of the KCC2 potassium-chloride cotransporter in neonatal rats during the brain growth spurt

    KAUST Repository

    Lacoh, Claudia Marvine

    2013-03-26

    BackgroundThe developmental transition from depolarizing to hyperpolarizing γ-aminobutyric acid-mediated neurotransmission is primarily mediated by an increase in the amount of the potassium-chloride cotransporter KCC2 during early postnatal life. However, it is not known whether early neuronal activity plays a modulatory role in the expression of total KCC2 mRNA and protein in the immature brain. As general anaesthetics are powerful modulators of neuronal activity, the purpose of this study was to explore how these drugs affect KCC2 expression during the brain growth spurt.MethodsWistar rat pups were exposed to either a single dose or 6 h of midazolam, propofol, or ketamine anaesthesia at postnatal days 0, 5, 10, or 15. KCC2 expression was assessed using immunoblotting, immunohistochemistry, or quantitative polymerase chain reaction analysis up to 3 days post-exposure in the medial prefrontal cortex.ResultsThere was a progressive and steep increase in the expression of KCC2 between birth and 2 weeks of age. Exposure to midazolam, propofol, or ketamine up to 6 h at any investigated stages of the brain growth spurt did not influence the expression of this cotransporter protein.ConclusionI.V. general anaesthetics do not seem to influence developmental expression of KCC2 during the brain growth spurt. © 2013 © The Author [2013].

  5. Intrapartum FHR monitoring and neonatal CT brain scan

    International Nuclear Information System (INIS)

    Takahashi, Yoshiki; Ukita, Masahiko; Nakada, Eizo

    1982-01-01

    The effect of fetal distress on the neonatal brain was investigated by neonatal CT brain scan, FHR monitoring and mode of delivery. This study involved 11 cases of full term vertex delivery in which FHR was recorded by fetal direct ECG during the second stage labor. All infants weighed 2,500 g or more. FHR monitoring was evaluated by Hon's classification. Neonatal brain edema was evaluated by cranial CT histgraphic analysis (Nakada's method). 1) Subdural hemorrhage was noted in 6 of 7 infants delivered by vacuum extraction or fundal pressure (Kristeller's method). 2) Intracranial hemorrhage was demonstrated in all of 3 infants with 5-min. Apgar score 7 or less. 3) Two cases with prolonged bradycardia and no variability had intraventricular or intracerebral hemorrhage which resulted in severe central nervous system damage. 4) The degree of neonatal brain edema correlated with 5-min. Apgar score. 5) One case with prolonged bradycardia and no variability resulted in severe neonatal brain edema. Four cases with variable deceleration and increased variability resulted in mild neonatal brain edema. Two cases with late deceleration and decreased variability resulted in no neonatal brain edema. (author)

  6. Neonatal hypoglycemic brain injury is a cause of infantile spasms

    OpenAIRE

    YANG, GUANG; ZOU, LI-PING; WANG, JING; SHI, XIUYU; TIAN, SHUPING; YANG, XIAOFAN; JU, JUN; YAO, HONGXIANG; LIU, YUJIE

    2016-01-01

    Neonatal hypoglycemic brain injury is one of the causes of infantile spasms. In the present study, the clinical history and auxiliary examination results of 18 patients who developed infantile spasms several months after neonatal hypoglycemia were retrospectively analyzed. Among the 666 patients with infantile spasms admitted to two pediatric centers between January 2008 and October 2012, 18 patients developed infantile spasms after being diagnosed with neonatal hypoglycemia, defined as a who...

  7. Effects of enriched uranium on developing brain damage of neonatal rats

    International Nuclear Information System (INIS)

    Gu Guixiong; Zhu Shoupeng; Wang Liuyi; Yang Shuqin; Zhu Lingli

    2001-01-01

    The model of irradiation-induced brain damage in vivo was settled first of all. The micro-auto-radiographic tracing showed that when the rat's brain at postnatal day after lateral ventricle injection with enriched uranium 235 U the radionuclides were mainly accumulated in the nucleus. At the same time autoradiographic tracks appeared in the cytoplasm and interval between cells. The effects of cerebrum exposure to alpha irradiation by enriched uranium on somatic growth and neuro-behavior development of neonatal rats were examined by determination of multiple parameters. In the growth and development of the neonatal rat's cerebrum exposure to enriched uranium, the somatic growth such as body weight and brain weight increase was lower significantly. The data indicated that the neonatal wistar rats having cerebrum exposure to alpha irradiation by enriched uranium showed delayed growth and abnormal neuro-behavior. The changes of neuron specific enolase (NSE), interleukin-1 β (IL- β), superoxide dismutase (SOD), and endothelin (ET) in cerebellum, cerebral cortex, hippocampus, diencephalons of the rat brain after expose to alpha irradiation by enriched uranium were examined with radioimmunoassay. The results showed that SOD and ET can be elevated by the low dose irradiation of enriched uranium, and can be distinctly inhibited by the high dose. The data in view of biochemistry indicated firstly that alpha irradiation from enriched uranium on the developing brain damage of neonatal rats were of sensibility, fragility and compensation in nervous cells

  8. Effects of enriched uranium on developing brain damage of neonatal rats

    Energy Technology Data Exchange (ETDEWEB)

    Guixiong, Gu; Shoupeng, Zhu; Liuyi, Wang; Shuqin, Yang; Lingli, Zhu [Suzhou Medical College, Suzhou (China)

    2001-04-01

    The model of irradiation-induced brain damage in vivo was settled first of all. The micro-auto-radiographic tracing showed that when the rat's brain at postnatal day after lateral ventricle injection with enriched uranium {sup 235}U the radionuclides were mainly accumulated in the nucleus. At the same time autoradiographic tracks appeared in the cytoplasm and interval between cells. The effects of cerebrum exposure to alpha irradiation by enriched uranium on somatic growth and neuro-behavior development of neonatal rats were examined by determination of multiple parameters. In the growth and development of the neonatal rat's cerebrum exposure to enriched uranium, the somatic growth such as body weight and brain weight increase was lower significantly. The data indicated that the neonatal wistar rats having cerebrum exposure to alpha irradiation by enriched uranium showed delayed growth and abnormal neuro-behavior. The changes of neuron specific enolase (NSE), interleukin-1 {beta} (IL- {beta}), superoxide dismutase (SOD), and endothelin (ET) in cerebellum, cerebral cortex, hippocampus, diencephalons of the rat brain after expose to alpha irradiation by enriched uranium were examined with radioimmunoassay. The results showed that SOD and ET can be elevated by the low dose irradiation of enriched uranium, and can be distinctly inhibited by the high dose. The data in view of biochemistry indicated firstly that alpha irradiation from enriched uranium on the developing brain damage of neonatal rats were of sensibility, fragility and compensation in nervous cells.

  9. Neonatal ischemic brain injury: what every radiologist needs to know

    Energy Technology Data Exchange (ETDEWEB)

    Badve, Chaitra A.; Khanna, Paritosh C.; Ishak, Gisele E. [Seattle Children' s Hospital, University of Washington Medical Center, Department of Radiology, Seattle, WA (United States)

    2012-05-15

    We present a pictorial review of neonatal ischemic brain injury and look at its pathophysiology, imaging features and differential diagnoses from a radiologist's perspective. The concept of perinatal stroke is defined and its distinction from hypoxic-ischemic injury is emphasized. A brief review of recent imaging advances is included and a diagnostic approach to neonatal ischemic brain injury is suggested. (orig.)

  10. Inflammation, caffeine and adenosine in neonatal hypoxic ischemic brain injury

    OpenAIRE

    Winerdal, Max

    2014-01-01

    Background: Brain injury during the neonatal period has potentially lifelong consequences for a child. Perinatal infections and inflammation can induce preterm birth and unfavorable cognitive development, Thus inflammation has received enthusiastic interest for potential therapeutic approaches seeking to protect the newborn brain. Experimental evidence demonstrates that inflammation induces brain injury succeeding the initial insult. A key cytokine in brain injury is the tumor necrosis factor...

  11. Transport, monitoring, and successful brain MR imaging in unsedated neonates

    International Nuclear Information System (INIS)

    Mathur, Amit M.; Neil, Jeffrey J.; McKinstry, Robert C.; Inder, Terrie E.

    2008-01-01

    Neonatal cerebral MR imaging is a sensitive technique for evaluating brain injury in the term and preterm infant. In term encephalopathic infants, MR imaging reliably detects not only the pattern of brain injury but might also provide clues about the timing of injury. In premature infants, MR imaging has surpassed US in the detection of white matter injury, a common lesion in this population. Concerns remain about the safety and transport of sedated neonates for MR examination to radiology suites, which are usually located at a distance from neonatal intensive care units. We present our own institutional experience and guidelines used to optimize the performance of cerebral MR examinations in neonates without sedation or anesthesia. (orig.)

  12. Lymphocytes Contribute to the Pathophysiology of Neonatal Brain Injury

    Directory of Open Access Journals (Sweden)

    Arshed Nazmi

    2018-03-01

    Full Text Available BackgroundPeriventricular leukomalacia (PVL is the most common form of preterm brain injury affecting the cerebral white matter. This type of injury involves a multiphase process and is induced by many factors, including hypoxia–ischemia (HI and infection. Previous studies have suggested that lymphocytes play a significant role in the pathogenesis of brain injury, and the aim of this study was to determine the contribution of lymphocyte subsets to preterm brain injury.MethodsImmunohistochemistry on brain sections from neonatal mice was performed to evaluate the extent of brain injury in wild-type and T cell and B cell-deficient neonatal mice (Rag1−/− mice using a mouse model of HI-induced preterm brain injury. Flow cytometry was performed to determine the presence of different types of immune cells in mouse brains following HI. In addition, immunostaining for CD3 T cells and CD20 B cells was performed on postmortem preterm human infant brains with PVL.ResultsMature lymphocyte-deficient Rag1−/− mice showed protection from white matter loss compared to wild type mice as indicated by myelin basic protein immunostaining of mouse brains. CD3+ T cells and CD20+ B cells were observed in the postmortem preterm infant brains with PVL. Flow cytometry analysis of mouse brains after HI-induced injury showed increased frequency of CD3+ T, αβT and B cells at 7 days after HI in the ipsilateral (injured hemisphere compared to the contralateral (control, uninjured hemisphere.ConclusionLymphocytes were found in the injured brain after injury in both mice and humans, and lack of mature lymphocytes protected neonatal mice from HI-induced brain white matter injury. This finding provides insight into the pathology of perinatal brain injury and suggests new avenues for the development of therapeutic strategies.

  13. Normal lactate concentration range in the neonatal brain.

    Science.gov (United States)

    Tomiyasu, Moyoko; Aida, Noriko; Shibasaki, Jun; Tachibana, Yasuhiko; Endo, Mamiko; Nozawa, Kumiko; Shimizu, Eiji; Tsuji, Hiroshi; Obata, Takayuki

    2016-11-01

    Lactate peaks are occasionally observed during in vivo magnetic resonance spectroscopy (MRS) scans of the neonatal brain, even in healthy patients. The purpose of this study was to investigate the normal range of neonatal brain lactate concentration, as a definitive normal range would be clinically valuable. Using a clinical 3T scanner (echo/repetition times, 30/5000ms), single-voxel MRS data were obtained from the basal ganglia (BG) and centrum semiovale (CS) in 48 healthy neonates (postconceptional age (PCA), 30-43weeks), nine infants (age, 1-12months old), and 20 children (age, 4-15years). Lactate concentrations were calculated using an MRS signal quantification program, LCModel. Correlations between regional lactate concentration and PCA (neonates), or age (all subjects) were investigated. Absolute lactate concentrations of the BG and CS were as follows: neonates, 0.77mM (0-2.02) [median (range)] and 0.77 (0-1.42), respectively; infants, 0.38 (0-0.79) and 0.49 (0.17-1.17); and children, 0.17 (0-0.76) and 0.22 (0-0.80). Overall, subjects' lactate concentrations decreased significantly with age (Spearman: BG, n=61, ρ=-0.38, p=0.003; CS, n=68, ρ=-0.57, p<0.001). However, during the neonatal period no correlations were detected between lactate concentration in either region and PCA. We determined normal ranges of neonatal lactate concentration, which may prove useful for diagnostic purposes. Further studies regarding changes in brain lactate concentration during development would help clarify the reasons for higher concentrations observed during the neonatal period, and contribute to improvements in diagnoses. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Stem cells for brain repair in neonatal hypoxia-ischemia.

    Science.gov (United States)

    Chicha, L; Smith, T; Guzman, R

    2014-01-01

    Neonatal hypoxic-ischemic insults are a significant cause of pediatric encephalopathy, developmental delays, and spastic cerebral palsy. Although the developing brain's plasticity allows for remarkable self-repair, severe disruption of normal myelination and cortical development upon neonatal brain injury are likely to generate life-persisting sensory-motor and cognitive deficits in the growing child. Currently, no treatments are available that can address the long-term consequences. Thus, regenerative medicine appears as a promising avenue to help restore normal developmental processes in affected infants. Stem cell therapy has proven effective in promoting functional recovery in animal models of neonatal hypoxic-ischemic injury and therefore represents a hopeful therapy for this unmet medical condition. Neural stem cells derived from pluripotent stem cells or fetal tissues as well as umbilical cord blood and mesenchymal stem cells have all shown initial success in improving functional outcomes. However, much still remains to be understood about how those stem cells can safely be administered to infants and what their repair mechanisms in the brain are. In this review, we discuss updated research into pathophysiological mechanisms of neonatal brain injury, the types of stem cell therapies currently being tested in this context, and the potential mechanisms through which exogenous stem cells might interact with and influence the developing brain.

  15. Growth restriction and gender influence cerebral oxygenation in preterm neonates

    NARCIS (Netherlands)

    Cohen, Emily; Baerts, Willem; Alderliesten, Thomas; Derks, Jan; Lemmers, Petra; van Bel, Frank

    2016-01-01

    OBJECTIVE: To investigate the effect of fetal growth restriction and gender on cerebral oxygenation in preterm neonates during the first 3 days of life. DESIGN: Case-control study. SETTING: Neonatal Intensive Care Unit of the Wilhelmina Children's Hospital, The Netherlands. PATIENTS: 68 (41 males)

  16. Brain injuries due to neonatal hypoglycemia: case report

    International Nuclear Information System (INIS)

    Kim, Dae Bong; Song, Chang Joon; Chang, Mae Young; Youn, Hyae Won

    2003-01-01

    Although hypoglycemia may be common among neonates, brain injuries resulting from isolated neonatal hypoglycemia are rare. The condition may cause neurological symptoms such as stupor, jitteriness, and seizures, though in their absence, diagnosis delayed or difficult. Hypoglycemia was diagnosed in a three-day-old neonate after he visited the emergency department with loose stool, poor oral intake, and decreased activity, first experienced two days earlier. Two days after his visity, several episodes of seizure occurred. T2 and diffusion-weighted magnetic resonance (MR) scanning, performed at 11 days of age, revealed bilateral and symmetrical high signal intensity lesions in occipital, parietal, and temporal lobes. We report the MR findings of hypoglycemic encephalopathy in a neonate

  17. Maternal depression and anxiety and fetal-neonatal growth

    Directory of Open Access Journals (Sweden)

    Tiago Miguel Pinto

    2017-09-01

    Conclusion: This study demonstrates the independent longitudinal effect of maternal anxiety on major markers of fetal-neonatal growth outcomes and trajectories, simultaneously considering the effect of maternal depression and anxiety.

  18. Neonatal Brain Tissue Classification with Morphological Adaptation and Unified Segmentation

    Directory of Open Access Journals (Sweden)

    Richard eBeare

    2016-03-01

    Full Text Available Measuring the distribution of brain tissue types (tissue classification in neonates is necessary for studying typical and atypical brain development, such as that associated with preterm birth, and may provide biomarkers for neurodevelopmental outcomes. Compared with magnetic resonance images of adults, neonatal images present specific challenges that require the development of specialized, population-specific methods. This paper introduces MANTiS (Morphologically Adaptive Neonatal Tissue Segmentation, which extends the unified segmentation approach to tissue classification implemented in Statistical Parametric Mapping (SPM software to neonates. MANTiS utilizes a combination of unified segmentation, template adaptation via morphological segmentation tools and topological filtering, to segment the neonatal brain into eight tissue classes: cortical gray matter, white matter, deep nuclear gray matter, cerebellum, brainstem, cerebrospinal fluid (CSF, hippocampus and amygdala. We evaluated the performance of MANTiS using two independent datasets. The first dataset, provided by the NeoBrainS12 challenge, consisted of coronal T2-weighted images of preterm infants (born ≤30 weeks’ gestation acquired at 30 weeks’ corrected gestational age (n= 5, coronal T2-weighted images of preterm infants acquired at 40 weeks’ corrected gestational age (n= 5 and axial T2-weighted images of preterm infants acquired at 40 weeks’ corrected gestational age (n= 5. The second dataset, provided by the Washington University NeuroDevelopmental Research (WUNDeR group, consisted of T2-weighted images of preterm infants (born <30 weeks’ gestation acquired shortly after birth (n= 12, preterm infants acquired at term-equivalent age (n= 12, and healthy term-born infants (born ≥38 weeks’ gestation acquired within the first nine days of life (n= 12. For the NeoBrainS12 dataset, mean Dice scores comparing MANTiS with manual segmentations were all above 0.7, except for

  19. General anaesthetics do not impair developmental expression of the KCC2 potassium-chloride cotransporter in neonatal rats during the brain growth spurt

    KAUST Repository

    Lacoh, Claudia Marvine; Bodogan, T.; Kaila, Kai K.; Fiumelli, Hubert; Vutskits, Lá szló

    2013-01-01

    . However, it is not known whether early neuronal activity plays a modulatory role in the expression of total KCC2 mRNA and protein in the immature brain. As general anaesthetics are powerful modulators of neuronal activity, the purpose of this study

  20. Magnetic resonance imaging of neonatal brain. Assessment of normal and abnormal findings

    International Nuclear Information System (INIS)

    Hasegawa, Koh; Kadono, Naoko; Kawase, Shohji; Kihara, Minako; Matsuo, Yasutaka; Yoshioka, Hiroshi; Kinugasa, Akihiko; Sawada, Tadashi

    1994-01-01

    To establish the normal MRI appearance of the neonatal brain, magnetic resonance imaging (MRI) was performed on 124 neonates who admitted to our neonatal intensive care unit. Degree of myelination, ventricular size, width of the extracerebral space and focal lesion in the brain were evaluated to investigate the relationship between MRI findings of neonatal brain and the neurological prognosis. 85 neonates underwent MRI both at neonatal period and at the corrected age of one year. The change of abnormal MRI findings was evaluated. 19 neonates had abnormal neurological outcome on subsequent examinations. Delayed myelination, ventriculomegaly and large extracerebral space were seen in 13, 7 and 9 neonates respectively. 4, 3 and 5 neonates out of them showed abnormal neurological prognosis respectively. Of the 19 neonates with focal lesion in MRI, 2 had parenchymal hematoma in the brain, 2 had subdural hematoma, 5 had chronic hematoma following subependymal hemorrhage, 6 had cystic formation following subependymal hemorrhage, 2 had subcortical leukomalacia, one had periventricular leukomalacia and one had cyst in the parenchyma of cerebellum. 4 neonates of 19 with focal lesion in MRI showed abnormal development. Of the neonates who had abnormal neurological prognosis, 7 neonates showed no abnormal finding in MRI at neonatal period. 3 of them had mild mental retardation. MRI shows promise in the neonatal period. It facilitates recognition of abnormalities of neonatal brain and may be used to predict abnormal neurologic outcome. However physiological change in the brain of neonates, especially of premature neonates, should be considered on interpreting these findings. Awareness of developmental features should help to minimize misinterpretation of normal changes in the neonatal brain. (author)

  1. Magnetic resonance imaging of neonatal brain. Assessment of normal and abnormal findings

    Energy Technology Data Exchange (ETDEWEB)

    Hasegawa, Koh; Kadono, Naoko; Kawase, Shohji; Kihara, Minako; Matsuo, Yasutaka; Yoshioka, Hiroshi; Kinugasa, Akihiko; Sawada, Tadashi (Kyoto Prefectural Univ. of Medicine (Japan))

    1994-11-01

    To establish the normal MRI appearance of the neonatal brain, magnetic resonance imaging (MRI) was performed on 124 neonates who admitted to our neonatal intensive care unit. Degree of myelination, ventricular size, width of the extracerebral space and focal lesion in the brain were evaluated to investigate the relationship between MRI findings of neonatal brain and the neurological prognosis. 85 neonates underwent MRI both at neonatal period and at the corrected age of one year. The change of abnormal MRI findings was evaluated. 19 neonates had abnormal neurological outcome on subsequent examinations. Delayed myelination, ventriculomegaly and large extracerebral space were seen in 13, 7 and 9 neonates respectively. 4, 3 and 5 neonates out of them showed abnormal neurological prognosis respectively. Of the 19 neonates with focal lesion in MRI, 2 had parenchymal hematoma in the brain, 2 had subdural hematoma, 5 had chronic hematoma following subependymal hemorrhage, 6 had cystic formation following subependymal hemorrhage, 2 had subcortical leukomalacia, one had periventricular leukomalacia and one had cyst in the parenchyma of cerebellum. 4 neonates of 19 with focal lesion in MRI showed abnormal development. Of the neonates who had abnormal neurological prognosis, 7 neonates showed no abnormal finding in MRI at neonatal period. 3 of them had mild mental retardation. MRI shows promise in the neonatal period. It facilitates recognition of abnormalities of neonatal brain and may be used to predict abnormal neurologic outcome. However physiological change in the brain of neonates, especially of premature neonates, should be considered on interpreting these findings. Awareness of developmental features should help to minimize misinterpretation of normal changes in the neonatal brain. (author).

  2. Pattern of chondroitin sulfate proteoglycan expression after ablation of the sensorimotor cortex of the neonatal and adult rat brain

    Directory of Open Access Journals (Sweden)

    Dacić Sanja

    2008-01-01

    Full Text Available The central nervous system has a limited capacity for self-repair after damage. However, the neonatal brain has agreater capacity for recovery than the adult brain. These differences in the regenerative capability depend on local environmental factors and the maturational stage of growing axons. Among molecules which have both growth-promoting and growth-inhibiting activities is the heterogeneous class of chondroitin sulfate proteoglycans (CSPGs. In this paper, we investigated the chondroitin-4 and chondroitin-6 sulfate proteoglycan expression profile after left sensorimotor cortex ablation of the neonatal and adult rat brain. Immunohistochemical analysis revealed that compared to the normal uninjured cortex, lesion provoked up regulation of CSPGs showing a different pattern of expression in the neonatal vs. the adult brain. Punctuate and membrane-bound labeling was predominate after neonatal lesion, where as heavy deposition of staining in the extracellular matrix was observed after adult lesion. Heavy deposition of CSPG immunoreactivity around the lesionsite in adult rats, in contrast to a less CSPG-rich environment in neonatal rats, indicated that enhancement of the recovery process after neonatal injury is due to amore permissive environment.

  3. MR imaging of the neonatal brain: Pathologic features

    International Nuclear Information System (INIS)

    McArdle, C.B.; Richardson, C.J.; Nicholas, D.A.; Hayden, C.K.; Amparo, E.G.

    1986-01-01

    Seventy-three neonates, aged 29-43 weeks since conception, were studied. US and/or CT correlations were obtained in most infants with pathology. In the first 4-5 days after hemorrhage, US and CT were superior to MR imaging, but after that time MR imaging was the single best modality for imaging blood. In early premature infants with very watery white matter, US detected infarction and brain edema that were poorly seen on both MR imaging and CT. However, in late premature and full-term infants, MR imaging was better than CT in distinguishing between normal white matter and infarction. Only MR imaging disclosed delayed myelination in 13 term infants with hydrocephalus and severe asphyxia. MR imaging with play an important role in imaging neonates once MR imaging-compatible monitors and neonatal head coils become widely available

  4. Functional photoacoustic tomography for neonatal brain imaging: developments and challenges

    Science.gov (United States)

    Hariri, Ali; Tavakoli, Emytis; Adabi, Saba; Gelovani, Juri; Avanaki, Mohammad R. N.

    2017-03-01

    Transfontanelle ultrasound imaging (TFUSI) is a routine diagnostic brain imaging method in infants who are born prematurely, whose skull bones have not completely fused together and have openings between them, so-called fontanelles. Open fontanelles in neonates provide acoustic windows, allowing the ultrasound beam to freely pass through. TFUSI is used to rule out neurological complications of premature birth including subarachnoid hemorrhage (SAH), intraventricular (IVH), subependimal (SEPH), subdural (SDH) or intracerebral (ICH) hemorrhages, as well as hypoxic brain injuries. TFUSI is widely used in the clinic owing to its low cost, safety, accessibility, and noninvasive nature. Nevertheless, the accuracy of TFUSI is limited. To address several limitations of current clinical imaging modalities, we develop a novel transfontanelle photoacoustic imaging (TFPAI) probe, which, for the first time, should allow for non-invasive structural and functional imaging of the infant brain. In this study, we test the feasibility of TFPAI for detection of experimentally-induced intra ventricular and Intraparenchymal hemorrhage phantoms in a sheep model with a surgically-induced cranial window which will serve as a model of neonatal fontanelle. This study is towards using the probe we develop for bedside monitoring of neonates with various disease conditions and complications affecting brain perfusion and oxygenation, including apnea, asphyxia, as well as for detection of various types of intracranial hemorrhages (SAH, IVH, SEPH, SDH, ICH).

  5. Plasticity in the Neonatal Brain following Hypoxic-Ischaemic Injury

    Directory of Open Access Journals (Sweden)

    Eridan Rocha-Ferreira

    2016-01-01

    Full Text Available Hypoxic-ischaemic damage to the developing brain is a leading cause of child death, with high mortality and morbidity, including cerebral palsy, epilepsy, and cognitive disabilities. The developmental stage of the brain and the severity of the insult influence the selective regional vulnerability and the subsequent clinical manifestations. The increased susceptibility to hypoxia-ischaemia (HI of periventricular white matter in preterm infants predisposes the immature brain to motor, cognitive, and sensory deficits, with cognitive impairment associated with earlier gestational age. In term infants HI causes selective damage to sensorimotor cortex, basal ganglia, thalamus, and brain stem. Even though the immature brain is more malleable to external stimuli compared to the adult one, a hypoxic-ischaemic event to the neonate interrupts the shaping of central motor pathways and can affect normal developmental plasticity through altering neurotransmission, changes in cellular signalling, neural connectivity and function, wrong targeted innervation, and interruption of developmental apoptosis. Models of neonatal HI demonstrate three morphologically different types of cell death, that is, apoptosis, necrosis, and autophagy, which crosstalk and can exist as a continuum in the same cell. In the present review we discuss the mechanisms of HI injury to the immature brain and the way they affect plasticity.

  6. Study on developing brain damage of neonatal rats induced by enriched uranium

    International Nuclear Information System (INIS)

    Gu Guixiong; Zhu Shoupeng; Yang Shuqin

    2000-01-01

    Objective: The injurious effects of enriched uranium 235 U on developing brain of neonatal Wistar pure bred rats were studied. Methods: The model of irradiation induced brain damage in vivo was settled. The effects of cerebrum exposure by 235 U on somatic growth and neuro-behavior development of neonatal rats were examined by thirteen index determination of multiple parameters. The dynamic retention of autoradiographic tracks of 235 U in cells of developing brain was observed. The changes of NSE, IL-1β, SOD, and ET in cerebral cortex, hippocampus, diencephalon, cerebellum after expose to 235 U were examined with radioimmunoassay. Results: The somatic growth such as increase of body weight and brain weight was lower significantly. The retardation of development was found such as eye opening, sensuous function as auditory startle, movement and coordination function and activity as swimming, physiological reflexes as negative geotaxis, surface righting, grasping reflex suspension and the tendency behavior. The data showed delayed growth and abnormal neuro-behavior. The micro-autoradiographic tracing showed that the tracks of 235 U were mainly accumulated in the nucleus of developing brain. At the same time only few tracks appeared in the cytoplasm and interval between cells. Experimental study showed that when the dose of 235 U irradiation was increased, the level of NSE was decreased and the IL-1β was increased. However, the results indicated that SOD and ET can be elevated by the low dose irradiation of 235 U, and can be inhibited by the high dose. Conclusion: The behavior of internal irradiation from 235 U on the developing brain damage of neonatal rats were of sensibility and compensation in nervous cells

  7. New Antioxidant Drugs for Neonatal Brain Injury

    Directory of Open Access Journals (Sweden)

    Maria Luisa Tataranno

    2015-01-01

    Full Text Available The brain injury concept covers a lot of heterogeneity in terms of aetiology involving multiple factors, genetic, hemodynamic, metabolic, nutritional, endocrinological, toxic, and infectious mechanisms, acting in antenatal or postnatal period. Increased vulnerability of the immature brain to oxidative stress is documented because of the limited capacity of antioxidant enzymes and the high free radicals (FRs generation in rapidly growing tissue. FRs impair transmembrane enzyme Na+/K+-ATPase activity resulting in persistent membrane depolarization and excessive release of FR and excitatory aminoacid glutamate. Besides being neurotoxic, glutamate is also toxic to oligodendroglia, via FR effects. Neuronal cells die of oxidative stress. Excess of free iron and deficient iron/binding metabolising capacity are additional features favouring oxidative stress in newborn. Each step in the oxidative injury cascade has become a potential target for neuroprotective intervention. The administration of antioxidants for suspected or proven brain injury is still not accepted for clinical use due to uncertain beneficial effects when treatments are started after resuscitation of an asphyxiated newborn. The challenge for the future is the early identification of high-risk babies to target a safe and not toxic antioxidant therapy in combination with standard therapies to prevent brain injury and long-term neurodevelopmental impairment.

  8. ischemic brain injury in neonatal rats

    African Journals Online (AJOL)

    Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, ... Methods: Forty-eight rats (P7-pups) were randomly assigned to one of four groups: ... Keywords: Hypoxic–ischemic brain injury, α-Lipoic acid, Cerebral infarct area, Edema, Antioxidants, .... Of the 48 rats initially used in the current study, 5.

  9. Magnetic resonance imaging based noninvasive measurements of brain hemodynamics in neonates

    DEFF Research Database (Denmark)

    De Vis, Jill B; Alderliesten, Thomas; Hendrikse, Jeroen

    2016-01-01

    Perinatal disturbances of brain hemodynamics can have a detrimental effect on the brain's parenchyma with consequently adverse neurodevelopmental outcome. Noninvasive, reliable tools to evaluate the neonate's brain hemodynamics are scarce. Advances in magnetic resonance imaging have provided new...

  10. Inflammatory injury to the neonatal brain – what can we do?

    Directory of Open Access Journals (Sweden)

    Noa eOfek-shlomai

    2014-04-01

    Full Text Available Abstract Perinatal brain damage is one of the leading causes of life long disability. This damage could be hypoxic-ischemic, inflammatory or both.This mini-review discusses different interventions aiming at minimizing inflammatory processes in the neonatal brain, both before and after insult. Current options of anti-inflammatory measures for neonates remain quite limited. We describe current anti-inflammatory intervention strategies such as avoiding perinatal infection and inflammation, and reducing exposure to inflammatory processes. We describe the known effects of anti-inflammatory drugs such as steroids, antibiotics, and indomethacin, and the possible anti-inflammatory role of other substances such as IL-1receptor antagonists, erythropoietin, caffeine, estradiol, insulin like growth factor and melatonin as well as endogenous protectors, and genetic regulation of inflammation. If successful, these may decrease mortality and long term morbidity among term and preterm infants.

  11. Hematopoietic growth factors in neonatal medicine: the use of enterally administered hematopoietic growth factors in the neonatal intensive care unit.

    Science.gov (United States)

    Calhoun, Darlene A; Christensen, Robert D

    2004-03-01

    The practice of complete bowel rest in prematurely delivered neonates and those who have undergone surgery for congenital anomalies of the gastrointestinal (GI) tract is common in neonatal intensive care units (NICU). However, increased recognition of the critical role of growth factors in GI development suggests that this practice might be modified to include the administration of synthetic amniotic fluid-like solutions designed to bridge the neonate between their intra-uterine environment and that of the NICU. This article reviews advances in administering synthetic amniotic fluid-like solutions in the NICU.

  12. Patterns of damage in the mature neonatal brain

    International Nuclear Information System (INIS)

    Triulzi, Fabio; Parazzini, Cecilia; Righini, Andrea

    2006-01-01

    Patterns of damage in the mature neonatal brain can be subdivided into focal, multifocal and diffuse. The main cause of diffuse brain damage in the term newborn is hypoxic-ischaemic encephalopathy (HIE). HIE is still the major recognized perinatal cause of neurological morbidity in full-term newborns. MRI offers today the highest sensitivity in detecting acute anoxic injury of the neonatal brain. Conventional acquisition techniques together with modern diffusion techniques can identify typical patterns of HIE injury, even in the early course of the disease. However, even though highly suggestive, these patterns cannot be considered as pathognomonic. Perinatal metabolic disease such as kernicterus and severe hypoglycaemia should be differentiated from classic HIE. Other conditions, such as infections, non-accidental injury and rarer metabolic diseases can be misinterpreted as HIE in their early course when diffuse brain swelling is still the predominant MRI feature. Diffusion techniques can help to differentiate different types of diffuse brain oedema. Typical examples of focal injuries are arterial or venous infarctions. In arterial infarction, diffusion techniques can define more precisely than conventional imaging the extent of focal infarction, even in the hyperacute phase. Moreover, diffusion techniques provide quantitative data of acute corticospinal tract injury, especially at the level of the cerebral peduncles. Venous infarction should be suspected in every case of unexplained cerebral haematoma in the full-term newborn. In the presence of spontaneous bleeding, venous structures should always be evaluated by MR angiography. (orig.)

  13. Patterns of damage in the mature neonatal brain

    Energy Technology Data Exchange (ETDEWEB)

    Triulzi, Fabio; Parazzini, Cecilia; Righini, Andrea [Children' s Hospital ' ' Vittore Buzzi' ' , Departments of Radiology and Neuroradiology, Milan (Italy)

    2006-07-15

    Patterns of damage in the mature neonatal brain can be subdivided into focal, multifocal and diffuse. The main cause of diffuse brain damage in the term newborn is hypoxic-ischaemic encephalopathy (HIE). HIE is still the major recognized perinatal cause of neurological morbidity in full-term newborns. MRI offers today the highest sensitivity in detecting acute anoxic injury of the neonatal brain. Conventional acquisition techniques together with modern diffusion techniques can identify typical patterns of HIE injury, even in the early course of the disease. However, even though highly suggestive, these patterns cannot be considered as pathognomonic. Perinatal metabolic disease such as kernicterus and severe hypoglycaemia should be differentiated from classic HIE. Other conditions, such as infections, non-accidental injury and rarer metabolic diseases can be misinterpreted as HIE in their early course when diffuse brain swelling is still the predominant MRI feature. Diffusion techniques can help to differentiate different types of diffuse brain oedema. Typical examples of focal injuries are arterial or venous infarctions. In arterial infarction, diffusion techniques can define more precisely than conventional imaging the extent of focal infarction, even in the hyperacute phase. Moreover, diffusion techniques provide quantitative data of acute corticospinal tract injury, especially at the level of the cerebral peduncles. Venous infarction should be suspected in every case of unexplained cerebral haematoma in the full-term newborn. In the presence of spontaneous bleeding, venous structures should always be evaluated by MR angiography. (orig.)

  14. Ceftriaxone attenuates hypoxic-ischemic brain injury in neonatal rats

    Directory of Open Access Journals (Sweden)

    Huang Yen

    2011-09-01

    Full Text Available Abstract Background Perinatal brain injury is the leading cause of subsequent neurological disability in both term and preterm baby. Glutamate excitotoxicity is one of the major factors involved in perinatal hypoxic-ischemic encephalopathy (HIE. Glutamate transporter GLT1, expressed mainly in mature astrocytes, is the major glutamate transporter in the brain. HIE induced excessive glutamate release which is not reuptaked by immature astrocytes may induce neuronal damage. Compounds, such as ceftriaxone, that enhance the expression of GLT1 may exert neuroprotective effect in HIE. Methods We used a neonatal rat model of HIE by unilateral ligation of carotid artery and subsequent exposure to 8% oxygen for 2 hrs on postnatal day 7 (P7 rats. Neonatal rats were administered three dosages of an antibiotic, ceftriaxone, 48 hrs prior to experimental HIE. Neurobehavioral tests of treated rats were assessed. Brain sections from P14 rats were examined with Nissl and immunohistochemical stain, and TUNEL assay. GLT1 protein expression was evaluated by Western blot and immunohistochemistry. Results Pre-treatment with 200 mg/kg ceftriaxone significantly reduced the brain injury scores and apoptotic cells in the hippocampus, restored myelination in the external capsule of P14 rats, and improved the hypoxia-ischemia induced learning and memory deficit of P23-24 rats. GLT1 expression was observed in the cortical neurons of ceftriaxone treated rats. Conclusion These results suggest that pre-treatment of infants at risk for HIE with ceftriaxone may reduce subsequent brain injury.

  15. Metabolomic profile of umbilical cord blood plasma from early and late intrauterine growth restricted (IUGR neonates with and without signs of brain vasodilation.

    Directory of Open Access Journals (Sweden)

    Magdalena Sanz-Cortés

    Full Text Available OBJECTIVES: To characterize via NMR spectroscopy the full spectrum of metabolic changes in umbilical vein blood plasma of newborns diagnosed with different clinical forms of intrauterine growth restriction (IUGR. METHODS: 23 early IUGR cases and matched 23 adequate-for-gestational-age (AGA controls and 56 late IUGR cases with 56 matched AGAs were included in this study. Early IUGR was defined as a birth weight 35 weeks. This group was subdivided in 18 vasodilated (VD and 38 non-VD late IUGR fetuses. All AGA patients had a birth weight >10(th centile. (1H nuclear magnetic resonance (NMR metabolomics of the blood samples collected from the umbilical vein at delivery was obtained. Multivariate statistical analysis identified several metabolites that allowed the discrimination between the different IUGR subgroups, and their comparative levels were quantified from the NMR data. RESULTS: The NMR-based analysis showed increased unsaturated lipids and VLDL levels in both early and late IUGR samples, decreased glucose and increased acetone levels in early IUGR. Non-significant trends for decreased glucose and increased acetone levels were present in late IUGR, which followed a severity gradient when the VD and non-VD subgroups were considered. Regarding amino acids and derivatives, early IUGR showed significantly increased glutamine and creatine levels, whereas the amounts of phenylalanine and tyrosine were decreased in early and late-VD IUGR samples. Valine and leucine were decreased in late IUGR samples. Choline levels were decreased in all clinical subforms of IUGR. CONCLUSIONS: IUGR is not associated with a unique metabolic profile, but important changes are present in different clinical subsets used in research and clinical practice. These results may help in characterizing comprehensively specific alterations underlying different IUGR subsets.

  16. Regional growth and atlasing of the developing human brain.

    Science.gov (United States)

    Makropoulos, Antonios; Aljabar, Paul; Wright, Robert; Hüning, Britta; Merchant, Nazakat; Arichi, Tomoki; Tusor, Nora; Hajnal, Joseph V; Edwards, A David; Counsell, Serena J; Rueckert, Daniel

    2016-01-15

    Detailed morphometric analysis of the neonatal brain is required to characterise brain development and define neuroimaging biomarkers related to impaired brain growth. Accurate automatic segmentation of neonatal brain MRI is a prerequisite to analyse large datasets. We have previously presented an accurate and robust automatic segmentation technique for parcellating the neonatal brain into multiple cortical and subcortical regions. In this study, we further extend our segmentation method to detect cortical sulci and provide a detailed delineation of the cortical ribbon. These detailed segmentations are used to build a 4-dimensional spatio-temporal structural atlas of the brain for 82 cortical and subcortical structures throughout this developmental period. We employ the algorithm to segment an extensive database of 420 MR images of the developing brain, from 27 to 45weeks post-menstrual age at imaging. Regional volumetric and cortical surface measurements are derived and used to investigate brain growth and development during this critical period and to assess the impact of immaturity at birth. Whole brain volume, the absolute volume of all structures studied, cortical curvature and cortical surface area increased with increasing age at scan. Relative volumes of cortical grey matter, cerebellum and cerebrospinal fluid increased with age at scan, while relative volumes of white matter, ventricles, brainstem and basal ganglia and thalami decreased. Preterm infants at term had smaller whole brain volumes, reduced regional white matter and cortical and subcortical grey matter volumes, and reduced cortical surface area compared with term born controls, while ventricular volume was greater in the preterm group. Increasing prematurity at birth was associated with a reduction in total and regional white matter, cortical and subcortical grey matter volume, an increase in ventricular volume, and reduced cortical surface area. Copyright © 2015 The Authors. Published by

  17. MRI findings of brain damage due to neonatal hypoglycemia

    International Nuclear Information System (INIS)

    Wang Lu; Fan Guoguang; Ji Xu; Sun Baohai; Guo Qiyong

    2009-01-01

    Objective: To report the MRI findings of brain damage observed in neonatal patients who suffered from isolated hypoglycemia and to explore the value of diffusion-weighted imaging(DWI) in early detection of neonatal hypoglycemic brain injury. Methods: Twelve neonates with isolated hypoglycemia (10 of the 12 were diagnosed to suffer from hypoglycemic encephalopathy) were enrolled in this study. They were first scanned at age from 3 days to 10 days with T 1 WI, T 2 WI and DWI(b is 0 s/mm 2 , 1000 s/mm 2 ), and 4 of them were then scanned from 7 days to 10 days following the initial scan. All acquired MR images were retrospectively analysed. Results: First series of DWI images showed distinct hyperintense signal in 11 cases in several areas including bilateral occipital cortex (2 cases), right occipital cortex (1 case), left occipital cortex and subcortical white matter(1 case), bilateral occipital cortex and subcortical white matter (2 cases), bilateral parieto-occipital cortex (2 cases), bilateral parieto-occipital cortex and subcortical white matter(2 cases), the splenium of corpus callosum (4 cases), bilateral corona radiata( 2 cases), left caudate nucleus and globus pallidus (1 case), bilateral thalamus (1 case), bilaterally posterior limb of internal capsule (1 case). In the initial T 1 WI and T 2 WI images, there were subtle hypointensity in the damaged cortical areas (3 cases), hyperintensity in the bilaterally affected occipital cortex( 1 case) on T 1 weighted images, and hyperintensity in the affected cortex and subcortical white matter with poor differentiation on T 2 weighted images. The followed-up MRI of 4 cases showed regional encephalomalacia in the affected occipital lobes(4 cases), slightly hyperintensity on T 2 weighted images in the damaged occipital cortex (2 cases), extensive demyelination (1 case), disappearance of hyperintensity of the splenium of corpus callosum (1 case), and persistent hyperintensity in the splenium of corpus callosum (1 case

  18. Neuroprotection by Caffeine in Hyperoxia-Induced Neonatal Brain Injury

    Directory of Open Access Journals (Sweden)

    Stefanie Endesfelder

    2017-01-01

    Full Text Available Sequelae of prematurity triggered by oxidative stress and free radical-mediated tissue damage have coined the term “oxygen radical disease of prematurity”. Caffeine, a potent free radical scavenger and adenosine receptor antagonist, reduces rates of brain damage in preterm infants. In the present study, we investigated the effects of caffeine on oxidative stress markers, anti-oxidative response, inflammation, redox-sensitive transcription factors, apoptosis, and extracellular matrix following the induction of hyperoxia in neonatal rats. The brain of a rat pups at postnatal Day 6 (P6 corresponds to that of a human fetal brain at 28–32 weeks gestation and the neonatal rat is an ideal model in which to investigate effects of oxidative stress and neuroprotection of caffeine on the developing brain. Six-day-old Wistar rats were pre-treated with caffeine and exposed to 80% oxygen for 24 and 48 h. Caffeine reduced oxidative stress marker (heme oxygenase-1, lipid peroxidation, hydrogen peroxide, and glutamate-cysteine ligase catalytic subunit (GCLC, promoted anti-oxidative response (superoxide dismutase, peroxiredoxin 1, and sulfiredoxin 1, down-regulated pro-inflammatory cytokines, modulated redox-sensitive transcription factor expression (Nrf2/Keap1, and NFκB, reduced pro-apoptotic effectors (poly (ADP-ribose polymerase-1 (PARP-1, apoptosis inducing factor (AIF, and caspase-3, and diminished extracellular matrix degeneration (matrix metalloproteinases (MMP 2, and inhibitor of metalloproteinase (TIMP 1/2. Our study affirms that caffeine is a pleiotropic neuroprotective drug in the developing brain due to its anti-oxidant, anti-inflammatory, and anti-apoptotic properties.

  19. Digital gene atlas of neonate common marmoset brain.

    Science.gov (United States)

    Shimogori, Tomomi; Abe, Ayumi; Go, Yasuhiro; Hashikawa, Tsutomu; Kishi, Noriyuki; Kikuchi, Satomi S; Kita, Yoshiaki; Niimi, Kimie; Nishibe, Hirozumi; Okuno, Misako; Saga, Kanako; Sakurai, Miyano; Sato, Masae; Serizawa, Tsuna; Suzuki, Sachie; Takahashi, Eiki; Tanaka, Mami; Tatsumoto, Shoji; Toki, Mitsuhiro; U, Mami; Wang, Yan; Windak, Karl J; Yamagishi, Haruhiko; Yamashita, Keiko; Yoda, Tomoko; Yoshida, Aya C; Yoshida, Chihiro; Yoshimoto, Takuro; Okano, Hideyuki

    2018-03-01

    Interest in the common marmoset (Callithrix jacchus) as a primate model animal has grown recently, in part due to the successful demonstration of transgenic marmosets. However, there is some debate as to the suitability of marmosets, compared to more widely used animal models, such as the macaque monkey and mouse. Especially, the usage of marmoset for animal models of human cognition and mental disorders, is still yet to be fully explored. To examine the prospects of the marmoset model for neuroscience research, the Marmoset Gene Atlas (https://gene-atlas.bminds.brain.riken.jp/) provides a whole brain gene expression atlas in the common marmoset. We employ in situ hybridization (ISH) to systematically analyze gene expression in neonate marmoset brains, which allows us to compare expression with other model animals such as mouse. We anticipate that these data will provide sufficient information to develop tools that enable us to reveal marmoset brain structure, function, cellular and molecular organization for primate brain research. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  20. Brain single photon emission computed tomography in neonates

    International Nuclear Information System (INIS)

    Denays, R.; Van Pachterbeke, T.; Tondeur, M.

    1989-01-01

    This study was designed to rate the clinical value of [ 123 I]iodoamphetamine (IMP) or [ 99m Tc] hexamethyl propylene amine oxyme (HM-PAO) brain single photon emission computed tomography (SPECT) in neonates, especially in those likely to develop cerebral palsy. The results showed that SPECT abnormalities were congruent in most cases with structural lesions demonstrated by ultrasonography. However, mild bilateral ventricular dilatation and bilateral subependymal porencephalic cysts diagnosed by ultrasound were not associated with an abnormal SPECT finding. In contrast, some cortical periventricular and sylvian lesions and all the parasagittal lesions well visualized in SPECT studies were not diagnosed by ultrasound scans. In neonates with subependymal and/or intraventricular hemorrhage the existence of a parenchymal abnormality was only diagnosed by SPECT. These results indicate that [ 123 I]IMP or [ 99m Tc]HM-PAO brain SPECT shows a potential clinical value as the neurodevelopmental outcome is clearly related to the site, the extent, and the number of cerebral lesions. Long-term clinical follow-up is, however, mandatory in order to define which SPECT abnormality is associated with neurologic deficit

  1. Parcellation of the Healthy Neonatal Brain into 107 Regions Using Atlas Propagation through Intermediate Time Points in Childhood.

    Science.gov (United States)

    Blesa, Manuel; Serag, Ahmed; Wilkinson, Alastair G; Anblagan, Devasuda; Telford, Emma J; Pataky, Rozalia; Sparrow, Sarah A; Macnaught, Gillian; Semple, Scott I; Bastin, Mark E; Boardman, James P

    2016-01-01

    Neuroimage analysis pipelines rely on parcellated atlases generated from healthy individuals to provide anatomic context to structural and diffusion MRI data. Atlases constructed using adult data introduce bias into studies of early brain development. We aimed to create a neonatal brain atlas of healthy subjects that can be applied to multi-modal MRI data. Structural and diffusion 3T MRI scans were acquired soon after birth from 33 typically developing neonates born at term (mean postmenstrual age at birth 39(+5) weeks, range 37(+2)-41(+6)). An adult brain atlas (SRI24/TZO) was propagated to the neonatal data using temporal registration via childhood templates with dense temporal samples (NIH Pediatric Database), with the final atlas (Edinburgh Neonatal Atlas, ENA33) constructed using the Symmetric Group Normalization (SyGN) method. After this step, the computed final transformations were applied to T2-weighted data, and fractional anisotropy, mean diffusivity, and tissue segmentations to provide a multi-modal atlas with 107 anatomical regions; a symmetric version was also created to facilitate studies of laterality. Volumes of each region of interest were measured to provide reference data from normal subjects. Because this atlas is generated from step-wise propagation of adult labels through intermediate time points in childhood, it may serve as a useful starting point for modeling brain growth during development.

  2. Parcellation of the healthy neonatal brain into 107 regions using atlas propagation through intermediate time points in childhood

    Directory of Open Access Journals (Sweden)

    Manuel eBlesa Cabez

    2016-05-01

    Full Text Available Neuroimage analysis pipelines rely on parcellated atlases generated from healthy individuals to provide anatomic context to structural and diffusion MRI data. Atlases constructed using adult data introduce bias into studies of early brain development. We aimed to create a neonatal brain atlas of healthy subjects that can be applied to multi-modal MRI data. Structural and diffusion 3T MRI scans were acquired soon after birth from 33 typically developing neonates born at term (mean postmenstrual age at birth 39+5 weeks, range 37+2-41+6. An adult brain atlas (SRI24/TZO was propagated to the neonatal data using temporal registration via childhood templates with dense temporal samples (NIH Pediatric Database, with the final atlas (Edinburgh Neonatal Atlas, ENA33 constructed using the Symmetric Group Normalization method. After this step, the computed final transformations were applied to T2-weighted data, and fractional anisotropy, mean diffusivity, and tissue segmentations to provide a multi-modal atlas with 107 anatomical regions; a symmetric version was also created to facilitate studies of laterality. Volumes of each region of interest were measured to provide reference data from normal subjects. Because this atlas is generated from step-wise propagation of adult labels through intermediate time points in childhood, it may serve as a useful starting point for modelling brain growth during development.

  3. Inflammation and oxidative stress biomarkers in neonatal brain hypoxia and prediction of adverse neurological outcome: a review

    Directory of Open Access Journals (Sweden)

    Marianna Varsami

    2013-06-01

    Full Text Available Despite advances in perinatal care, the outcome of newborns with hypoxic-ischemic encephalopathy is poor and the issue still remains challenging in neonatology. The use of an easily approachable and practical biomarker not only could identify neonates with severe brain damage and subsequent adverse outcome, but could also target the group of infants that would benefit from a neuroprotective intervention. Recent studies have suggested interleukin-1b, interleukin-6, tumour necrosis alpha (TNF-a and neuron specific enolase (NSE to be potential biomarkers of brain damage in asphyxiated newborns. S100B, lactate dehydrogenase, nitrated albumin-nitrotyrosine, adrenomedullin, activin-A, non protein bound iron, isoprostanes, vascular endothelial growth factor and metalloproteinases have also been proposed by single-centre studies to play a similar role in the field. With this review we aim to provide an overview of existing data in the literature regarding biomarkers for neonatal brain damage.

  4. Enhancement of intestinal growth in neonatal rats by epidermal growth factor in milk

    International Nuclear Information System (INIS)

    Berseth, C.L.

    1987-01-01

    Breast milk has been shown to enhance neonatal intestinal growth. Because epidermal growth factor (EGF) is present in the milk of various mammalian species, the hypothesis was tested that EGF in rodent milk mediates, in part, the breast milk-enhanced intestinal growth in neonatal rat. Fifty-eight rat pups fed artificial formal that contained 1.2, 3.0, and 6.0 μg/ml EGF for 39 h had greater incorporation of [ 3 H]thymidine into DNA and DNA content of intestine than 29 pups fed unsupplemented formula. Pups fed EGF for 5 days had significantly greater body weight, intestinal weight, length, and DNA content than control pups. Conversely, pups fed pooled rat milk containing rabbit-derived antibody to EGF for 39 h had intestines of lower weight that contained less DNA than animals fed rat milk containing normal rabbit serum. EGF appears to mediate, in part, breast milk-enhanced neonatal intestinal growth

  5. Smaller Cerebellar Growth and Poorer Neurodevelopmental Outcomes in Very Preterm Infants Exposed to Neonatal Morphine.

    Science.gov (United States)

    Zwicker, Jill G; Miller, Steven P; Grunau, Ruth E; Chau, Vann; Brant, Rollin; Studholme, Colin; Liu, Mengyuan; Synnes, Anne; Poskitt, Kenneth J; Stiver, Mikaela L; Tam, Emily W Y

    2016-05-01

    To examine the relationship between morphine exposure and growth of the cerebellum and cerebrum in very preterm neonates from early in life to term-equivalent age, as well as to examine morphine exposure and brain volumes in relation to neurodevelopmental outcomes at 18 months corrected age (CA). A prospective cohort of 136 very preterm neonates (24-32 weeks gestational age) was serially scanned with magnetic resonance imaging near birth and at term-equivalent age for volumetric measurements of the cerebellum and cerebrum. Motor outcomes were assessed with the Peabody Developmental Motor Scales, Second Edition and cognitive outcomes with the Bayley Scales of Infant and Toddler Development, Third Edition at 18 months CA. Generalized least squares models and linear regression models were used to assess relationships between morphine exposure, brain volumes, and neurodevelopmental outcomes. A 10-fold increase in morphine exposure was associated with a 5.5% decrease in cerebellar volume, after adjustment for multiple clinical confounders and total brain volume (P = .04). When infants exposed to glucocorticoids were excluded, the association of morphine was more pronounced, with an 8.1% decrease in cerebellar volume. Morphine exposure was not associated with cerebral volume (P = .30). Greater morphine exposure also predicted poorer motor (P growth. Morphine exposure in very preterm neonates is independently associated with impaired cerebellar growth in the neonatal period and poorer neurodevelopmental outcomes in early childhood. Alternatives to better manage pain in preterm neonates that optimize brain development and functional outcomes are urgently needed. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Evaluation of an automatic brain segmentation method developed for neonates on adult MR brain images

    Science.gov (United States)

    Moeskops, Pim; Viergever, Max A.; Benders, Manon J. N. L.; Išgum, Ivana

    2015-03-01

    Automatic brain tissue segmentation is of clinical relevance in images acquired at all ages. The literature presents a clear distinction between methods developed for MR images of infants, and methods developed for images of adults. The aim of this work is to evaluate a method developed for neonatal images in the segmentation of adult images. The evaluated method employs supervised voxel classification in subsequent stages, exploiting spatial and intensity information. Evaluation was performed using images available within the MRBrainS13 challenge. The obtained average Dice coefficients were 85.77% for grey matter, 88.66% for white matter, 81.08% for cerebrospinal fluid, 95.65% for cerebrum, and 96.92% for intracranial cavity, currently resulting in the best overall ranking. The possibility of applying the same method to neonatal as well as adult images can be of great value in cross-sectional studies that include a wide age range.

  7. Adenosine A1 receptors contribute to immune regulation after neonatal hypoxic ischemic brain injury

    OpenAIRE

    Winerdal, Max; Winerdal, Malin E.; Wang, Ying-Qing; Fredholm, Bertil B.; Winqvist, Ola; Ådén, Ulrika

    2015-01-01

    Neonatal brain hypoxic ischemia (HI) often results in long-term motor and cognitive impairments. Post-ischemic inflammation greatly effects outcome and adenosine receptor signaling modulates both HI and immune cell function. Here, we investigated the influence of adenosine A1 receptor deficiency (A1R−/−) on key immune cell populations in a neonatal brain HI model. Ten-day-old mice were subjected to HI. Functional outcome was assessed by open locomotion and beam walking test and infarction siz...

  8. Developmental vitamin D deficiency alters multiple neurotransmitter systems in the neonatal rat brain.

    Science.gov (United States)

    Kesby, James P; Turner, Karly M; Alexander, Suzanne; Eyles, Darryl W; McGrath, John J; Burne, Thomas H J

    2017-11-01

    Epidemiological evidence suggests that developmental vitamin D (DVD) deficiency is a risk factor for neuropsychiatric disorders, such as schizophrenia. DVD deficiency in rats is associated with altered brain structure and adult behaviours indicating alterations in dopamine and glutamate signalling. Developmental alterations in dopamine neurotransmission have also been observed in DVD-deficient rats but a comprehensive assessment of brain neurochemistry has not been undertaken. Thus, the current study determined the regional concentrations of dopamine, noradrenaline, serotonin, glutamine, glutamate and γ-aminobutyric acid (GABA), and associated metabolites, in DVD-deficient neonates. Sprague-Dawley rats were fed a vitamin D deficient diet or control diet six weeks prior to mating until birth and housed under UVB-free lighting conditions. Neurotransmitter concentration was assessed by high-performance liquid chromatography on post-mortem neonatal brain tissue. Ubiquitous reductions in the levels of glutamine (12-24%) were observed in DVD-deficient neonates compared with control neonates. Similarly, in multiple brain regions DVD-deficient neonates had increased levels of noradrenaline and serine compared with control neonates. In contrast, increased levels of dopamine and decreased levels of serotonin in DVD-deficient neonates were limited to striatal subregions compared with controls. Our results confirm that DVD deficiency leads to changes in multiple neurotransmitter systems in the neonate brain. Importantly, this regionally-based assessment in DVD-deficient neonates identified both widespread neurotransmitter changes (glutamine/noradrenaline) and regionally selective neurotransmitter changes (dopamine/serotonin). Thus, vitamin D may have both general and local actions depending on the neurotransmitter system being investigated. Taken together, these data suggest that DVD deficiency alters neurotransmitter systems relevant to schizophrenia in the developing rat

  9. Population differences in brain morphology and microstructure among Chinese, Malay, and Indian neonates.

    Science.gov (United States)

    Bai, Jordan; Abdul-Rahman, Muhammad Farid; Rifkin-Graboi, Anne; Chong, Yap-Seng; Kwek, Kenneth; Saw, Seang-Mei; Godfrey, Keith M; Gluckman, Peter D; Fortier, Marielle V; Meaney, Michael J; Qiu, Anqi

    2012-01-01

    We studied a sample of 75 Chinese, 73 Malay, and 29 Indian healthy neonates taking part in a cohort study to examine potential differences in neonatal brain morphology and white matter microstructure as a function of ethnicity using both structural T2-weighted magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). We first examined the differences in global size and morphology of the brain among the three groups. We then constructed the T2-weighted MRI and DTI atlases and employed voxel-based analysis to investigate ethnic differences in morphological shape of the brain from the T2-weighted MRI, and white matter microstructure measured by fractional anisotropy derived from DTI. Compared with Malay neonates, the brains of Indian neonates' tended to be more elongated in anterior and posterior axis relative to the superior-inferior axis of the brain even though the total brain volume was similar among the three groups. Although most anatomical regions of the brain were similar among Chinese, Malay, and Indian neonates, there were anatomical variations in the spinal-cerebellar and cortical-striatal-thalamic neural circuits among the three populations. The population-related brain regions highlighted in our study are key anatomical substrates associated with sensorimotor functions.

  10. Feeding Vitamin C during Neonatal and Juvenile Growth Improves Learning and Memory of Rats.

    Science.gov (United States)

    Hosseini, Mahmoud; Beheshti, Farimah; Sohrabi, Farzaneh; Vafaee, Farzaneh; Shafei, Mohammad Naser; Reza Sadeghnia, Hamid

    2018-09-03

    We investigated the effects of feeding vitamin C (Vit C) during neonatal and juvenile growth on learning and memory of rats. Rats after delivery were randomly divided into four groups and treated. Group 1, control group, received normal drinking water. Groups 2-4 received Vit C 10, 100, and 500 mg/kg, respectively, from the first day. After 8 weeks, 10 male offspring of each group were randomly selected and tested in the Morris water maze (MWM) and passive avoidance (PA) tests. Finally, the brains were removed for biochemical measurement. In MWM, 10-500 mg/kg Vit C reduced the latency and traveled distance and increased time spent in the target quadrant. In PA, 10 and 100 mg/kg of Vit C increased the latency; 10-500 mg/kg of Vit C decreased the malondialdehyde (MDA) in the brain tissues and increased thiol and catalase (CAT) activity compared to the control group. We showed that feeding rats Vit C during neonatal and juvenile growth has positive effects on learning and memory.

  11. Developmental synchrony of thalamocortical circuits in the neonatal brain.

    Science.gov (United States)

    Poh, Joann S; Li, Yue; Ratnarajah, Nagulan; Fortier, Marielle V; Chong, Yap-Seng; Kwek, Kenneth; Saw, Seang-Mei; Gluckman, Peter D; Meaney, Michael J; Qiu, Anqi

    2015-08-01

    The thalamus is a deep gray matter structure and consists of axonal fibers projecting to the entire cortex, which provide the anatomical support for its sensorimotor and higher-level cognitive functions. There is limited in vivo evidence on the normal thalamocortical development, especially in early life. In this study, we aimed to investigate the developmental patterns of the cerebral cortex, the thalamic substructures, and their connectivity with the cortex in the first few weeks of the postnatal brain. We hypothesized that there is developmental synchrony of the thalamus, its cortical projections, and corresponding target cortical structures. We employed diffusion tensor imaging (DTI) and divided the thalamus into five substructures respectively connecting to the frontal, precentral, postcentral, temporal, and parietal and occipital cortex. T2-weighted magnetic resonance imaging (MRI) was used to measure cortical thickness. We found age-related increases in cortical thickness of bilateral frontal cortex and left temporal cortex in the early postnatal brain. We also found that the development of the thalamic substructures was synchronized with that of their respective thalamocortical connectivity in the first few weeks of the postnatal life. In particular, the right thalamo-frontal substructure had the fastest growth in the early postnatal brain. Our study suggests that the distinct growth patterns of the thalamic substructures are in synchrony with those of the cortex in early life, which may be critical for the development of the cortical and subcortical functional specialization. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Programmed Necrosis: A Prominent Mechanism of Cell Death following Neonatal Brain Injury

    Directory of Open Access Journals (Sweden)

    Raul Chavez-Valdez

    2012-01-01

    Full Text Available Despite the introduction of therapeutic hypothermia, neonatal hypoxic ischemic (HI brain injury remains a common cause of developmental disability. Development of rational adjuvant therapies to hypothermia requires understanding of the pathways of cell death and survival modulated by HI. The conceptualization of the apoptosis-necrosis “continuum” in neonatal brain injury predicts mechanistic interactions between cell death and hydrid forms of cell death such as programmed or regulated necrosis. Many of the components of the signaling pathway regulating programmed necrosis have been studied previously in models of neonatal HI. In some of these investigations, they participate as part of the apoptotic pathways demonstrating clear overlap of programmed death pathways. Receptor interacting protein (RIP-1 is at the crossroads between types of cellular death and survival and RIP-1 kinase activity triggers formation of the necrosome (in complex with RIP-3 leading to programmed necrosis. Neuroprotection afforded by the blockade of RIP-1 kinase following neonatal HI suggests a role for programmed necrosis in the HI injury to the developing brain. Here, we briefly review the state of the knowledge about the mechanisms behind programmed necrosis in neonatal brain injury recognizing that a significant proportion of these data derive from experiments in cultured cell and some from in vivo adult animal models. There are still more questions than answers, yet the fascinating new perspectives provided by the understanding of programmed necrosis in the developing brain may lay the foundation for new therapies for neonatal HI.

  13. Correlation between Doppler flow patterns in growth-restricted fetuses and neonatal circulation

    NARCIS (Netherlands)

    Tanis, J. C.; Boelen, M. R.; Schmitz, D. M.; Casarella, L.; van der Laan, M. E.; Bos, A. F.; Bilardo, C. M.

    Objectives To investigate whether prenatal Doppler parameters in growth-restricted fetuses are correlated with neonatal circulatory changes. Methods In 43 cases of suspected fetal growth restriction (FGR), serial Doppler measurements of umbilical artery (UA) and middle cerebral artery (MCA)

  14. In vitro growth of Plasmodium falciparum in neonatal blood.

    Science.gov (United States)

    Sauerzopf, Ulrich; Honkpehedji, Yabo J; Adgenika, Ayôla A; Feugap, Elianne N; Ngoma, Ghyslain Mombo; Mackanga, Jean-Rodolphe; Lötsch, Felix; Loembe, Marguerite M; Kremsner, Peter G; Mordmüller, Benjamin; Ramharter, Michael

    2014-11-18

    Children below the age of six months suffer less often from malaria than older children in sub-Saharan Africa. This observation is commonly attributed to the persistence of foetal haemoglobin (HbF), which is considered not to permit growth of Plasmodium falciparum and therefore providing protection against malaria. Since this concept has recently been challenged, this study evaluated the effect of HbF erythrocytes and maternal plasma on in vitro parasite growth of P. falciparum in Central African Gabon. Umbilical cord blood and peripheral maternal blood were collected at delivery at the Albert Schweitzer Hospital in Gabon. Respective erythrocyte suspension and plasma were used in parallel for in vitro culture. In vitro growth rates were compared between cultures supplemented with either maternal or cord erythrocytes. Plasma of maternal blood and cord blood was evaluated. Parasite growth rates were assessed by the standard HRP2-assay evaluating the increase of HRP2 concentration in Plasmodium culture. Culture of P. falciparum using foetal erythrocytes led to comparable growth rates (mean growth rate = 4.2, 95% CI: 3.5 - 5.0) as cultures with maternal red blood cells (mean growth rate =4.2, 95% CI: 3.4 - 5.0) and those from non-malaria exposed individuals (mean growth rate = 4.6, 95% CI: 3.8 - 5.5). Standard in vitro culture of P. falciparum supplemented with either maternal or foetal plasma showed both significantly lower growth rates than a positive control using non-malaria exposed donor plasma. These data challenge the concept of HbF serving as intrinsic inhibitor of P. falciparum growth in the first months of life. Erythrocytes containing HbF are equally permissive to P. falciparum growth in vitro. However, addition of maternal and cord plasma led to reduced in vitro growth which may translate to protection against clinical disease or show synergistic effects with HbF in vivo. Further studies are needed to elucidate the pathophysiology of innate and acquired

  15. Characterization of cortical neuronal and glial alterations during culture of organotypic whole brain slices from neonatal and mature mice.

    Science.gov (United States)

    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.

  16. Can induced hypothermia be assured during brain MRI in neonates with hypoxic-ischemic encephalopathy?

    International Nuclear Information System (INIS)

    Wintermark, Pia; Labrecque, Michelle; Hansen, Anne; Warfield, Simon K.; DeHart, Stephanie

    2010-01-01

    Until now, brain MRIs in asphyxiated neonates who are receiving therapeutic hypothermia have been performed after treatment is complete. However, there is increasing interest in utilizing early brain MRI while hypothermia is still being provided to rapidly understand the degree of brain injury and possibly refine neuroprotective strategies. This study was designed to assess whether therapeutic hypothermia can be maintained while performing a brain MRI. Twenty MRI scans were obtained in 12 asphyxiated neonates while they were treated with hypothermia. The median difference between esophageal temperature on NICU departure and return was 0.1 C (range: -0.8 to 0.8 C). We found that therapeutic hypothermia can be safely and reproducibly maintained during a brain MRI. Hypothermia treatment should not prevent obtaining an early brain MRI if clinically indicated. (orig.)

  17. Can induced hypothermia be assured during brain MRI in neonates with hypoxic-ischemic encephalopathy?

    Energy Technology Data Exchange (ETDEWEB)

    Wintermark, Pia [Children' s Hospital Boston, Division of Newborn Medicine, Boston, MA (United States); Children' s Hospital Boston, Department of Radiology, Boston, MA (United States); Montreal Children' s Hospital, Division of Newborn Medicine, Montreal, QC (Canada); Labrecque, Michelle; Hansen, Anne [Children' s Hospital Boston, Division of Newborn Medicine, Boston, MA (United States); Warfield, Simon K.; DeHart, Stephanie [Children' s Hospital Boston, Department of Radiology, Boston, MA (United States)

    2010-12-15

    Until now, brain MRIs in asphyxiated neonates who are receiving therapeutic hypothermia have been performed after treatment is complete. However, there is increasing interest in utilizing early brain MRI while hypothermia is still being provided to rapidly understand the degree of brain injury and possibly refine neuroprotective strategies. This study was designed to assess whether therapeutic hypothermia can be maintained while performing a brain MRI. Twenty MRI scans were obtained in 12 asphyxiated neonates while they were treated with hypothermia. The median difference between esophageal temperature on NICU departure and return was 0.1 C (range: -0.8 to 0.8 C). We found that therapeutic hypothermia can be safely and reproducibly maintained during a brain MRI. Hypothermia treatment should not prevent obtaining an early brain MRI if clinically indicated. (orig.)

  18. Neonatal manipulation of oxytocin prevents lipopolysaccharide-induced decrease in gene expression of growth factors in two developmental stages of the female rat.

    Science.gov (United States)

    Bakos, Jan; Lestanova, Zuzana; Strbak, Vladimir; Havranek, Tomas; Bacova, Zuzana

    2014-10-01

    Oxytocin production and secretion is important for early development of the brain. Long-term consequences of manipulation of oxytocin system might include changes in markers of brain plasticity - cytoskeletal proteins and neurotrophins. The aim of the present study was (1) to determine whether neonatal oxytocin administration affects gene expression of nestin, microtubule-associated protein-2 (MAP-2), brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the brain of two developmental stages of rat and (2) to evaluate whether neonatal oxytocin administration protects against lipopolysaccharide (LPS) induced inflammation. Neonatal oxytocin did not prevent a decrease of body weight in the LPS treated animals. Oxytocin significantly increased gene expression of BDNF in the right hippocampus in 21-day and 2-month old rats of both sexes. Gene expression of NGF and MAP-2 significantly increased in males treated with oxytocin. Both, growth factors and intermediate filament-nestin mRNA levels, were reduced in females exposed to LPS. Oxytocin treatment prevented a decrease in the gene expression of only growth factors. In conclusion, neonatal manipulation of oxytocin has developmental and sex-dependent effect on markers of brain plasticity. These results also indicate, that oxytocin may be protective against inflammation particularly in females. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Distortion-product otoacoustic emission growth curves in neonates

    Directory of Open Access Journals (Sweden)

    Tania Alves Barbosa

    2014-12-01

    Full Text Available Background: The recording of otoacoustic emissions (OAE enabled us to prove that the cochlea is able not only to receive sounds but also to produce acoustic energy. Through the use of distortion-product otoacoustic emission measurements, the growth of the response was seen according to the intensity of the sound stimulus presented (growth curve. Objective: to determine the thresholds for the emergence of distortion-product otoacoustic emissions (DPOAE on frequencies of 2000 and 4000 Hz with a stimulus varying from 20 to 65dB SPL, and to establish the slope values obtained in the growth curves. Methods: 39 neonates aged 5 to 28 days without risk indicators of hearing loss were studied. The DPOAE growth curves were obtained on the frequencies from 2000 Hz and 4000 Hz with a level of intensity ranging from 20 to 65dB SPL divided into two paradigms (20 to 40dB SPL and 40-65dB SPL. Results: there was a statistically significant difference in the thresholds for the emergence of DPOAE depending on the criteria used. The thresholds were on average higher at 4000 Hz than 2000 Hz and the slope was higher on average at 2000 Hz than 4000 Hz, although not statistically significant in either case. Conclusion: the thresholds were on average 30dB SPL at 2000Hz and 35dB SPL at 4000Hz. The slope values varied between 3 and 4 on average, reaching 15 in some cases.

  20. Maternal MDMA administration in mice leads to neonatal growth delay.

    Science.gov (United States)

    Kaizaki, Asuka; Tanaka, Sachiko; Yoshida, Takemi; Numazawa, Satoshi

    2014-02-01

    The psychoactive recreational drug 3,4-methylenedioxymethamphetamine (MDMA) is widely abused. The fact that MDMA induces neurotoxic damage in serotonergic nerve endings is well known. However, the effects of MDMA on pregnant and neonatal animals remain unknown. Therefore, we studied the effects of gestational exposure to MDMA on birth, growth, and behavior of pups. Female BALB/c mice were orally administered either water (10 ml/kg) or MDMA (20 mg/10 ml/kg) from gestational day 1 to postnatal day (P) 21. MDMA did not affect the birth rate, but the survival rate of the pups significantly decreased. A significant reduction in body weight gain was observed in pups from MDMA-administered dams during P3-P21. Maternal MDMA treatment caused an attenuated cliff avoidance reaction and decreased motor function in the pups, as determined by the wire hanging test. These results suggest that MDMA treatment during pregnancy and lactation causes growth retardation and dysfunction of motor neurons in mouse pups.

  1. Cytosine methylation dysregulation in neonates following intrauterine growth restriction.

    Directory of Open Access Journals (Sweden)

    Francine Einstein

    2010-01-01

    Full Text Available Perturbations of the intrauterine environment can affect fetal development during critical periods of plasticity, and can increase susceptibility to a number of age-related diseases (e.g., type 2 diabetes mellitus; T2DM, manifesting as late as decades later. We hypothesized that this biological memory is mediated by permanent alterations of the epigenome in stem cell populations, and focused our studies specifically on DNA methylation in CD34+ hematopoietic stem and progenitor cells from cord blood from neonates with intrauterine growth restriction (IUGR and control subjects.Our epigenomic assays utilized a two-stage design involving genome-wide discovery followed by quantitative, single-locus validation. We found that changes in cytosine methylation occur in response to IUGR of moderate degree and involving a restricted number of loci. We also identify specific loci that are targeted for dysregulation of DNA methylation, in particular the hepatocyte nuclear factor 4alpha (HNF4A gene, a well-known diabetes candidate gene not previously associated with growth restriction in utero, and other loci encoding HNF4A-interacting proteins.Our results give insights into the potential contribution of epigenomic dysregulation in mediating the long-term consequences of IUGR, and demonstrate the value of this approach to studies of the fetal origin of adult disease.

  2. Cytosine Methylation Dysregulation in Neonates Following Intrauterine Growth Restriction

    Science.gov (United States)

    Bhagat, Tushar D.; Fazzari, Melissa J.; Verma, Amit; Barzilai, Nir; Greally, John M.

    2010-01-01

    Background Perturbations of the intrauterine environment can affect fetal development during critical periods of plasticity, and can increase susceptibility to a number of age-related diseases (e.g., type 2 diabetes mellitus; T2DM), manifesting as late as decades later. We hypothesized that this biological memory is mediated by permanent alterations of the epigenome in stem cell populations, and focused our studies specifically on DNA methylation in CD34+ hematopoietic stem and progenitor cells from cord blood from neonates with intrauterine growth restriction (IUGR) and control subjects. Methods and Findings Our epigenomic assays utilized a two-stage design involving genome-wide discovery followed by quantitative, single-locus validation. We found that changes in cytosine methylation occur in response to IUGR of moderate degree and involving a restricted number of loci. We also identify specific loci that are targeted for dysregulation of DNA methylation, in particular the hepatocyte nuclear factor 4α (HNF4A) gene, a well-known diabetes candidate gene not previously associated with growth restriction in utero, and other loci encoding HNF4A-interacting proteins. Conclusions Our results give insights into the potential contribution of epigenomic dysregulation in mediating the long-term consequences of IUGR, and demonstrate the value of this approach to studies of the fetal origin of adult disease. PMID:20126273

  3. Sulfur amino acid deficiency upregulates intestinal methionine cycle activity and suppresses epithelial growth in neonatal pigs.

    Science.gov (United States)

    We recently showed that the developing gut is a significant site of methionine transmethylation to homocysteine and transsulfuration to cysteine. We hypothesized that sulfur amino acid (SAA) deficiency would preferentially reduce mucosal growth and antioxidant function in neonatal pigs. Neonatal pi...

  4. Increased MMP-9 and TIMP-1 in mouse neonatal brain and plasma and in human neonatal plasma after hypoxia-ischemia: a potential marker of neonatal encephalopathy.

    Science.gov (United States)

    Bednarek, Nathalie; Svedin, Pernilla; Garnotel, Roselyne; Favrais, Géraldine; Loron, Gauthier; Schwendiman, Leslie; Hagberg, Henrik; Morville, Patrice; Mallard, Carina; Gressens, Pierre

    2012-01-01

    To implement neuroprotective strategies in newborns, sensitive and specific biomarkers are needed for identifying those who are at risk for brain damage. We evaluated the effectiveness of matrix metalloproteinases (MMPs) and their naturally occurring tissue inhibitors of metalloproteinases (TIMPs) in predicting neonatal encephalopathy (NE) damage in newborns. Plasma MMP-9 and TIMP-1 levels were upregulated as early as 1 h after the HI insult but not did not show such elevations after other types of injury (ibotenate-induced excitotoxicity, hypoxia, lipopolysaccharide-induced inflammation), and brain levels reflected this increase soon thereafter. We confirmed these results by carrying out plasma MMP-9 and TIMP-1 measurements in human newborns with NE. In these infants, protein levels of MMP-9 and TIMP-1 were found to be elevated during a short window up to 6 h after birth. This feature is particularly useful in identifying newborns in need of neuroprotection. A second peak observed 72 h after birth is possibly related to the second phase of energy failure after a HI insult. Our data, although preliminary, support the use of MMP-9 and TIMP-1 as early biomarkers for the presence and extent of perinatal brain injury in human term newborns. We first used a mouse model of neonatal HI injury to explore mechanistic aspects such as the time course of these markers after the hypoxia-ischemia event, and the correlation between the levels of these candidate markers in brain and plasma.

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

    Science.gov (United States)

    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.

  6. Comparison of blood lead levels of mothers and cord blood in intrauterine growth retarded neonates and normal term neonates

    International Nuclear Information System (INIS)

    Iranpour, R.; Besharati, Amir A.; Nasseri, F.; Hashemipour, M.; Kelishadi, R.; Balali-Mood, M.

    2007-01-01

    Objective was to compare the blood lead levels of mothers and cord blood in intrauterine growth retarded (IUGR) neonates and normal term neonates. From April 2005, we carried out a cross-sectional, prospective study in Isfahan University of Medical Sciences, Isfahan, Iran. Blood lead levels were measured in the umbilical cord and maternal venous blood samples in the 32 mother-infant pairs with IUGR full term neonates and 34 mother-infant pairs with normal full term neonates. Blood-lead levels were analyzed by atomic absorption spectrometry. The mean lead concentration in neonates of IUGR and normal groups was not significantly different (107.47+- 16.75 versus 113.08+-19.08 ug/L, p=0.2). The mean lead concentration in mothers of IUGR group was lower than normal groups, but this difference was not significant (124.56+-19.71 versus 135.26+-26.91 ug/L, p=0.07). Maternal lead levels were strongly related with related with cord blood in both IUGR and normal groups (r=0.8, p 100ug/L by the centers for disease control; however, this was not statistically different between the groups. Our results indicate that the mean lead level was not higher in IUGR neonates, and the whole blood lead was not related to the birth weight. In addition, maternal and cord blood lead levels were strongly correlated, and there were remarkable lead burdens on both the mothers and their neonates in this industrial area. (author)

  7. The neonatal brain : early connectome development and childhood cognition

    NARCIS (Netherlands)

    Keunen, K.

    2017-01-01

    The human brain is a vastly complex system that develops rapidly during human gestation. Its developmental pace is unprecedented in any other period of human development. By the time of normal birth the brain's layout verges on the adult human brain. All major structures have come into place,

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

    Science.gov (United States)

    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.

  9. Sodium Pyruvate Reduced Hypoxic-Ischemic Injury to Neonatal Rat Brain

    OpenAIRE

    Pan, Rui; Rong, Zhihui; She, Yun; Cao, Yuan; Chang, Li-Wen; Lee, Wei-Hua

    2012-01-01

    Background Neonatal hypoxia-ischemia (HI) remains a major cause of severe brain damage and is often associated with high mortality and lifelong disability. Immature brains are extremely sensitive to hypoxia-ischemia, shown as prolonged mitochondrial neuronal death. Sodium pyruvate (SP), a substrate of the tricarboxylic acid cycle and an extracellular antioxidant, has been considered as a potential treatment for hypoxic-ischemic encephalopathy (HIE), but its effects have not been evaluated in ...

  10. Neonatal Pain in Very Preterm Infants: Long-Term Effects on Brain, Neurodevelopment and Pain Reactivity

    Directory of Open Access Journals (Sweden)

    Ruth Eckstein Grunau

    2013-10-01

    Full Text Available Effects of early life psychosocial adversity have received a great deal of attention, such as maternal separation in experimental animal models and abuse/neglect in young humans. More recently, long-term effects of the physical stress of repetitive procedural pain have begun to be addressed in infants hospitalized in neonatal intensive care. Preterm infants are more sensitive to pain and stress, which cannot be distinguished in neonates. The focus of this review is clinical studies of long-term effects of repeated procedural pain-related stress in the neonatal intensive care unit (NICU in relation to brain development, neurodevelopment, programming of stress systems, and later pain sensitivity in infants born very preterm (24–32 weeks’ gestational age. Neonatal pain exposure has been quantified as the number of invasive and/or skin-breaking procedures during hospitalization in the NICU. Emerging studies provide convincing clinical evidence for an adverse impact of neonatal pain/stress in infants at a time of physiological immaturity, rapidly developing brain microstructure and networks, as well as programming of the hypothalamic-pituitary-adrenal axis. Currently it appears that early pain/stress may influence the developing brain and thereby neurodevelopment and stress-sensitive behaviors, particularly in the most immature neonates. However, there is no evidence for greater prevalence of pain syndromes compared to children and adults born healthy at full term. In addressing associations between pain/stress and outcomes, careful consideration of confounding clinical factors related to prematurity is essential. The need for pain management for humanitarian care is widely advocated. Non-pharmacological interventions to help parents reduce their infant’s stress may be brain-protective.

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

    National Research Council Canada - National Science Library

    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...

  12. Repair of neonatal brain injury : bringing stem cell-based therapy into clinical practice

    NARCIS (Netherlands)

    Wagenaar, Nienke; Nijboer, Cora H.; van Bel, Frank

    2017-01-01

    Hypoxic-ischaemic brain injury is one of most important causes of neonatal mortality and long-term neurological morbidity in infants born at term. At present, only hypothermia in infants with perinatal hypoxic-ischaemic encephalopathy has shown benefit as a neuroprotective strategy. Otherwise,

  13. Neuroprotective Effect of Dexmedetomidine on Hyperoxia-Induced Toxicity in the Neonatal Rat Brain

    Directory of Open Access Journals (Sweden)

    Marco Sifringer

    2015-01-01

    Full Text Available Dexmedetomidine is a highly selective agonist of α2-receptors with sedative, anxiolytic, analgesic, and anesthetic properties. Neuroprotective effects of dexmedetomidine have been reported in various brain injury models. In the present study, we investigated the effects of dexmedetomidine on neurodegeneration, oxidative stress markers, and inflammation following the induction of hyperoxia in neonatal rats. Six-day-old Wistar rats received different concentrations of dexmedetomidine (1, 5, or 10 µg/kg bodyweight and were exposed to 80% oxygen for 24 h. Sex-matched littermates kept in room air and injected with normal saline or dexmedetomidine served as controls. Dexmedetomidine pretreatment significantly reduced hyperoxia-induced neurodegeneration in different brain regions of the neonatal rat. In addition, dexmedetomidine restored the reduced/oxidized glutathione ratio and attenuated the levels of malondialdehyde, a marker of lipid peroxidation, after exposure to high oxygen concentration. Moreover, administration of dexmedetomidine induced downregulation of IL-1β on mRNA and protein level in the developing rat brain. Dexmedetomidine provides protections against toxic oxygen induced neonatal brain injury which is likely associated with oxidative stress signaling and inflammatory cytokines. Our results suggest that dexmedetomidine may have a therapeutic potential since oxygen administration to neonates is sometimes inevitable.

  14. Magnetic resonance imaging of the brain in neonates. Preliminary results

    International Nuclear Information System (INIS)

    Dumoulin, M.; Legrand, M.; Gremillet, C.; Lecouffe, P.; Rousseau, J.; Pruvo, J.P.; Marchandise, X.

    1991-01-01

    The place of neonatal cerebral MRI and its specific contribution compared with conventional imaging techniques were evaluated in 36 patients. The difficulties specific to the patient population studied met during this preliminary period are described, with their local solutions. A preliminary evaluation of the diagnostic and prognostic value of MRI according to the disease state and gestational age is presented. The specific contribution of MRI compared with transfontanellar ultrasonography and CT scan is discussed [fr

  15. Hypoglycemia is associated with increased risk for brain injury and adverse neurodevelopmental outcome in neonates at risk for encephalopathy.

    Science.gov (United States)

    Tam, Emily W Y; Haeusslein, Laurel A; Bonifacio, Sonia L; Glass, Hannah C; Rogers, Elizabeth E; Jeremy, Rita J; Barkovich, A James; Ferriero, Donna M

    2012-07-01

    To investigate the contribution of hypoglycemia in the first 24 hours after birth to brain injury in term newborns at risk for neonatal encephalopathy. A prospective cohort of 94 term neonates born between 1994 and 2010 with early postnatal brain magnetic resonance imaging studies were analyzed for regions of brain injury. Neurodevelopmental outcome was assessed at 1 year of age. Hypoglycemia (glucose encephalopathy with increased corticospinal tract injury and adverse motor and cognitive outcomes. Copyright © 2012 Mosby, Inc. All rights reserved.

  16. Functional neuroanatomy of executive function after neonatal brain injury in adults who were born very preterm.

    Directory of Open Access Journals (Sweden)

    Anastasia K Kalpakidou

    Full Text Available Individuals who were born very preterm (VPT; <33 gestational weeks are at risk of experiencing deficits in tasks involving executive function in childhood and beyond. In addition, the type and severity of neonatal brain injury associated with very preterm birth may exert differential effects on executive functioning by altering its neuroanatomical substrates. Here we addressed this question by investigating with functional magnetic resonance imaging (fMRI the haemodynamic response during executive-type processing using a phonological verbal fluency and a working memory task in VPT-born young adults who had experienced differing degrees of neonatal brain injury. 12 VPT individuals with a history of periventricular haemorrhage and ventricular dilatation (PVH+VD, 17 VPT individuals with a history of uncomplicated periventricular haemorrhage (UPVH, 13 VPT individuals with no history of neonatal brain injury and 17 controls received an MRI scan whilst completing a verbal fluency task with two cognitive loads ('easy' and 'hard' letters. Two groups of VPT individuals (PVH+VD; n = 10, UPVH; n = 8 performed an n-back task with three cognitive loads (1-, 2-, 3-back. Results demonstrated that VPT individuals displayed hyperactivation in frontal, temporal, and parietal cortices and in caudate nucleus, insula and thalamus compared to controls, as demands of the verbal fluency task increased, regardless of type of neonatal brain injury. On the other hand, during the n-back task and as working memory load increased, the PVH+VD group showed less engagement of the frontal cortex than the UPVH group. In conclusion, this study suggests that the functional neuroanatomy of different executive-type processes is altered following VPT birth and that neural activation associated with specific aspects of executive function (i.e., working memory may be particularly sensitive to the extent of neonatal brain injury.

  17. Optimising nutrition to improve growth and reduce neurodisabilities in neonates at risk of neurological impairment, and children with suspected or confirmed cerebral palsy.

    Science.gov (United States)

    Andrew, Morag J; Parr, Jeremy R; Montague-Johnson, Chris; Braddick, Oliver; Laler, Karen; Williams, Nicola; Baker, Bonny; Sullivan, Peter B

    2015-03-17

    Neurological impairment is a common sequelae of perinatal brain injury. Plasticity of the developing brain is due to a rich substrate of developing neurones, synaptic elements and extracellular matrix. Interventions supporting this inherent capacity for plasticity may improve the developmental outcome of infants following brain injury. Nutritional supplementation with combination docosahexaenoic acid, uridine and choline has been shown to increase synaptic elements, dendritic density and neurotransmitter release in rodents, improving performance on cognitive tests. It remains elusive whether such specific 'neurotrophic' supplementation enhances brain plasticity and repair after perinatal brain injury. This is a two year double-blind, randomised placebo controlled study with two cohorts to investigate whether nutritional intervention with a neurotrophic dietary supplement improves growth and neurodevelopmental outcomes in neonates at significant risk of neurological impairment (the D1 cohort), and infants with suspected or confirmed cerebral palsy (the D2 cohort). 120 children will be randomised to receive dietetic and nutritional intervention, and either active supplement or placebo. Eligible D1 neonates are those born Toddler Development III at 24 months. Secondary outcomes include visuobehavioural and visual neurophysiological assessments, and growth parameters including weight, height, and head circumference. This is the first study to supplement neonates and infants with perinatal brain injury with the combination of factors required for healthy brain development, throughout the period of maximal brain growth. A further study strength is the comprehensive range of outcome measures employed. If beneficial, supplementation with brain phosphatide precursors could improve the quality of life of thousands of children with perinatal brain injury. Current Controlled trials: ISRCTN39264076 (registration assigned 09/11/2012), ISRCTN15239951 (registration assigned 23/04/2010).

  18. Neonatal brain MRI: how reliable is the radiologist's eye?

    Energy Technology Data Exchange (ETDEWEB)

    Morel, B. [A. Trousseau Hospital APHP, Pediatric Radiology, Paris (France); LTCI, CNRS, Telecom ParisTech, Universite Paris-Saclay, Paris (France); Antoni, G.; Teglas, J.P. [INSERM, CESP Centre for Research in Epidemiology and Population Health, U1018, Reproduction and Child Development, Villejuif (France); Bloch, I. [LTCI, CNRS, Telecom ParisTech, Universite Paris-Saclay, Paris (France); Adamsbaum, C. [Paris Sud University, Pediatric Radiology Department Bicetre Hospital APHP, Faculty of Medicine, Paris (France)

    2016-02-15

    White matter (WM) analysis in neonatal brain magnetic resonance imaging (MRI) is challenging, as demonstrated by the issue of diffuse excessive high signal intensity (DEHSI). We evaluated the reliability of the radiologist's eye in this context. Three experienced observers graded the WM signal intensity on axial T2-weighted 1.5T images from 60 different premature newborns on 2 occasions 4 weeks apart with a semi-quantitative classification under identical viewing conditions. The intra- and inter-observer correlation coefficients were fair to moderate (Fleiss' kappa between 0.21 and 0.60). This is a serious limitation of which we need to be aware, as it can lead to contradictory conclusions in the challenging context of term-equivalent age brain MRI in premature infants. These results highlight the need for a semiautomatic tool to help in objectively analyzing MRI signal intensity in the neonatal brain. (orig.)

  19. Diffusion MRI of the neonate brain: acquisition, processing and analysis techniques

    Energy Technology Data Exchange (ETDEWEB)

    Pannek, Kerstin [University of Queensland, Centre for Clinical Research, Brisbane (Australia); University of Queensland, School of Medicine, Brisbane (Australia); University of Queensland, Centre for Advanced Imaging, Brisbane (Australia); Guzzetta, Andrea [IRCCS Stella Maris, Department of Developmental Neuroscience, Calambrone Pisa (Italy); Colditz, Paul B. [University of Queensland, Centre for Clinical Research, Brisbane (Australia); University of Queensland, Perinatal Research Centre, Brisbane (Australia); Rose, Stephen E. [University of Queensland, Centre for Clinical Research, Brisbane (Australia); University of Queensland, Centre for Advanced Imaging, Brisbane (Australia); University of Queensland Centre for Clinical Research, Royal Brisbane and Women' s Hospital, Brisbane (Australia)

    2012-10-15

    Diffusion MRI (dMRI) is a popular noninvasive imaging modality for the investigation of the neonate brain. It enables the assessment of white matter integrity, and is particularly suited for studying white matter maturation in the preterm and term neonate brain. Diffusion tractography allows the delineation of white matter pathways and assessment of connectivity in vivo. In this review, we address the challenges of performing and analysing neonate dMRI. Of particular importance in dMRI analysis is adequate data preprocessing to reduce image distortions inherent to the acquisition technique, as well as artefacts caused by head movement. We present a summary of techniques that should be used in the preprocessing of neonate dMRI data, and demonstrate the effect of these important correction steps. Furthermore, we give an overview of available analysis techniques, ranging from voxel-based analysis of anisotropy metrics including tract-based spatial statistics (TBSS) to recently developed methods of statistical analysis addressing issues of resolving complex white matter architecture. We highlight the importance of resolving crossing fibres for tractography and outline several tractography-based techniques, including connectivity-based segmentation, the connectome and tractography mapping. These techniques provide powerful tools for the investigation of brain development and maturation. (orig.)

  20. On the edge of language acquisition: inherent constraints on encoding multisyllabic sequences in the neonate brain.

    Science.gov (United States)

    Ferry, Alissa L; Fló, Ana; Brusini, Perrine; Cattarossi, Luigi; Macagno, Francesco; Nespor, Marina; Mehler, Jacques

    2016-05-01

    To understand language, humans must encode information from rapid, sequential streams of syllables - tracking their order and organizing them into words, phrases, and sentences. We used Near-Infrared Spectroscopy (NIRS) to determine whether human neonates are born with the capacity to track the positions of syllables in multisyllabic sequences. After familiarization with a six-syllable sequence, the neonate brain responded to the change (as shown by an increase in oxy-hemoglobin) when the two edge syllables switched positions but not when two middle syllables switched positions (Experiment 1), indicating that they encoded the syllables at the edges of sequences better than those in the middle. Moreover, when a 25 ms pause was inserted between the middle syllables as a segmentation cue, neonates' brains were sensitive to the change (Experiment 2), indicating that subtle cues in speech can signal a boundary, with enhanced encoding of the syllables located at the edges of that boundary. These findings suggest that neonates' brains can encode information from multisyllabic sequences and that this encoding is constrained. Moreover, subtle segmentation cues in a sequence of syllables provide a mechanism with which to accurately encode positional information from longer sequences. Tracking the order of syllables is necessary to understand language and our results suggest that the foundations for this encoding are present at birth. © 2015 John Wiley & Sons Ltd.

  1. Statistical language learning in neonates revealed by event-related brain potentials

    Directory of Open Access Journals (Sweden)

    Näätänen Risto

    2009-03-01

    Full Text Available Abstract Background Statistical learning is a candidate for one of the basic prerequisites underlying the expeditious acquisition of spoken language. Infants from 8 months of age exhibit this form of learning to segment fluent speech into distinct words. To test the statistical learning skills at birth, we recorded event-related brain responses of sleeping neonates while they were listening to a stream of syllables containing statistical cues to word boundaries. Results We found evidence that sleeping neonates are able to automatically extract statistical properties of the speech input and thus detect the word boundaries in a continuous stream of syllables containing no morphological cues. Syllable-specific event-related brain responses found in two separate studies demonstrated that the neonatal brain treated the syllables differently according to their position within pseudowords. Conclusion These results demonstrate that neonates can efficiently learn transitional probabilities or frequencies of co-occurrence between different syllables, enabling them to detect word boundaries and in this way isolate single words out of fluent natural speech. The ability to adopt statistical structures from speech may play a fundamental role as one of the earliest prerequisites of language acquisition.

  2. Neonatal brain hemorrhage (NBH) of prematurity: translational mechanisms of the vascular-neural network.

    Science.gov (United States)

    Lekic, Tim; Klebe, Damon; Poblete, Roy; Krafft, Paul R; Rolland, William B; Tang, Jiping; Zhang, John H

    2015-01-01

    Neonatal brain hemorrhage (NBH) of prematurity is an unfortunate consequence of preterm birth. Complications result in shunt dependence and long-term structural changes such as posthemorrhagic hydrocephalus, periventricular leukomalacia, gliosis, and neurological dysfunction. Several animal models are available to study this condition, and many basic mechanisms, etiological factors, and outcome consequences, are becoming understood. NBH is an important clinical condition, of which treatment may potentially circumvent shunt complication, and improve functional recovery (cerebral palsy, and cognitive impairments). This review highlights key pathophysiological findings of the neonatal vascular-neural network in the context of molecular mechanisms targeting the posthemorrhagic hydrocephalus affecting this vulnerable infant population.

  3. Neonatal Brain Hemorrhage (NBH) of Prematurity: Translational Mechanisms of the Vascular-Neural Network

    Science.gov (United States)

    Lekic, Tim; Klebe, Damon; Poblete, Roy; Krafft, Paul R.; Rolland, William B.; Tang, Jiping; Zhang, John H.

    2015-01-01

    Neonatal brain hemorrhage (NBH) of prematurity is an unfortunate consequence of preterm birth. Complications result in shunt dependence and long-term structural changes such as post-hemorrhagic hydrocephalus, periventricular leukomalacia, gliosis, and neurological dysfunction. Several animal models are available to study this condition, and many basic mechanisms, etiological factors, and outcome consequences, are becoming understood. NBH is an important clinical condition, of which treatment may potentially circumvent shunt complication, and improve functional recovery (cerebral palsy, and cognitive impairments). This review highlights key pathophysiological findings of the neonatal vascular-neural network in the context of molecular mechanisms targeting the post-hemorrhagic hydrocephalus affecting this vulnerable infant population. PMID:25620100

  4. Enterobacter sakazakii brain abscess in the neonate: the importance of neuroradiologic imaging

    International Nuclear Information System (INIS)

    Burdette, J.H.; Santos, C.

    2000-01-01

    Background. Enterobacter sakazakii is a rare but important cause of life-threatening neonatal sepsis and meningitis complicated by the development of brain abscess. Objective. Given the neurotropic qualities of this organism, early diagnosis and treatment are crucial as a poor prognosis follows brain abscess formation. Materials and methods. Cross-sectional imaging (CT and MRI) play an important role in the diagnostic work-up. Conclusion. A biopsy-proven case of E. sakazakii brain abscess, which was diagnosed on MR images, is presented, and the importance of prompt radiologic imaging of the central nervous system in the work-up of patients with this life-threatening disease is discussed. (orig.)

  5. Morphological features of the neonatal brain support development of subsequent cognitive, language, and motor abilities.

    Science.gov (United States)

    Spann, Marisa N; Bansal, Ravi; Rosen, Tove S; Peterson, Bradley S

    2014-09-01

    Knowledge of the role of brain maturation in the development of cognitive abilities derives primarily from studies of school-age children to adults. Little is known about the morphological features of the neonatal brain that support the subsequent development of abilities in early childhood, when maturation of the brain and these abilities are the most dynamic. The goal of our study was to determine whether brain morphology during the neonatal period supports early cognitive development through 2 years of age. We correlated morphological features of the cerebral surface assessed using deformation-based measures (surface distances) of high-resolution MRI scans for 33 healthy neonates, scanned between the first to sixth week of postmenstrual life, with subsequent measures of their motor, language, and cognitive abilities at ages 6, 12, 18, and 24 months. We found that morphological features of the cerebral surface of the frontal, mesial prefrontal, temporal, and occipital regions correlated with subsequent motor scores, posterior parietal regions correlated with subsequent language scores, and temporal and occipital regions correlated with subsequent cognitive scores. Measures of the anterior and middle portions of the cingulate gyrus correlated with scores across all three domains of ability. Most of the significant findings were inverse correlations located bilaterally in the brain. The inverse correlations may suggest either that a more protracted morphological maturation or smaller local volumes of neonatal brain tissue supports better performance on measures of subsequent motor, language, and cognitive abilities throughout the first 2 years of postnatal life. The correlations of morphological measures of the cingulate with measures of performance across all domains of ability suggest that the cingulate supports a broad range of skills in infancy and early childhood, similar to its functions in older children and adults. Copyright © 2014 Wiley Periodicals, Inc.

  6. Growth evaluation in infants with neonatal cholestasis Antropometria em crianças com colestase neonatal

    Directory of Open Access Journals (Sweden)

    Camila Carbone Prado

    2006-12-01

    Full Text Available BACKGROUD: Chronic liver diseases in childhood often cause undernutrition and growth failure. To our knowledge, growth parameters in infants with neonatal cholestasis are not available AIM: To evaluate the nutritional status and growth pattern in infants with intrahepatic cholestasis and extrahepatic cholestasis. PATIENTS AND METHODS: One hundred forty-four patients with neonatal cholestasis were followed up at the Pediatric Gastroenterology Service of the Teaching Hospital, State University of Campinas, Campinas, SP, Brazil, in a 23-year period, from 1980 to 2003. The records of these patients were reviewed and patients were classified into two groups, according to their anatomical diagnosis: patients with intrahepatic cholestasis - group 1, and patients with extrahepatic cholestasis - group 2. Records of weight and height measurements were collected at 4 age stages of growth, in the first year of life: 1 from the time of the first medical visit to the age of 4 months (T1; 2 from the 5th to the 7th month (T2; 3 from the 8th to the 10th month (T3; and 4 from the 11th to the 13th month (T4. The weight-by-age and height-by-age Z-scores were calculated for each patient at each stage. In order for the patient to be included in the study it was necessary to have the weight and/or height measurements at the 4 stages. Analyses of variance and Tukey's tests were used for statistical analysis. Repeated measurement analyses of variance of the weight-by-age Z-score were performed in a 60-patient sample, including 29 patients from group 1 and 31 patients from group 2. The height-by-age data of 33 patients were recorded, 15 from group 1 and 18 from group 2 RESULTS: The mean weight-by-age Z-scores of group 1 patients at the 4 age stages were: T1=-1.54; T2=-1.40; T3=-0.94; T4=-0.78. There was a significant difference between T2 X T3 and T1 X T4. The weight-by-age Z-scores for group 2 patients were :T1=-1.04; T2=-1.67; T3=-1.93 and T4=-1.77, with a significant

  7. Intrauterine Growth Restriction Impairs Small Intestinal Mucosal Immunity in Neonatal Piglets

    Science.gov (United States)

    Dong, Li; Zhong, Xiang; Ahmad, Hussain; Li, Wei; Wang, Yuanxiao; Zhang, Lili

    2014-01-01

    Intrauterine growth restriction (IUGR) is a very common problem in both piglet and human neonate populations. We hypothesized that IUGR neonates have impaired intestinal mucosal immunity from birth. Using neonatal piglets as IUGR models, immune organ weights, the weight and length of the small intestine (SI), intestinal morphology, intraepithelial immune cell numbers, levels of cytokines and immunoglobulins, and the relative gene expression of cytokines in the SI were investigated. IUGR neonatal piglets were observed to have lower absolute immune organ weight and SI length, decreased relative weights of the thymus, spleen, mesenteric lymph node, and thinner but longer SIs. Damaged and jagged villi, shorter microvilli, presence of autophagosomes, swelled mitochondria, and decreased villus surface areas were also found in the SIs of IUGR neonatal piglets. We also found a smaller number of epithelial goblet cells and lymphocytes in the SIs of IUGR neonates. In addition, we detected reduced levels of the cytokines TNF-α and IFN-γ and decreased gene expression of cytokines in IUGR neonates. In conclusion, IUGR was shown to impair the mucosal immunity of the SI in neonatal piglets, and the ileum was the major site of impairment. PMID:24710659

  8. Neonatal intensive care practices harmful to the developing brain.

    Science.gov (United States)

    Chaudhari, Sudha

    2011-06-01

    There has been a marked increase in the survival of extremely low birth weight (ELBW) infants, but these babies have a long stay in the NICU. Strategies to decrease their neurodevelopmental impairment become very important. The maximum development of the brain occurs between 29-41 weeks. From the warm, dark, acquatic econiche, where the baby hears pleasant sounds like the mother's heart beat, the baby suddenly finds itself in the dry, cold, excessively bright, noisy, environment of the NICU. Noise, bright light, painful procedures, and ill-timed caregiving activities, adversely affect the infant's development. Excessive radiation from X-rays of babies on the ventilator and CT scans also affect the brain. Medications like steroids for chronic lung disease also cause damage to the brain. Aminoglycides and frusemide are known to cause hearing impairment. Hence a developmentally supportive, humanized care will go a long way in enhancing the developmental outcome of these babies.

  9. Impact of prolonged leucine supplementation on protein synthesis and lean growth in neonatal pigs

    Science.gov (United States)

    Most low-birth weight infants experience extrauterine growth failure due to reduced nutrient intake as a result of feeding intolerance. The objective of this study was to determine whether prolonged enteral leucine supplementation improves lean growth in neonatal pigs fed a restricted protein diet. ...

  10. Neonatal Brain Abnormalities and Memory and Learning Outcomes at 7 Years in Children Born Very Preterm

    Science.gov (United States)

    Omizzolo, Cristina; Scratch, Shannon E; Stargatt, Robyn; Kidokoro, Hiroyuki; Thompson, Deanne K; Lee, Katherine J; Cheong, Jeanie; Neil, Jeffrey; Inder, Terrie E; Doyle, Lex W; Anderson, Peter J

    2014-01-01

    Using prospective longitudinal data from 198 very preterm and 70 full term children, this study characterised the memory and learning abilities of very preterm children at 7 years of age in both verbal and visual domains. The relationship between the extent of brain abnormalities on neonatal magnetic resonance imaging (MRI) and memory and learning outcomes at 7 years of age in very preterm children was also investigated. Neonatal MRI scans were qualitatively assessed for global, white-matter, cortical grey-matter, deep grey-matter, and cerebellar abnormalities. Very preterm children performed less well on measures of immediate memory, working memory, long-term memory, and learning compared with term born controls. Neonatal brain abnormalities, and in particular deep grey matter abnormality, were associated with poorer memory and learning performance at 7 years in very preterm children, especially global, white-matter, grey-matter and cerebellar abnormalities. Findings support the importance of cerebral neonatal pathology for predicting later memory and learning function. PMID:23805915

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

    Science.gov (United States)

    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.

  12. Neuroprotective effects of Ellagic acid on Neonatal Hypoxic Brain ...

    African Journals Online (AJOL)

    Purpose: To investigate if ellagic acid exerts neuroprotective effects in hypoxic ischemic (HI) brain injury by inhibiting apoptosis and inflammatory responses. Methods: Separate groups of rat pups from post-natal day 4 (D4) were administered with ellagic acid (10, 20 or 40 mg/kg body weight) orally till post- natal day 10 ...

  13. Glucocorticoids Protect Neonatal Rat Brain in Model of Hypoxic-Ischemic Encephalopathy (HIE

    Directory of Open Access Journals (Sweden)

    Benjamin Harding

    2016-12-01

    Full Text Available Hypoxic-ischemic encephalopathy (HIE resulting from asphyxia in the peripartum period is the most common cause of neonatal brain damage and can result in significant neurologic sequelae, including cerebral palsy. Currently therapeutic hypothermia is the only accepted treatment in addition to supportive care for infants with HIE, however, many additional neuroprotective therapies have been investigated. Of these, glucocorticoids have previously been shown to have neuroprotective effects. HIE is also frequently compounded by infectious inflammatory processes (sepsis and as such, the infants may be more amenable to treatment with an anti-inflammatory agent. Thus, the present study investigated dexamethasone and hydrocortisone treatment given after hypoxic-ischemic (HI insult in neonatal rats via intracerebroventricular (ICV injection and intranasal administration. In addition, we examined the effects of hydrocortisone treatment in HIE after lipopolysaccharide (LPS sensitization in a model of HIE and sepsis. We found that dexamethasone significantly reduced rat brain infarction size when given after HI treatment via ICV injection; however it did not demonstrate any neuroprotective effects when given intranasally. Hydrocortisone after HI insult also significantly reduced brain infarction size when given via ICV injection; and the intranasal administration showed to be protective of brain injury in male rats at a dose of 300 µg. LPS sensitization did significantly increase the brain infarction size compared to controls, and hydrocortisone treatment after LPS sensitization showed a significant decrease in brain infarction size when given via ICV injection, as well as intranasal administration in both genders at a dose of 300 µg. To conclude, these results show that glucocorticoids have significant neuroprotective effects when given after HI injury and that these effects may be even more pronounced when given in circumstances of additional

  14. A Novel Dynamic Neonatal Blood-Brain Barrier on a Chip.

    Directory of Open Access Journals (Sweden)

    Sudhir P Deosarkar

    Full Text Available Studies of neonatal neural pathologies and development of appropriate therapeutics are hampered by a lack of relevant in vitro models of neonatal blood-brain barrier (BBB. To establish such a model, we have developed a novel blood-brain barrier on a chip (B3C that comprises a tissue compartment and vascular channels placed side-by-side mimicking the three-dimensional morphology, size and flow characteristics of microvessels in vivo. Rat brain endothelial cells (RBEC isolated from neonatal rats were seeded in the vascular channels of B3C and maintained under shear flow conditions, while neonatal rat astrocytes were cultured under static conditions in the tissue compartment of the B3C. RBEC formed continuous endothelial lining with a central lumen along the length of the vascular channels of B3C and exhibited tight junction formation, as measured by the expression of zonula occludens-1 (ZO-1. ZO-1 expression significantly increased with shear flow in the vascular channels and with the presence of astrocyte conditioned medium (ACM or astrocytes cultured in the tissue compartment. Consistent with in vivo BBB, B3C allowed endfeet-like astrocyte-endothelial cell interactions through a porous interface that separates the tissue compartment containing cultured astrocytes from the cultured RBEC in the vascular channels. The permeability of fluorescent 40 kDa dextran from vascular channel to the tissue compartment significantly decreased when RBEC were cultured in the presence of astrocytes or ACM (from 41.0 ± 0.9 x 10-6 cm/s to 2.9 ± 1.0 x 10-6 cm/s or 1.1±0.4 x 10-6 cm/s, respectively. Measurement of electrical resistance in B3C further supports that the addition of ACM significantly improves the barrier function in neonatal RBEC. Moreover, B3C exhibits significantly improved barrier characteristics compared to the transwell model and B3C permeability was not significantly different from the in vivo BBB permeability in neonatal rats. In summary, we

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

    Science.gov (United States)

    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

  16. Plasma Brain-Derived Neurotrophic Factor Levels in Newborn Infants with Neonatal Abstinence Syndrome.

    Science.gov (United States)

    Subedi, Lochan; Huang, Hong; Pant, Amrita; Westgate, Philip M; Bada, Henrietta S; Bauer, John A; Giannone, Peter J; Sithisarn, Thitinart

    2017-01-01

    Brain-derived neurotrophic factor (BDNF) is a type of growth factor that promotes growth and survival of neurons. Fetal exposure to opiates can lead to postnatal withdrawal syndrome, which is referred as neonatal abstinence syndrome (NAS). Preclinical and clinical studies have shown an association between opiates exposure and alteration in BDNF expression in the brain and serum levels in adult. However, to date, there are no data available on the effects of opiate exposure on BDNF levels in infant who are exposed to opiates in utero and whether BDNF level may correlate with the severity of NAS. To compare plasma BDNF levels among NAS and non-NAS infants and to determine the correlation of BDNF levels and the severity of NAS. This is a prospective cohort study with no intervention involved. Infants ≥35 weeks of gestation were enrolled. BDNF level was measured using enzyme-linked immunosorbent assay technique from blood samples drawn within 48 h of life. The severity of NAS was determined by the length of hospital stay, number of medications required to treat NAS. 67 infants were enrolled, 34 NAS and 33 non-NAS. Mean gestational age did not differ between the two groups. Mean birth weight of NAS infants was significantly lower than the non-NAS infants (3,070 ± 523 vs. 3,340 ± 459 g, p  = 0.028). Mean BDNF level in NAS group was 252.2 ± 91.6 ng/ml, significantly higher than 211.3 ± 66.3 ng/ml in the non-NAS group ( p  = 0.04). There were no differences in BDNF levels between NAS infants that required one medication vs. more than one medication (254 ± 91 vs. 218 ± 106 ng/ml, p  = 0.47). There was no correlation between the BDNF levels and length of hospital stay ( p  = 0.68) among NAS infants. Overall, there were no significant correlations between BDNF levels and NAS scores except at around 15 h after admission (correlation 0.35, p  = 0.045). Plasma BDNF level was significantly increased in NAS infants

  17. Biomarkers of brain injury in neonatal encephalopathy treated with hypothermia.

    Science.gov (United States)

    Massaro, An N; Chang, Taeun; Kadom, Nadja; Tsuchida, Tammy; Scafidi, Joseph; Glass, Penny; McCarter, Robert; Baumgart, Stephen; Vezina, Gilbert; Nelson, Karin B

    2012-09-01

    To determine if early serum S100B and neuron-specific enolase (NSE) levels are associated with neuroradiographic and clinical evidence of brain injury in newborns with encephalopathy. Patients who received therapeutic whole-body hypothermia were prospectively enrolled in this observational study. Serum specimens were collected at 0, 12, 24, and 72 hours of cooling. S100B and NSE levels were measured by enzyme linked immunosorbent assay. Magnetic resonance imaging was performed in surviving infants at 7-10 days of life. Standardized neurologic examination was performed by a child neurologist at 14 days of life. Multiple linear regression analyses were performed to evaluate the association between S100B and NSE levels and unfavorable outcome (death or severe magnetic resonance imaging injury/significant neurologic deficit). Cutoff values were determined by receiver operating curve analysis. Newborns with moderate to severe encephalopathy were enrolled (n = 75). Median pH at presentation was 6.9 (range, 6.5-7.35), and median Apgar scores of 1 at 1 minute, 3 at 5 minutes, and 5 at 10 minutes. NSE and S100B levels were higher in patients with unfavorable outcomes across all time points. These results remained statistically significant after controlling for covariables, including encephalopathy grade at presentation, Apgar score at 5 minutes of life, initial pH, and clinical seizures. Elevated serum S100B and NSE levels measured during hypothermia were associated with neuroradiographic and clinical evidence of brain injury in encephalopathic newborns. These brain-specific proteins may be useful immediate biomarkers of cerebral injury severity. Copyright © 2012 Mosby, Inc. All rights reserved.

  18. USE OF DIFFUSION-WEIGHTED MAGNETIC RESONANCE IMAGING FOR REVEALING HYPOXIC-ISCHEMIC BRAIN LESIONS IN NEONATES

    Directory of Open Access Journals (Sweden)

    E. V. Shimchenko

    2014-01-01

    Full Text Available The article presents advantages of use of diffusion-weighted magnetic resonance imaging (DW MRI for revealing hypoxic-ischemic brain lesions in neonates. The trial included 97 neonates with perinatal brain lesion who had been undergoing treatment at a resuscitation department or neonatal pathology department in the first month of life. The article shows high information value of diffusion-weighted images (DWI for diagnostics of hypoxic-ischemic lesions in comparison with regular standard modes. In the event of no structural brain lesions of neonates, pronounced increase in signal characteristics revealed by DWI indicated considerable pathophysiological alterations. Subsequently, children developed structural alterations in the form of cystic encephalomalacia with expansion of cerebrospinal fluid spaces manifested with pronounced neurological deficit. DW MRI has been offered as a method of prognosticating further neurological development of children on early stages. 

  19. Evaluation of neonatal brain myelination using the T1- and T2-weighted MRI ratio.

    Science.gov (United States)

    Soun, Jennifer E; Liu, Michael Z; Cauley, Keith A; Grinband, Jack

    2017-09-01

    To validate the T1- and T2-weighted (T1w/T2w) MRI ratio technique in evaluating myelin in the neonatal brain. T1w and T2w MR images of 10 term neonates with normal-appearing brain parenchyma were obtained from a single 1.5 Tesla MRI and retrospectively analyzed. T1w/T2w ratio images were created with a postprocessing pipeline and qualitatively compared with standard clinical sequences (T1w, T2w, and apparent diffusion coefficient [ADC]). Quantitative assessment was also performed to assess the ratio technique in detecting areas of known myelination (e.g., posterior limb of the internal capsule) and very low myelination (e.g., optic radiations) using linear regression analysis and the Michelson Contrast equation, a measure of luminance contrast intensity. The ratio image provided qualitative improvements in the ability to visualize regional variation in myelin content of neonates. Linear regression analysis demonstrated a significant inverse relationship between the ratio intensity values and ADC values in the posterior limb of the internal capsule and the optic radiations (R 2  = 0.96 and P ratio images were 1.6 times higher than T1w, 2.6 times higher than T2w, and 1.8 times higher than ADC (all P ratio improved visualization of the corticospinal tract, one of the earliest myelinated pathways. The T1w/T2w ratio accentuates contrast between myelinated and less myelinated structures and may enhance our diagnostic ability to detect myelination patterns in the neonatal brain. 2 Technical Efficacy: Stage2 J. MAGN. RESON. IMAGING 2017;46:690-696. © 2016 International Society for Magnetic Resonance in Medicine.

  20. The role of growth retardation in lasting effects of neonatal dexamethasone treatment on hippocampal synaptic function.

    Directory of Open Access Journals (Sweden)

    Yu-Chen Wang

    Full Text Available BACKGROUND: Dexamethasone (DEX, a synthetic glucocorticoid, is commonly used to prevent or lessen the morbidity of chronic lung disease in preterm infants. However, evidence is now increasing that this clinical practice negatively affects somatic growth and may result in long-lasting neurodevelopmental deficits. We therefore hypothesized that supporting normal somatic growth may overcome the lasting adverse effects of neonatal DEX treatment on hippocampal function. METHODOLOGY/PRINCIPAL FINDINGS: To test this hypothesis, we developed a rat model using a schedule of tapering doses of DEX similar to that used in premature infants and examined whether the lasting influence of neonatal DEX treatment on hippocampal synaptic plasticity and memory performance are correlated with the deficits in somatic growth. We confirmed that neonatal DEX treatment switched the direction of synaptic plasticity in hippocampal CA1 region, favoring low-frequency stimulation- and group I metabotropic glutamate receptor agonist (S-3,5,-dihydroxyphenylglycine-induced long-term depression (LTD, and opposing the induction of long-term potentiation (LTP by high-frequency stimulation in the adolescent period. The effects of DEX on LTP and LTD were correlated with an increase in the autophosphorylation of Ca(2+/calmodulin-dependent protein kinase II at threonine-286 and a decrease in the protein phosphatase 1 expression. Neonatal DEX treatment resulted in a disruption of memory retention subjected to object recognition task and passive avoidance learning. The adverse effects of neonatal DEX treatment on hippocampal synaptic plasticity and memory performance of the animals from litters culled to 4 pups were significantly less than those for the 8-pup litters. However, there was no significant difference in maternal care between groups. CONCLUSION/SIGNIFICANCE: Our results demonstrate that growth retardation plays a crucial role in DEX-induced long-lasting influence of

  1. Neuroprotective actions of taurine on hypoxic-ischemic brain damage in neonatal rats.

    Science.gov (United States)

    Zhu, Xiao-Yun; Ma, Peng-Sheng; Wu, Wei; Zhou, Ru; Hao, Yin-Ju; Niu, Yang; Sun, Tao; Li, Yu-Xiang; Yu, Jian-Qiang

    2016-06-01

    Taurine is an abundant amino acid in the nervous system, which has been proved to possess antioxidation, osmoregulation and membrane stabilization. Previously it has been demonstrated that taurine exerts ischemic brain injury protective effect. This study was designed to investigate whether the protective effect of taurine has the possibility to be applied to treat neonatal hypoxic-ischemic brain damage. Seven-day-old Sprague-Dawley rats were treated with left carotid artery ligation followed by exposure to 8% oxygen to generate the experimental group. The cerebral damage area was measured after taurine post-treatment with 2,3,5-triphenyltetrazolium chloride (TTC) staining, Hematoxyline-Eosin (HE) staining and Nissl staining. The activities of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), myeloperoxtidase (MPO), ATP and Lactic Acid productions were assayed with ipsilateral hemisphere homogenates. Western-blot and immunofluorescence assay were processed to detect the expressions of AIF, Cyt C, Bax, Bcl-2 in brain. We found that taurine significantly reduced brain infarct volume and ameliorated morphological injury obviously reversed the changes of SOD, MDA, GSH-Px, T-AOC, ATP, MPO, and Lactic Acid levels. Compared with hypoxic-ischemic group, it showed marked reduction of AIF, Cyt C and Bax expressions and increase of Bcl-2 after post-treatment. We conclude that taurine possesses an efficacious neuroprotective effect after cerebral hypoxic-ischemic damage in neonatal rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Apolipoprotein E Genotype in Very Preterm Neonates with Intrauterine Growth Restriction: An Analysis of the German Neonatal Network Cohort

    Directory of Open Access Journals (Sweden)

    Stephen Norda

    2017-01-01

    Full Text Available Aim. Cord blood of intrauterine growth restricted (IUGR neonates displays lipid changes towards atherosclerotic profiles. Apolipoprotein E (ApoE and its isoforms (e2, e3, and e4 are involved in the regulation of lipid metabolism. Specifically, ApoE e4 has been associated with atherosclerotic diseases, while e2 has a favorable effect. We therefore hypothesized that ApoE e4 haplotype is frequently observed in IUGR neonates and contributes to impaired fetal growth and the association of IUGR with cardiovascular and metabolic diseases later in life. Methods. A cohort of 4885 preterm infants (≥22+0 and 10th birth weight percentile. Analysis of the single nucleotides rs429358 and rs7412, identifying the ApoE genotype, was carried out using TaqMan® SNP genotyping assays. The proportional odds model was used to assess data. Results. No association was found between genotype and birth weight percentiles in each of the subgroups. Conclusion. ApoE genotype and low birth weight depict two distinct risk factors for cardiovascular disease without being directly associated.

  3. Apolipoprotein E Genotype in Very Preterm Neonates with Intrauterine Growth Restriction: An Analysis of the German Neonatal Network Cohort.

    Science.gov (United States)

    Norda, Stephen; Rausch, Tanja K; Orlikowsky, Thorsten; Hütten, Matthias; Schulz, Sören; Göpel, Wolfgang; Pecks, Ulrich

    2017-01-01

    Aim. Cord blood of intrauterine growth restricted (IUGR) neonates displays lipid changes towards atherosclerotic profiles. Apolipoprotein E (ApoE) and its isoforms (e2, e3, and e4) are involved in the regulation of lipid metabolism. Specifically, ApoE e4 has been associated with atherosclerotic diseases, while e2 has a favorable effect. We therefore hypothesized that ApoE e4 haplotype is frequently observed in IUGR neonates and contributes to impaired fetal growth and the association of IUGR with cardiovascular and metabolic diseases later in life. Methods. A cohort of 4885 preterm infants (≥22+0 and 10th birth weight percentile. Analysis of the single nucleotides rs429358 and rs7412, identifying the ApoE genotype, was carried out using TaqMan® SNP genotyping assays. The proportional odds model was used to assess data. Results. No association was found between genotype and birth weight percentiles in each of the subgroups. Conclusion. ApoE genotype and low birth weight depict two distinct risk factors for cardiovascular disease without being directly associated.

  4. Neonatal morbidity after induction vs expectant monitoring in intrauterine growth restriction at term: a subanalysis of the DIGITAT RCT

    NARCIS (Netherlands)

    Boers, Kim E.; van Wyk, Linda; van der Post, Joris A. M.; Kwee, Anneke; van Pampus, Maria G.; Spaanderdam, Marc E. A.; Duvekot, Johannes J.; Bremer, Henk A.; Delemarre, Friso M. C.; Bloemenkamp, Kitty W. M.; de Groot, Christianne J. M.; Willekes, Christine; Rijken, Monique; Roumen, Frans J. M. E.; Thornton, Jim G.; van Lith, Jan M. M.; Mol, Ben W. J.; le Cessie, Saskia; Scherjon, Sicco A.

    2012-01-01

    OBJECTIVE: The Disproportionate Intrauterine Growth Intervention Trial at Term (DIGITAT) compared induction of labor and expectant management in suspected intrauterine growth restriction (IUGR) at term. In this subanalysis, we report neonatal morbidity between the policies based on the Morbidity

  5. Volumetric analysis of the normal infant brain and in intrauterine growth retardation

    DEFF Research Database (Denmark)

    Toft, P B; Leth, H; Ring, P B

    1995-01-01

    and the volumes were determined by encircling each structure of interest on every slice. Segmentation into grey matter, white matter and CSF was done by semi-automatic discriminant analysis. Growth charts for the cerebrum, cerebellum, corpora striata, thalami, ventricles, and grey and white matter are provided...... for infants with appropriate birth weight. The striatal (P = 0.02) and thalamic (P matter to white matter (G/W-ratio) increased (P = 0.01). In the neonatal patients, brain volumes were independently associated...... growth retardation reduces grey matter volume more than white matter....

  6. Dynamic changes in water ADC, energy metabolism, extracellular space volume and tortuosity in neonatal rat brain during irreversible ischemia

    NARCIS (Netherlands)

    Toorn, van der A.; Syková, E.; Dijkhuizen, R.M.; Voríšek, I.; Vargová, L.; Skobisová, E.; Lookeren Campagne, van M.; Reese, T.; Nicolaij, K.

    1996-01-01

    To obtain a better understanding of the mechanisms underlying early changes in the brain water apparent diffusion coefficient (ADC) observed in cerebral ischemia, dynamic changes in the ADC of water and in the energy status were measured at postnatal day 8 or 9 in neonatal rat brains after cardiac

  7. Increased Viral Dissemination in the Brain and Lethality in MCMV-Infected, Dicer-Deficient Neonates

    Directory of Open Access Journals (Sweden)

    Eleonore Ostermann

    2015-05-01

    Full Text Available Among Herpesviruses, Human Cytomegalovirus (HCMV or HHV-5 represents a major threat during congenital or neonatal infections, which may lead to encephalitis with serious neurological consequences. However, as opposed to other less prevalent pathogens, the mechanisms and genetic susceptibility factors for CMV encephalitis are poorly understood. This lack of information considerably reduces the prognostic and/or therapeutic possibilities. To easily monitor the effects of genetic defects on brain dissemination following CMV infection we used a recently developed in vivo mouse model based on the neonatal inoculation of a MCMV genetically engineered to express Luciferase. Here, we further validate this protocol for live imaging, and demonstrate increased lethality associated with viral infection and encephalitis in mutant mice lacking Dicer activity. Our data indicate that miRNAs are important players in the control of MCMV pathogenesis and suggest that miRNA-based endothelial functions and integrity are crucial for CMV encephalitis.

  8. Brain Biomarkers of Long-Term Outcome of Neonatal Onset Urea Cycle Disorder

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    Maha Mourad

    2016-11-01

    Full Text Available Urea cycle disorders (UCDs are common inborn errors of metabolism, with an incidence of one in 30,000 births. They are caused by deficiencies in any of six enzymes and two carrier proteins, the most common being Ornithine Transcarbamylase Deficiency (OTCD. OTCD results in impairment to excrete nitrogen, causing toxic buildup of ammonia with resultant encephalopathy. Hyperammonemia (HA induces the conversion of glutamate to glutamine in the brain. Excess glutamine in the brain causes osmotic changes, cerebral edema, changes in astrocyte morphology, and cell death. Acute symptoms of HA include vomiting, hyperventilation, seizures, and irritability. Long-term neurological effects include deficits in working memory and executive function. To date, there are no predictors of prognosis of infants with neonatal onset OTCD outside of the plasma ammonia level at presentation and duration of a hyperammonemic coma. We provide a comprehensive analysis of a 16-year-old male with neonatal onset of OTCD as an example of how brain biomarkers may be useful to monitor disease course and outcome. This male presented at 8 days of life with plasma ammonia and glutamine of 677 and 4024 micromol/L respectively, and was found to have a missense mutation in Exon 4 (p. R129H. Treatment included protein restriction, sodium benzoate, and citrulline, arginine, and iron. Despite compliance, he suffered recurrent acute hyperammonemic episodes triggered by infections or catabolic stressors. We discuss the long-term effects of the hyperammonemic episodes by following MRI-based disease biomarkers.

  9. Sex-related differences in effects of progesterone following neonatal hypoxic brain injury.

    Science.gov (United States)

    Peterson, Bethany L; Won, Soonmi; Geddes, Rastafa I; Sayeed, Iqbal; Stein, Donald G

    2015-06-01

    There is no satisfactory therapeutic intervention for neonatal hypoxic-ischemic (HI) encephalopathy. Progesterone is known to be effective in treating traumatic brain injury in adult animals but its effects in neonatal brains have not been reported. Brain injuries were induced by a unilateral common carotid artery ligation plus hypoxia exposure. Progesterone was administered immediately after hypoxia and daily for 5 days at 8 mg/kg, followed by a tapered dose for two days. At six weeks post-injury, lesion size and inflammatory factors were evaluated. Progesterone-treated, HI-injured male animals, but not females, showed significant long-term tissue protection compared to vehicle, suggesting an important sex difference in neuroprotection. Progesterone-treated, HI-injured male rats had fewer activated microglia in the cortex and hippocampus compared to controls. The rats were tested for neurological reflexes, motor asymmetry, and cognitive performance at multiple time points. The injured animals exhibited few detectable motor deficits, suggesting a high level of age- and injury-related neuroplasticity. There were substantial sex differences on several behavioral tests, indicating that immature males and females should be analyzed separately. Progesterone-treated animals showed modest beneficial effects in both sexes compared to vehicle-treated injured animals. Sham animals given progesterone did not behave differently from vehicle-treated sham animals on any measures. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    OpenAIRE

    Morken, Tora Sund; Brekke, Eva Mari Førland; 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 duri...

  11. Astrogliosis in the neonatal and adult murine brain post-trauma

    DEFF Research Database (Denmark)

    Rostworowski, M; Balasingam, V; Chabot, S

    1997-01-01

    inflammatory cytokines in injury systems in which the presence or absence of astrogliosis could be produced selectively. A stab injury to the adult mouse brain using a piece of nitrocellulose (NC) membrane elicited a prompt and marked increase in levels of transcripts for interleukin (IL)-1alpha, IL-1beta......, and because its exogenous administration to rodents enhanced astrogliosis after adult or neonatal insults. A lack of requirement for endogenous IFN-gamma was demonstrated by three lines of evidence. First, no increase in IFN-gamma transcripts could be found at injury. Second, the administration...

  12. Interaction of neonatal irradiation and single-genes upon growth and behavior in mice

    International Nuclear Information System (INIS)

    Nash, D.J.

    1977-01-01

    Postnatal growth and behavior following neonatal irradiation were studied in congenic strains of mice. Mice were genetically similar except for single-gene substitutions at either the steel or dominant spotting loci. Adult behavior was measured by locomotion and elimination in the open field and by spontaneous activity in exercise wheels. In general, neonatal irradiation caused a decrease in body weight, activity in exercise wheels, and elimination in the open field, but an increase in locomotion in the open field. Significant differences due to genotype and sex were observed for locomotion and body weight. Differential responses of the genotypes to neonatal irradiation were observed in body weight and in activity in exercise wheels. The genotypes, in order of increasing sensitivity, were +/+, Wsup(a)/+, and Slsup(gb)/+. (author)

  13. Adenosine A1 receptors contribute to immune regulation after neonatal hypoxic ischemic brain injury.

    Science.gov (United States)

    Winerdal, Max; Winerdal, Malin E; Wang, Ying-Qing; Fredholm, Bertil B; Winqvist, Ola; Ådén, Ulrika

    2016-03-01

    Neonatal brain hypoxic ischemia (HI) often results in long-term motor and cognitive impairments. Post-ischemic inflammation greatly effects outcome and adenosine receptor signaling modulates both HI and immune cell function. Here, we investigated the influence of adenosine A1 receptor deficiency (A1R(-/-)) on key immune cell populations in a neonatal brain HI model. Ten-day-old mice were subjected to HI. Functional outcome was assessed by open locomotion and beam walking test and infarction size evaluated. Flow cytometry was performed on brain-infiltrating cells, and semi-automated analysis of flow cytometric data was applied. A1R(-/-) mice displayed larger infarctions (+33%, p beam walking tests (44% more mistakes, p < 0.05) than wild-type (WT) mice. Myeloid cell activation after injury was enhanced in A1R(-/-) versus WT brains. Activated B lymphocytes expressing IL-10 infiltrated the brain after HI in WT, but were less activated and did not increase in relative frequency in A1R(-/-). Also, A1R(-/-) B lymphocytes expressed less IL-10 than their WT counterparts, the A1R antagonist DPCPX decreased IL-10 expression whereas the A1R agonist CPA increased it. CD4(+) T lymphocytes including FoxP3(+) T regulatory cells, were unaffected by genotype, whereas CD8(+) T lymphocyte responses were smaller in A1R(-/-) mice. Using PCA to characterize the immune profile, we could discriminate the A1R(-/-) and WT genotypes as well as sham operated from HI-subjected animals. We conclude that A1R signaling modulates IL-10 expression by immune cells, influences the activation of these cells in vivo, and affects outcome after HI.

  14. Maternal obesity increases inflammation and exacerbates damage following neonatal hypoxic-ischaemic brain injury in rats.

    Science.gov (United States)

    Teo, Jonathan D; Morris, Margaret J; Jones, Nicole M

    2017-07-01

    In humans, maternal obesity is associated with an increase in the incidence of birth related difficulties. However, the impact of maternal obesity on the severity of brain injury in offspring is not known. Recent studies have found evidence of increased glial response and inflammatory mediators in the brains as a result of obesity in humans and rodents. We hypothesised that hypoxic-ischaemic (HI) brain injury is greater in neonatal offspring from obese rat mothers compared to lean controls. Female Sprague Dawley rats were randomly allocated to high fat (HFD, n=8) or chow (n=4) diet and mated with lean male rats. On postnatal day 7 (P7), male and female pups were randomly assigned to HI injury or control (C) groups. HI injury was induced by occlusion of the right carotid artery followed by 3h exposure to 8% oxygen, at 37°C. Control pups were removed from the mother for the same duration under ambient conditions. Righting behaviour was measured on day 1 and 7 following HI. The extent of brain injury was quantified in brain sections from P14 pups using cresyl violet staining and the difference in volume between brain hemispheres was measured. Before mating, HFD mothers were 11% heavier than Chow mothers (pmaternal weight. Similar observations were made with neuronal staining showing a greater loss of neurons in the brain of offspring from HFD-mothers following HI compared to Chow. Astrocytes appeared to more hypertrophic and a greater number of microglia were present in the injured hemisphere in offspring from mothers on HFD. HI caused an increase in the proportion of amoeboid microglia and exposure to maternal HFD exacerbated this response. In the contralateral hemisphere, offspring exposed to maternal HFD displayed a reduced proportion of ramified microglia. Our data clearly demonstrate that maternal obesity can exacerbate the severity of brain damage caused by HI in neonatal offspring. Given that previous studies have shown enhanced inflammatory responses in

  15. Post-traumatic growth in parents after infants' neonatal intensive care unit hospitalisation.

    Science.gov (United States)

    Aftyka, Anna; Rozalska-Walaszek, Ilona; Rosa, Wojciech; Rybojad, Beata; Karakuła-Juchnowicz, Hanna

    2017-03-01

    To determine the incidence and severity of post-traumatic growth in a group of parents of children hospitalised in the intensive care unit in the past. A premature birth or a birth with life-threatening conditions is a traumatic event for the parents and may lead to a number of changes, some of which are positive, known as post-traumatic growth. The survey covered 106 parents of 67 infants aged 3-12 months. An original questionnaire and standardised research tools were used in the study: Impact Event Scale - Revised, Perceived Stress Scale, COPE Inventory: Positive Reinterpretation and Growth, Coping Inventory for Stressful Situations, Post-traumatic Growth Inventory and Parent and Infant Characteristic Questionnaire. Due to a stepwise backward variables selection, we found three main factors that explain post-traumatic growth: post-traumatic stress symptoms, positive reinterpretation and growth and dichotomic variable infants' survival. This model explained 29% of the post-traumatic growth variation. Similar models that were considered separately for mothers and fathers showed no significantly better properties. Post-traumatic growth was related to a lesser extent to sociodemographic variables or the stressor itself, and related to a far greater extent to psychological factors. Our study highlights the fact that post-traumatic growth in the parents of neonates hospitalised in the neonatal intensive care units remains under-evaluated. © 2016 John Wiley & Sons Ltd.

  16. Lipid peroxidation in neonatal mouse brain subjected to two different types of hypoxia.

    Science.gov (United States)

    Hasegawa, K; Yoshioka, H; Sawada, T; Nishikawa, H

    1991-01-01

    To elucidate the role of free radicals in the pathogenesis of neonatal hypoxic encephalopathy, we determined the content of thiobarbituric acid reactants (TBARs), as an index of lipid peroxidation related with a free radical reaction, in the brains of newborn mice during hypoxia and recovery from hypoxia. Hypoxic stress was induced by 100% nitrogen gas breathing (N2 group) or 100% carbon dioxide gas breathing (CO2 group). TBARs increased with 20 minutes of hypoxia and returned to the control level during the recovery period in both groups. The increase in TBARs in the CO2 group was greater than that in the N2 group. These results may suggest that free radical reaction occurs during the hypoxic period and that CO2 hypoxia is more effective on free radical production in the newborn brain than N2 hypoxia.

  17. Overweight worsens apoptosis, neuroinflammation and blood-brain barrier damage after hypoxic ischemia in neonatal brain through JNK hyperactivation

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    Wu Hsin-Chieh

    2011-04-01

    Full Text Available Abstract Background Apoptosis, neuroinflammation and blood-brain barrier (BBB damage affect the susceptibility of the developing brain to hypoxic-ischemic (HI insults. c-Jun N-terminal kinase (JNK is an important mediator of insulin resistance in obesity. We hypothesized that neonatal overweight aggravates HI brain damage through JNK hyperactivation-mediated upregulation of neuronal apoptosis, neuroinflammation and BBB leakage in rat pups. Methods Overweight (OF pups were established by reducing the litter size to 6, and control (NF pups by keeping the litter size at 12 from postnatal (P day 1 before HI on P7. Immunohistochemistry and immunoblotting were used to determine the TUNEL-(+ cells and BBB damage, cleaved caspase-3 and poly (ADP-ribose polymerase (PARP, and phospho-JNK and phospho-BimEL levels. Immunofluorescence was performed to determine the cellular distribution of phospho-JNK. Results Compared with NF pups, OF pups had a significantly heavier body-weight and greater fat deposition on P7. Compared with the NF-HI group, the OF-HI group showed significant increases of TUNEL-(+ cells, cleaved levels of caspase-3 and PARP, and ED1-(+ activated microglia and BBB damage in the cortex 24 hours post-HI. Immunofluorescence of the OF-HI pups showed that activated-caspase 3 expression was found mainly in NeuN-(+ neurons and RECA1-(+ vascular endothelial cells 24 hours post-HI. The OF-HI group also had prolonged escape latency in the Morris water maze test and greater brain-volume loss compared with the NF-HI group when assessed at adulthood. Phospho-JNK and phospho-BimEL levels were higher in OF-HI pups than in NF-HI pups immediately post-HI. JNK activation in OF-HI pups was mainly expressed in neurons, microglia and vascular endothelial cells. Inhibiting JNK activity by AS601245 caused more attenuation of cleaved caspase-3 and PARP, a greater reduction of microglial activation and BBB damage post-HI, and significantly reduced brain damage in

  18. Impaired rate of microsomal fatty acid elongation in undernourished neonatal rat brain

    International Nuclear Information System (INIS)

    Yeh, Y.Y.

    1986-01-01

    Hypomyelination caused by undernourishment in characterized by low concentrations of myelin lipids and marked reduction in lignocerate (C/sub 24:0/) and nervonate (C/sub 24:1/) moiety of cerebroside and sulfatide. Since microsomal elongation is the major source of long chain (22 to 24 carbons) fatty acids in the brain, the effect of neonatal undernourishment on acyl elongation was investigated. Undernourishment of suckling rats were induced after birth by restricting maternal dietary intake to 40% of that consumed by dams fed ad libitum. Neonates suckled by the normally fed dams served as controls. Microsomal elongation was measured as nmol from [2- 14 C] malonyl CoA incorporated/h per mg of protein. At 19 days of age, rates of behenoyl CoA (C/sub 22:0/) and erucoyl CoA (C/sub 22:1/) elongation in whole brain of undernourished neonates were 30-40% lower than that of the control, whereas the elongation rates of acyl CoA 16, 18 and 20 carbons in length either saturated or monounsaturated were similar in both groups. Undernourishment had no effect on cytoplasmic de novo fatty acid synthesis from acetyl CoA. If there are multiple elongation factors, the results indicate that the depressed activity of elongating enzyme(s) for C/sub 22:0/ and C/sub 22:1/ is an important contributing factor in lowering S/sub 24:0/ and C/sub 24:1/ content in cerebroside and sulfatide. This impairment may be a specific lesion leading to hypomyelination in undernourished rats

  19. Plasma Brain-Derived Neurotrophic Factor Levels in Newborn Infants with Neonatal Abstinence Syndrome

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    Lochan Subedi

    2017-11-01

    Full Text Available BackgroundBrain-derived neurotrophic factor (BDNF is a type of growth factor that promotes growth and survival of neurons. Fetal exposure to opiates can lead to postnatal withdrawal syndrome, which is referred as neonatal abstinence syndrome (NAS. Preclinical and clinical studies have shown an association between opiates exposure and alteration in BDNF expression in the brain and serum levels in adult. However, to date, there are no data available on the effects of opiate exposure on BDNF levels in infant who are exposed to opiates in utero and whether BDNF level may correlate with the severity of NAS.ObjectiveTo compare plasma BDNF levels among NAS and non-NAS infants and to determine the correlation of BDNF levels and the severity of NAS.MethodsThis is a prospective cohort study with no intervention involved. Infants ≥35 weeks of gestation were enrolled. BDNF level was measured using enzyme-linked immunosorbent assay technique from blood samples drawn within 48 h of life. The severity of NAS was determined by the length of hospital stay, number of medications required to treat NAS.Results67 infants were enrolled, 34 NAS and 33 non-NAS. Mean gestational age did not differ between the two groups. Mean birth weight of NAS infants was significantly lower than the non-NAS infants (3,070 ± 523 vs. 3,340 ± 459 g, p = 0.028. Mean BDNF level in NAS group was 252.2 ± 91.6 ng/ml, significantly higher than 211.3 ± 66.3 ng/ml in the non-NAS group (p = 0.04. There were no differences in BDNF levels between NAS infants that required one medication vs. more than one medication (254 ± 91 vs. 218 ± 106 ng/ml, p = 0.47. There was no correlation between the BDNF levels and length of hospital stay (p = 0.68 among NAS infants. Overall, there were no significant correlations between BDNF levels and NAS scores except at around 15 h after admission (correlation 0.35, p = 0.045.ConclusionPlasma BDNF

  20. Modelling Blood Flow and Metabolism in the Preclinical Neonatal Brain during and Following Hypoxic-Ischaemia.

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    Matthew Caldwell

    Full Text Available Hypoxia-ischaemia (HI is a major cause of neonatal brain injury, often leading to long-term damage or death. In order to improve understanding and test new treatments, piglets are used as preclinical models for human neonates. We have extended an earlier computational model of piglet cerebral physiology for application to multimodal experimental data recorded during episodes of induced HI. The data include monitoring with near-infrared spectroscopy (NIRS and magnetic resonance spectroscopy (MRS, and the model simulates the circulatory and metabolic processes that give rise to the measured signals. Model extensions include simulation of the carotid arterial occlusion used to induce HI, inclusion of cytoplasmic pH, and loss of metabolic function due to cell death. Model behaviour is compared to data from two piglets, one of which recovered following HI while the other did not. Behaviourally-important model parameters are identified via sensitivity analysis, and these are optimised to simulate the experimental data. For the non-recovering piglet, we investigate several state changes that might explain why some MRS and NIRS signals do not return to their baseline values following the HI insult. We discover that the model can explain this failure better when we include, among other factors such as mitochondrial uncoupling and poor cerebral blood flow restoration, the death of around 40% of the brain tissue.

  1. Left ventricular dimensions, systolic functions, and mass in term neonates with symmetric and asymmetric intrauterine growth restriction.

    Science.gov (United States)

    Cinar, Bahar; Sert, Ahmet; Gokmen, Zeynel; Aypar, Ebru; Aslan, Eyup; Odabas, Dursun

    2015-02-01

    Previous studies have demonstrated structural changes in the heart and cardiac dysfunction in foetuses with intrauterine growth restriction. There are no available data that evaluated left ventricular dimensions and mass in neonates with symmetric and asymmetric intrauterine growth restriction. Therefore, we aimed to evaluate left ventricular dimensions, systolic functions, and mass in neonates with symmetric and asymmetric intrauterine growth restriction. We also assessed associated maternal risk factors, and compared results with healthy appropriate for gestational age neonates. In all, 62 asymmetric intrauterine growth restriction neonates, 39 symmetric intrauterine growth restriction neonates, and 50 healthy appropriate for gestational age neonates were evaluated by transthoracic echocardiography. The asymmetric intrauterine growth restriction group had significantly lower left ventricular end-systolic and end-diastolic diameters and posterior wall diameter in systole and diastole than the control group. The symmetric intrauterine growth restriction group had significantly lower left ventricular end-diastolic diameter than the control group. All left ventricular dimensions were lower in the asymmetric intrauterine growth restriction neonates compared with symmetric intrauterine growth restriction neonates (p>0.05), but not statistically significant except left ventricular posterior wall diameter in diastole (3.08±0.83 mm versus 3.54 ±0.72 mm) (pintrauterine growth restriction groups had significantly lower relative posterior wall thickness (0.54±0.19 versus 0.48±0.13 versus 0.8±0.12), left ventricular mass (9.8±4.3 g versus 8.9±3.4 g versus 22.2±5.7 g), and left ventricular mass index (63.6±29.1 g/m2 versus 54.5±24.4 g/m2 versus 109±28.8 g/m2) when compared with the control group. Our study has demonstrated that although neonates with both symmetric and asymmetric intrauterine growth restriction had lower left ventricular dimensions, relative

  2. Nerve growth factor actions on the brain

    International Nuclear Information System (INIS)

    Martinez, H.J.

    1989-01-01

    We examined the effect of the trophic protein, nerve growth factor (NGF), on cultures of fetal rat neostriatum and basal forebrain-medial septal area (BF-MS) to define its role in brain development. Treatment of cultures with NGF resulted in an increase in the specific activity of the cholinergic enzyme choline acetyltransferase (CAT) in both brain areas. CAT was immunocytochemically localized to neurons. In the BF-MS, NGF treatment elicited a marked increase in staining intensity and an apparent increase in the number of CAT-positive neurons. Moreover, treatment of BF-MS cultures with NGF increased the activity of acetylcholinesterase, suggesting that the cholinergic neuron as a whole was affected. To begin defining mechanisms of action of NGF in the BF-MS, we detected NGF receptors by two independent methods. Receptors were localized to two different cellular populations: neuron-like cells, and non-neuron-like cells. Dissociation studies with [ 125 I]NGF suggested that high affinity receptors were localized to the neuron-like population. Only low-affinity receptors were localized to the non-neuron-like cells. Moreover, employing combined immunocytochemistry and [ 125 I]NGF autoradiography, we detected a subpopulation of CAT-containing neutrons that exhibited high-affinity binding. Unexpectedly, a gamma-aminobutyric acid (GABA)-containing cell group also expressed high affinity binding. However, only subsets of cholinergic or GABA neurons expressed high-affinity biding, suggesting that these transmitter populations are composed of differentially response subpopulations

  3. Early changes in brain structure correlate with language outcomes in children with neonatal encephalopathy.

    Science.gov (United States)

    Shapiro, Kevin A; Kim, Hosung; Mandelli, Maria Luisa; Rogers, Elizabeth E; Gano, Dawn; Ferriero, Donna M; Barkovich, A James; Gorno-Tempini, Maria Luisa; Glass, Hannah C; Xu, Duan

    2017-01-01

    Global patterns of brain injury correlate with motor, cognitive, and language outcomes in survivors of neonatal encephalopathy (NE). However, it is still unclear whether local changes in brain structure predict specific deficits. We therefore examined whether differences in brain structure at 6 months of age are associated with neurodevelopmental outcomes in this population. We enrolled 32 children with NE, performed structural brain MR imaging at 6 months, and assessed neurodevelopmental outcomes at 30 months. All subjects underwent T1-weighted imaging at 3 T using a 3D IR-SPGR sequence. Images were normalized in intensity and nonlinearly registered to a template constructed specifically for this population, creating a deformation field map. We then used deformation based morphometry (DBM) to correlate variation in the local volume of gray and white matter with composite scores on the Bayley Scales of Infant and Toddler Development (Bayley-III) at 30 months. Our general linear model included gestational age, sex, birth weight, and treatment with hypothermia as covariates. Regional brain volume was significantly associated with language scores, particularly in perisylvian cortical regions including the left supramarginal gyrus, posterior superior and middle temporal gyri, and right insula, as well as inferior frontoparietal subcortical white matter. We did not find significant correlations between regional brain volume and motor or cognitive scale scores. We conclude that, in children with a history of NE, local changes in the volume of perisylvian gray and white matter at 6 months are correlated with language outcome at 30 months. Quantitative measures of brain volume on early MRI may help identify infants at risk for poor language outcomes.

  4. Early changes in brain structure correlate with language outcomes in children with neonatal encephalopathy

    Directory of Open Access Journals (Sweden)

    Kevin A. Shapiro

    2017-01-01

    Full Text Available Global patterns of brain injury correlate with motor, cognitive, and language outcomes in survivors of neonatal encephalopathy (NE. However, it is still unclear whether local changes in brain structure predict specific deficits. We therefore examined whether differences in brain structure at 6 months of age are associated with neurodevelopmental outcomes in this population. We enrolled 32 children with NE, performed structural brain MR imaging at 6 months, and assessed neurodevelopmental outcomes at 30 months. All subjects underwent T1-weighted imaging at 3 T using a 3D IR-SPGR sequence. Images were normalized in intensity and nonlinearly registered to a template constructed specifically for this population, creating a deformation field map. We then used deformation based morphometry (DBM to correlate variation in the local volume of gray and white matter with composite scores on the Bayley Scales of Infant and Toddler Development (Bayley-III at 30 months. Our general linear model included gestational age, sex, birth weight, and treatment with hypothermia as covariates. Regional brain volume was significantly associated with language scores, particularly in perisylvian cortical regions including the left supramarginal gyrus, posterior superior and middle temporal gyri, and right insula, as well as inferior frontoparietal subcortical white matter. We did not find significant correlations between regional brain volume and motor or cognitive scale scores. We conclude that, in children with a history of NE, local changes in the volume of perisylvian gray and white matter at 6 months are correlated with language outcome at 30 months. Quantitative measures of brain volume on early MRI may help identify infants at risk for poor language outcomes.

  5. Development of electrocardiogram intervals during growth of FVB/N neonate mice

    Science.gov (United States)

    2010-01-01

    Background Electrocardiography remains the best diagnostic tool and therapeutic biomarker for a spectrum of pediatric diseases involving cardiac or autonomic nervous system defects. As genetic links to these disorders are established and transgenic mouse models produced in efforts to understand and treat them, there is a surprising lack of information on electrocardiograms (ECGs) and ECG abnormalities in neonate mice. This is likely due to the trauma and anaesthesia required of many legacy approaches to ECG recording in mice, exacerbated by the fragility of many mutant neonates. Here, we use a non-invasive system to characterize development of the heart rate and electrocardiogram throughout the growth of conscious neonate FVB/N mice. Results We examine ECG waveforms as early as two days after birth. At this point males and females demonstrate comparable heart rates that are 50% lower than adult mice. Neonatal mice exhibit very low heart rate variability. Within 12 days of birth PR, QRS and QTc interval durations are near adult values while heart rate continues to increase until weaning. Upon weaning FVB/N females quickly develop slower heart rates than males, though PR intervals are comparable between sexes until a later age. This suggests separate developmental events may contribute to these gender differences in electrocardiography. Conclusions We provide insight with a new level of detail to the natural course of heart rate establishment in neonate mice. ECG can now be conveniently and repeatedly used in neonatal mice. This should serve to be of broad utility, facilitating further investigations into development of a diverse group of diseases and therapeutics in preclinical mouse studies. PMID:20735846

  6. Neonatal brain injury and neuroanatomy of memory processing following very preterm birth in adulthood: an fMRI study.

    Directory of Open Access Journals (Sweden)

    Anastasia K Kalpakidou

    Full Text Available Altered functional neuroanatomy of high-order cognitive processing has been described in very preterm individuals (born before 33 weeks of gestation; VPT compared to controls in childhood and adolescence. However, VPT birth may be accompanied by different types of adverse neonatal events and associated brain injury, the severity of which may have differential effects on brain development and subsequent neurodevelopmental outcome. We conducted a functional magnetic resonance imaging (fMRI study to investigate how differing degrees of neonatal brain injury, detected by neonatal ultrasounds, affect the functional neuroanatomy of memory processing in VPT young adults. We used a verbal paired associates learning task, consisting of four encoding, four cued-recall and four baseline condition blocks. To further investigate whether differences in neural activation between the groups were modulated by structural brain changes, structural MRI data were also collected. We studied 12 VPT young adults with a history of periventricular haemorrhage with associated ventricular dilatation, 17 VPT individuals with a history of uncomplicated periventricular haemorrhage, 12 individuals with normal ultrasonographic findings, and 17 controls. Results of a linear trend analysis demonstrated that during completion of the paired associates learning task right frontal and right parietal brain activation decreased as the severity of neonatal brain injury increased. There were no statistically significant between-group differences in on-line task performance and participants' intelligence quotient (IQ at assessment. This pattern of differential activation across the groups was observed particularly in the right middle frontal gyrus during encoding and in the right posterior cingulate gyrus during recall. Structural MRI data analysis revealed that grey matter volume in the right superior temporal gyrus, right cerebellum, left middle temporal gyrus, right globus pallidus and

  7. Palatal growth in complete unilateral cleft lip and palate patients following neonatal cheiloplasty: Classic and geometric morphometric assessment.

    Science.gov (United States)

    Hoffmannova, Eva; Bejdová, Šárka; Borský, Jiri; Dupej, Ján; Cagáňová, Veronika; Velemínská, Jana

    2016-11-01

    A new method of early neonatal cheiloplasty has recently been employed on patients having complete unilateral cleft lip and palate (cUCLP). We aimed to investigate (1) their detailed palatal morphology before surgery and growth during the 10 months after neonatal cheiloplasty, (2) the growth of eight dimensions of the maxilla in these patients, (3) the development of these dimensions compared with published data on noncleft controls and on cUCLP patients operated using later operation protocol (LOP; 6 months of age). Sixty-six virtual dental models of 33 longitudinally evaluated cUCLP patients were analysed using metric analysis, a dense correspondence model, and multivariate statistics. We compared the palatal surfaces before neonatal cheiloplasty (mean age, 4 days) and before palatoplasty (mean age, 10 months). The palatal form variability of 10-month-old children was considerably reduced during the observed period thanks to their undisturbed growth, that is, the palate underwent the same growth changes following neonatal cheiloplasty. A detailed colour-coded map identified the most marked growth at the anterior and posterior ends of both segments. The maxilla of cUCLP patients after neonatal cheiloplasty had a growth tendency similar to noncleft controls (unlike LOP). Both methodological approaches showed that early neonatal cheiloplasty in cUCLP patients did not prevent forward growth of the upper jaw segments and did not reduce either the length or width of the maxilla during the first 10 months of life. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Zcchc11 Uridylates Mature miRNAs to Enhance Neonatal IGF-1 Expression, Growth, and Survival

    Science.gov (United States)

    Kozlowski, Elyse; Matsuura, Kori Y.; Ferrari, Joseph D.; Morris, Samantha A.; Powers, John T.; Daley, George Q.; Quinton, Lee J.; Mizgerd, Joseph P.

    2012-01-01

    The Zcchc11 enzyme is implicated in microRNA (miRNA) regulation. It can uridylate let-7 precursors to decrease quantities of the mature miRNA in embryonic stem cell lines, suggested to mediate stem cell maintenance. It can uridylate mature miR-26 to relieve silencing activity without impacting miRNA content in cancer cell lines, suggested to mediate cytokine and growth factor expression. Broader roles of Zcchc11 in shaping or remodeling the miRNome or in directing biological or physiological processes remain entirely speculative. We generated Zcchc11-deficient mice to address these knowledge gaps. Zcchc11 deficiency had no impact on embryogenesis or fetal development, but it significantly decreased survival and growth immediately following birth, indicating a role for this enzyme in early postnatal fitness. Deep sequencing of small RNAs from neonatal livers revealed roles of this enzyme in miRNA sequence diversity. Zcchc11 deficiency diminished the lengths and terminal uridine frequencies for diverse mature miRNAs, but it had no influence on the quantities of any miRNAs. The expression of IGF-1, a liver-derived protein essential to early growth and survival, was enhanced by Zcchc11 expression in vitro, and miRNA silencing of IGF-1 was alleviated by uridylation events observed to be Zcchc11-dependent in the neonatal liver. In neonatal mice, Zcchc11 deficiency significantly decreased IGF-1 mRNA in the liver and IGF-1 protein in the blood. We conclude that the Zcchc11-mediated terminal uridylation of mature miRNAs is pervasive and physiologically significant, especially important in the neonatal period for fostering IGF-1 expression and enhancing postnatal growth and survival. We propose that the miRNA 3′ terminus is a regulatory node upon which multiple enzymes converge to direct silencing activity and tune gene expression. PMID:23209448

  9. Zcchc11 uridylates mature miRNAs to enhance neonatal IGF-1 expression, growth, and survival.

    Directory of Open Access Journals (Sweden)

    Matthew R Jones

    Full Text Available The Zcchc11 enzyme is implicated in microRNA (miRNA regulation. It can uridylate let-7 precursors to decrease quantities of the mature miRNA in embryonic stem cell lines, suggested to mediate stem cell maintenance. It can uridylate mature miR-26 to relieve silencing activity without impacting miRNA content in cancer cell lines, suggested to mediate cytokine and growth factor expression. Broader roles of Zcchc11 in shaping or remodeling the miRNome or in directing biological or physiological processes remain entirely speculative. We generated Zcchc11-deficient mice to address these knowledge gaps. Zcchc11 deficiency had no impact on embryogenesis or fetal development, but it significantly decreased survival and growth immediately following birth, indicating a role for this enzyme in early postnatal fitness. Deep sequencing of small RNAs from neonatal livers revealed roles of this enzyme in miRNA sequence diversity. Zcchc11 deficiency diminished the lengths and terminal uridine frequencies for diverse mature miRNAs, but it had no influence on the quantities of any miRNAs. The expression of IGF-1, a liver-derived protein essential to early growth and survival, was enhanced by Zcchc11 expression in vitro, and miRNA silencing of IGF-1 was alleviated by uridylation events observed to be Zcchc11-dependent in the neonatal liver. In neonatal mice, Zcchc11 deficiency significantly decreased IGF-1 mRNA in the liver and IGF-1 protein in the blood. We conclude that the Zcchc11-mediated terminal uridylation of mature miRNAs is pervasive and physiologically significant, especially important in the neonatal period for fostering IGF-1 expression and enhancing postnatal growth and survival. We propose that the miRNA 3' terminus is a regulatory node upon which multiple enzymes converge to direct silencing activity and tune gene expression.

  10. Relationship between opioid therapy, tissue-damaging procedures, and brain metabolites as measured by proton MRS in asphyxiated term neonates.

    Science.gov (United States)

    Angeles, Danilyn M; Ashwal, Stephen; Wycliffe, Nathaniel D; Ebner, Charlotte; Fayard, Elba; Sowers, Lawrence; Holshouser, Barbara A

    2007-05-01

    To examine the effects of opioid and tissue-damaging procedures (TDPs) [i.e. procedures performed in the neonatal intensive care unit (NICU) known to result in pain, stress, and tissue damage] on brain metabolites, we reviewed the medical records of 28 asphyxiated term neonates (eight opioid-treated, 20 non-opioid treated) who had undergone magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) within the first month of life as well as eight newborns with no clinical findings of asphyxial injury. We found that lower creatine (Cr), myoinositol (Ins), and N-acetylaspartate (NAA)/choline (Cho) (p OGM) NAA/Cr was decreased (p = 0.03) and lactate (Lac) was present in a significantly higher amount (40%; p = 0.03) in non-opioid-treated neonates compared with opioid-treated neonates. Compared with controls, untreated neonates showed larger changes in more metabolites in basal ganglia (BG), thalami (TH), and OGM with greater significance than treated neonates. Our data suggest that TDPs affect spectral metabolites and that opioids do not cause harm in asphyxiated term neonates exposed to repetitive TDPs in the first 2-4 DOL and may provide a degree of neuroprotection.

  11. Impaired growth of denervated muscle contributes to contracture formation following neonatal brachial plexus injury.

    Science.gov (United States)

    Nikolaou, Sia; Peterson, Elizabeth; Kim, Annie; Wylie, Christopher; Cornwall, Roger

    2011-03-02

    The etiology of shoulder and elbow contractures following neonatal brachial plexus injury is incompletely understood. With use of a mouse model, the current study tests the novel hypothesis that reduced growth of denervated muscle contributes to contractures following neonatal brachial plexus injury. Unilateral brachial plexus injuries were created in neonatal mice by supraclavicular C5-C6 nerve root excision. Shoulder and elbow range of motion was measured four weeks after injury. Fibrosis, cross-sectional area, and functional length of the biceps, brachialis, and subscapularis muscles were measured over four weeks following injury. Muscle satellite cells were cultured from denervated and control biceps muscles to assess myogenic capability. In a comparison group, shoulder motion and subscapularis length were assessed following surgical excision of external rotator muscles. Shoulder internal rotation and elbow flexion contractures developed on the involved side within four weeks following brachial plexus injury. Excision of the biceps and brachialis muscles relieved the elbow flexion contractures. The biceps muscles were histologically fibrotic, whereas fatty infiltration predominated in the brachialis and rotator cuff muscles. The biceps and brachialis muscles displayed reduced cross-sectional and longitudinal growth compared with the contralateral muscles. The upper subscapularis muscle similarly displayed reduced longitudinal growth, with the subscapularis shortening correlating with internal rotation contracture. However, excision of the external rotators without brachial plexus injury caused no contractures or subscapularis shortening. Myogenically capable satellite cells were present in denervated biceps muscles despite impaired muscle growth in vivo. Injury of the upper trunk of the brachial plexus leads to impaired growth of the biceps and brachialis muscles, which are responsible for elbow flexion contractures, and impaired growth of the subscapularis

  12. Fetal and neonatal programming of postnatal growth and feed efficiency in swine.

    Science.gov (United States)

    Ji, Yun; Wu, Zhenlong; Dai, Zhaolai; Wang, Xiaolong; Li, Ju; Wang, Binggen; Wu, Guoyao

    2017-01-01

    Maternal undernutrition or overnutrition during pregnancy alters organ structure, impairs prenatal and neonatal growth and development, and reduces feed efficiency for lean tissue gains in pigs. These adverse effects may be carried over to the next generation or beyond. This phenomenon of the transgenerational impacts is known as fetal programming, which is mediated by stable and heritable alterations of gene expression through covalent modifications of DNA and histones without changes in DNA sequences (namely, epigenetics). The mechanisms responsible for the epigenetic regulation of protein expression and functions include chromatin remodeling; DNA methylation (occurring at the 5´-position of cytosine residues within CpG dinucleotides); and histone modifications (acetylation, methylation, phosphorylation, and ubiquitination). Like maternal malnutrition, undernutrition during the neonatal period also reduces growth performance and feed efficiency (weight gain:feed intake; also known as weight-gain efficiency) in postweaning pigs by 5-10%, thereby increasing the days necessary to reach the market body-weight. Supplementing functional amino acids (e.g., arginine and glutamine) and vitamins (e.g., folate) play a key role in activating the mammalian target of rapamycin signaling and regulating the provision of methyl donors for DNA and protein methylation. Therefore, these nutrients are beneficial for the dietary treatment of metabolic disorders in offspring with intrauterine growth restriction or neonatal malnutrition. The mechanism-based strategies hold great promise for the improvement of the efficiency of pork production and the sustainability of the global swine industry.

  13. Insulin and insulin-like growth factor-1 increased in preterm neonates following massage therapy.

    Science.gov (United States)

    Field, Tiffany; Diego, Miguel; Hernandez-Reif, Maria; Dieter, John N I; Kumar, Adarsh M; Schanberg, Saul; Kuhn, Cynthia

    2008-12-01

    To determine if massage therapy increased serum insulin and insulin-like growth factor-1 (IGF-1) in preterm neonates. Forty-two preterm neonates who averaged 34.6 weeks (M = 29.5 wk gestational age; M birth weight = 1237 g) and were in the "grower" (step-down) nursery were randomly assigned to a massage therapy group (body stroking and passive limb movements for three, 15-minute periods per day for 5 days) or a control group that received the standard nursery care without massage therapy. On Days 1 and 5, the serum collected by clinical heelsticks was also assayed for insulin and IGF-1, and weight gain and kilocalories consumed were recorded daily. Despite similar formula intake, the massaged preterm neonates showed greater increases during the 5-day period in (1) weight gain; (2) serum levels of insulin; and (3) IGF-1. Increased weight gain was significantly correlated with insulin and IGF-1. Previous data suggested that preterm infant weight gain following massage therapy related to increased vagal activity, which suggests decreased stress and gastric motility, which may contribute to more efficient food absorption. The data from this study suggest for the first time that weight gain was also related to increased serum insulin and IGF-1 levels following massage therapy. Preterm infants who received massage therapy not only showed greater weight gain but also a greater increase in serum insulin and IGF-1 levels, suggesting that massage therapy might be prescribed for all growing neonates.

  14. Growth of melanoma brain tumors monitored by photoacoustic microscopy

    Science.gov (United States)

    Staley, Jacob; Grogan, Patrick; Samadi, Abbas K.; Cui, Huizhong; Cohen, Mark S.; Yang, Xinmai

    2010-07-01

    Melanoma is a primary malignancy that is known to metastasize to the brain and often causes death. The ability to image the growth of brain melanoma in vivo can provide new insights into its evolution and response to therapies. In our study, we use a reflection mode photoacoustic microscopy (PAM) system to detect the growth of melanoma brain tumor in a small animal model. The melanoma tumor cells are implanted in the brain of a mouse at the beginning of the test. Then, PAM is used to scan the region of implantation in the mouse brain, and the growth of the melanoma is monitored until the death of the animal. It is demonstrated that PAM is capable of detecting and monitoring the brain melanoma growth noninvasively in vivo.

  15. Developmental Thyroid Hormone Insufficiency Reduces Expression of Brain-Derived Neurotrophic Factor (BDNF) in Adults But Not in Neonates

    Science.gov (United States)

    Brain-derived neurotrophic factor (BDNF) is a neurotrophin critical for many developmental and physiological aspects of CNS function. Severe hypothyroidism in the early neonatal period results in developmental and cognitive impairments and reductions in mRNA and protein expressio...

  16. Accurate Learning with Few Atlases (ALFA): an algorithm for MRI neonatal brain extraction and comparison with 11 publicly available methods.

    Science.gov (United States)

    Serag, Ahmed; Blesa, Manuel; Moore, Emma J; Pataky, Rozalia; Sparrow, Sarah A; Wilkinson, A G; Macnaught, Gillian; Semple, Scott I; Boardman, James P

    2016-03-24

    Accurate whole-brain segmentation, or brain extraction, of magnetic resonance imaging (MRI) is a critical first step in most neuroimage analysis pipelines. The majority of brain extraction algorithms have been developed and evaluated for adult data and their validity for neonatal brain extraction, which presents age-specific challenges for this task, has not been established. We developed a novel method for brain extraction of multi-modal neonatal brain MR images, named ALFA (Accurate Learning with Few Atlases). The method uses a new sparsity-based atlas selection strategy that requires a very limited number of atlases 'uniformly' distributed in the low-dimensional data space, combined with a machine learning based label fusion technique. The performance of the method for brain extraction from multi-modal data of 50 newborns is evaluated and compared with results obtained using eleven publicly available brain extraction methods. ALFA outperformed the eleven compared methods providing robust and accurate brain extraction results across different modalities. As ALFA can learn from partially labelled datasets, it can be used to segment large-scale datasets efficiently. ALFA could also be applied to other imaging modalities and other stages across the life course.

  17. Studies on cerebral protection of digoxin against hypoxic-ischemic brain damage in neonatal rats.

    Science.gov (United States)

    Peng, Kaiwei; Tan, Danfeng; He, Miao; Guo, Dandan; Huang, Juan; Wang, Xia; Liu, Chentao; Zheng, Xiangrong

    2016-08-17

    Hypoxic-ischemic brain damage (HIBD) is a major cause of neonatal acute deaths and chronic nervous system damage. Our present study was designed to investigate the possible neuroprotective effect of digoxin-induced pharmacological preconditioning after hypoxia-ischemia and underlying mechanisms. Neonatal rats were assigned randomly to control, HIBD, or HIBD+digoxin groups. Pharmacological preconditioning was induced by administration of digoxin 72 h before inducing HIBD by carotid occlusion+hypoxia. Behavioral assays, and neuropathological and apoptotic assessments were performed to examine the effects; the expression of Na/K ATPase was also assessed. Rats in the HIBD group showed deficiencies on the T-maze, radial water maze, and postural reflex tests, whereas the HIBD+digoxin group showed significant improvements on all behavioral tests. The rats treated with digoxin showed recovery of pathological conditions, increased number of neural cells and proliferative cells, and decreased number of apoptotic cells. Meanwhile, an increased expression level of Na/K ATPase was observed after digoxin preconditioning treatment. The preconditioning treatment of digoxin contributed toward an improved functional recovery and exerted a marked neuroprotective effect including promotion of cell proliferation and reduction of apoptosis after HIBD, and the neuroprotective action was likely associated with increased expression of Na/K ATPase.

  18. Neonatal cardiovascular system adaptation in babies with intrauterine growth retardation

    Directory of Open Access Journals (Sweden)

    I. N. Petrova

    2016-01-01

    Full Text Available Objective: to reveal the adaptive features of the cardiovascular system in newborn infants with intrauterine growth retardation (IUGR on the basis of a clinical instrumental study.Subjects and methods. A study group included 100 newborn infants with IUGR; a control group consisted of 40 babies with normal anthropometric measurements at birth. Medical history and clinical data and electrocardiographic and echocardiographic findings were analyzed.Results. All the examinees with IUGR had manifestations of cardiovascular system dysadaptation. There was a high rate of electrocardiographic changes, such as cardiac arrhythmias; low voltage; systolic overload of the right heart and left ventricle; signs of ventricular hypertrophy; and transient myocardial ischemia. The specific features of cardiac hemodynamics were decreased sizes of the left ventricle, lower parameters of its systolic function, and longer functioning of fetal communications.Conclusion. IUGR is associated with the development of cardiovascular system dysadaptation syndrome, which is due to prior perinatal hypoxia. The findings necessitate a follow-up of children by involving a cardiologist.

  19. Intranasal mesenchymal stem cell treatment for neonatal brain damage: long-term cognitive and sensorimotor improvement.

    Directory of Open Access Journals (Sweden)

    Vanessa Donega

    Full Text Available Mesenchymal stem cell (MSC administration via the intranasal route could become an effective therapy to treat neonatal hypoxic-ischemic (HI brain damage. We analyzed long-term effects of intranasal MSC treatment on lesion size, sensorimotor and cognitive behavior, and determined the therapeutic window and dose response relationships. Furthermore, the appearance of MSCs at the lesion site in relation to the therapeutic window was examined. Nine-day-old mice were subjected to unilateral carotid artery occlusion and hypoxia. MSCs were administered intranasally at 3, 10 or 17 days after hypoxia-ischemia (HI. Motor, cognitive and histological outcome was investigated. PKH-26 labeled cells were used to localize MSCs in the brain. We identified 0.5 × 10(6 MSCs as the minimal effective dose with a therapeutic window of at least 10 days but less than 17 days post-HI. A single dose was sufficient for a marked beneficial effect. MSCs reach the lesion site within 24 h when given 3 or 10 days after injury. However, no MSCs were detected in the lesion when administered 17 days following HI. We also show for the first time that intranasal MSC treatment after HI improves cognitive function. Improvement of sensorimotor function and histological outcome was maintained until at least 9 weeks post-HI. The capacity of MSCs to reach the lesion site within 24 h after intranasal administration at 10 days but not at 17 days post-HI indicates a therapeutic window of at least 10 days. Our data strongly indicate that intranasal MSC treatment may become a promising non-invasive therapeutic tool to effectively reduce neonatal encephalopathy.

  20. Minocycline causes widespread cell death and increases microglial labeling in the neonatal mouse brain.

    Science.gov (United States)

    Strahan, J Alex; Walker, William H; Montgomery, Taylor R; Forger, Nancy G

    2017-06-01

    Minocycline, an antibiotic of the tetracycline family, inhibits microglia in many paradigms and is among the most commonly used tools for examining the role of microglia in physiological processes. Microglia may play an active role in triggering developmental neuronal cell death, although findings have been contradictory. To determine whether microglia influence developmental cell death, we treated perinatal mice with minocycline (45 mg/kg) and quantified effects on dying cells and microglial labeling using immunohistochemistry for activated caspase-3 (AC3) and ionized calcium-binding adapter molecule 1 (Iba1), respectively. Contrary to our expectations, minocycline treatment from embryonic day 18 to postnatal day (P)1 caused a > tenfold increase in cell death 8 h after the last injection in all brain regions examined, including the primary sensory cortex, septum, hippocampus and hypothalamus. Iba1 labeling was also increased in most regions. Similar effects, although of smaller magnitude, were seen when treatment was delayed to P3-P5. Minocycline treatment from P3 to P5 also decreased overall cell number in the septum at weaning, suggesting lasting effects of the neonatal exposure. When administered at lower doses (4.5 or 22.5 mg/kg), or at the same dose 1 week later (P10-P12), minocycline no longer increased microglial markers or cell death. Taken together, the most commonly used microglial "inhibitor" increases cell death and Iba1 labeling in the neonatal mouse brain. Minocycline is used clinically in infant and pediatric populations; caution is warrented when using minocycline in developing animals, or extrapolating the effects of this drug across ages. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 753-766, 2017. © 2016 Wiley Periodicals, Inc.

  1. Effect of manganese on neonatal rat: manganese concentration and enzymatic alterations in brain

    Energy Technology Data Exchange (ETDEWEB)

    Seth, P K; Husain, R; Mushtaq, M; Chandra, S V

    1977-01-01

    Suckling rats were exposed for 15 and 30 days to manganese through the milk of nursing dams receiving 15 mg MnCl/sub 2/.4H/sub 2/O/kg/day orally and after which the neurological manifestations of metal poisoning were studied. No significant differences in the growth rate, developmental landmarks and walking movements were observed between the control and manganese-exposed pups. The metal concentration was significantly increased in the brain of manganese-fed pups at 15 days and exhibited a further three-fold increase over the control, at 30 days. The accumulation of the metal in the brain of manganese-exposed nursing dams was comparatively much less. A significant decrease in succinic dehydrogenase, adenosine triphosphatase, adenosine deaminase, acetylcholine esterase and an increase in monoamine oxidase activity was observed in the brain of experimental pups and dams. The results suggest that the developing brain may also be susceptible to manganese.

  2. Disruption to functional networks in neonates with perinatal brain injury predicts motor skills at 8 months.

    Science.gov (United States)

    Linke, Annika C; Wild, Conor; Zubiaurre-Elorza, Leire; Herzmann, Charlotte; Duffy, Hester; Han, Victor K; Lee, David S C; Cusack, Rhodri

    2018-01-01

    Functional connectivity magnetic resonance imaging (fcMRI) of neonates with perinatal brain injury could improve prediction of motor impairment before symptoms manifest, and establish how early brain organization relates to subsequent development. This cohort study is the first to describe and quantitatively assess functional brain networks and their relation to later motor skills in neonates with a diverse range of perinatal brain injuries. Infants ( n  = 65, included in final analyses: n  = 53) were recruited from the neonatal intensive care unit (NICU) and were stratified based on their age at birth (premature vs. term), and on whether neuropathology was diagnosed from structural MRI. Functional brain networks and a measure of disruption to functional connectivity were obtained from 14 min of fcMRI acquired during natural sleep at term-equivalent age. Disruption to connectivity of the somatomotor and frontoparietal executive networks predicted motor impairment at 4 and 8 months. This disruption in functional connectivity was not found to be driven by differences between clinical groups, or by any of the specific measures we captured to describe the clinical course. fcMRI was predictive over and above other clinical measures available at discharge from the NICU, including structural MRI. Motor learning was affected by disruption to somatomotor networks, but also frontoparietal executive networks, which supports the functional importance of these networks in early development. Disruption to these two networks might be best addressed by distinct intervention strategies.

  3. Neonatal hyperthyroidism impairs epinephrine-provoked secretion of nerve growth factor and epidermal growth factor in mouse saliva.

    Science.gov (United States)

    Lakshmanan, J; Landel, C P

    1986-07-01

    We examined long-term effects of neonatal hyperthyroidism on salivary secretions of nerve growth factor and epidermal growth factor in male and female mice at the age of 31 days. Hyperthyroidism was induced by thyroxine (T4) injections (0.4 microgram/g body weight/day) during days 0-6. Littermate control mice were treated with vehicle. T4 treatment did not alter the amounts of protein secreted into saliva but hormone administration induced alteration in the types of protein secreted. T4 treatment decreased the contents of both nerve growth factor and epidermal growth factor secreted into the saliva. A Sephadex G-200 column chromatographic profile revealed the presence of two distinct nerve growth factor immunoreactive peaks, while epidermal growth factor immunoreactivity predominantly eluted as a single low molecular weight form. T4 treatment did not alter the molecular nature of their secretion, but the treatment decreased their contents. These results indicate an impairment in salivary secretion of nerve growth factor and epidermal growth factor long after T4 treatment has been discontinued.

  4. Intranasally administered mesenchymal stem cells promote a regenerative niche for repair of neonatal ischemic brain injury.

    Science.gov (United States)

    Donega, Vanessa; Nijboer, Cora H; van Tilborg, Geralda; Dijkhuizen, Rick M; Kavelaars, Annemieke; Heijnen, Cobi J

    2014-11-01

    Previous work from our group has shown that intranasal MSC-treatment decreases lesion volume and improves motor and cognitive behavior after hypoxic-ischemic (HI) brain damage in neonatal mice. Our aim was to determine the kinetics of MSC migration after intranasal administration, and the early effects of MSCs on neurogenic processes and gliosis at the lesion site. HI brain injury was induced in 9-day-old mice and MSCs were administered intranasally at 10days post-HI. The kinetics of MSC migration were investigated by immunofluorescence and MRI analysis. BDNF and NGF gene expression was determined by qPCR analysis following MSC co-culture with HI brain extract. Nestin, Doublecortin, NeuN, GFAP, Iba-1 and M1/M2 phenotypic expression was assessed over time. MRI and immunohistochemistry analyses showed that MSCs reach the lesion site already within 2h after intranasal administration. At 12h after administration the number of MSCs at the lesion site peaks and decreases significantly at 72h. The number of DCX(+) cells increased 1 to 3days after MSC administration in the SVZ. At the lesion, GFAP(+)/nestin(+) and DCX(+) expression increased 3 to 5days after MSC-treatment. The number of NeuN(+) cells increased within 5days, leading to a dramatic regeneration of the somatosensory cortex and hippocampus at 18days after intranasal MSC administration. Interestingly, MSCs expressed significantly more BDNF gene when exposed to HI brain extract in vitro. Furthermore, MSC-treatment resulted in the resolution of the glial scar surrounding the lesion, represented by a decrease in reactive astrocytes and microglia and polarization of microglia towards the M2 phenotype. In view of the current lack of therapeutic strategies, we propose that intranasal MSC administration is a powerful therapeutic option through its functional repair of the lesion represented by regeneration of the cortical and hippocampal structure and decrease of gliosis. Copyright © 2014. Published by Elsevier Inc.

  5. [Isoflurane provides neuroprotection in neonatal hypoxic ischemic brain injury by suppressing apoptosis].

    Science.gov (United States)

    Zhao, De-An; Bi, Ling-Yun; Huang, Qian; Zhang, Fang-Min; Han, Zi-Ming

    Isoflurane is halogenated volatile ether used for inhalational anesthesia. It is widely used in clinics as an inhalational anesthetic. Neonatal hypoxic ischemia injury ensues in the immature brain that results in delayed cell death via excitotoxicity and oxidative stress. Isoflurane has shown neuroprotective properties that make a beneficial basis of using isoflurane in both cell culture and animal models, including various models of brain injury. We aimed to determine the neuroprotective effect of isoflurane on hypoxic brain injury and elucidated the underlying mechanism. A hippocampal slice, in artificial cerebrospinal fluid with glucose and oxygen deprivation, was used as an in vitro model for brain hypoxia. The orthodromic population spike and hypoxic injury potential were recorded in the CA1 and CA3 regions. Amino acid neurotransmitters concentration in perfusion solution of hippocampal slices was measured. Isoflurane treatment caused delayed elimination of population spike and improved the recovery of population spike; decreased frequency of hypoxic injury potential, postponed the onset of hypoxic injury potential and increased the duration of hypoxic injury potential. Isoflurane treatment also decreased the hypoxia-induced release of amino acid neurotransmitters such as aspartate, glutamate and glycine induced by hypoxia, but the levels of γ-aminobutyric acid were elevated. Morphological studies showed that isoflurane treatment attenuated edema of pyramid neurons in the CA1 region. It also reduced apoptosis as evident by lowered expression of caspase-3 and PARP genes. Isoflurane showed a neuro-protective effect on hippocampal neuron injury induced by hypoxia through suppression of apoptosis. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  6. Isoflurane provides neuroprotection in neonatal hypoxic ischemic brain injury by suppressing apoptosis.

    Science.gov (United States)

    Zhao, De-An; Bi, Ling-Yun; Huang, Qian; Zhang, Fang-Min; Han, Zi-Ming

    Isoflurane is halogenated volatile ether used for inhalational anesthesia. It is widely used in clinics as an inhalational anesthetic. Neonatal hypoxic ischemia injury ensues in the immature brain that results in delayed cell death via excitotoxicity and oxidative stress. Isoflurane has shown neuroprotective properties that make a beneficial basis of using isoflurane in both cell culture and animal models, including various models of brain injury. We aimed to determine the neuroprotective effect of isoflurane on hypoxic brain injury and elucidated the underlying mechanism. A hippocampal slice, in artificial cerebrospinal fluid with glucose and oxygen deprivation, was used as an in vitro model for brain hypoxia. The orthodromic population spike and hypoxic injury potential were recorded in the CA1 and CA3 regions. Amino acid neurotransmitters concentration in perfusion solution of hippocampal slices was measured. Isoflurane treatment caused delayed elimination of population spike and improved the recovery of population spike; decreased frequency of hypoxic injury potential, postponed the onset of hypoxic injury potential and increased the duration of hypoxic injury potential. Isoflurane treatment also decreased the hypoxia-induced release of amino acid neurotransmitters such as aspartate, glutamate and glycine induced by hypoxia, but the levels of γ-aminobutyric acid were elevated. Morphological studies showed that isoflurane treatment attenuated edema of pyramid neurons in the CA1 region. It also reduced apoptosis as evident by lowered expression of caspase-3 and PARP genes. Isoflurane showed a neuro-protective effect on hippocampal neuron injury induced by hypoxia through suppression of apoptosis. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  7. Isoflurane provides neuroprotection in neonatal hypoxic ischemic brain injury by suppressing apoptosis

    Directory of Open Access Journals (Sweden)

    De-An Zhao

    Full Text Available Abstract Background and objectives: Isoflurane is halogenated volatile ether used for inhalational anesthesia. It is widely used in clinics as an inhalational anesthetic. Neonatal hypoxic ischemia injury ensues in the immature brain that results in delayed cell death via excitotoxicity and oxidative stress. Isoflurane has shown neuroprotective properties that make a beneficial basis of using isoflurane in both cell culture and animal models, including various models of brain injury. We aimed to determine the neuroprotective effect of isoflurane on hypoxic brain injury and elucidated the underlying mechanism. Methods: A hippocampal slice, in artificial cerebrospinal fluid with glucose and oxygen deprivation, was used as an in vitro model for brain hypoxia. The orthodromic population spike and hypoxic injury potential were recorded in the CA1 and CA3 regions. Amino acid neurotransmitters concentration in perfusion solution of hippocampal slices was measured. Results: Isoflurane treatment caused delayed elimination of population spike and improved the recovery of population spike; decreased frequency of hypoxic injury potential, postponed the onset of hypoxic injury potential and increased the duration of hypoxic injury potential. Isoflurane treatment also decreased the hypoxia-induced release of amino acid neurotransmitters such as aspartate, glutamate and glycine induced by hypoxia, but the levels of γ-aminobutyric acid were elevated. Morphological studies showed that isoflurane treatment attenuated edema of pyramid neurons in the CA1 region. It also reduced apoptosis as evident by lowered expression of caspase-3 and PARP genes. Conclusions: Isoflurane showed a neuro-protective effect on hippocampal neuron injury induced by hypoxia through suppression of apoptosis.

  8. Primary microglia isolation from mixed glial cell cultures of neonatal rat brain tissue.

    Science.gov (United States)

    Tamashiro, Tami T; Dalgard, Clifton Lee; Byrnes, Kimberly R

    2012-08-15

    Microglia account for approximately 12% of the total cellular population in the mammalian brain. While neurons and astrocytes are considered the major cell types of the nervous system, microglia play a significant role in normal brain physiology by monitoring tissue for debris and pathogens and maintaining homeostasis in the parenchyma via phagocytic activity. Microglia are activated during a number of injury and disease conditions, including neurodegenerative disease, traumatic brain injury, and nervous system infection. Under these activating conditions, microglia increase their phagocytic activity, undergo morpohological and proliferative change, and actively secrete reactive oxygen and nitrogen species, pro-inflammatory chemokines and cytokines, often activating a paracrine or autocrine loop. As these microglial responses contribute to disease pathogenesis in neurological conditions, research focused on microglia is warranted. Due to the cellular heterogeneity of the brain, it is technically difficult to obtain sufficient microglial sample material with high purity during in vivo experiments. Current research on the neuroprotective and neurotoxic functions of microglia require a routine technical method to consistently generate pure and healthy microglia with sufficient yield for study. We present, in text and video, a protocol to isolate pure primary microglia from mixed glia cultures for a variety of downstream applications. Briefly, this technique utilizes dissociated brain tissue from neonatal rat pups to produce mixed glial cell cultures. After the mixed glial cultures reach confluency, primary microglia are mechanically isolated from the culture by a brief duration of shaking. The microglia are then plated at high purity for experimental study. The principle and protocol of this methodology have been described in the literature. Additionally, alternate methodologies to isolate primary microglia are well described. Homogenized brain tissue may be separated

  9. Formation of binucleated myocardial cells in the neonatal rat. An index for growth hypertrophy

    International Nuclear Information System (INIS)

    Clubb, F.J. Jr.; Bishop, S.P.

    1984-01-01

    The purposes of this study were to characterize myocardial cell growth in neonatal rats and investigate the mechanism of binucleation in myocardial cells. To test the hypothesis that binucleated myocardial cells result from karyokinesis without cytokinesis, experiments were designed to measure the rate of DNA synthesis and the percentage of binucleated myocardial cells in neonatal rats during growth. Estimates of myocardial cell nuclear divisions were obtained from rats pulsed with tritiated thymidine at 17 days of gestation. Autoradiograms were prepared from isolated myocardial cells of rats killed at various ages postpartum, and the number of developed silver halide grains over myocardial cell nuclei was calculated. This estimated the mitotic activity of nuclei. To determine myocardial cell DNA synthesis postpartum, another set of rats were injected at various time periods with 4 hourly doses of tritiated thymidine, and hearts were fixed by perfusion 1 hour later. Labeling index of myocardial cells was calculated (labeled/total myocardial cells) from autoradiograms. Results indicated that the growth of myocardial cells in period can be divided into three phases: (a) a hyperplastic phase, (b) a transitional phase, and (c) a hypertrophic phase. Binucleation of myocardial cells was not due to fusion of mononucleated cells

  10. Intermittent hypoxia suppression of growth hormone and insulin-like growth factor-I in the neonatal rat liver.

    Science.gov (United States)

    Cai, Charles; Ahmad, Taimur; Valencia, Gloria B; Aranda, Jacob V; Xu, Jiliu; Beharry, Kay D

    2018-03-08

    Extremely low gestational age neonates with chronic lung disease requiring oxygen therapy frequently experience fluctuations in arterial oxygen saturation or intermittent hypoxia (IH). These infants are at risk for multi-organ developmental delay, reduced growth, and short stature. The growth hormone (GH)/insulin-like growth factor-I (IGF-1) system, an important hormonal regulator of lipid and carbohydrate metabolism, promotes neonatal growth and development. We tested the hypothesis that increasing episodes of IH delay neonatal growth by influencing the GH/IGF-I axis. Newborn rats were exposed to 2, 4, 6, 8, 10, or 12 hypoxic episodes (12% O 2 ) during hyperoxia (50% O 2 ) from P0-P7, P0-P14 (IH), or allowed to recover from P7-P21 or P14-P21 (IHR) in room air (RA). RA littermates at P7, P14, and P21 served as RA controls; and groups exposed to hyperoxia only (50% O 2 ) served as zero IH controls. Histopathology of the liver; hepatic levels of GH, GHBP, IGF-I, IGFBP-3, and leptin; and immunoreactivities of GH, GHR, IGF-I and IGF-IR were determined. Pathological findings of the liver, including cellular swelling, steatosis, necrosis and focal sinusoid congestion were seen in IH, and were particularly severe in the P7 animals. Hepatic GH levels were significantly suppressed in the IH groups exposed to 6-12 hypoxic episodes per day and were not normalized during IHR. Deficits in the GH levels were associated with reduced body length and increase body weight during IHR suggesting increased adiposity and catchup fat. Catchup fat was also associated with elevations in GHBP, IGF-I, leptin. IH significantly impairs hepatic GH/IGF-1 signaling during the first few weeks of life, which is likely responsible for hepatic GH resistance, increased body fat, and hepatic steatosis. These hormonal perturbations may contribute to long-term organ and body growth impairment, and metabolic dysfunction in preterm infants experiencing frequent IH and/or apneic episodes. Copyright © 2018

  11. Quantification of ante-mortem hypoxic ischemic brain injury by post-mortem cerebral magnetic resonance imaging in neonatal encephalopathy.

    Science.gov (United States)

    Montaldo, Paolo; Chaban, Badr; Lally, Peter J; Sebire, Neil J; Taylor, Andrew M; Thayyil, Sudhin

    2015-11-01

    Post-mortem (PM) magnetic resonance imaging (MRI) is increasingly used as an alternative to conventional autopsy in babies dying from neonatal encephalopathy. However, the confounding effect of post-mortem changes on the detection of ante-mortem ischemic injury is unclear. We examined whether quantitative MR measurements can accurately distinguish ante-mortem ischemic brain injury from artifacts using post-mortem MRI. We compared PM brain MRI (1.5 T Siemens, Avanto) in 7 infants who died with neonatal encephalopathy (NE) of presumed hypoxic-ischemic origin with 7 newborn infants who had sudden unexplained neonatal death (SUND controls) without evidence of hypoxic-ischemic brain injury at autopsy. We measured apparent diffusion coefficients (ADCs), T1-weighted signal intensity ratios (SIRs) compared to vitreous humor and T2 relaxation times from 19 predefined brain areas typically involved in neonatal encephalopathy. There were no differences in mean ADC values, SIRs on T1-weighted images or T2 relaxation times in any of the 19 predefined brain areas between NE and SUND infants. All MRI images showed loss of cortical gray/white matter differentiation, loss of the normal high signal intensity (SI) in the posterior limb of the internal capsule on T1-weighted images, and high white matter SI on T2-weighted images. Normal post-mortem changes may be easily mistaken for ante-mortem ischemic injury, and current PM MRI quantitative assessment cannot reliably distinguish these. These findings may have important implications for appropriate interpretation of PM imaging findings, especially in medico-legal practice. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  12. Neonatal pain and reduced maternal care: Early-life stressors interacting to impact brain and behavioral development.

    Science.gov (United States)

    Mooney-Leber, Sean M; Brummelte, Susanne

    2017-02-07

    Advances in neonatal intensive care units (NICUs) have drastically increased the survival chances of preterm infants. However, preterm infants are still exposed to a wide range of stressors during their stay in the NICU, which include painful procedures and reduced maternal contact. The activation of the hypothalamic-pituitary-adrenal (HPA) axis, in response to these stressors during this critical period of brain development, has been associated with many acute and long-term adverse biobehavioral outcomes. Recent research has shown that Kangaroo care, a non-pharmacological analgesic based on increased skin-to-skin contact between the neonate and the mother, negates the adverse outcomes associated with neonatal pain and reduced maternal care, however the biological mechanism remains widely unknown. This review summarizes findings from both human and rodent literature investigating neonatal pain and reduced maternal care independently, primarily focusing on the role of the HPA axis and biobehavioral outcomes. The physiological and positive outcomes of Kangaroo care will also be discussed in terms of how dampening of the HPA axis response to neonatal pain and increased maternal care may account for positive outcomes associated with Kangaroo care. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. Early Environmental Enrichment Enhances Abnormal Brain Connectivity in a Rabbit Model of Intrauterine Growth Restriction.

    Science.gov (United States)

    Illa, Miriam; Brito, Verónica; Pla, Laura; Eixarch, Elisenda; Arbat-Plana, Ariadna; Batallé, Dafnis; Muñoz-Moreno, Emma; Crispi, Fatima; Udina, Esther; Figueras, Francesc; Ginés, Silvia; Gratacós, Eduard

    2017-10-12

    The structural correspondence of neurodevelopmental impairments related to intrauterine growth restriction (IUGR) that persists later in life remains elusive. Moreover, early postnatal stimulation strategies have been proposed to mitigate these effects. Long-term brain connectivity abnormalities in an IUGR rabbit model and the effects of early postnatal environmental enrichment (EE) were explored. IUGR was surgically induced in one horn, whereas the contralateral one produced the controls. Postnatally, a subgroup of IUGR animals was housed in an enriched environment. Functional assessment was performed at the neonatal and long-term periods. At the long-term period, structural brain connectivity was evaluated by means of diffusion-weighted brain magnetic resonance imaging and by histological assessment focused on the hippocampus. IUGR animals displayed poorer functional results and presented altered whole-brain networks and decreased median fractional anisotropy in the hippocampus. Reduced density of dendritic spines and perineuronal nets from hippocampal neurons were also observed. Of note, IUGR animals exposed to enriched environment presented an improvement in terms of both function and structure. IUGR is associated with altered brain connectivity at the global and cellular level. A strategy based on early EE has the potential to restore the neurodevelopmental consequences of IUGR. © 2017 S. Karger AG, Basel.

  14. Nitric oxide induces hypoxia ischemic injury in the neonatal brain via the disruption of neuronal iron metabolism.

    Science.gov (United States)

    Lu, Qing; Harris, Valerie A; Rafikov, Ruslan; Sun, Xutong; Kumar, Sanjiv; Black, Stephen M

    2015-12-01

    We have recently shown that increased hydrogen peroxide (H2O2) generation is involved in hypoxia-ischemia (HI)-mediated neonatal brain injury. H2O2 can react with free iron to form the hydroxyl radical, through Fenton Chemistry. Thus, the objective of this study was to determine if there was a role for the hydroxyl radical in neonatal HI brain injury and to elucidate the underlying mechanisms. Our data demonstrate that HI increases the deposition of free iron and hydroxyl radical formation, in both P7 hippocampal slice cultures exposed to oxygen-glucose deprivation (OGD), and the neonatal rat exposed to HI. Both these processes were found to be nitric oxide (NO) dependent. Further analysis demonstrated that the NO-dependent increase in iron deposition was mediated through increased transferrin receptor expression and a decrease in ferritin expression. This was correlated with a reduction in aconitase activity. Both NO inhibition and iron scavenging, using deferoxamine administration, reduced hydroxyl radical levels and neuronal cell death. In conclusion, our results suggest that increased NO generation leads to neuronal cell death during neonatal HI, at least in part, by altering iron homeostasis and hydroxyl radical generation. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  17. Customized versus population-based birth weight charts for the detection of neonatal growth and perinatal morbidity in a cross-sectional study of term neonates.

    Science.gov (United States)

    Carberry, Angela E; Raynes-Greenow, Camille H; Turner, Robin M; Jeffery, Heather E

    2013-10-15

    Customized birth weight charts that incorporate maternal characteristics are now being adopted into clinical practice. However, there is controversy surrounding the value of these charts in the prediction of growth and perinatal outcomes. The objective of this study was to assess the use of customized charts in predicting growth, defined by body fat percentage, and perinatal morbidity. A total of 581 term (≥37 weeks' gestation) neonates born in Sydney, Australia, in 2010 were included. Body fat percentage measurements were taken by using air displacement plethysmography. Objective composite measurements of perinatal morbidity were used to identify neonates who had poor outcomes; these data were extracted from medical records. The value of customized charts was assessed by calculating positive predictive values, negative predictive values, and odds ratios with 95% confidence intervals. Customized versus population-based charts did not improve the prediction of either low body fat percentage (59% vs. 66% positive predictive value and 87% vs. 89% negative predictive value, respectively) or high body fat percentage (48% vs. 53% positive predictive value and 90% vs. 89% negative predictive value, respectively). Customized charts were not better than population-based charts at predicting perinatal morbidity (for customized charts, odds ratio = 1.02, 95% confidence interval: 1.01, 1.04; for population-based charts, odds ratio = 1.03, 95% confidence interval: 1.01, 1.05) per percentile decrease in birth weight. Customized birth weight charts do not provide significant improvements over population-based charts in predicting neonatal growth and morbidity.

  18. Rodent neonatal germinal matrix hemorrhage mimics the human brain injury, neurological consequences, and post-hemorrhagic hydrocephalus

    OpenAIRE

    Lekic, Tim; Manaenko, Anatol; Rolland, William; Krafft, Paul R.; Peters, Regina; Hartman, Richard E.; Altay, Orhan; Tang, Jiping; Zhang, John H.

    2012-01-01

    Germinal matrix hemorrhage (GMH) is the most common neurological disease of premature newborns. GMH causes neurological sequelae such as cerebral palsy, post-hemorrhagic hydrocephalus, and mental retardation. Despite this, there is no standardized animal model of spontaneous GMH using newborn rats to depict the condition. We asked whether stereotactic injection of collagenase type VII (0.3 U) into the ganglionic eminence of neonatal rats would reproduce the acute brain injury, gliosis, hydroc...

  19. The effects of electronic cigarette emissions on systemic cotinine levels, weight and postnatal lung growth in neonatal mice.

    Directory of Open Access Journals (Sweden)

    Sharon A McGrath-Morrow

    Full Text Available Electronic cigarette (E-cigarettes emissions present a potentially new hazard to neonates through inhalation, dermal and oral contact. Exposure to nicotine containing E-cigarettes may cause significant systemic absorption in neonates due to the potential for multi-route exposure. Systemic absorption of nicotine and constituents of E-cigarette emissions may adversely impact weight and lung development in the neonate. To address these questions we exposed neonatal mice to E-cigarette emissions and measured systemic cotinine levels and alveolar lung growth.Neonatal mice were exposed to E-cigarettes for the first 10 days of life. E-cigarette cartridges contained either 1.8% nicotine in propylene glycol (PG or PG vehicle alone. Daily weights, plasma and urine cotinine levels and lung growth using the alveolar mean linear intercept (MLI method were measured at 10 days of life and compared to room air controls. Mice exposed to 1.8% nicotine/PG had a 13.3% decrease in total body weight compared to room air controls. Plasma cotinine levels were found to be elevated in neonatal mice exposed to 1.8% nicotine/PG E-cigarettes (mean 62.34± 3.3 ng/ml. After adjusting for sex and weight, the nicotine exposed mice were found to have modestly impaired lung growth by MLI compared to room air control mice (p<.054 trial 1; p<.006 trial 2. These studies indicate that exposure to E-cigarette emissions during the neonatal period can adversely impact weight gain. In addition exposure to nicotine containing E-cigarettes can cause detectable levels of systemic cotinine, diminished alveolar cell proliferation and a modest impairment in postnatal lung growth.

  20. The effects of electronic cigarette emissions on systemic cotinine levels, weight and postnatal lung growth in neonatal mice.

    Science.gov (United States)

    McGrath-Morrow, Sharon A; Hayashi, Madoka; Aherrera, Angela; Lopez, Armando; Malinina, Alla; Collaco, Joseph M; Neptune, Enid; Klein, Jonathan D; Winickoff, Jonathan P; Breysse, Patrick; Lazarus, Philip; Chen, Gang

    2015-01-01

    Electronic cigarette (E-cigarettes) emissions present a potentially new hazard to neonates through inhalation, dermal and oral contact. Exposure to nicotine containing E-cigarettes may cause significant systemic absorption in neonates due to the potential for multi-route exposure. Systemic absorption of nicotine and constituents of E-cigarette emissions may adversely impact weight and lung development in the neonate. To address these questions we exposed neonatal mice to E-cigarette emissions and measured systemic cotinine levels and alveolar lung growth. Neonatal mice were exposed to E-cigarettes for the first 10 days of life. E-cigarette cartridges contained either 1.8% nicotine in propylene glycol (PG) or PG vehicle alone. Daily weights, plasma and urine cotinine levels and lung growth using the alveolar mean linear intercept (MLI) method were measured at 10 days of life and compared to room air controls. Mice exposed to 1.8% nicotine/PG had a 13.3% decrease in total body weight compared to room air controls. Plasma cotinine levels were found to be elevated in neonatal mice exposed to 1.8% nicotine/PG E-cigarettes (mean 62.34± 3.3 ng/ml). After adjusting for sex and weight, the nicotine exposed mice were found to have modestly impaired lung growth by MLI compared to room air control mice (pE-cigarette emissions during the neonatal period can adversely impact weight gain. In addition exposure to nicotine containing E-cigarettes can cause detectable levels of systemic cotinine, diminished alveolar cell proliferation and a modest impairment in postnatal lung growth.

  1. Glycogen metabolism in brain and neurons - astrocytes metabolic cooperation can be altered by pre- and neonatal lead (Pb) exposure.

    Science.gov (United States)

    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.

  2. Impact of intrauterine growth retardation and body proportionality on fetal and neonatal outcome.

    Science.gov (United States)

    Kramer, M S; Olivier, M; McLean, F H; Willis, D M; Usher, R H

    1990-11-01

    Previous prognostic studies of infants with intrauterine growth retardation (IUGR) have not adequately considered the heterogeneity of IUGR in terms of cause, severity, and body proportionality and have been prone to misclassification of IUGR because of errors in estimation of gestational age. Based on a cohort of 8719 infants with early-ultrasound-validated gestational ages and indexes of body proportionality standardized for birth weight, the consequences of severity and cause-specific IUGR and proportionality for fetal and neonatal morbidity and mortality were assessed. With progressive severity of IUGR, there were significant (all P less than .001) linear trends for increasing risks of stillbirth, fetal distress (abnormal electronic fetal heart tracings)O during parturition, neonatal hypoglycemia (minimum plasma glucose less than 40 mg/dL), hypocalcemia (minimum Ca less than 7 mg/dL), polycythemia (maximum capillary hemoglobin greater than or equal to 21 g/dL), severe depression at birth (manual ventilation greater than 3 minutes), 1-minute and 5-minute Apgar scores less than or equal to 6, 1-minute Apgar score less than or equal to 3, and in-hospital death. These trends persisted for the more common outcomes even after restriction to term (37 to 42 weeks) births. There was no convincing evidence that outcome among infants with a given degree of growth retardation varied as a function of cause of that growth retardation. Among infants with IUGR, increased length-for-weight had significant crude associations with hypoglycemia and polycythemia, but these associations disappeared after adjustment for severity of growth retardation and gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Minocycline Transiently Reduces Microglia/Macrophage Activation but Exacerbates Cognitive Deficits Following Repetitive Traumatic Brain Injury in the Neonatal Rat

    Science.gov (United States)

    Hanlon, Lauren A.; Huh, Jimmy W.

    2016-01-01

    Elevated microglial/macrophage-associated biomarkers in the cerebrospinal fluid of infant victims of abusive head trauma (AHT) suggest that these cells play a role in the pathophysiology of the injury. In a model of AHT in 11-day-old rats, 3 impacts (24 hours apart) resulted in spatial learning and memory deficits and increased brain microglial/macrophage reactivity, traumatic axonal injury, neuronal degeneration, and cortical and white-matter atrophy. The antibiotic minocycline has been effective in decreasing injury-induced microglial/macrophage activation while simultaneously attenuating cellular and functional deficits in models of neonatal hypoxic ischemia, but the potential for this compound to rescue deficits after impact-based trauma to the immature brain remains unexplored. Acute minocycline administration in this model of AHT decreased microglial/macrophage reactivity in the corpus callosum of brain-injured animals at 3 days postinjury, but this effect was lost by 7 days postinjury. Additionally, minocycline treatment had no effect on traumatic axonal injury, neurodegeneration, tissue atrophy, or spatial learning deficits. Interestingly, minocycline-treated animals demonstrated exacerbated injury-induced spatial memory deficits. These results contrast with previous findings in other models of brain injury and suggest that minocycline is ineffective in reducing microglial/macrophage activation and ameliorating injury-induced deficits following repetitive neonatal traumatic brain injury. PMID:26825312

  4. Insulin Like Growth Factor System: How Does it Affect Neonatal Anthropometry?

    Directory of Open Access Journals (Sweden)

    Emine Kacar

    2016-09-01

    Full Text Available Aim: The present study aims to clarify the role of insulin like growth factor-1 (IGF-1, insulin like growth factor binding protein-3 (IGFBP-3, ghrelin, and insulin in fetal growth. Material and Method: Based on Turkish standards, 14 newborns were defined as small for gestational age (SGA, 33 newborns were described as appropriate for gestational age (AGA, and 13 newborns were identified as large for gestational age (LGA. IGF-1, IGFBP-3, ghrelin, and insulin levels were measured in umbilical cord and maternal serum. Results: The LGA group had significantly higher levels of IGF-1, IGFBP-3, ghrelin, and insulin in umbilical cord and maternal serum than the SGA group. Umbilical cord and maternal serum levels of IGF-1 and IGFBP-3 correlated significantly and positively with body weight, body length, head circumference, and abdominal circumference of the neonates. Discussion: Based on the findings of the present study, it may be postulated that insulin like growth factor system has a role in fetal growth.

  5. Brain injury and altered brain growth in preterm infants: predictors and prognosis.

    Science.gov (United States)

    Kidokoro, Hiroyuki; Anderson, Peter J; Doyle, Lex W; Woodward, Lianne J; Neil, Jeffrey J; Inder, Terrie E

    2014-08-01

    To define the nature and frequency of brain injury and brain growth impairment in very preterm (VPT) infants by using MRI at term-equivalent age and to relate these findings to perinatal risk factors and 2-year neurodevelopmental outcomes. MRI scans at term-equivalent age from 3 VPT cohorts (n = 325) were reviewed. The severity of brain injury, including periventricular leukomalacia and intraventricular and cerebellar hemorrhage, was graded. Brain growth was assessed by using measures of biparietal width (BPW) and interhemispheric distance. Neurodevelopmental outcome at age 2 years was assessed across all cohorts (n = 297) by using the Bayley Scales of Infant Development, Second Edition (BSID-II) or Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), and evaluation for cerebral palsy. Of 325 infants, 107 (33%) had some grade of brain injury and 33 (10%) had severe injury. Severe brain injury was more common in infants with lower Apgar scores, necrotizing enterocolitis, inotropic support, and patent ductus arteriosus. Severe brain injury was associated with delayed cognitive and motor development and cerebral palsy. Decreased BPW was related to lower gestational age, inotropic support, patent ductus arteriosus, necrotizing enterocolitis, prolonged parenteral nutrition, and oxygen at 36 weeks and was associated with delayed cognitive development. In contrast, increased interhemispheric distance was related to male gender, dexamethasone use, and severe brain injury. It was also associated with reduced cognitive development, independent of BPW. At term-equivalent age, VPT infants showed both brain injury and impaired brain growth on MRI. Severe brain injury and impaired brain growth patterns were independently associated with perinatal risk factors and delayed cognitive development. Copyright © 2014 by the American Academy of Pediatrics.

  6. Impact of Early Versus Late Diuretic Exposure on Metabolic Bone Disease and Growth in Premature Neonates.

    Science.gov (United States)

    Orth, Lucas E; O'Mara, Keliana L

    2018-01-01

    This study aimed to determine whether there are differences in the incidence of metabolic bone disease (MBD) between preterm neonates first exposed to diuretics prior to 2 weeks of life versus those exposed after 2 weeks. This study was a retrospective analysis of premature neonates born at a tertiary care center between 2011 and 2015 who received either furosemide or chlorothiazide. The primary outcome was incidence of MBD. Secondary outcomes included growth, electrolyte disturbances, oxygen requirement, and length of stay. A total of 147 patients were included. Early initiation (n = 90) and late initiation (n = 57) arms were balanced with respect to birth weight and gestational age. There was no difference in incidence of MBD in the early group (76%) versus the late group (65%; p = 0.164). Stratification by cumulative dose showed incidence of 85% in patients receiving ≥8 mg/kg of furosemide, compared with 68% and 64% of those in the <4 mg/kg and 4 to 7.9 mg/kg strata, respectively (p = 0.06). The early group experienced greater reductions in length-for-age growth during diuretic therapy (-70% versus -40%; p = 0.009). Electrolyte abnormalities were more prevalent in the early group. Although there was no difference in duration of mechanical ventilation, duration of supplemental oxygen requirement was reduced in the late group (75 versus 89 days; p = 0.003). Timing of diuretic initiation did not affect incidence of MBD. Increased cumulative furosemide exposure may be associated with higher incidence. Patients first exposed to diuretics within 2 weeks of life are at higher risk for electrolyte abnormalities and reduced growth velocity.

  7. Oxcarbazepine causes neurocyte apoptosis and developing brain damage by triggering Bax/Bcl-2 signaling pathway mediated caspase 3 activation in neonatal rats.

    Science.gov (United States)

    Song, Y; Zhong, M; Cai, F-C

    2018-01-01

    Anti-epileptic drugs (AEDs) are the main methods for treatment of neonatal seizures; however, a few AEDs may cause developing brain damage of neonate. This study aims to investigate effects of oxcarbazepine (OXC) on developing brain damage of neonatal rats. Both of neonatal and adult rats were divided into 6 groups, including Control, OXC 187.5 mg/kg, OXC 281.25 mg/kg, OXC 375 mg/kg group, LEV and PHT group. Body weight and brain weight were evaluated. Hematoxylin and eosin (HE) and Nissl staining were used to observe neurocyte morphology and Nissl bodies, respectively. Apoptosis was examined using TUNEL assay, and caspase 8 activity was evaluated using spectrophotometer method. Cytochrome C-release was evaluated using flow cytometry. Western blot was used to examine Bax and Bcl-2 expression. OXC 375 mg/kg treatment significantly decreased brain weight compared to Control group in neonatal rats (P5 rats) (pOxcarbazepine at a concentration of 281.25 mg/kg or more causes neurocyte apoptosis and developing brain damage by triggering Bax/Bcl-2 signaling pathway mediated caspase 3 activation in neonatal rats.

  8. Brain ultrasonography findings in neonates with exposure to cocaine during pregnancy

    NARCIS (Netherlands)

    van Huis, M.; van Kempen, A.A.M.W.; Peelen, M.; Timmers, M.; Boer, K.; Smit, B.J.; van Rijn, R.R.

    2009-01-01

    BACKGROUND: Cocaine exposure during pregnancy has been reported to have detrimental effects on the fetus. OBJECTIVE: To describe the findings on cranial ultrasonography (CUS) as part of a neonatal screening programme for exposed neonates. MATERIALS AND METHODS: The study was a semiprospective

  9. Netherton Syndrome in a Neonate with Possible Growth Hormone Deficiency and Transient Hyperaldosteronism

    Directory of Open Access Journals (Sweden)

    Chatziioannidis Ilias

    2015-01-01

    Full Text Available Netherton syndrome, a rare autosomal recessive genetic disorder, is classified as an ichthyosiform syndrome. In this report we present the case of a neonate with erythroderma shortly after birth, accompanied by severe hypernatremia, recurrent infections, transient hyperaldosteronism, and signs of growth hormone (GH deficiency. DNA molecular analysis in the SPINK5 gene revealed heterozygosity in our index patient for 238insG and 2468delA frameshift mutations in exons 4 and 26, respectively, in the maternal allele and 1431-12G>A splice-site mutation in intron 15 in the paternal allele as well as the missense variation E420K in homozygous state. Combination of the identified mutations along with transient hyperaldosteronism and possible GH deficiency have not been described before. Accordingly, the importance of early multidisciplinary approach is highlighted, in order to reach accurate diagnosis, initiate prompt treatment, and ensure survival with fewer disease complications.

  10. Effect of Growth Hormone Deficiency on Brain Structure, Motor Function and Cognition

    Science.gov (United States)

    Webb, Emma A.; O'Reilly, Michelle A.; Clayden, Jonathan D.; Seunarine, Kiran K.; Chong, Wui K.; Dale, Naomi; Salt, Alison; Clark, Chris A.; Dattani, Mehul T.

    2012-01-01

    The growth hormone-insulin-like growth factor-1 axis plays a role in normal brain growth but little is known of the effect of growth hormone deficiency on brain structure. Children with isolated growth hormone deficiency (peak growth hormone less than 6.7 [micro]g/l) and idiopathic short stature (peak growth hormone greater than 10 [micro]g/l)…

  11. Relationship between general movements in neonates who were growth restricted in utero and prenatal Doppler flow patterns

    NARCIS (Netherlands)

    Tanis, J. C.; Schmitz, D. M.; Boelen, M. R.; Casarella, L.; Berg, van den Paul; Bilardo, C. M.; Bos, A. F.

    2016-01-01

    Objective To investigate whether Doppler pulsatility indices (PIs) of the fetal circulation in cases of fetal growth restriction (FGR) are associated with the general movements (GMs) of the neonate after birth. Methods This was a prospective observational cohort study including pregnancies with FGR

  12. Growth of Malignant Non-CNS Tumors Alters Brain Metabolome

    Science.gov (United States)

    Kovalchuk, Anna; Nersisyan, Lilit; Mandal, Rupasri; Wishart, David; Mancini, Maria; Sidransky, David; Kolb, Bryan; Kovalchuk, Olga

    2018-01-01

    Cancer survivors experience numerous treatment side effects that negatively affect their quality of life. Cognitive side effects are especially insidious, as they affect memory, cognition, and learning. Neurocognitive deficits occur prior to cancer treatment, arising even before cancer diagnosis, and we refer to them as “tumor brain.” Metabolomics is a new area of research that focuses on metabolome profiles and provides important mechanistic insights into various human diseases, including cancer, neurodegenerative diseases, and aging. Many neurological diseases and conditions affect metabolic processes in the brain. However, the tumor brain metabolome has never been analyzed. In our study we used direct flow injection/mass spectrometry (DI-MS) analysis to establish the effects of the growth of lung cancer, pancreatic cancer, and sarcoma on the brain metabolome of TumorGraft™ mice. We found that the growth of malignant non-CNS tumors impacted metabolic processes in the brain, affecting protein biosynthesis, and amino acid and sphingolipid metabolism. The observed metabolic changes were similar to those reported for neurodegenerative diseases and brain aging, and may have potential mechanistic value for future analysis of the tumor brain phenomenon. PMID:29515623

  13. Neonatal physiological correlates of near-term brain development on MRI and DTI in very-low-birth-weight preterm infants

    Directory of Open Access Journals (Sweden)

    Jessica Rose, PhD

    2014-01-01

    Results suggest that at near-term age, thalamus WM microstructure may be particularly vulnerable to certain neonatal risk factors. Interactions between albumin, bilirubin, phototherapy, and brain development warrant further investigation. Identification of physiological risk factors associated with selective vulnerability of certain brain regions at near-term age may clarify the etiology of neurodevelopmental impairment and inform neuroprotective treatment for VLBW preterm infants.

  14. Adult naked mole-rat brain retains the NMDA receptor subunit GluN2D associated with hypoxia tolerance in neonatal mammals.

    Science.gov (United States)

    Peterson, Bethany L; Park, Thomas J; Larson, John

    2012-01-11

    Adult naked mole-rats show a number of systemic adaptations to a crowded underground habitat that is low in oxygen and high in carbon dioxide. Remarkably, brain slice tissue from adult naked mole-rats also is extremely tolerant to oxygen deprivation as indicated by maintenance of synaptic transmission under hypoxic conditions as well as by a delayed neuronal depolarization during anoxia. These characteristics resemble hypoxia tolerance in brain slices from neonates in a variety of mammal species. An important component of neonatal tolerance to hypoxia involves the subunit composition of NMDA receptors. Neonates have a high proportion of NMDA receptors with GluN2D subunits which are protective because they retard calcium entry into neurons during hypoxic episodes. Therefore, we hypothesized that adult naked mole-rats retain a protective, neonatal-like, NMDA receptor subunit profile. We used immunoblotting to assess age-related changes in NMDA receptor subunits in naked mole-rats and mice. The results show that adult naked mole-rat brain retains a much greater proportion of the hypoxia-protective GluN2D subunit compared to adult mice. However, age-related changes in other subunits (GluN2A and GluN2B) from the neonatal period to adulthood were comparable in mice and naked mole-rats. Hence, adult naked mole-rat brain only retains the neonatal NMDA receptor subunit that is associated with hypoxia tolerance. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  15. Hypothermia Modulates Cytokine Responses After Neonatal Rat Hypoxic-Ischemic Injury and Reduces Brain Damage

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    Xiangpeng Yuan

    2014-11-01

    Full Text Available While hypothermia (HT is the standard-of-care for neonates with hypoxic ischemic injury (HII, the mechanisms underlying its neuroprotective effect are poorly understood. We examined ischemic core/penumbra and cytokine/chemokine evolution in a 10-day-old rat pup model of HII. Pups were treated for 24 hr after HII with HT (32℃; n = 18 or normothermia (NT, 35℃; n = 15. Outcomes included magnetic resonance imaging (MRI, neurobehavioral testing, and brain cytokine/chemokine profiling (0, 24, 48, and 72 hr post-HII. Lesion volumes (24 hr were reduced in HT pups (total 74%, p < .05; penumbra 68%, p < .05; core 85%, p = .19. Lesion volumes rebounded at 72 hr (48 hr post-HT with no significant differences between NT and HT pups. HT reduced interleukin-1β (IL-1β at all time points (p < .05; monocyte chemoattractant protein-1 (MCP-1 trended toward being decreased in HT pups (p = .09. The stem cell signaling molecule, stromal cell-derived factor-1 (SDF-1 was not altered by HT. Our data demonstrate that HT reduces total and penumbral lesion volumes (at 24 and 48 hr, potentially by decreasing IL-1β without affecting SDF-1. Disassociation between the increasing trend in HII volumes from 48 to 72 hr post-HII when IL-1β levels remained low suggests that after rewarming, mechanisms unrelated to IL-1β expression are likely to contribute to this delayed increase in injury. Additional studies should be considered to determine what these mechanisms might be and also to explore whether extending the duration or degree of HT might ameliorate this delayed increase in injury.

  16. [Mechanism of potassium channel in hypoxia-ischemic brain edema: experiment with neonatal rat astrocyte].

    Science.gov (United States)

    Fu, Xue-mei; Xiang, Long; Liao, Da-qing; Feng, Zhi-chun; Mu, De-zhi

    2008-11-04

    To investigate the mechanism of potassium channel in brain edema caused by hypoxia-ischemia (HI). Astrocytes were obtained from 3-day-old SD rats, cultured, and randomly divided into 2 groups: normoxia group, cultured under normoxic condition, and hypoxic-ischemic group, cultured under hypoxic-ischemic condition. The cell volume was measured by radiologic method. Patch-clamp technique was used to observe the electric physiological properties of the voltage-gated potassium channels (Kv) in a whole cell configuration, and the change of voltage-gated potassium channel current (IKv) was recorded in cultured neonatal rat astrocyte during HI. Aquaporin 4 (AQP4) expression vector was constructed from pSUPER vector and transfected into the astrocytes (AQP4 RNAi) to construct AQP4 knockdown (AQP4-/-) cells. cellular volume was determined using [3H]-3-O-methyl-D-glucose uptake in both AQP4-/- and AQP4+/+ cells under the condition of HI. Real time PCR and Western blotting were used to detect the mRNA and protein expression of AQP4. The percentages of the AQP4+/+ and AQP4-/- astrocyte volumes in the condition of HI for 0.5, 1, 2, and 4 h were 104+/-7, 109+/-6, 126+/-12, and 152+/-9 times, and 97+/-7, 105+/-9, 109+/-7, and 132+/-6 times as those of their corresponding control groups (all Pastrocytes significantly increased during HI and the degrees of edema mediated by AQP4 knockdown at different time points were all significantly milder (all Pastrocytes via aquaporin-4 and then cell swelling.

  17. Elevated endogenous erythropoietin concentrations are associated with increased risk of brain damage in extremely preterm neonates.

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    Steven J Korzeniewski

    Full Text Available We sought to determine, in very preterm infants, whether elevated perinatal erythropoietin (EPO concentrations are associated with increased risks of indicators of brain damage, and whether this risk differs by the co-occurrence or absence of intermittent or sustained systemic inflammation (ISSI.Protein concentrations were measured in blood collected from 786 infants born before the 28th week of gestation. EPO was measured on postnatal day 14, and 25 inflammation-related proteins were measured weekly during the first 2 postnatal weeks. We defined ISSI as a concentration in the top quartile of each of 25 inflammation-related proteins on two separate days a week apart. Hypererythropoietinemia (hyperEPO was defined as the highest quartile for gestational age on postnatal day 14. Using logistic regression and multinomial logistic regression models, we compared risks of brain damage among neonates with hyperEPO only, ISSI only, and hyperEPO+ISSI, to those who had neither hyperEPO nor ISSI, adjusting for gestational age.Newborns with hyperEPO, regardless of ISSI, were more than twice as likely as those without to have very low (< 55 Mental (OR 2.3; 95% CI 1.5-3.5 and/or Psychomotor (OR 2.4; 95% CI 1.6-3.7 Development Indices (MDI, PDI, and microcephaly at age two years (OR 2.4; 95%CI 1.5-3.8. Newborns with both hyperEPO and ISSI had significantly increased risks of ventriculomegaly, hemiparetic cerebral palsy, microcephaly, and MDI and PDI < 55 (ORs ranged from 2.2-6.3, but not hypoechoic lesions or other forms of cerebral palsy, relative to newborns with neither hyperEPO nor ISSI.hyperEPO, regardless of ISSI, is associated with elevated risks of very low MDI and PDI, and microcephaly, but not with any form of cerebral palsy. Children with both hyperEPO and ISSI are at higher risk than others of very low MDI and PDI, ventriculomegaly, hemiparetic cerebral palsy, and microcephaly.

  18. Hypoxia-ischemia or excitotoxin-induced tissue plasminogen activator- dependent gelatinase activation in mice neonate brain microvessels.

    Directory of Open Access Journals (Sweden)

    Priscilla L Omouendze

    Full Text Available Hypoxia-ischemia (HI and excitotoxicity are validated causes of neonatal brain injuries and tissue plasminogen activator (t-PA participates in the processes through proteolytic and receptor-mediated pathways. Brain microvascular endothelial cells from neonates in culture, contain and release more t-PA and gelatinases upon glutamate challenge than adult cells. We have studied t-PA to gelatinase (MMP-2 and MMP-9 activity links in HI and excitotoxicity lesion models in 5 day-old pups in wild type and in t-PA or its inhibitor (PAI-1 genes inactivated mice. Gelatinolytic activities were detected in SDS-PAGE zymograms and by in situ fluorescent DQ-gelatin microscopic zymographies. HI was achieved by unilateral carotid ligature followed by a 40 min hypoxia (8%O₂. Excitotoxic lesions were produced by intra parenchymal cortical (i.c. injections of 10 µg ibotenate (Ibo. Gel zymograms in WT cortex revealed progressive extinction of MMP-2 and MMP-9 activities near day 15 or day 8 respectively. MMP-2 expression was the same in all strains while MMP-9 activity was barely detectable in t-PA⁻/⁻ and enhanced in PAI-1⁻/⁻ mice. HI or Ibo produced activation of MMP-2 activities 6 hours post-insult, in cortices of WT mice but not in t-PA⁻/⁻ mice. In PAI-1⁻/⁻ mice, HI or vehicle i.c. injection increased MMP-2 and MMP-9 activities. In situ zymograms using DQ-gelatin revealed vessel associated gelatinolytic activity in lesioned areas in PAI-1⁻/⁻ and in WT mice. In WT brain slices incubated ex vivo, glutamate (200 µM induced DQ-gelatin activation in vessels. The effect was not detected in t-PA⁻/⁻ mice, but was restored by concomitant exposure to recombinant t-PA (20 µg/mL. In summary, neonatal brain lesion paradigms and ex vivo excitotoxic glutamate evoked t-PA-dependent gelatinases activation in vessels. Both MMP-2 and MMP-9 activities appeared t-PA-dependent. The data suggest that vascular directed protease inhibition may have

  19. An overview of international literature from cystic fibrosis registries 2. Neonatal screening and nutrition/growth.

    Science.gov (United States)

    Salvatore, Donatello; Buzzetti, Roberto; Baldo, Ermanno; Forneris, Maria Pia; Lucidi, Vincenzina; Manunza, Daniela; Marinelli, Italo; Messore, Barbara; Neri, Anna Silvia; Raia, Valeria; Furnari, Maria Lucia; Mastella, Gianni

    2010-03-01

    This is the second article related to a review of the literature based on data from national cystic fibrosis (CF) registries up to June 2008 and covering a total of 115 studies. It focuses on two topics: neonatal screening (NS) and nutritional status, with particular reference to growth. Ten papers meeting the inclusion criteria were found on the topic of NS and its impact on the course of the disease, and were analyzed according to a dedicated grid. The issue of nutrition was addressed by 14 studies, analyzed according to similar criteria. Most of the studies report benefits of early diagnosis by NS, albeit to variable degrees. The benefits were assessed in terms of better nutritional status and growth, but also in terms of lower overall morbidity rate as compared to subjects diagnosed by symptoms. The main biases of these studies, which partly undermine the validity of their results, are also analyzed. A part of our analysis on nutrition/growth is dedicated to the identification of the most suitable parameters to define malnutrition: in children older than two years the body mass index percentile (BMIp) appears to be the most sensitive and significantly associated with respiratory function. Better nutritional status and satisfactory growth appear to be associated with better lung function and lower risk of death. The relationship between nutritional status and socio-economic status is also of interest. CF registry studies support the outcome of cohort observational studies i.e. that pre-symptomatic early diagnosis is beneficial, especially in terms of nutritional status and growth. Studies on nutrition indicate that good nutritional status is associated with better respiratory function and prognosis. Regarding methods, the need emerged to manage potential biases of this kind of non randomized studies, resorting to suitable statistical techniques, such as matching and stratification and, above all, to multivariate methods able to provide estimates adjusted for the

  20. Influence of neonatal and adult hyperthyroidism on behavior and biosynthetic capacity for norepinephrine, dopamine and 5-hydroxytryptamine in rat brain.

    Science.gov (United States)

    Rastogi, R B; Singhal, R L

    1976-09-01

    In neonatal rats, administration of l-triiodothyronine (10 mug/100 g/day) for 30 days presented signs of hyperthyroidism which included accelerated development of a variety of physical and behavioral characteristics accompanying maturation. The spontaneous motor activity was increased by 69%. Exposure of developing rats to thyroid hormone significantly increased the endogenous concentration of striatal tyrosine and the activity of tyrosine hydroxylase as well as the levels of dopamine in several brain regions. The concentration of striatal homovanillic acid and 3,4-dihydroxyphenylacetic acid, the chief metabolites of dopamine, was also increased and the magnitude of change was greater than the rise in dopamine. Despite increases in the activity of tyrosine hydroxylase and the availability of the substrate tyrosine, the steady-state levels of norepinephrine remained unaltered in various regions of brain except in cerebellum. Futhermore, neonatal hyperthyroidism significantly increased the levels of midbrain tryptophan and tryptophan hydroxylase activity but produced no change in 5-hydroxytryptamine levels of several discrete brain regions, except hypothalamus and cerebellum where its concentration was slightly decreased. However, the 5-hydroxyindoleacetic acid levels were enhanced in hypothalamus, ponsmedulla, midbrain, striatum and hippocampus. The elevated levels of 5-hydroxyindoleacetic acid did not seem to be due to increased intraneuronal deamination of 5-hydroxytryptamine since monoamine oxidase activity was not affected in cerebral cortex and midbrain of hyperthyroid rats. The data demonstrate that hyperthyroidism significantly increased the synthesis as well as the utilization of catecholamines and 5-hydroxytryptamine in maturing brain. Since the mature brain is known to respond differently to thyroid hormone action than does the developing brain, the effect of L-triiodothyronine treatment on various putative neurohumors also was examined in adult rats

  1. Early functional and morphological brain disturbances in late-onset intrauterine growth restriction.

    Science.gov (United States)

    Starčević, Mirta; Predojević, Maja; Butorac, Dražan; Tumbri, Jasna; Konjevoda, Paško; Kadić, Aida Salihagić

    2016-02-01

    To determine whether the brain disturbances develop in late-onset intrauterine growth restriction (IUGR) before blood flow redistribution towards the fetal brain (detected by Doppler measurements in the middle cerebral artery and umbilical artery). Further, to evaluate predictive values of Doppler arterial indices and umbilical cord blood gases and pH for early functional and/or morphological brain disturbances in late-onset IUGR. This cohort study included 60 singleton term pregnancies with placental insufficiency caused late-onset IUGR (IUGR occurring after 34 gestational weeks). Umbilical artery resistance index (URI), middle cerebral artery resistance index (CRI), and cerebroumbilical (C/U) ratio (CRI/URI) were monitored once weekly. Umbilical blood cord samples (arterial and venous) were collected for the analysis of pO2, pCO2 and pH. Morphological neurological outcome was evaluated by cranial ultrasound (cUS), whereas functional neurological outcome by Amiel-Tison Neurological Assessment at Term (ATNAT). 50 fetuses had C/U ratio>1, and 10 had C/U ratio≤1; among these 10 fetuses, 9 had abnormal neonatal cUS findings and all 10 had non-optimal ATNAT. However, the total number of abnormal neurological findings was much higher. 32 neonates had abnormal cUS (53.37%), and 42 (70.00%) had non-optimal ATNAT. Furthermore, Doppler indices had higher predictive validity for early brain disturbances than umbilical cord blood gases and pH. C/U ratio had the highest predictive validity with threshold for adverse neurological outcome at value 1.13 (ROC analysis), i.e., 1.18 (party machine learning algorithm). Adverse neurological outcome at average values of C/U ratios>1 confirmed that early functional and/or structural brain disturbances in late-onset IUGR develop even before activation of fetal cardiovascular compensatory mechanisms, i.e., before Doppler signs of blood flow redistribution between the fetal brain and the placenta. Copyright © 2015 Elsevier Ireland Ltd

  2. Rodent neonatal germinal matrix hemorrhage mimics the human brain injury, neurological consequences, and post-hemorrhagic hydrocephalus.

    Science.gov (United States)

    Lekic, Tim; Manaenko, Anatol; Rolland, William; Krafft, Paul R; Peters, Regina; Hartman, Richard E; Altay, Orhan; Tang, Jiping; Zhang, John H

    2012-07-01

    Germinal matrix hemorrhage (GMH) is the most common neurological disease of premature newborns. GMH causes neurological sequelae such as cerebral palsy, post-hemorrhagic hydrocephalus, and mental retardation. Despite this, there is no standardized animal model of spontaneous GMH using newborn rats to depict the condition. We asked whether stereotactic injection of collagenase type VII (0.3 U) into the ganglionic eminence of neonatal rats would reproduce the acute brain injury, gliosis, hydrocephalus, periventricular leukomalacia, and attendant neurological consequences found in humans. To test this hypothesis, we used our neonatal rat model of collagenase-induced GMH in P7 pups, and found that the levels of free-radical adducts (nitrotyrosine and 4-hyroxynonenal), proliferation (mammalian target of rapamycin), inflammation (COX-2), blood components (hemoglobin and thrombin), and gliosis (vitronectin and GFAP) were higher in the forebrain of GMH pups, than in controls. Neurobehavioral testing showed that pups with GMH had developmental delay, and the juvenile animals had significant cognitive and motor disability, suggesting clinical relevance of the model. There was also evidence of white-matter reduction, ventricular dilation, and brain atrophy in the GMH animals. This study highlights an instructive animal model of the neurological consequences after germinal matrix hemorrhage, with evidence of brain injuries that can be used to evaluate strategies in the prevention and treatment of post-hemorrhagic complications. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Optimized T1- and T2-weighted volumetric brain imaging as a diagnostic tool in very preterm neonates

    International Nuclear Information System (INIS)

    Nossin-Manor, Revital; Chung, Andrew D.; Morris, Drew; Thomas, Bejoy; Shroff, Manohar M.; Soares-Fernandes, Joao P.; Cheng, Hai-Ling M.; Whyte, Hilary E.A.; Taylor, Margot J.; Sled, John G.

    2011-01-01

    T1- and T2-W MR sequences used for obtaining diagnostic information and morphometric measurements in the neonatal brain are frequently acquired using different imaging protocols. Optimizing one protocol for obtaining both kinds of information is valuable. To determine whether high-resolution T1- and T2-W volumetric sequences optimized for preterm brain imaging could provide both diagnostic and morphometric value. Thirty preterm neonates born between 24 and 32 weeks' gestational age were scanned during the first 2 weeks after birth. T1- and T2-W high-resolution sequences were optimized in terms of signal-to-noise ratio, contrast-to-noise ratio and scan time and compared to conventional spin-echo-based sequences. No differences were found between conventional and high-resolution T1-W sequences for diagnostic confidence, image quality and motion artifacts. A preference for conventional over high-resolution T2-W sequences for image quality was observed. High-resolution T1 images provided better delineation of thalamic myelination and the superior temporal sulcus. No differences were found for detection of myelination and sulcation using conventional and high-resolution T2-W images. High-resolution T1- and T2-W volumetric sequences can be used in clinical MRI in the very preterm brain to provide both diagnostic and morphometric information. (orig.)

  4. Tumor necrosis factor-alpha during neonatal brain development affects anxiety- and depression-related behaviors in adult male and female mice.

    Science.gov (United States)

    Babri, Shirin; Doosti, Mohammad-Hossein; Salari, Ali-Akbar

    2014-03-15

    A nascent literature suggests that neonatal infection is a risk factor for the development of brain, behavior and hypothalamic-pituitary-adrenal axis which can affect anxiety- and depression-related behaviors in later life. It has been documented that neonatal infection raises the concentrations of tumor necrosis factor-alpha (TNF-α) in neonate rodents and such infections may result in neonatal brain injury, at least in part, through pro-inflammatory cytokines. In addition, previous studies have shown that TNF-α is involved in cellular differentiation, neurogenesis and programmed cell death during the development of the central nervous system. We investigated for the first time whether neonatal exposure to TNF-α can affect body weight, stress-induced corticosterone (COR), anxiety- and depression-related behaviors in adult mice. In the present study, neonatal mice were treated to recombinant mouse TNF-α (0.2, 0.4, 0.7 and 1 μg/kg) or saline on postnatal days 3 and 5, then adult male and female mice were exposed to different behavioral tests. The results indicated that neonatal TNF-α treatment reduced body weight in neonatal period in both sexes. In addition, this study presents findings indicating that high doses of TNF- increase stress-induced COR levels, anxiety- and depression-related behaviors in adult males, but increase levels of anxiety without significantly influencing depression in adult female mice [corrected]. Our findings suggest that TNF-α exposure during neonatal period can alter brain and behavior development in a dose and sex-dependent manner in mice. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Fetal and Neonatal Levels of Omega-3: Effects on Neurodevelopment, Nutrition, and Growth

    Directory of Open Access Journals (Sweden)

    Juliana Rombaldi Bernardi

    2012-01-01

    Full Text Available Nutrition in pregnancy, during lactation, childhood, and later stages has a fundamental influence on overall development. There is a growing research interest on the role of key dietary nutrients in fetal health. Omega-3 polyunsaturated fatty acids (n-3 LCPUFAs play an important role in brain development and function. Evidence from animal models of dietary n-3 LCPUFAs deficiency suggests that these fatty acids promote early brain development and regulate behavioral and neurochemical aspects related to mood disorders (stress responses, depression, and aggression and growth, memory, and cognitive functions. Preclinical and clinical studies suggest the role of n-3 LCPUFAs on neurodevelopment and growth. n-3 LCPUFAs may be an effective adjunctive factor for neural development, growth, and cognitive development, but further large-scale, well-controlled trials and preclinical studies are needed to examine its clinical mechanisms and possible benefits. The present paper discusses the use of n-3 LCPUFAs during different developmental stages and the investigation of different sources of consumption. The paper summarizes the role of n-3 LCPUFAs levels during critical periods and their effects on the children’s neurodevelopment, nutrition, and growth.

  6. A competitive advantage by neonatally engrafted human glial progenitors yields mice whose brains are chimeric for human glia.

    Science.gov (United States)

    Windrem, Martha S; Schanz, Steven J; Morrow, Carolyn; Munir, Jared; Chandler-Militello, Devin; Wang, Su; Goldman, Steven A

    2014-11-26

    Neonatally transplanted human glial progenitor cells (hGPCs) densely engraft and myelinate the hypomyelinated shiverer mouse. We found that, in hGPC-xenografted mice, the human donor cells continue to expand throughout the forebrain, systematically replacing the host murine glia. The differentiation of the donor cells is influenced by the host environment, such that more donor cells differentiated as oligodendrocytes in the hypomyelinated shiverer brain than in myelin wild-types, in which hGPCs were more likely to remain as progenitors. Yet in each recipient, both the number and relative proportion of mouse GPCs fell as a function of time, concomitant with the mitotic expansion and spread of donor hGPCs. By a year after neonatal xenograft, the forebrain GPC populations of implanted mice were largely, and often entirely, of human origin. Thus, neonatally implanted hGPCs outcompeted and ultimately replaced the host population of mouse GPCs, ultimately generating mice with a humanized glial progenitor population. These human glial chimeric mice should permit us to define the specific contributions of glia to a broad variety of neurological disorders, using human cells in vivo. Copyright © 2014 the authors 0270-6474/14/3416153-09$15.00/0.

  7. Discrimination of Fearful and Angry Emotional Voices in Sleeping Human Neonates: a Study of the Mismatch Brain Responses

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    Dandan eZhang

    2014-12-01

    Full Text Available Appropriate processing of human voices with different threat-related emotions is of evolutionarily adaptive value for the survival of individuals. Nevertheless, it is still not clear whether the sensitivity to threat-related information is present at birth. Using an oddball paradigm, the current study investigated the neural correlates underlying automatic processing of emotional voices of fear and anger in sleeping neonates. Event-related potential data showed that the frontocentral scalp distribution of the neonatal brain could discriminate fearful voices from angry voices; the mismatch response (MMR was larger in response to the deviant stimuli of anger, compared with the standard stimuli of fear. Furthermore, this fear-anger MMR discrimination was observed only when neonates were in active sleep state. Although the neonates’ sensitivity to threat-related voices is not likely associated with a conceptual understanding of fearful and angry emotions, this special discrimination in early life may provide a foundation for later emotion and social cognition development.

  8. [Prenatal lead exposure related to cord blood brain derived neurotrophic factor (BDNF) levels and impaired neonatal neurobehavioral development].

    Science.gov (United States)

    Ren, L H; Mu, X Y; Chen, H Y; Yang, H L; Qi, W

    2016-06-01

    To explore the relationship between umbilical cord blood brain-derived neurotrophic factor (BDNF) and neonatal neurobehavioral development in lead exposure infants. All infants and their mother were randomly selected during 2011 to 2012, subjects were selected according to the umbilical cord blood lead concentrations, which contcentration of lead was higher than 0.48 μmol/L were taken into high lead exposure group, about 60 subjects included. Comparing to the high lead exposure group, according to gender, weight, pregnant week, length and head circumferenece, the level of cord blood lead concentration under 0.48 μmol/L were taken into control group, 60 cases included. Lead content was determined by graphite furnace atomic absorption spectrometry. Neonatal behavioral neurological assessment (NBNA) was used to determine the development of neonatal neuronal behavior. The content of BDNF was detected by ELISA. Comparing the BDNF and the NBNA score between two groups, and linear correlation was given on analysis the correlation between lead concentration in cord blood and BDNF, BDNF and the NBNA score. Lead content in high exposure group was (0.613±0.139) μmol/L, and higher than (0.336±0.142) μmol/L in low exposure group (t=3.21, PBDNF content in high exposure group which was (3.538±1.203) ng/ml was higher than low exposure group (2.464±0.918) ng/ml (t=7.60, PBDNF content was negatively correlated with NBNA summary score, passive muscle tension and active muscle tone score (r was -0.27, -0.29, -0.30, respectively, P values were BDNF was negatively correlated with neonatal neurodevelopment, may serve as a useful biomarker.

  9. Brain oxygen saturation assessment in neonates using T2-prepared blood imaging of oxygen saturation and near-infrared spectroscopy

    DEFF Research Database (Denmark)

    Alderliesten, Thomas; De Vis, Jill B; Lemmers, Petra Ma

    2017-01-01

    saturation in the sagittal sinus (R(2 )= 0.49, p = 0.023), but no significant correlations could be demonstrated with frontal and whole brain cerebral blood flow. These results suggest that measuring oxygen saturation by T2-prepared blood imaging of oxygen saturation is feasible, even in neonates. Strong...... sinus. A strong linear relation was found between the oxygen saturation measured by magnetic resonance imaging and the oxygen saturation measured by near-infrared spectroscopy (R(2 )= 0.64, p ..., and magnetic resonance imaging measures of frontal cerebral blood flow, whole brain cerebral blood flow and venous oxygen saturation in the sagittal sinus (R(2 )= 0.71, 0.50, 0.65; p 

  10. Neonatal neurosonography

    Energy Technology Data Exchange (ETDEWEB)

    Riccabona, Michael, E-mail: michael.riccabona@klinikum-graz.at

    2014-09-15

    Paediatric and particularly neonatal neurosonography still remains a mainstay of imaging the neonatal brain. It can be performed at the bedside without any need for sedation or specific monitoring. There are a number of neurologic conditions that significantly influence morbidity and mortality in neonates and infants related to the brain and the spinal cord; most of them can be addressed by ultrasonography (US). However, with the introduction of first CT and then MRI, neonatal neurosonography is increasingly considered just a basic first line technique that offers only orienting information and does not deliver much relevant information. This is partially caused by inferior US performance – either by restricted availability of modern equipment or by lack of specialized expertise in performing and reading neurosonographic scans. This essay tries to highlight the value and potential of US in the neonatal brain and briefly touching also on the spinal cord imaging. The common pathologies and their US appearance as well as typical indication and applications of neurosonography are listed. The review aims at encouraging paediatric radiologists to reorient there imaging algorithms and skills towards the potential of modern neurosonography, particularly in the view of efficacy, considering growing economic pressure, and the low invasiveness as well as the good availability of US that can easily be repeated any time at the bedside.

  11. Maternal hypoxia increases the activity of MMPs and decreases the expression of TIMPs in the brain of neonatal rats.

    Science.gov (United States)

    Tong, Wenni; Chen, Wanqiu; Ostrowski, Robert P; Ma, Qingyi; Souvenir, Rhonda; Zhang, Lubo; Zhang, John H; Tang, Jiping

    2010-02-15

    A recent study has shown that increased activity of matrix metalloproteinases-2 and metalloproteinases-9 (MMP-2 and MMP-9) has detrimental effect on the brain after neonatal hypoxia. The present study determined the effect of maternal hypoxia on neuronal survivability and the activity of MMP-2 and MMP-9, as well as the expression of tissue inhibitors of metalloproteinase 1 and 2 (TIMP-1 and TIMP-2) in the brain of neonatal rats. Pregnant rats were exposed to 10.5% oxygen for 6 days from the gestation day 15 to day 21. Pups were sacrificed at day 0, 4, 7, 14, and 21 after birth. Body weight and brain weight of the pups were measured at each time point. The activity of MMP-2 and MMP-9 and the protein abundance of TIMP-1 and TIMP-2 were determined by zymography and Western blotting, respectively. The tissue distribution of MMPs was examined by immunofluorescence staining. The neuronal death was detected by Nissl staining. Maternal hypoxia caused significant decreases in body and brain size, increased activity of MMP-2 at day 0, and increased MMP-9 at day 0 and 4. The increased activity of the MMPs was accompanied by an overall tendency towards a reduced expression of TIMPs at all ages with the significance observed for TIMPs at day 0, 4, and 7. Immunofluorescence analysis showed an increased expression of MMP-2, MMP-9 in the hippocampus at day 0 and 4. Nissl staining revealed significant cell death in the hippocampus at day 0, 4, and 7. Functional tests showed worse neurobehavioral outcomes in the hypoxic animals.

  12. Semi-quantitative Assessment of Brain Maturation by Conventional Magnetic Resonance Imaging in Neonates with Clinically Mild Hypoxic-ischemic Encephalopathy

    Science.gov (United States)

    Gao, Jie; Sun, Qin-Li; Zhang, Yu-Miao; Li, Yan-Yan; Li, Huan; Hou, Xin; Yu, Bo-Lang; Zhou, Xi-Hui; Yang, Jian

    2015-01-01

    Background: Mild hypoxic-ischemic encephalopathy (HIE) injury is becoming the major type in neonatal brain diseases. The aim of this study was to assess brain maturation in mild HIE neonatal brains using total maturation score (TMS) based on conventional magnetic resonance imaging (MRI). Methods: Totally, 45 neonates with clinically mild HIE and 45 matched control neonates were enrolled. Gestated age, birth weight, age after birth and postmenstrual age at magnetic resonance (MR) scan were homogenous in the two groups. According to MR findings, mild HIE neonates were divided into three subgroups: Pattern I, neonates with normal MR appearance; Pattern II, preterm neonates with abnormal MR appearance; Pattern III, full-term neonates with abnormal MR appearance. TMS and its parameters, progressive myelination (M), cortical infolding (C), involution of germinal matrix tissue (G), and glial cell migration bands (B), were employed to assess brain maturation and compare difference between HIE and control groups. Results: The mean of TMS was significantly lower in mild HIE group than it in the control group (mean ± standard deviation [SD] 11.62 ± 1.53 vs. 12.36 ± 1.26, P < 0.001). In four parameters of TMS scores, the M and C scores were significantly lower in mild HIE group. Of the three patterns of mild HIE, Pattern I (10 cases) showed no significant difference of TMS compared with control neonates, while Pattern II (22 cases), III (13 cases) all had significantly decreased TMS than control neonates (mean ± SD 10.56 ± 0.93 vs. 11.48 ± 0.55, P < 0.05; 12.59 ± 1.28 vs. 13.25 ± 1.29, P < 0.05). It was M, C, and GM scores that significantly decreased in Pattern II, while for Pattern III, only C score significantly decreased. Conclusions: The TMS system, based on conventional MRI, is an effective method to detect delayed brain maturation in clinically mild HIE. The conventional MRI can reveal the different retardations in subtle structures and development processes

  13. Co-bedding in neonatal nursery for promoting growth and neurodevelopment in stable preterm twins.

    Science.gov (United States)

    Lai, Nai Ming; Foong, Siew Cheng; Foong, Wai Cheng; Tan, Kenneth

    2016-04-14

    The increased birth rate of twins during recent decades and the improved prognosis of preterm infants have resulted in the need to explore measures that could optimize their growth and neurodevelopmental outcomes. It has been postulated that co-bedding simulates twins' intrauterine experiences in which co-regulatory behaviors between them are observed. These behaviors are proposed to benefit twins by reducing their stress, which may promote growth and development. However, in practice, uncertainty surrounds the benefit-risk profile of co-bedding. We aimed to assess the effectiveness of co-bedding compared with separate (individual) care for stable preterm twins in the neonatal nursery in promoting growth and neurodevelopment and reducing short- and long-term morbidities, and to determine whether co-bedding is associated with significant adverse effects.As secondary objectives, we sought to evaluate effects of co-bedding via the following subgroup analyses: twin pairs with different weight ranges (very low birth weight [VLBW] growth discordance at birth, preterm versus borderline preterm twins, twins co-bedded in incubator versus cot at study entry, and twins randomized by twin pair versus neonatal unit. We used the standard search strategy of the Cochrane Neonatal Review Group (CNRG). We used keywords and medical subject headings (MeSH) to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 2), MEDLINE (via PubMed), EMBASE (hosted by EBSCOHOST), the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and references cited in our short-listed articles, up to February 29, 2016. We included randomized controlled trials with randomization by twin pair and/or by neonatal unit. We excluded cross-over studies. We extracted data using standard methods of the CNRG. Two review authors independently assessed the relevance and risk of bias of retrieved records. We contacted the authors of included studies to request important

  14. DHA but Not EPA Emulsions Preserve Neurological and Mitochondrial Function after Brain Hypoxia-Ischemia in Neonatal Mice

    Science.gov (United States)

    Sosunov, Sergey A.; Williams, Jill J.; Zirpoli, Hylde; Vlasakov, Iliyan; Deckelbaum, Richard J.; Ten, Vadim S.

    2016-01-01

    Background and Purpose Treatment with triglyceride emulsions of docosahexaenoic acid (tri-DHA) protected neonatal mice against hypoxia-ischemia (HI) brain injury. The mechanism of this neuroprotection remains unclear. We hypothesized that administration of tri-DHA enriches HI-brains with DHA/DHA metabolites. This reduces Ca2+-induced mitochondrial membrane permeabilization and attenuates brain injury. Methods 10-day-old C57BL/6J mice following HI-brain injury received tri-DHA, tri-EPA or vehicle. At 4–5 hours of reperfusion, mitochondrial fatty acid composition and Ca2+ buffering capacity were analyzed. At 24 hours and at 8–9 weeks of recovery, oxidative injury, neurofunctional and neuropathological outcomes were evaluated. In vitro, hyperoxia-induced mitochondrial generation of reactive oxygen species (ROS) and Ca2+ buffering capacity were measured in the presence or absence of DHA or EPA. Results Only post-treatment with tri-DHA reduced oxidative damage and improved short- and long-term neurological outcomes. This was associated with increased content of DHA in brain mitochondria and DHA-derived bioactive metabolites in cerebral tissue. After tri-DHA administration HI mitochondria were resistant to Ca2+-induced membrane permeabilization. In vitro, hyperoxia increased mitochondrial ROS production and reduced Ca2+ buffering capacity; DHA, but not EPA, significantly attenuated these effects of hyperoxia. Conclusions Post-treatment with tri-DHA resulted in significant accumulation of DHA and DHA derived bioactive metabolites in the HI-brain. This was associated with improved mitochondrial tolerance to Ca2+-induced permeabilization, reduced oxidative brain injury and permanent neuroprotection. Interaction of DHA with mitochondria alters ROS release and improves Ca2+ buffering capacity. This may account for neuroprotective action of post-HI administration of tri-DHA. PMID:27513579

  15. DHA but Not EPA Emulsions Preserve Neurological and Mitochondrial Function after Brain Hypoxia-Ischemia in Neonatal Mice.

    Science.gov (United States)

    Mayurasakorn, Korapat; Niatsetskaya, Zoya V; Sosunov, Sergey A; Williams, Jill J; Zirpoli, Hylde; Vlasakov, Iliyan; Deckelbaum, Richard J; Ten, Vadim S

    2016-01-01

    Treatment with triglyceride emulsions of docosahexaenoic acid (tri-DHA) protected neonatal mice against hypoxia-ischemia (HI) brain injury. The mechanism of this neuroprotection remains unclear. We hypothesized that administration of tri-DHA enriches HI-brains with DHA/DHA metabolites. This reduces Ca2+-induced mitochondrial membrane permeabilization and attenuates brain injury. 10-day-old C57BL/6J mice following HI-brain injury received tri-DHA, tri-EPA or vehicle. At 4-5 hours of reperfusion, mitochondrial fatty acid composition and Ca2+ buffering capacity were analyzed. At 24 hours and at 8-9 weeks of recovery, oxidative injury, neurofunctional and neuropathological outcomes were evaluated. In vitro, hyperoxia-induced mitochondrial generation of reactive oxygen species (ROS) and Ca2+ buffering capacity were measured in the presence or absence of DHA or EPA. Only post-treatment with tri-DHA reduced oxidative damage and improved short- and long-term neurological outcomes. This was associated with increased content of DHA in brain mitochondria and DHA-derived bioactive metabolites in cerebral tissue. After tri-DHA administration HI mitochondria were resistant to Ca2+-induced membrane permeabilization. In vitro, hyperoxia increased mitochondrial ROS production and reduced Ca2+ buffering capacity; DHA, but not EPA, significantly attenuated these effects of hyperoxia. Post-treatment with tri-DHA resulted in significant accumulation of DHA and DHA derived bioactive metabolites in the HI-brain. This was associated with improved mitochondrial tolerance to Ca2+-induced permeabilization, reduced oxidative brain injury and permanent neuroprotection. Interaction of DHA with mitochondria alters ROS release and improves Ca2+ buffering capacity. This may account for neuroprotective action of post-HI administration of tri-DHA.

  16. DHA but Not EPA Emulsions Preserve Neurological and Mitochondrial Function after Brain Hypoxia-Ischemia in Neonatal Mice.

    Directory of Open Access Journals (Sweden)

    Korapat Mayurasakorn

    Full Text Available Treatment with triglyceride emulsions of docosahexaenoic acid (tri-DHA protected neonatal mice against hypoxia-ischemia (HI brain injury. The mechanism of this neuroprotection remains unclear. We hypothesized that administration of tri-DHA enriches HI-brains with DHA/DHA metabolites. This reduces Ca2+-induced mitochondrial membrane permeabilization and attenuates brain injury.10-day-old C57BL/6J mice following HI-brain injury received tri-DHA, tri-EPA or vehicle. At 4-5 hours of reperfusion, mitochondrial fatty acid composition and Ca2+ buffering capacity were analyzed. At 24 hours and at 8-9 weeks of recovery, oxidative injury, neurofunctional and neuropathological outcomes were evaluated. In vitro, hyperoxia-induced mitochondrial generation of reactive oxygen species (ROS and Ca2+ buffering capacity were measured in the presence or absence of DHA or EPA.Only post-treatment with tri-DHA reduced oxidative damage and improved short- and long-term neurological outcomes. This was associated with increased content of DHA in brain mitochondria and DHA-derived bioactive metabolites in cerebral tissue. After tri-DHA administration HI mitochondria were resistant to Ca2+-induced membrane permeabilization. In vitro, hyperoxia increased mitochondrial ROS production and reduced Ca2+ buffering capacity; DHA, but not EPA, significantly attenuated these effects of hyperoxia.Post-treatment with tri-DHA resulted in significant accumulation of DHA and DHA derived bioactive metabolites in the HI-brain. This was associated with improved mitochondrial tolerance to Ca2+-induced permeabilization, reduced oxidative brain injury and permanent neuroprotection. Interaction of DHA with mitochondria alters ROS release and improves Ca2+ buffering capacity. This may account for neuroprotective action of post-HI administration of tri-DHA.

  17. Possible physiological role of milk epidermal growth factor in neonatal eyelid opening

    International Nuclear Information System (INIS)

    Tsutsumi, O.; Tsutsumi, A.; Oka, T.

    1987-01-01

    The eyelid opening of newborn mice occurs normally on day 13.9 +/- 1.8 after birth. When newborn mice were injected with anti-epidermal growth factor (EGF) antibody every other day starting on day 1 after birth, the eyelid opening was delayed by ∼ 3 days. The effect of anti-EGF became less prominent as the treatment was started at later times: when it was give from day 7, no delay in eyelid opening was observed. On the other hand, eyelid opening was enhanced by ∼ 3 days by EGF injection given on day 3 for every other day. This effect of EGF was antagonized by simultaneous administration of anti-EGF antibody. EGF was present at a concentration of 6.6 ng/ml in the plasma of 1-wk-old pups nursed by their mother, but it was not detectable in the plasma of 3-wk-old weaned pups. EGF concentration in the submandibular glands, however, was 17 times greater in 3- than in 1-wk-old pups. EGF was measured by radioimmunoassay. These results suggest that milk EGF may play a physiological role in eyelid opening during the neonatal period

  18. Critical periods of brain growth and cognitive function in children.

    Science.gov (United States)

    Gale, Catharine R; O'Callaghan, Finbar J; Godfrey, Keith M; Law, Catherine M; Martyn, Christopher N

    2004-02-01

    There is evidence that IQ tends to be higher in those who were heavier at birth or who grew taller in childhood and adolescence. Although these findings imply that growth in both foetal and postnatal life influences cognitive performance, little is known about the relative importance of brain growth during different periods of development. We investigated the relationship between brain growth in different periods of pre- and postnatal life and cognitive function in 221 9-year-old children whose mothers had taken part in a study of nutrition in pregnancy and whose head circumference had been measured at 18 weeks gestation, birth and 9 months of age. Cognitive function of the children and their mothers was assessed with the Wechsler Abbreviated Scale of Intelligence. Full-scale IQ at age 9 years rose by 1.98 points [95% confidence interval (CI) 0.34 to 3.62] for each SD increase in head circumference at 9 months and by 2.87 points (95% CI 1.05 to 4.69) for each SD increase in head circumference at 9 years of age, after adjustment for sex, number of older siblings, maternal IQ, age, education, social class, duration of breastfeeding and history of low mood in the post-partum period. Postnatal head growth was significantly greater in children whose mothers were educated to degree level or of higher socio-economic status. There was no relation between IQ and measurements of head size at 18 weeks gestation or at birth. These results suggest that brain growth during infancy and early childhood is more important than growth during foetal life in determining cognitive function.

  19. Parthenogenetic reproduction of Diaphanosoma celebensis (Crustacea: Cladocera). Effect of algae and algal density on survival, growth, life span and neonate production

    Digital Repository Service at National Institute of Oceanography (India)

    Shrivastava, Y.; Mahambre, G.G.; Achuthankutty, C.T.; Fernandes, Brenda; Goswami, S.C.; Madhupratap, M.

    ) and Tetraselmis gracilis (Kylin), was determined. Growth was faster in the initial stage with all three diets but slowed down in later life. Increased food concentrations resulted in higher neonate production but reduced the life span of females. However, long...

  20. Growth hormone deficiency in children with brain tumors

    International Nuclear Information System (INIS)

    Shalet, S.M.; Beardwell, C.G.; Morris-Jones, P.; Bamford, F.N.; Ribeiro, G.G.; Pearson, D.

    1976-01-01

    Nine children with brain tumors are described who have received various combinations of treatment, including surgery, radiotherapy, and chemotherapy. Many of the children were noted to be of short stature. Endocrine assessment was carried out from 2 to 10 years after treatment. The combined results of insulin tolerance and Bovril stimulation tests show an impaired growth hormone response in six of the nine children. Bone age is retarded in all cases, and the present height is below the 10th percentile in five of the six. The cause of this growth hormone deficiency is obscure, but further studies are in progress

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

    International Nuclear Information System (INIS)

    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.)

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  3. Vascular Endothelial Growth Factor Receptor 1 Contributes to Escherichia coli K1 Invasion of Human Brain Microvascular Endothelial Cells through the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway▿ †

    OpenAIRE

    Zhao, Wei-Dong; Liu, Wei; Fang, Wen-Gang; Kim, Kwang Sik; Chen, Yu-Hua

    2010-01-01

    Escherichia coli is the most common Gram-negative organism causing neonatal meningitis. Previous studies demonstrated that E. coli K1 invasion of brain microvascular endothelial cells (BMEC) is required for penetration into the central nervous system, but the microbe-host interactions that are involved in this process remain incompletely understood. Here we report the involvement of vascular endothelial growth factor receptor 1 (VEGFR1) expressed on human brain microvascular endothelial cells...

  4. Effect of hyperbaric oxygen on lipid peroxidation and visual development in neonatal rats with hypoxia-ischemia brain damage.

    Science.gov (United States)

    Chen, Jing; Chen, Yan-Hui; Lv, Hong-Yan; Chen, Li-Ting

    2016-07-01

    The aim of the present study was to investigate the effect of hyperbaric oxygen (HBO) on lipid peroxidation and visual development in a neonatal rat model of hypoxic-ischemic brain damage (HIBD). The rat models of HIBD were established by delayed uterus dissection and were divided randomly into two groups (10 rats each): HIBD and HBO-treated HIBD (HIBD+HBO) group. Another 20 rats that underwent sham-surgery were also divided randomly into the HBO-treated and control groups. The rats that underwent HBO treatment received HBO (0.02 MPa, 1 h/day) 24 h after the surgery and this continued for 14 days. When rats were 4 weeks old, their flash visual evoked potentials (F-VEPs) were monitored and the ultrastructures of the hippocampus were observed under transmission electron microscope. The levels of superoxide dismutase (SOD) and malonyldialdehyde (MDA) in the brain tissue homogenate were detected by xanthine oxidase and the thiobarbituric acid colorimetric method. Compared with the control group, the ultrastructures of the pyramidal neurons in the hippocampal CA3 area were distorted, the latencies of F-VEPs were prolonged (P0.05). HBO enhances antioxidant capacity and reduces the ultrastructural damage induced by hypoxic-ischemia, which may improve synaptic reconstruction and alleviate immature brain damage to promote the habilitation of brain function.

  5. Growth hormone concentrations in mammary secretions and plasma of the periparturient bitch and in plasma of the neonate.

    Science.gov (United States)

    Schoenmakers, I; Kooistra, H S; Okkens, A C; Hazewinkel, H A; Bevers, M M; Mol, J A

    1997-01-01

    The presence of growth hormone (GH) in mammary secretions of bitches was investigated in relation to plasma GH concentrations at about the time of parturition and during the first weeks of lactation. Plasma GH concentrations in neonates were measured during the first weeks of lactation, to determine whether GH in maternal milk contributes to plasma concentrations of GH in the neonate. Gastrointestinal uptake of GH was studied by measurement of plasma bovine GH (bGH) concentrations after intragastric administration of bGH. High concentrations of GH were found in the mammary secretions of the bitches, particularly before parturition and in colostrum, exceeding maternal plasma concentration up to 100-1000 times. GH concentrations in milk were not not significantly correlated with GH concentrations in plasma of bitches or neonates. Bovine GH could not be detected in neonatal plasma for 4 h after intragastric administration of bGH. The presence of high concentrations of canine GH (cGH) in ante-partum and colostral mammary secretions is consistent with the progesterone-induced mammary biosynthesis of GH. GH in milk is probably not absorbed from the gastrointestinal tract into the blood circulation of the newborn in its intact form.

  6. On the Edge of Language Acquisition: Inherent Constraints on Encoding Multisyllabic Sequences in the Neonate Brain

    Science.gov (United States)

    Ferry, Alissa L.; Fló, Ana; Brusini, Perrine; Cattarossi, Luigi; Macagno, Francesco; Nespor, Marina; Mehler, Jacques

    2016-01-01

    To understand language, humans must encode information from rapid, sequential streams of syllables--tracking their order and organizing them into words, phrases, and sentences. We used Near-Infrared Spectroscopy (NIRS) to determine whether human neonates are born with the capacity to track the positions of syllables in multisyllabic sequences.…

  7. Early evolution and recovery from excitotoxic injury in the neonatal rat brain

    NARCIS (Netherlands)

    Lookeren Campagne, van M.; Verheul, H.B.; Nicolaij, K.; Balázs, R.E.

    1994-01-01

    We explored the therapeutic potentials of two N-methyl-D-aspartate (NMDA) receptor antagonists in vivo using different techniques. NMDA injected into the striatum of neonatal rats (20 nmol/0.5 microliters) induced a rapid increase in the diffusion-weighted (DW) image intensity, spreading over a

  8. Does Neonatal Brain Ischemia Induce Schizophrenia-Like Behavior in Young Adult Rats?

    Czech Academy of Sciences Publication Activity Database

    Tejkalová, H.; Kaiser, M.; Klaschka, Jan; Šťastný, František

    2007-01-01

    Roč. 56, č. 6 (2007), s. 815-823 ISSN 0862-8408 R&D Projects: GA MZd(CZ) NR8797 Institutional research plan: CEZ:AV0Z10300504; CEZ:AV0Z50110509 Keywords : neonatal ischemia * schizophrenia * rat * prepulse inhibition Subject RIV: FL - Psychiatry, Sexuology Impact factor: 1.505, year: 2007

  9. Early amplitude‐integrated electroencephalography for monitoring neonates at high risk for brain injury

    Directory of Open Access Journals (Sweden)

    Gabriel Fernando Todeschi Variane

    2017-09-01

    Conclusion: This study supports previous results and demonstrates the utility of amplitude‐integrated electroencephalography for monitoring brain function and predicting early outcome in the studied groups of infants at high risk for brain injury.

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

    Science.gov (United States)

    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.

  11. Neuroprotection of lamotrigine on hypoxic-ischemic brain damage in neonatal rats: Relations to administration time and doses

    Directory of Open Access Journals (Sweden)

    Yong-Hong Yi

    2008-06-01

    Full Text Available Yong-Hong Yi1, Wen-Chao Guo1, Wei-Wen Sun1, Tao Su1, Han Lin1, Sheng-Qiang Chen1, Wen-Yi Deng1, Wei Zhou2, Wei-Ping Liao11Department of Neurology, Institute of Neurosciences and the Second Affiliated Hospital, 2Department of Neonatology, Affiliated Guangzhou Children’s Hospital, Guangzhou Medical College, Guangzhou, Guangdong Province, P.R. ChinaAbstract: Lamotrigine (LTG, an antiepileptic drug, has been shown to be able to improve cerebral ischemic damage by limiting the presynaptic release of glutamate. The present study investigated further the neuroprotective effect of LTG on hypoxic-ischemic brain damage (HIBD in neonatal rats and its relations to administration time and doses. The HIBD model was produced in 7-days old SD rats by left common carotid artery ligation followed by 2 h hypoxic exposure (8% oxygen. LTG was administered intraperitoneally with the doses of 5, 10, 20, and 40 mg/kg 3 h after operation and the dose of 20 mg/kg 1 h before and 3 h, 6 h after operation. Blood and brain were sampled 24 h after operation. Nissl staining, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL, and neuron-specific enolase (NSE immunohistochemical staining were used for morphological studies. Water content in left cortex and NSE concentration in serum were determined. LTG significantly reduced water content in the cerebral cortex, as well as the number of TUNEL staining neurons in the dentate gyrus and cortex in hypoxic-ischemia (HI model. Furthermore, LTG significantly decreased the NSE level in serum and increased the number of NSE staining neurons in the cortex. These effects, except that on water content, were dose-dependent and were more remarkable in the pre-treated group than in the post-treated groups. These results demonstrate that LTG may have a neuroprotective effect on acute HIBD in neonates. The effect is more prominent when administrated with higher doses and before HI.Keywords: hypoxic-ischemic brain

  12. Effect of mannose targeting of hydroxyl PAMAM dendrimers on cellular and organ biodistribution in a neonatal brain injury model.

    Science.gov (United States)

    Sharma, Anjali; Porterfield, Joshua E; Smith, Elizabeth; Sharma, Rishi; Kannan, Sujatha; Kannan, Rangaramanujam M

    2018-06-05

    Neurotherapeutics for the treatment of central nervous system (CNS) disorders must overcome challenges relating to the blood-brain barrier (BBB), brain tissue penetration, and the targeting of specific cells. Neuroinflammation mediated by activated microglia is a major hallmark of several neurological disorders, making these cells a desirable therapeutic target. Building on the promise of hydroxyl-terminated generation four polyamidoamine (PAMAM) dendrimers (D4-OH) for penetrating the injured BBB and targeting activated glia, we explored if conjugation of targeting ligands would enhance and modify brain and organ uptake. Since mannose receptors [cluster of differentiation (CD) 206] are typically over-expressed on injured microglia, we conjugated mannose to the surface of multifunctional D4-OH using highly efficient, atom-economical, and orthogonal Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC) click chemistry and evaluated the effect of mannose conjugation on the specific cell uptake of targeted and non-targeted dendrimers both in vitro and in vivo. In vitro results indicate that the conjugation of mannose as a targeting ligand significantly changes the mechanism of dendrimer internalization, giving mannosylated dendrimer a preference for mannose receptor-mediated endocytosis as opposed to non-specific fluid phase endocytosis. We further investigated the brain uptake and biodistribution of targeted and non-targeted fluorescently labeled dendrimers in a maternal intrauterine inflammation-induced cerebral palsy (CP) rabbit model using quantification methods based on fluorescence spectroscopy and confocal microscopy. We found that the conjugation of mannose modified the distribution of D4-OH throughout the body in this neonatal rabbit CP model without lowering the amount of dendrimer delivered to injured glia in the brain, even though significantly higher glial uptake was not observed in this model. Mannose conjugation to the dendrimer modifies the dendrimer

  13. Selected Abstracts of the 1st Congress of joint European Neonatal Societies (jENS 2015; Budapest (Hungary; September 16-20, 2015; Session “Brain & Development”

    Directory of Open Access Journals (Sweden)

    Various Authors

    2015-09-01

    -ACETYLCYSTEINE AMIDE (NACA REDUCES CELL DEATH AFTER EXPOSURE TO OXIDATIVE STRESS IN A PORCINE EPITHELIAL-LIKE EMBRYONIC EFN-R KIDNEY CELL LINE • T. Benterud, S. Manueldas, L. Pankratov, R. Solberg, A. Nordgren, O.D. Saugstad, L.O. BaumbuschABS 7. MELATONIN-INDUCED IMMUNE CELL RESPONSES IN INFANTS WITH NEONATAL ENCEPHALOPATHY PRE AND POST THERAPEUTIC HYPOTHERMIA TREATMENT • S. Aslam, V. McEneaney, R.W.G. Watson, A. O’Neill, E.J. MolloyABS 8. BLOOD PRESSURE DURING THE IMMEDIATE NEONATES TRANSITION: IS THE MIDDLE ARTERY PRESSURE (MAP RELEVANT FOR THE REGIONAL CEREBRAL OXYGENATION (crSO2? • N. Baik, B. Urlesberger, B. Schwaberger, G. Schmölzer, A. Avian, G. PichlerABS 9. BETWEEN 1993 AND 2012: EVOLUTION OF CEREBRAL PALSY IN PRETERM CHILDREN • M. Bickle Graz, J. Schneider, A.C. TruttmannABS 10. N-ACETYLCYSTEINE AMIDE (NACA MAY HAVE NEUROPROTECTIVE PROPERTIES AFTER PERINATAL ASPHYXIA • T. Benterud, L. Pankratov, R. Solberg, A. Nordgren, L.O. Baumbusch, O.D. SaugstadABS 11. BRAIN INTERSTITIAL PH CHANGES DURING THE SUBACUTE PHASE IN A NEWBORN PIGLET PERINATAL ASPHYXIA MODEL • J. Németh, G. Remzső, V. Tóth-Szűki, F. DomokiABS 12. NEUROPROTECTIVE EFFECT OF REMIFENTANIL ON EXCITOTOXIC-INDUCED BRAIN DAMAGE IN NEONATAL MICE • C. Chollat, F. Tourrel, M. Lecointre, Y. Ramdani, S. Marret, B. Gonzalez, S. JégouABS 13. THE SafeBoosC II TRIAL: REDUCING CEREBRAL HYPOXIA WITHOUT CHANGING EARLY BIOMARKERS OF BRAIN INJURY • A.M. Plomgaard, W. van Oeveren, T.H. Petersen, T. Alderliesten, T. Austin, F. van Bel, M. Benders, O. Claris, E. Dempsey, A. Franz, M. Fumagalli, C. Gluud, C. Hagmann, S. Hyttel-Soerensen, P. Lemmers, A. Pellicer, G. PicABS 14. PREDICTING WHITE MATTER DAMAGE BY EVALUATION OF THE LINEAR GROWTH RATE OF CORPUS CALLOSUM IN VERY LOW BIRTH WEIGHT INFANTS • H. Huang, C. Chen, H. Chou, P. Tsao, W. HsiehABS 15. REGIONAL AND DEVELOPMENTAL SCREENING OF BILIRUBIN TOXICITY: HIPPOCAMPUS IS THE MOST SENSIBLE REGION • M. Dal Ben, C. Tiribelli, S. GazzinABS 16. EFFICACY

  14. Effect of neonatal nociceptin or nocistatin imprinting on the brain concentration of biogenic amines and their metabolites.

    Science.gov (United States)

    Tekes, Kornélia; Gyenge, Melinda; Sótonyi, Péter; Csaba, György

    2009-04-01

    Noradrenaline (NA), dopamine (DA), homovanillic acid (HA), serotonin (5HT) and 5-hydroxyindole acetic acid (5HIAA) content of five brain regions (hypothalamus, hippocampus, brainstem, striatum and frontal cortex) and the cerebrospinal fluid (CSF) was measured in adult (three months old) male and female rats treated neonatally with a single dose of 10 microg nociceptin (NC) or 10 microg nocistatin (NS) for hormonal imprinting. The biogenic amine and metabolite content of cerebrospinal fluid was also determined. In NC treated animals the serotonergic, dopaminergic as well as noradrenergic systems were influenced by the imprinting. The 5HT level increased in hypothalamus, the 5HIAA tissue levels were found increased in hypothalamus. Hippocampus and striatum and the HVA levels increased highly significantly in brainstem. Dopamine level decreased significantly in striatum, however in frontal cortex both noradrenalin and 5HIAA level decreased. Nevertheless, in NS-treated rats decreased NA tissue levels were found in hypothalamus, brainstem and frontal cortex. Decreased DA levels were found in the hypothalamus, brainstem and striatum. NS imprinting resulted in decreased HVA level, but increased one in the brainstem. The 5HT levels decreased in the hypothalamus, brainstem, striatum and frontal cortex, while 5HIAA content of CSF, and frontal cortex decreased, and that of hypothalamus, hippocampus and striatum increased. There was no significant difference between genders except in the 5HT tissue levels of NC treated rats. Data presented show that neonatal imprinting both by NC and NS have long-lasting and brain area specific effects. In earlier experiments endorphin imprinting also influenced the serotonergic system suggesting that during labour release of pain-related substances may durably affect the serotonergic (dopaminergic, adrenergic) system which can impress the animals' later behavior.

  15. An in vivo three-dimensional magnetic resonance imaging-based averaged brain collection of the neonatal piglet (Sus scrofa.

    Directory of Open Access Journals (Sweden)

    Matthew S Conrad

    Full Text Available Due to the fact that morphology and perinatal growth of the piglet brain is similar to humans, use of the piglet as a translational animal model for neurodevelopmental studies is increasing. Magnetic resonance imaging (MRI can be a powerful tool to study neurodevelopment in piglets, but many of the MRI resources have been produced for adult humans. Here, we present an average in vivo MRI-based atlas specific for the 4-week-old piglet. In addition, we have developed probabilistic tissue classification maps. These tools can be used with brain mapping software packages (e.g. SPM and FSL to aid in voxel-based morphometry and image analysis techniques. The atlas enables efficient study of neurodevelopment in a highly tractable translational animal with brain growth and development similar to humans.

  16. Neonatal Brain Pathology Predicts Adverse Attention and Processing Speed Outcomes in Very Preterm and/or Very Low Birth Weight Children

    Science.gov (United States)

    Murray, Andrea L; Scratch, Shannon E; Thompson, Deanne K; Inder, Terrie E; Doyle, Lex W; Anderson, Jacqueline F. I.; Anderson, Peter J

    2014-01-01

    Objective This study aimed to examine attention and processing speed outcomes in very preterm (VPT; deep gray matter, and cerebellar abnormalities. Attention and processing speed were assessed at 7 years using standardized neuropsychological tests. Group differences were tested in attention and processing speed, and the relationships between these cognitive domains and brain abnormalities at birth were investigated. Results At 7 years of age, the VPT/VLBW group performed significantly poorer than term controls on all attention and processing speed outcomes. Associations between adverse attention and processing speed performances at 7 years and higher neonatal brain abnormality scores were found; in particular, white matter and deep gray matter abnormalities were reasonable predictors of long-term cognitive outcomes. Conclusion Attention and processing speed are significant areas of concern in VPT/VLBW children. This is the first study to show that adverse attention and processing speed outcomes at 7 years are associated with neonatal brain pathology. PMID:24708047

  17. Combination of Constraint-Induced Movement Therapy with Electroacupuncture Improves Functional Recovery following Neonatal Hypoxic-Ischemic Brain Injury in Rats

    Directory of Open Access Journals (Sweden)

    Hyunha Kim

    2018-01-01

    Full Text Available Aim. Neonatal hypoxic-ischemia (HI due to insufficient oxygen supply and blood flow during the prenatal and postnatal periods can cause cerebral palsy, a serious developmental condition. The purpose of this study was to investigate the efficacy of combining constraint-induced movement therapy (CIMT and electroacupuncture to treat rat neonatal HI brain injury. Methods. The left common carotid arteries of postnatal day 7 rats were ligated to induce HI brain injury, and the neonates were kept in a hypoxia chamber containing 8% oxygen for 2 hrs. Electroacupuncture at Baihui (GV 20 and Zusanli (ST 36 was performed concurrently with CIMT 3 weeks after HI induction for 4 weeks. Results. Motor asymmetry after HI was significantly improved in the CIMT and electroacupuncture combination group, but HI lesion size was not improved. The combination of CIMT and electroacupuncture after HI injury increases NeuN and decreases GFAP levels in the cerebral cortex, suggesting that this combination treatment inversely regulates neurons and astrocytes. In addition, the combination treatment group reduced the level of cleaved caspase-3, a crucial mediator of apoptosis, in the cortex. Conclusions. Our findings indicate that a combination of CIMT and electroacupuncture is an effective method to treat hemiplegia due to neonatal HI brain injury.

  18. Paracetamol (acetaminophen) administration during neonatal brain development affects cognitive function and alters its analgesic and anxiolytic response in adult male mice.

    Science.gov (United States)

    Viberg, Henrik; Eriksson, Per; Gordh, Torsten; Fredriksson, Anders

    2014-03-01

    Paracetamol (acetaminophen) is one of the most commonly used drugs for the treatment of pain and fever in children, both at home and in the clinic, and is now also found in the environment. Paracetamol is known to act on the endocannabinoid system, involved in normal development of the brain. We examined if neonatal paracetamol exposure could affect the development of the brain, manifested as adult behavior and cognitive deficits, as well as changes in the response to paracetamol. Ten-day-old mice were administered a single dose of paracetamol (30 mg/kg body weight) or repeated doses of paracetamol (30 + 30 mg/kg body weight, 4h apart). Concentrations of paracetamol and brain-derived neurotrophic factor (BDNF) were measured in the neonatal brain, and behavioral testing was done when animals reached adulthood. This study shows that acute neonatal exposure to paracetamol (2 × 30 mg) results in altered locomotor activity on exposure to a novel home cage arena and a failure to acquire spatial learning in adulthood, without affecting thermal nociceptive responding or anxiety-related behavior. However, mice neonatally exposed to paracetamol (2 × 30 mg) fail to exhibit paracetamol-induced antinociceptive and anxiogenic-like behavior in adulthood. Behavioral alterations in adulthood may, in part, be due to paracetamol-induced changes in BDNF levels in key brain regions at a critical time during development. This indicates that exposure to and presence of paracetamol during a critical period of brain development can induce long-lasting effects on cognitive function and alter the adult response to paracetamol in mice.

  19. Diminished growth and lower adiposity in hyperglycemic very low birth weight neonates at 4 months corrected age.

    Science.gov (United States)

    Scheurer, J M; Gray, H L; Demerath, E W; Rao, R; Ramel, S E

    2016-02-01

    Characterize the relationship between neonatal hyperglycemia and growth and body composition at 4 months corrected age (CA) in very low birth weight (VLBW) preterm infants. A prospective study of VLBW appropriate-for-gestation infants (N=53). All blood glucose measurements in the first 14 days and nutritional intake and illness markers until discharge were recorded. Standard anthropometrics and body composition via air displacement plethysmography were measured near term CA and 4 months CA. Relationships between hyperglycemia and anthropometrics and body composition were examined using multivariate linear regression. Infants with >5 days of hyperglycemia were lighter (5345 vs 6455 g, P⩽0.001), shorter (57.9 vs 60.9 cm, P⩽0.01), had smaller occipital-frontal head circumference (39.4 vs 42.0 cm, P⩽0.05) and were leaner (percent body fat 15.0 vs 23.8, P⩽0.01) at 4 months CA than those who did not have hyperglycemia, including after correcting for nutritional and illness factors. Neonatal hyperglycemia in VLBW infants is associated with decreased body size and lower adiposity at 4 months CA independent of nutritional deficit, insulin use and illness. Downregulation of the growth hormone axis may be responsible. These changes may influence long-term growth and cognitive development.

  20. [Perinatal outcome and cardiac dysfunction in preterm growth-restricted neonates in relation to placental impairment severity].

    Science.gov (United States)

    Candel Pau, Júlia; Castillo Salinas, Félix; Perapoch López, Josep; Carrascosa Lezcano, Antonio; Sánchez García, Olga; Llurba Olivé, Elisa

    2016-10-01

    Intrauterine growth restriction (IUGR) and prematurity have been associated with increased perinatal morbidity and mortality and also with cardiovascular foetal programming. However, there are few studies on the impact of placenta-related IUGR on perinatal outcomes and cardiovascular biomarkers in pre-term infants. To determine differences in neonatal morbidity, mortality and cord blood biomarkers of cardiovascular dysfunction between pre-term placenta-related IUGR and non-IUGR new-borns, and to analyse their relationship with the severity of IUGR according to foetal Doppler evaluation. Prospective cohort study: pre-term infants with placenta-related IUGR and matched pre-term infants without IUGR. A Doppler scan was performed, and placenta-IUGR was classified according to severity. Comparative analysis of perinatal outcomes, neonatal morbidity and mortality, and cord blood levels of biomarkers of cardiovascular dysfunction was performed. IUGR new-borns present lower weight, length, head circumference, and Apgar score at birth, as well as increased neonatal and cardiovascular dysfunction biomarker levels, compared with pre-term new-borns without IUGR. These differences increase with the severity of IUGR determined by prenatal umbilical artery Doppler scan. Placenta-related-IUGR pre-term infants, irrespective of gestational age, present increased neonatal morbidity and mortality that is significantly proportional to the severity of IUGR. Placental impairment and severity also determine levels of cardiovascular dysfunction biomarkers at birth. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Association of brain injury and neonatal cytokine response during therapeutic hypothermia in newborns with hypoxic-ischemic encephalopathy.

    Science.gov (United States)

    Orrock, Janet E; Panchapakesan, Karuna; Vezina, Gilbert; Chang, Taeun; Harris, Kari; Wang, Yunfei; Knoblach, Susan; Massaro, An N

    2016-05-01

    Cytokines have been proposed as mediators of neonatal brain injury via neuroinflammatory pathways triggered by hypoxia-ischemia. Limited data are available on cytokine profiles in larger cohorts of newborns with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). Serum cytokines interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, tumor necrosis factor-α, and interferon-γ were measured in newborns with HIE at 24 and 72 h of TH. Differences between infants with favorable (survivors with mild/no magnetic resonance imaging (MRI) injury) vs. adverse outcome (death or moderate/severe MRI injury) were compared using mixed models to adjust for covariates. Data from 36 term newborns with HIE (favorable outcome: n = 20, adverse outcome: n = 16) were evaluated. Cytokines IL-1β, IL-2, IL-6, IL-8, IL-10, and IL-13 were elevated in the adverse relative to favorable outcome group at 24 h. IL-6 remained significantly elevated in the adverse outcome group at 72 h. IL-6 and IL-10 remained significantly associated with outcome group after controlling for covariates. Inflammatory cytokines are elevated in HIE newborns with brain injury by MRI. In particular, IL-6 and IL-10 were associated with adverse outcomes after controlling for baseline characteristics and severity of presentation. These data suggest that cytokine response may identify infants in need of additional neuroprotective interventions.

  2. Attenuation of alpha2A-adrenergic receptor expression in neonatal rat brain by RNA interference or antisense oligonucleotide reduced anxiety in adulthood.

    Science.gov (United States)

    Shishkina, G T; Kalinina, T S; Dygalo, N N

    2004-01-01

    Brain alpha2-adrenergic receptors (alpha2-ARs) have been implicated in the regulation of anxiety, which is associated with stress. Environmental treatments during neonatal development could modulate the level of brain alpha2-AR expression and alter anxiety in adults, suggesting possible involvement of these receptors in early-life programming of anxiety state. The present study was undertaken to determine whether the reduction of the expression of A subtype of these receptors most abundant in the neonatal brain affects anxiety-related behavior in adulthood. We attenuated the expression of alpha2A-ARs during neonatal life by two different sequence specific approaches, antisense technology and RNA interference. Treatment of rats with the antisense oligodeoxynucleotide or short interfering RNA (siRNA) against alpha2A-ARs on the days 2-4 of their life, produced a marked acute decrease in the levels of both alpha2A-AR mRNA and [3H]RX821002 binding sites in the brainstem into which drugs were injected. The decrease of alpha2A-AR expression in the neonatal brainstem influenced the development of this receptor system in the brain regions as evidenced by the increased number of [3H]RX821002 binding sites in the hypothalamus of adult animals with both neonatal alpha2A-AR knockdown treatments; also in the frontal cortex of antisense-treated, and in the hippocampus of siRNA-treated adult rats. These adult animals also demonstrated a decreased anxiety in the elevated plus-maze as evidenced by an increased number of the open arm entries, greater proportion of time spent in the open arms, and more than a two-fold increase in the number of exploratory head dips. The results provide the first evidence that the reduction in the brain expression of a gene encoding for alpha2A-AR during neonatal life led to the long-term neurochemical and behavioral alterations. The data suggests that alterations in the expression of the receptor-specific gene during critical periods of brain

  3. Sex and intrauterine growth restriction modify brain neurotransmitters profile of newborn piglets.

    Science.gov (United States)

    Vázquez-Gómez, M; Valent, D; García-Contreras, C; Arroyo, L; Óvilo, C; Isabel, B; Bassols, A; González-Bulnes, A

    2016-12-01

    The current study aimed to determine, using a swine model of intrauterine growth restriction (IUGR), whether short- and long-term neurological deficiencies and interactive dysfunctions of Low Birth-Weight (LBW) offspring might be related to altered pattern of neurotransmitters. Hence, we compared the quantities of different neurotransmitters (catecholamines and indoleamines), which were determined by HPLC, at brain structures related to the limbic system (hippocampus and amygdala) in 14 LBW and 10 Normal Body-Weight (NBW) newborn piglets. The results showed, firstly, significant effects of sex on the NBW newborns, with females having higher dopamine (DA) concentrations than males. The IUGR processes affected DA metabolism, with LBW piglets having lower concentrations of noradrenaline at the hippocampus and higher concentrations of the DA metabolites, homovanillic acid (HVA), at both the hippocampus and the amygdala than NBW neonates. The effects of IUGR were modulated by sex; there were no significant differences between LBW and NBW females, but LBW males had higher HVA concentration at the amygdala and higher concentration of 5-hydroxyindoleacetic acid, the serotonin metabolite, at the hippocampus than NBW males. In conclusion, the present study shows that IUGR is mainly related to changes, modulated by sex, in the concentrations of catecholamine neurotransmitters, which are related to adaptation to physical activity and to essential cognitive functions such as learning, memory, reward-motivated behavior and stress. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

  4. Astrocyte-derived proinflammatory cytokines induce hypomyelination in the periventricular white matter in the hypoxic neonatal brain.

    Directory of Open Access Journals (Sweden)

    Yiyu Deng

    Full Text Available Hypoxic exposure in the perinatal period causes periventricular white matter damage (PWMD, a condition associated with myelination abnormalities. Under hypoxic conditions, glial cells were activated and released a large number of inflammatory mediators in the PWM in neonatal brain, which may result in oligodendrocyte (OL loss and axonal injury. This study aims to determine if astrocytes are activated and generate proinflammatory cytokines that may be coupled with the oligodendroglial loss and hypomyelination observed in hypoxic PWMD. Twenty-four 1-day-old Wistar rats were exposed to hypoxia for 2 h. The rats were then allowed to recover under normoxic conditions for 7 or 28 days before being killed. Another group of 24 rats kept outside the chamber was used as age-matched controls. Upregulated expression of TNF-α and IL-1β was observed in astrocytes in the PWM of P7 hypoxic rats by double immunofluorescence, western blotting and real time RT-PCR. This was linked to apoptosis and enhanced expression of TNF-R1 and IL-1R1 in APC(+ OLs. PLP expression was decreased significantly in the PWM of P28d hypoxic rats. The proportion of myelinated axons was markedly reduced by electron microscopy (EM and the average g-ratios were higher in P28d hypoxic rats. Upregulated expression of TNF-α and IL-1β in primary cultured astrocytes as well as their corresponding receptors in primary culture APC(+ oligodendrocytes were detected under hypoxic conditions. Our results suggest that following a hypoxic insult, astrocytes in the PWM of neonatal rats produce inflammatory cytokines such as TNF-α and IL-1β, which induce apoptosis of OLs via their corresponding receptors associated with them. This results in hypomyelination in the PWM of hypoxic rats.

  5. A Pilot Study of Inhaled CO Therapy in Neonatal Hypoxia-Ischemia: Carboxyhemoglobin Concentrations and Brain Volumes.

    Science.gov (United States)

    Douglas-Escobar, Martha; Mendes, Monique; Rossignol, Candace; Bliznyuk, Nikolay; Faraji, Ariana; Ahmad, Abdullah S; Doré, Sylvain; Weiss, Michael D

    2018-01-01

    Objective: The objective of this pilot study was to start evaluating the efficacy and the safety (i.e., carboxyhemoglobin concentration of carbon monoxide (CO)) as a putative neuroprotective therapy in neonates. Study Design: Neonatal C57BL/6 mice were exposed to CO at a concentration of either 200 or 250 ppm for a period of 1 h. The pups were then sacrificed at 0, 10, 20, 60, 120, 180, and 240 min after exposure to either concentration of CO, and blood was collected for analysis of carboxyhemoglobin. Following the safety study, 7-day-old pups underwent a unilateral carotid ligation. After recovery, the pups were exposed to a humidified gas mixture of 8% oxygen and 92% nitrogen for 20 min in a hypoxia chamber. One hour after the hypoxia exposure, the pups were randomized to one of two groups: air (HI+A) or carbon monoxide (HI+CO). An inhaled dose of 250 ppm of CO was administered to the pups for 1 h per day for a period of 3 days. At 7 days post-injury, the pups were sacrificed and the brains analyzed for cortical and hippocampal volumes. Results: CO exposure at 200 and 250 ppm produced a peak carboxyhemoglobin concentration of 21.52 ± 1.18% and 27.55 ± 3.58%, respectively. The carboxyhemoglobin concentrations decreased rapidly, reaching control concentrations by 60 min post exposure. At 14 days of age (7 days post injury), the HI+CO (treated with 1 h per day of 250 ppm of CO for 3 days post injury) had significant preservation of the ratio of ipsilateral to contralateral cortex (median 1.07, 25% 0.97, 75% 1.23, n = 10) compared the HI+A group ( p carboxyhemoglobin concentrations which would induce acute neurologic abnormalities and was effective in preserving cortical volumes following hypoxic-ischemic injury.

  6. Brain abscesses after Serratia marcescens infection on a neonatal intensive care unit: differences on serial imaging

    International Nuclear Information System (INIS)

    Messerschmidt, A.; Olischar, M.; Pollak, A.; Birnbacher, R.; Prayer, D.

    2004-01-01

    Serratia are known to be a possible cause of severe cerebral infections in neonates. We describe imaging of three premature infants infected with Serratia marcescens. Born in the 31 st , 25 th and 28 th weeks of gestation, they presented with signs of septicaemia on postnatal days 9, 24 and 32. Initial sonography showed cysts in the first child, two areas with anechoic centre and echogenic rim in the second, and several echogenic areas in the third. Lesions were seen on CT, of low density in two cases and minimally increased density in the third. MRI in the first patient showed cysts with incomplete contrast enhancement of the lesions, while patient 2 showed five ring-enhancing fluid-containing lesions with thick walls. In the third patient two abscesses with contrast enhancement and several high-signal spots were seen. We discuss the pathophysiology of the lesions and the impact of the various imaging methods. (orig.)

  7. Brain abscesses after Serratia marcescens infection on a neonatal intensive care unit: differences on serial imaging

    Energy Technology Data Exchange (ETDEWEB)

    Messerschmidt, A.; Olischar, M.; Pollak, A.; Birnbacher, R. [Division of Neonatology and Intensive Care, Department of Paediatrics, University of Vienna, Wahringer Guertel 18-20, 1090, Vienna (Austria); Prayer, D. [Division of Radiology, University of Vienna, Waehringer Guertel 18-20, 1090, Vienna (Austria)

    2004-02-01

    Serratia are known to be a possible cause of severe cerebral infections in neonates. We describe imaging of three premature infants infected with Serratia marcescens. Born in the 31{sup st}, 25{sup th} and 28{sup th} weeks of gestation, they presented with signs of septicaemia on postnatal days 9, 24 and 32. Initial sonography showed cysts in the first child, two areas with anechoic centre and echogenic rim in the second, and several echogenic areas in the third. Lesions were seen on CT, of low density in two cases and minimally increased density in the third. MRI in the first patient showed cysts with incomplete contrast enhancement of the lesions, while patient 2 showed five ring-enhancing fluid-containing lesions with thick walls. In the third patient two abscesses with contrast enhancement and several high-signal spots were seen. We discuss the pathophysiology of the lesions and the impact of the various imaging methods. (orig.)

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

    Science.gov (United States)

    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.

  9. Influence of neonatal vitamin A or vitamin D treatment on the concentration of biogenic amines and their metabolites in the adult rat brain.

    Science.gov (United States)

    Tekes, K; Gyenge, M; Folyovich, A; Csaba, G

    2009-04-01

    Newborn male rats were treated with a single dose of 3 mg vitamin A (retinol) or 0.05 mg vita-min D (cholecalciferol), and three months later five brain regions (frontopolar cortex, hypothalamus, hippocampus, striatum, and brainstem) were studied for tissue levels of dopamine (DA), serotonin (5HT), and metabolites such as homovanillic acid (HVA), as well as 5-hydroxyindole-3-acetic acid (5HIAA). Vitamin A treatment as hormonal imprinting significantly decreased 5HIAA levels in each brain region. Vitamin D imprinting significantly elevated DA only in the brainstem and HVA levels in striatum and hypothalamus. Present and earlier brain-imprinting results (with brain-produced substances), show that the profound and life-long effect of neonatal hormonal imprinting on neurotransmitter production of the adult brain seems to be well established. As prophylactic treatment with these vitamins is frequent in the perinatal period, the imprinting effect of vitamin A and vitamin D must be taken into consideration.

  10. Effects of different endocrine disruptor (EDC) mixtures on gene expression in neonatal rat brain regions

    DEFF Research Database (Denmark)

    Lichtensteiger, Walter; Bassetti-Gaille, Catherine; Faass, Oliver

    2013-01-01

    Sexual brain differentiation is a potential EDC target. It depends on a combination of estrogen receptor- and androgen receptor-mediated effects in males and on estrogens in females. It is not known how these processes are affected by real-world mixtures of EDCs. We investigated the effect of three...... EDC mixtures on gene expression in developing brain. Amix (8 anti-androgenic chemicals), Emix (4 estrogenic chemicals) and Tmix (Amix + Emix + paracetamol recently identified as anti-androgenic) were administered by oral gavage to rat dams from gestational day 7 until weaning, at doses corresponding...... to 450×, 200× and 100× high end human intakes (S. Christiansen et al., 2012. International Journal of Andrology 35, 303). At postnatal day 6, during the last part of sexual brain differentiation, exon microarray analyses were performed in medial preoptic area (MPO) in the highest dose group, and real...

  11. Vascular endothelial growth factor and basic fibroblast growth factor expression positively correlates with angiogenesis and peritumoural brain oedema in astrocytoma

    International Nuclear Information System (INIS)

    Jang, F.F.; Wei, W.

    2008-01-01

    Astrocytoma is the most malignant intracranial neoplasm and is characterized by high neovascularization and peritumoural brain oedema. Angiogenesis is a complicated process in oncogenesis regulated by the balance between angiogenic and antiangiogenic factors. The expression of two angiogenic growth factors, vascular endothelial growth factor and basic fibroblast growth factor were investigated using immunohistochemistry for astrocytoma from 82 patients and 11 normal human tissues. The expression of vascular endothelial growth factor and basic fibroblast growth factor positively correlate with the pathological grade of astrocytoma, microvessel density numbers and brain oedema, which may be responsible for the increased tumour neovascularization and peritumoural brain oedema. The results support the idea that inhibiting vascular endothelial growth factor and basic fibroblast growth factor are useful for the treatment of human astrocytoma and to improve patient's clinical outcomes and prognosis. (author)

  12. Advances in near-infrared spectroscopy to study the brain of the preterm and term neonate

    DEFF Research Database (Denmark)

    Wolf, Martin; Greisen, Gorm

    2009-01-01

    This article reviews tissue oximetry and imaging to study the preterm and newborn infant brain by near-infrared spectroscopy. These two technologies are now advanced; nearly 100 reports on their use in newborn infants have been published, and commercial instruments are available. The precision...

  13. Coping with Childbirth: Brain Structural Associations of Personal Growth Initiative

    Directory of Open Access Journals (Sweden)

    Judith Mangelsdorf

    2017-10-01

    Full Text Available Major life events require psychological adaptations and can be accompanied by brain structural and functional changes. The goal of the current study was to investigate the association of personal growth initiative (PGI as a form of proactive coping strategy before childbirth, with gray matter volume after delivery. Childbirth is one of the few predictable major life events, which, while being one of the most positive experiences for many, is also accompanied by multidimensional stress for the mother. Previous research has shown that high stress is associated with reductions in gray matter volume in limbic cortices as well as the prefrontal cortex (PFC. We hypothesized that PGI before childbirth is positively related to gray matter volume after delivery, especially in the ventromedial PFC (vmPFC. In a prospective study, 22 first-time mothers answered questionnaires about their PGI level 1 month before birth (T1 and 1 month after delivery (T2. Four months after giving birth, a follow-up assessment was applied with 16 of these mothers (T3. Structural brain data were acquired at both postpartal measurement occasions. Voxel-based morphometry was used to correlate prenatal PGI levels with postpartal gray matter volume. Higher PGI levels before delivery were positively associated with larger gray matter volume in the vmPFC directly after childbirth. Previous structural neuroimaging research in the context of major life events focused primarily on pathological reactions to stress (e.g., post-traumatic stress disorder; PTSD. The current study gives initial indications that proactive coping may be positively associated with gray matter volume in the vmPFC, a brain region which shows volumetric reductions in PTSD patients.

  14. MRI evaluation and functional assessment of brain injury after hypoxic ischemia in neonatal mice.

    Science.gov (United States)

    Adén, Ulrika; Dahlberg, Viktoria; Fredholm, Bertil B; Lai, Li-Ju; Chen, Zhengguan; Bjelke, Börje

    2002-05-01

    Severe perinatal asphyxia is an important cause of brain injury in the newborn infant. We examined early events after hypoxic ischemia (HI) in the 7-day-old mouse brain by MRI and related them to long-term functional effects and histopathology in the same animals at 4 to 5 weeks of age. HI was induced in 7-day-old CD1 mice by exposure to 8% oxygen for 30 minutes after occlusion of the left common carotid artery. The resulting unilateral focal lesion was evaluated in vivo by MRI (T2 maps and apparent diffusion coefficient maps) at 3, 6, and 24 hours and 5 days after hypoxia. Locomotion and sensorimotor function were analyzed after 3 weeks. Four weeks after HI, the mice were killed, and cresyl violet-stained brain sections were examined morphologically. A decrease in apparent diffusion coefficient values in cortex on the affected side was found at 3 hours after HI. T2 values were significantly increased after 6 hours and remained so for 5 days. Maximal size of the lesion was attained at 3 to 6 hours after HI and declined thereafter. Animals with MRI-detected lesions had decreased forward locomotion, performed worse than controls in the beam-walking test, and showed a unilateral hypotrophy in the cresyl violet-stained brain sections 4 weeks later. The temporal progression of the damage after HI in 7-day-old mice differs from that of the adult brain as judged by MRI. The early lesions detected by MRI were related to functional impairments for these mice in near-adult life.

  15. Short-term treatment with VEGF receptor inhibitors induces retinopathy of prematurity-like abnormal vascular growth in neonatal rats.

    Science.gov (United States)

    Nakano, Ayuki; Nakahara, Tsutomu; Mori, Asami; Ushikubo, Hiroko; Sakamoto, Kenji; Ishii, Kunio

    2016-02-01

    Retinal arterial tortuosity and venous dilation are hallmarks of plus disease, which is a severe form of retinopathy of prematurity (ROP). In this study, we examined whether short-term interruption of vascular endothelial growth factor (VEGF) signals leads to the formation of severe ROP-like abnormal retinal blood vessels. Neonatal rats were treated subcutaneously with the VEGF receptor (VEGFR) tyrosine kinase inhibitors, KRN633 (1, 5, or 10 mg/kg) or axitinib (10 mg/kg), on postnatal day (P) 7 and P8. The retinal vasculatures were examined on P9, P14, or P21 in retinal whole-mounts stained with an endothelial cell marker. Prevention of vascular growth and regression of some preformed capillaries were observed on P9 in retinas of rats treated with KRN633. However, on P14 and P21, density of capillaries, tortuosity index of arterioles, and diameter of veins significantly increased in KRN633-treated rats, compared to vehicle (0.5% methylcellulose)-treated animals. Similar observations were made with axitinib-treated rats. Expressions of VEGF and VEGFR-2 were enhanced on P14 in KRN633-treated rat retinas. The second round of KRN633 treatment on P11 and P12 completely blocked abnormal retinal vascular growth on P14, but thereafter induced ROP-like abnormal retinal blood vessels by P21. These results suggest that an interruption of normal retinal vascular development in neonatal rats as a result of short-term VEGFR inhibition causes severe ROP-like abnormal retinal vascular growth in a VEGF-dependent manner. Rats treated postnatally with VEGFR inhibitors could serve as an animal model for studying the mechanisms underlying the development of plus disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Neonatal brain microstructure correlates of neurodevelopment and gait in preterm children 18-22 mo of age: an MRI and DTI study.

    Science.gov (United States)

    Rose, Jessica; Cahill-Rowley, Katelyn; Vassar, Rachel; Yeom, Kristen W; Stecher, Ximena; Stevenson, David K; Hintz, Susan R; Barnea-Goraly, Naama

    2015-12-01

    Near-term brain structure was examined in preterm infants in relation to neurodevelopment. We hypothesized that near-term macrostructural brain abnormalities identified using conventional magnetic resonance imaging (MRI), and white matter (WM) microstructure detected using diffusion tensor imaging (DTI), would correlate with lower cognitive and motor development and slower, less-stable gait at 18-22 mo of age. One hundred and two very-low-birth-weight preterm infants (≤1,500 g birth weight; ≤32 wk gestational age) were recruited prior to routine near-term brain MRI at 36.6 ± 1.8 wk postmenstrual age. Cerebellar and WM macrostructure was assessed on conventional structural MRI. DTI was obtained in 66 out of 102 and WM microstructure was assessed using fractional anisotropy and mean diffusivity (MD) in six subcortical brain regions defined by DiffeoMap neonatal atlas. Neurodevelopment was assessed with Bayley-Scales-of-Infant-Toddler-Development, 3rd-Edition (BSID-III); gait was assessed using an instrumented mat. Neonates with cerebellar abnormalities identified using MRI demonstrated lower mean BSID-III cognitive composite scores (89.0 ± 10.1 vs. 97.8 ± 12.4; P = 0.002) at 18-22 mo. Neonates with higher DTI-derived left posterior limb of internal capsule (PLIC) MD demonstrated lower cognitive and motor composite scores (r = -0.368; P = 0.004; r = -0.354; P = 0.006) at 18-22 mo; neonates with higher genu MD demonstrated slower gait velocity (r = -0.374; P = 0.007). Multivariate linear regression significantly predicted cognitive (adjusted r(2) = 0.247; P = 0.002) and motor score (adjusted r(2) = 0.131; P = 0.017). Near-term cerebellar macrostructure and PLIC and genu microstructure were predictive of early neurodevelopment and gait.

  17. Inhibition of Inducible Nitric Oxide Controls Pathogen Load and Brain Damage by Enhancing Phagocytosis of Escherichia coli K1 in Neonatal Meningitis

    OpenAIRE

    Mittal, Rahul; Gonzalez-Gomez, Ignacio; Goth, Kerstin A.; Prasadarao, Nemani V.

    2010-01-01

    Escherichia coli K1 is a leading cause of neonatal meningitis in humans. In this study, we sought to determine the pathophysiologic relevance of inducible nitric oxide (iNOS) in experimental E. coli K1 meningitis. By using a newborn mouse model of meningitis, we demonstrate that E. coli infection triggered the expression of iNOS in the brains of mice. Additionally, iNOS−/− mice were resistant to E. coli K1 infection, displaying normal brain histology, no bacteremia, no disruption of the blood...

  18. Bidirectional Effects of Mother-Young Contact on the Maternal and Neonatal Brains.

    Science.gov (United States)

    González-Mariscal, Gabriela; Melo, Angel I

    2017-01-01

    Adaptive plasticity occurs intensely during the early postnatal period through processes like proliferation, migration, differentiation, synaptogenesis, myelination and apoptosis. Exposure to particular stimuli during this critical period has long-lasting effects on cognition, stress reactivity and behavior. Maternal care is the main source of social, sensory and chemical stimulation to the young and is, therefore, critical to "fine-tune" the offspring's neural development. Mothers providing a low quantity or quality of stimulation produce offspring that will exhibit reduced cognitive performance, impaired social affiliation and increased agonistic behaviors. Transgenerational transmission of such traits occurs epigenetically, i.e., through mechanisms like DNA methylation and post-translational modification of nucleosomal histones, processes that silence or increase gene expression without affecting the DNA sequence. Reciprocally, providing maternal care profoundly affects the behavior, learning, memory and fine neuroanatomy of the adult female. Such effects are in many cases permanent and sometimes they involve the hormones of pregnancy and lactation. The above evidence supports the idea that the mother-young dyad exerts profound and permanent effects on the brains of both adult and developing organisms, respectively. Effects on the latter can be explained by the neural developmental processes taking place during the early postnatal period. In contrast, little is known about the mechanisms mediating the plasticity of the adult maternal brain. The bidirectional effects that mother and young exert on each other's brains exemplify a remarkable plasticity of this organ for organizing itself and provide an immense source of variability for adaptation and evolution in mammals.

  19. Assessing signal-driven mechanism in neonates: brain responses to temporally and spectrally different sounds

    Directory of Open Access Journals (Sweden)

    Yasuyo eMinagawa-Kawai

    2011-06-01

    Full Text Available Past studies have found that in adults that acoustic properties of sound signals (such as fast vs. slow temporal features differentially activate the left and right hemispheres, and some have hypothesized that left-lateralization for speech processing may follow from left-lateralization to rapidly changing signals. Here, we tested whether newborns’ brains show some evidence of signal-specific lateralization responses using near-infrared spectroscopy (NIRS and auditory stimuli that elicits lateralized responses in adults, composed of segments that vary in duration and spectral diversity. We found significantly greater bilateral responses of oxygenated hemoglobin (oxy-Hb in the temporal areas for stimuli with a minimum segment duration of 21 ms, than stimuli with a minimum segment duration of 667 ms. However, we found no evidence for hemispheric asymmetries dependent on the stimulus characteristics. We hypothesize that acoustic-based functional brain asymmetries may develop throughout early infancy, and discuss their possible relationship with brain asymmetries for language.

  20. Whole-head functional brain imaging of neonates at cot-side using time-resolved diffuse optical tomography

    Science.gov (United States)

    Dempsey, Laura A.; Cooper, Robert J.; Powell, Samuel; Edwards, Andrea; Lee, Chuen-Wai; Brigadoi, Sabrina; Everdell, Nick; Arridge, Simon; Gibson, Adam P.; Austin, Topun; Hebden, Jeremy C.

    2015-07-01

    We present a method for acquiring whole-head images of changes in blood volume and oxygenation from the infant brain at cot-side using time-resolved diffuse optical tomography (TR-DOT). At UCL, we have built a portable TR-DOT device, known as MONSTIR II, which is capable of obtaining a whole-head (1024 channels) image sequence in 75 seconds. Datatypes extracted from the temporal point spread functions acquired by the system allow us to determine changes in absorption and reduced scattering coefficients within the interrogated tissue. This information can then be used to define clinically relevant measures, such as oxygen saturation, as well as to reconstruct images of relative changes in tissue chromophore concentration, notably those of oxy- and deoxyhaemoglobin. Additionally, the effective temporal resolution of our system is improved with spatio-temporal regularisation implemented through a Kalman filtering approach, allowing us to image transient haemodynamic changes. By using this filtering technique with intensity and mean time-of-flight datatypes, we have reconstructed images of changes in absorption and reduced scattering coefficients in a dynamic 2D phantom. These results demonstrate that MONSTIR II is capable of resolving slow changes in tissue optical properties within volumes that are comparable to the preterm head. Following this verification study, we are progressing to imaging a 3D dynamic phantom as well as the neonatal brain at cot-side. Our current study involves scanning healthy babies to demonstrate the quality of recordings we are able to achieve in this challenging patient population, with the eventual goal of imaging functional activation and seizures.

  1. Use of an eight-arm radial water maze to assess working and reference memory following neonatal brain injury.

    Science.gov (United States)

    Penley, Stephanie C; Gaudet, Cynthia M; Threlkeld, Steven W

    2013-12-04

    Working and reference memory are commonly assessed using the land based radial arm maze. However, this paradigm requires pretraining, food deprivation, and may introduce scent cue confounds. The eight-arm radial water maze is designed to evaluate reference and working memory performance simultaneously by requiring subjects to use extra-maze cues to locate escape platforms and remedies the limitations observed in land based radial arm maze designs. Specifically, subjects are required to avoid the arms previously used for escape during each testing day (working memory) as well as avoid the fixed arms, which never contain escape platforms (reference memory). Re-entries into arms that have already been used for escape during a testing session (and thus the escape platform has been removed) and re-entries into reference memory arms are indicative of working memory deficits. Alternatively, first entries into reference memory arms are indicative of reference memory deficits. We used this maze to compare performance of rats with neonatal brain injury and sham controls following induction of hypoxia-ischemia and show significant deficits in both working and reference memory after eleven days of testing. This protocol could be easily modified to examine many other models of learning impairment.

  2. Neonatal domoic acid decreases in vivo binding of [11C]yohimbine to α2 adrenoceptors in adult rat brain

    DEFF Research Database (Denmark)

    Thomsen, Majken; Lillethorup, Thea Pinholt; Jakobsen, Steen

    day 8-14 with saline or one of two low sub-convulsive doses, 20µg/kg [DOM20] or 60µg/kg [DOM60] of DOM, an AMPA/kainate receptor agonist. The behaviour of the rats was observed in an open field test, a social interaction test and the forced swim test at day 50, 75 and 98, respectively. At ~120 days...... of age 3-4 rats per group were injected with [11C]yohimbine, an α2 adrenergic receptor antagonist and scanned in a micro positron emission tomography (PET) scanner. DOM60 spent more time in the periphery during the open field test and less time struggling in the forced swim test compared to the saline...... treated rats. microPET data revealed that DOM60 rats had a 40-47 % reduction in [11C]yohimbine binding in limbic and cortical brain regions relative to saline treated rats. We conclude that neonatal administration of DOM combined with the potential stress associated with behavioural testing results...

  3. Neonatal physiological correlates of near-term brain development on MRI and DTI in very-low-birth-weight preterm infants.

    Science.gov (United States)

    Rose, Jessica; Vassar, Rachel; Cahill-Rowley, Katelyn; Stecher Guzman, Ximena; Hintz, Susan R; Stevenson, David K; Barnea-Goraly, Naama

    2014-01-01

    Structural brain abnormalities identified at near-term age have been recognized as potential predictors of neurodevelopment in children born preterm. The aim of this study was to examine the relationship between neonatal physiological risk factors and early brain structure in very-low-birth-weight (VLBW) preterm infants using structural MRI and diffusion tensor imaging (DTI) at near-term age. Structural brain MRI, diffusion-weighted scans, and neonatal physiological risk factors were analyzed in a cross-sectional sample of 102 VLBW preterm infants (BW ≤ 1500 g, gestational age (GA) ≤ 32 weeks), who were admitted to the Lucile Packard Children's Hospital, Stanford NICU and recruited to participate prior to routine near-term brain MRI conducted at 36.6 ± 1.8 weeks postmenstrual age (PMA) from 2010 to 2011; 66/102 also underwent a diffusion-weighted scan. Brain abnormalities were assessed qualitatively on structural MRI, and white matter (WM) microstructure was analyzed quantitatively on DTI in six subcortical regions defined by DiffeoMap neonatal brain atlas. Specific regions of interest included the genu and splenium of the corpus callosum, anterior and posterior limbs of the internal capsule, the thalamus, and the globus pallidus. Regional fractional anisotropy (FA) and mean diffusivity (MD) were calculated using DTI data and examined in relation to neonatal physiological risk factors including gestational age (GA), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), and sepsis, as well as serum levels of C-reactive protein (CRP), glucose, albumin, and total bilirubin. Brain abnormalities were observed on structural MRI in 38/102 infants including 35% of females and 40% of males. Infants with brain abnormalities observed on MRI had higher incidence of BPD (42% vs. 25%) and sepsis (21% vs. 6%) and higher mean and peak serum CRP levels, respectively, (0.64 vs. 0.34 mg/dL, p = .008; 1.57 vs. 0.67

  4. Neonatal Death

    Science.gov (United States)

    ... Home > Complications & Loss > Loss & grief > Neonatal death Neonatal death E-mail to a friend Please fill in ... cope with your baby’s death. What is neonatal death? Neonatal death is when a baby dies in ...

  5. Fetal, neonatal, infant, and child international growth standards: an unprecedented opportunity for an integrated approach to assess growth and development.

    Science.gov (United States)

    Garza, Cutberto

    2015-07-01

    The recent publication of fetal growth and gestational age-specific growth standards by the International Fetal and Newborn Growth Consortium for the 21st Century Project and the previous publication by the WHO of infant and young child growth standards based on the WHO Multicentre Growth Reference Study enable evaluations of growth from ∼9 wk gestation to 5 y. The most important features of these projects are the prescriptive approach used for subject selection and the rigorous testing of the assertion that growth is very similar among geographically and ethnically diverse nonisolated populations when health, nutrition, and other care needs are met and the environment imposes minimal constraints on growth. Both studies documented that with adequate controls, the principal source of variability in growth during gestation and early childhood resides among individuals. Study sites contributed much less to observed variability. The agreement between anthropometric measurements common to both studies also is noteworthy. Jointly, these studies provide for the first time, to my knowledge, a conceptually consistent basis for worldwide and localized assessments and comparisons of growth performance in early life. This is an important contribution to improving the health care of children across key periods of growth and development, especially given the appropriate interest in pursuing "optimal" health in the "first 1000 d," i.e., the period covering fertilization/implantation, gestation, and postnatal life to 2 y of age. © 2015 American Society for Nutrition.

  6. A Pilot Study of Inhaled CO Therapy in Neonatal Hypoxia-Ischemia: Carboxyhemoglobin Concentrations and Brain Volumes

    Directory of Open Access Journals (Sweden)

    Martha Douglas-Escobar

    2018-05-01

    Full Text Available Objective: The objective of this pilot study was to start evaluating the efficacy and the safety (i.e., carboxyhemoglobin concentration of carbon monoxide (CO as a putative neuroprotective therapy in neonates.Study Design: Neonatal C57BL/6 mice were exposed to CO at a concentration of either 200 or 250 ppm for a period of 1 h. The pups were then sacrificed at 0, 10, 20, 60, 120, 180, and 240 min after exposure to either concentration of CO, and blood was collected for analysis of carboxyhemoglobin. Following the safety study, 7-day-old pups underwent a unilateral carotid ligation. After recovery, the pups were exposed to a humidified gas mixture of 8% oxygen and 92% nitrogen for 20 min in a hypoxia chamber. One hour after the hypoxia exposure, the pups were randomized to one of two groups: air (HI+A or carbon monoxide (HI+CO. An inhaled dose of 250 ppm of CO was administered to the pups for 1 h per day for a period of 3 days. At 7 days post-injury, the pups were sacrificed and the brains analyzed for cortical and hippocampal volumes.Results: CO exposure at 200 and 250 ppm produced a peak carboxyhemoglobin concentration of 21.52 ± 1.18% and 27.55 ± 3.58%, respectively. The carboxyhemoglobin concentrations decreased rapidly, reaching control concentrations by 60 min post exposure. At 14 days of age (7 days post injury, the HI+CO (treated with 1 h per day of 250 ppm of CO for 3 days post injury had significant preservation of the ratio of ipsilateral to contralateral cortex (median 1.07, 25% 0.97, 75% 1.23, n = 10 compared the HI+A group (p < 0.05.Conclusion: CO exposure of 250 ppm did not reach carboxyhemoglobin concentrations which would induce acute neurologic abnormalities and was effective in preserving cortical volumes following hypoxic-ischemic injury.

  7. Neonatal brain structure on MRI and diffusion tensor imaging, sex, and neurodevelopment in very-low-birthweight preterm children.

    Science.gov (United States)

    Rose, Jessica; Butler, Erin E; Lamont, Lauren E; Barnes, Patrick D; Atlas, Scott W; Stevenson, David K

    2009-07-01

    The neurological basis of an increased incidence of cerebral palsy (CP) in preterm males is unknown. This study examined neonatal brain structure on magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) at term-equivalent age, sex, and neurodevelopment at 1 year 6 months on the basis of the Amiel-Tison neurological examination, Gross Motor Function Classification System, and Bayley Scales of Infant Development in 78 very-low-birthweight preterm children (41 males, 37 females; mean gestational age 27.6 wks, SD 2.5; mean birthweight 1021 g, SD 339). Brain abnormalities on MRI and DTI were not different between males and females except in the splenium of the corpus callosum, where males had lower DTI fractional anisotropy (p=0.025) and a higher apparent diffusion coefficient (p=0.013), indicating delayed splenium development. In the 26 infants who were at higher risk on the basis of DTI, males had more abnormalities on MRI (p=0.034) and had lower fractional anisotropy and a higher apparent diffusion coefficient in the splenium (p=0.049; p=0.025) and right posterior limb of the internal capsule (PLIC; p=0.003; p=0.033). Abnormal neurodevelopment was more common in males (n=9) than in females (n=2; p=0.036). Children with abnormal neurodevelopment had more abnormalities on MRI (p=0.014) and reduced splenium and right PLIC fractional anisotropy (p=0.001; p=0.035). In children with abnormal neurodevelopment, right PLIC fractional anisotropy was lower than left (p=0.035), whereas in those with normal neurodevelopment right PLIC fractional anisotropy was higher than left (p=0.001). Right PLIC fractional anisotropy correlated to neurodevelopment (rho=0.371, p=0.002). Logistic regression predicted neurodevelopment with 94% accuracy; only right PLIC fractional anisotropy was a significant logistic coefficient. Results indicate that the higher incidence of abnormal neurodevelopment in preterm males relates to greater incidence and severity of brain abnormalities

  8. Growth and growth hormone secretion in children following treatment of brain tumours with radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Darendeliler, F.; Livesey, E.A.; Hindmarsh, P.C.; Brook, C.G.D. (Endocrine Unit, The Middlesex Hospital, London (UK))

    1990-01-01

    We have studied the growth of 144 children after treatment of brain tumours distant from the hypothalamo-pituitary axis. All had cranial irradiation and 87 spinal irradiation. In 56 patients observed without intervention for 3 years, height SDS in the cranial (CR) group (n=20) declined from 0.02 to -0.44 and in the craniospinal (CS) group (n=36) from -0.28 to -1.11. Failure of spinal growth had a marked effect in the CS group. The onset of puberty was slightly but not significantly advanced; median ages at onset of puberty were 10.3 years in girls and 12.1 years in boys. Of the total group 86.4% had clinical and biochemical evidence of growth hormone insufficiency. Fifty-two children, 33 (28 CS; 5 CR) of whome were prepubertal, received biosynthetic human growth hormone, in a dose of 15 mU/m{sup 2}/week by daily injection for a period of one year. Height velocity SDS increased significantly in both groups from -2.74 to +1.90 (CS) and from -1.0 to +4.26 (CR). Spinal response to GH treatment was restricted in the craniospinal group. (authors).

  9. Growth and growth hormone secretion in children following treatment of brain tumours with radiotherapy

    International Nuclear Information System (INIS)

    Darendeliler, F.; Livesey, E.A.; Hindmarsh, P.C.; Brook, C.G.D.

    1990-01-01

    We have studied the growth of 144 children after treatment of brain tumours distant from the hypothalamo-pituitary axis. All had cranial irradiation and 87 spinal irradiation. In 56 patients observed without intervention for 3 years, height SDS in the cranial (CR) group (n=20) declined from 0.02 to -0.44 and in the craniospinal (CS) group (n=36) from -0.28 to -1.11. Failure of spinal growth had a marked effect in the CS group. The onset of puberty was slightly but not significantly advanced; median ages at onset of puberty were 10.3 years in girls and 12.1 years in boys. Of the total group 86.4% had clinical and biochemical evidence of growth hormone insufficiency. Fifty-two children, 33 (28 CS; 5 CR) of whome were prepubertal, received biosynthetic human growth hormone, in a dose of 15 mU/m 2 /week by daily injection for a period of one year. Height velocity SDS increased significantly in both groups from -2.74 to +1.90 (CS) and from -1.0 to +4.26 (CR). Spinal response to GH treatment was restricted in the craniospinal group. (authors)

  10. The effect of thyroxine treatment started in the neonatal period on development and growth of two-year-old Down syndrome children: A randomized clinical trial

    NARCIS (Netherlands)

    van Trotsenburg, A. S. Paul; Vulsma, Thomas; van Rozenburg-Marres, Susanne L. Rutgers; van Baar, Anneloes L.; Ridder, Jeannette C. D.; Heymans, Hugo S. A.; Tijssen, Jan G. P.; de Vijlder, Jan J. M.

    2005-01-01

    Context: Young Down syndrome children appear to have a mild form of congenital hypothyroidism that is rarely detected by neonatal screening and usually left untreated. Objective: To investigate the effects of thyroxine treatment on development and growth of young Down syndrome children. Design,

  11. Maternal early pregnancy vitamin D status in relation to fetal and neonatal growth: results of the multi-ethnic Amsterdam Born Children and their Development cohort

    NARCIS (Netherlands)

    Leffelaar, Evelien R.; Vrijkotte, Tanja G. M.; van Eijsden, Manon

    2010-01-01

    Low vitamin D levels during pregnancy may account for reduced fetal growth and for altered neonatal development. The present study explored the association between maternal vitamin D status measured early in pregnancy and birth weight, prevalence of small-for-gestational-age (SGA) infants and

  12. MONSTIR II: A 32-channel, multispectral, time-resolved optical tomography system for neonatal brain imaging

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, Robert J., E-mail: robert.cooper@ucl.ac.uk; Magee, Elliott; Everdell, Nick; Magazov, Salavat; Varela, Marta; Airantzis, Dimitrios; Gibson, Adam P.; Hebden, Jeremy C. [Biomedical Optics Research Laboratory, Department of Medical Physics and Bioengineering, University College London, London WC1E 6BT (United Kingdom)

    2014-05-15

    We detail the design, construction and performance of the second generation UCL time-resolved optical tomography system, known as MONSTIR II. Intended primarily for the study of the newborn brain, the system employs 32 source fibres that sequentially transmit picosecond pulses of light at any four wavelengths between 650 and 900 nm. The 32 detector channels each contain an independent photo-multiplier tube and temporally correlated photon-counting electronics that allow the photon transit time between each source and each detector position to be measured with high temporal resolution. The system's response time, temporal stability, cross-talk, and spectral characteristics are reported. The efficacy of MONSTIR II is demonstrated by performing multi-spectral imaging of a simple phantom.

  13. Elevated platelet-derived growth factor-BB concentrations in premature neonates who develop chronic lung disease

    Directory of Open Access Journals (Sweden)

    Adcock Kim G

    2004-06-01

    Full Text Available Abstract Background Chronic lung disease (CLD in the preterm newborn is associated with inflammation and fibrosis. Platelet-derived growth factor-BB (PDGF-BB, a potent chemotactic growth factor, may mediate the fibrotic component of CLD. The objectives of this study were to determine if tracheal aspirate (TA concentrations of PDGF-BB increase the first 2 weeks of life in premature neonates undergoing mechanical ventilation for respiratory distress syndrome (RDS, its relationship to the development of CLD, pulmonary hemorrhage (PH and its relationship to airway colonization with Ureaplasma urealyticum (Uu. Methods Infants with a birth weight less than 1500 grams who required mechanical ventilation for RDS were enrolled into this study with parental consent. Tracheal aspirates were collected daily during clinically indicated suctioning. Uu cultures were performed on TA collected in the first week of life. TA supernatants were assayed for PDGF-BB and secretory component of IgA concentrations using ELISA techniques. Results Fifty premature neonates were enrolled into the study. Twenty-eight infants were oxygen dependent at 28 days of life and 16 infants were oxygen dependent at 36 weeks postconceptual age. PDGF-BB concentrations peaked between 4 and 6 days of life. Maximum PDGF-BB concentrations were significantly higher in infants who developed CLD or died from respiratory failure. PH was associated with increased risk of CLD and was associated with higher PDGF-BB concentrations. There was no correlation between maximum PDGF-BB concentrations and Uu isolation from the airway. Conclusions PDGF-BB concentrations increase in TAs of infants who undergo mechanical ventilation for RDS during the first 2 weeks of life and maximal concentrations are greater in those infants who subsequently develop CLD. Elevation in lung PDGF-BB may play a role in the development of CLD.

  14. Nitrous oxide discretely up-regulates nNOS and p53 in neonatal rat brain.

    Science.gov (United States)

    Cattano, D; Valleggi, S; Abramo, A; Forfori, F; Maze, M; Giunta, F

    2010-06-01

    Animal studies suggest that neuronal cell death often results from anesthetic administration during synaptogenesis. Volatile anesthetics are strongly involved in triggering neuronal apoptosis, whereas other inhalational agents (xenon) demonstrate protective effects. Nitrous oxide (N2O) has modest pro-apoptotic effects on its own and potent, synergistic toxic effects when combined with volatile agents. Recent findings suggest that, during periods of rapid brain development, the enhanced neurodegeneration triggered by anesthetic drugs may be caused by a compensatory increase in intracellular free calcium, a potent activator of neuronal nitric oxide synthase (nNOS). Anesthesia-induced neuro-apoptosis is also activated via the intrinsic and the extrinsic apoptotic pathways because both pathways involve p53, a key regulatory gene. The molecular events related to neuronal cell apoptosis are not completely understood. To gain further insight into the events underlying neuro-apoptosis, we analyzed the transcriptional consequences of N2O exposure on nNOS, iNOS and p53 mRNA levels. The study used 2 groups of postnatal day seven Sprague/Dawley rats (N=6 each) that were exposed for 120 minutes to air (75% N2, 25% O2) or N2O (75% N2O, 25% O2; this N2O concentration is commonly used to induce anesthesia and has been demonstrated to trigger neurodegeneration in postnatal day seven rats). Total RNA was isolated from each brain and expression analyses on iNOS and nNOS transcripts were performed using relative Real-Time C-reactive protein PCR (using G3PDH as a housekeeping gene). A semi-quantitative RT-PCR analysis was performed on the p53 transcript (using Ciclophylin A as a housekeeping gene). Statistical analysis (REST 2005) revealed a significant, 11-fold up-regulation (P=0.026) of the nNOS transcript but no significant changes in iNOS transcription. The p53 mRNA was up-regulated almost 2-fold (P=0.0002; Student's t-Test; GraphPad Prism 4.00) in N2O-treated samples relative to

  15. Customized vs population-based growth charts to identify neonates at risk of adverse outcome: systematic review and Bayesian meta-analysis of observational studies.

    Science.gov (United States)

    Chiossi, G; Pedroza, C; Costantine, M M; Truong, V T T; Gargano, G; Saade, G R

    2017-08-01

    To compare the effectiveness of customized vs population-based growth charts for the prediction of adverse pregnancy outcomes. MEDLINE, ClinicalTrials.gov and The Cochrane Library were searched up to 31 May 2016 to identify interventional and observational studies comparing adverse outcomes among large- (LGA) and small- (SGA) for-gestational-age neonates, when classified according to customized vs population-based growth charts. Perinatal mortality and admission to the neonatal intensive care unit (NICU) of both SGA and LGA neonates, intrauterine fetal demise (IUFD) and neonatal mortality of SGA neonates, and neonatal shoulder dystocia and hypoglycemia as well as maternal third- and fourth-degree perineal lacerations in LGA pregnancies were evaluated. The electronic search identified 237 records that were examined based on title and abstract, of which 27 full-text articles were examined for eligibility. After excluding seven articles, 20 observational studies were included in a Bayesian meta-analysis. Neonates classified as SGA according to customized growth charts had higher risks of IUFD (odds ratio (OR), 7.8 (95% CI, 4.2-12.3)), neonatal death (OR, 3.5 (95% CI, 1.1-8.0)), perinatal death (OR, 5.8 (95% CI, 3.8-7.8)) and NICU admission (OR, 3.6 (95% CI, 2.0-5.5)) than did non-SGA cases. Neonates classified as SGA according to population-based growth charts also had increased risk for adverse outcomes, albeit the point estimates of the pooled ORs were smaller: IUFD (OR, 3.3 (95% CI, 1.9-5.0)), neonatal death (OR, 2.9 (95% CI, 1.2-4.5)), perinatal death (OR, 4.0 (95% CI, 2.8-5.1)) and NICU admission (OR, 2.4 (95% CI, 1.7-3.2)). For LGA vs non-LGA, there were no differences in pooled ORs for perinatal death, NICU admission, hypoglycemia and maternal third- and fourth-degree perineal lacerations when classified according to either the customized or the population-based approach. In contrast, both approaches indicated that LGA neonates are at increased risk for

  16. l-Arginine-Dependent Epigenetic Regulation of Interleukin-10, but Not Transforming Growth Factor-β, Production by Neonatal Regulatory T Lymphocytes

    Science.gov (United States)

    Yu, Hong-Ren; Tsai, Ching-Chang; Chang, Ling-Sai; Huang, Hsin-Chun; Cheng, Hsin-Hsin; Wang, Jiu-Yao; Sheen, Jiunn-Ming; Kuo, Ho-Chang; Hsieh, Kai-Sheng; Huang, Ying-Hsien; Yang, Kuender D.; Hsu, Te-Yao

    2017-01-01

    A growing number of diseases in humans, including trauma, certain cancers, and infection, are known to be associated with l-arginine deficiency. In addition, l-arginine must be supplemented by diet during pregnancy to aid fetal development. In conditions of l-arginine depletion, T cell proliferation is impaired. We have previously shown that neonatal blood has lower l-arginine levels than adult blood, which is associated with poor neonatal lymphocyte proliferation, and that l-arginine enhances neonatal lymphocyte proliferation through an interleukin (IL)-2-independent pathway. In this study, we have further investigated how exogenous l-arginine enhances neonatal regulatory T-cells (Tregs) function in relation to IL-10 production under epigenetic regulation. Results showed that cord blood mononuclear cells (CBMCs) produced higher levels of IL-10 than adult peripheral blood mononuclear cells (PBMCs) by phytohemagglutinin stimulation but not by anti-CD3/anti-CD28 stimulation. Addition of exogenous l-arginine had no effect on transforming growth factor-β production by PBMCs or CBMCs, but enhanced IL-10 production by neonatal CD4+CD25+FoxP3+ Tregs. Further studies showed that IL-10 promoter DNA hypomethylation, rather than histone modification, corresponded to the l-arginine-induced increase in IL-10 production by neonatal CD4+ T cells. These results suggest that l-arginine modulates neonatal Tregs through the regulation of IL-10 promoter DNA methylation. l-arginine supplementation may correct the Treg function in newborns with l-arginine deficiency. PMID:28487700

  17. l-Arginine-Dependent Epigenetic Regulation of Interleukin-10, but Not Transforming Growth Factor-β, Production by Neonatal Regulatory T Lymphocytes

    Directory of Open Access Journals (Sweden)

    Kuender D. Yang

    2017-04-01

    Full Text Available A growing number of diseases in humans, including trauma, certain cancers, and infection, are known to be associated with l-arginine deficiency. In addition, l-arginine must be supplemented by diet during pregnancy to aid fetal development. In conditions of l-arginine depletion, T cell proliferation is impaired. We have previously shown that neonatal blood has lower l-arginine levels than adult blood, which is associated with poor neonatal lymphocyte proliferation, and that l-arginine enhances neonatal lymphocyte proliferation through an interleukin (IL-2-independent pathway. In this study, we have further investigated how exogenous l-arginine enhances neonatal regulatory T-cells (Tregs function in relation to IL-10 production under epigenetic regulation. Results showed that cord blood mononuclear cells (CBMCs produced higher levels of IL-10 than adult peripheral blood mononuclear cells (PBMCs by phytohemagglutinin stimulation but not by anti-CD3/anti-CD28 stimulation. Addition of exogenous l-arginine had no effect on transforming growth factor-β production by PBMCs or CBMCs, but enhanced IL-10 production by neonatal CD4+CD25+FoxP3+ Tregs. Further studies showed that IL-10 promoter DNA hypomethylation, rather than histone modification, corresponded to the l-arginine-induced increase in IL-10 production by neonatal CD4+ T cells. These results suggest that l-arginine modulates neonatal Tregs through the regulation of IL-10 promoter DNA methylation. l-arginine supplementation may correct the Treg function in newborns with l-arginine deficiency.

  18. From early stress to 12-month development in very preterm infants: Preliminary findings on epigenetic mechanisms and brain growth.

    Science.gov (United States)

    Fumagalli, Monica; Provenzi, Livio; De Carli, Pietro; Dessimone, Francesca; Sirgiovanni, Ida; Giorda, Roberto; Cinnante, Claudia; Squarcina, Letizia; Pozzoli, Uberto; Triulzi, Fabio; Brambilla, Paolo; Borgatti, Renato; Mosca, Fabio; Montirosso, Rosario

    2018-01-01

    Very preterm (VPT) infants admitted to Neonatal Intensive Care Unit (NICU) are at risk for altered brain growth and less-than-optimal socio-emotional development. Recent research suggests that early NICU-related stress contributes to socio-emotional impairments in VPT infants at 3 months through epigenetic regulation (i.e., DNA methylation) of the serotonin transporter gene (SLC6A4). In the present longitudinal study we assessed: (a) the effects of NICU-related stress and SLC6A4 methylation variations from birth to discharge on brain development at term equivalent age (TEA); (b) the association between brain volume at TEA and socio-emotional development (i.e., Personal-Social scale of Griffith Mental Development Scales, GMDS) at 12 months corrected age (CA). Twenty-four infants had complete data at 12-month-age. SLC6A4 methylation was measured at a specific CpG previously associated with NICU-related stress and socio-emotional stress. Findings confirmed that higher NICU-related stress associated with greater increase of SLC6A4 methylation at NICU discharge. Moreover, higher SLC6A4 discharge methylation was associated with reduced anterior temporal lobe (ATL) volume at TEA, which in turn was significantly associated with less-than-optimal GMDS Personal-Social scale score at 12 months CA. The reduced ATL volume at TEA mediated the pathway linking stress-related increase in SLC6A4 methylation at NICU discharge and socio-emotional development at 12 months CA. These findings suggest that early adversity-related epigenetic changes might contribute to the long-lasting programming of socio-emotional development in VPT infants through epigenetic regulation and structural modifications of the developing brain.

  19. Polyploidization of glia in neural development links tissue growth to blood-brain barrier integrity.

    Science.gov (United States)

    Unhavaithaya, Yingdee; Orr-Weaver, Terry L

    2012-01-01

    Proper development requires coordination in growth of the cell types composing an organ. Many plant and animal cells are polyploid, but how these polyploid tissues contribute to organ growth is not well understood. We found the Drosophila melanogaster subperineurial glia (SPG) to be polyploid, and ploidy is coordinated with brain mass. Inhibition of SPG polyploidy caused rupture of the septate junctions necessary for the blood-brain barrier. Thus, the increased SPG cell size resulting from polyploidization is required to maintain the SPG envelope surrounding the growing brain. Polyploidization likely is a conserved strategy to coordinate tissue growth during organogenesis, with potential vertebrate examples.

  20. Neonatal Listeriosis

    Directory of Open Access Journals (Sweden)

    Shih-Yu Chen

    2007-01-01

    Full Text Available In Western developed countries, Listeria monocytogenes is not an uncommon pathogen in neonates. However, neonatal listeriosis has rarely been reported in Taiwan. We describe two cases collected from a single medical institute between 1990 and 2005. Case 1 was a male premature baby weighing 1558 g with a gestational age of 31 weeks whose mother had fever with chills 3 days prior to delivery. Generalized maculopapular rash was found after delivery and subtle seizure developed. Both blood and cerebrospinal fluid culture collected on the 1st day yielded L. monocytogenes. In addition, he had ventriculitis complicated with hydrocephalus. Neurologic development was normal over 1 year of follow-up after ventriculoperitoneal shunt operation. Case 2 was a 28-weeks' gestation male premature baby weighing 1180 g. Endotracheal intubation and ventilator support were provided after delivery due to respiratory distress. Blood culture yielded L. monocyto-genes. Cerebrospinal fluid showed pleocytosis but the culture was negative. Brain ultrasonography showed ventriculitis. Sudden deterioration with cyanosis and bradycardia developed on the 8th day and he died on the same day. Neonatal listeriosis is uncommon in Taiwan, but has significant mortality and morbidity. Early diagnosis of perinatal infection relies on high index of suspicion in perinatal health care professionals. [J Formos Med Assoc 2007;106(2:161-164

  1. Neonatal Tele-Homecare

    DEFF Research Database (Denmark)

    Holm, Kristina Garne

    Neonatal homecare (NH) implies that parents manage tube feeding and care of their preterm infant at home supported by home visits from neonatal nurses, to monitor infant growth and the well-being of the family. Home visits are costly and time consuming in rural areas. The overall aim of this study...

  2. Quantitative Shear-Wave Elastography of the Liver in Preterm Neonates with Intra-Uterine Growth Restriction.

    Directory of Open Access Journals (Sweden)

    Marianne Alison

    Full Text Available The feasibility and reproducibility of liver stiffness measurements using Supersonic Shear-wave Imaging (SSI in preterm neonate have not been reported. Our aim was to determine if liver stiffness differs between intra-uterine growth restriction (IUGR and appropriate for gestational age (AGA preterm infants with/without cholestasis. We measured liver stiffness (in kPa in 45 AGA and 18 IUGR preterm infants, and assessed reproducibility in 26 preterms using Intraclass Correlation Coefficients (ICC and Bland-Altman tests. Liver stiffness values were compared between AGA and IUGR with and without cholestasis and correlated with birth weight. Measurements showed high reproducibility (ICC = 0.94-0.98 for intra-operator, 0.86 for inter-operator with good agreement (95% limits: -1.24 to 1.24 kPa. During the first postnatal week, liver stiffness was higher in IUGR (7.50 ±1.53 kPa than in AGA infants (5.11 ±0.80 kPa, p<0.001. After day 8, liver stiffness remained unchanged in AGA but increased progressively in IUGR infants (15.57 ±6.49 kPa after day 21. Liver stiffness was higher in IUGR neonates with cholestasis (19.35 ± 9.80 kPa than without cholestasis (7.72 ± 1.27 kPa, p<0.001. In conclusion, quantitative liver SSI in preterms is feasible and reproducible. IUGR preterms who will develop cholestasis present high liver stiffness even at birth, before biological cholestasis occurs.

  3. Melatonin reduces hypoxic-ischaemic (HI) induced autophagy and apoptosis: An in vivo and in vitro investigation in experimental models of neonatal HI brain injury.

    Science.gov (United States)

    Hu, Yingying; Wang, Zhouguang; Liu, Yanlong; Pan, Shulin; Zhang, Hao; Fang, Mingchu; Jiang, Huai; Yin, Jiayu; Zou, Shuangshuang; Li, Zhenmao; Zhang, Hongyu; Lin, Zhenlang; Xiao, Jian

    2017-07-13

    Melatonin has neuroprotective effects in many diseases, including neonatal hypoxic-ischaemic (HI) brain injury. The purpose of this study was to evaluate the neuroprotective effects of melatonin both in vivo and in vitro and associated molecular mechanisms behind these effects. Postnatal day 7 male and female rat pups were subjected to unilateral HI, melatonin was injected intraperitoneally 1h before HI and an additional six doses were administered at 24h intervals. The pups were sacrificed at 24h and 7 d after HI. Pre-treatment with melatonin significantly reduced brain damage at 7 d after HI, with 15mg/kg melatonin achieving over 30% recovery in tissue loss compared to vehicle-treated animals. Autophagy and apoptotic cell death as indicated by autophagy associated proteins, cleaved caspase 3 and Tunel staining, was significantly inhibited after melatonin treatment in vivo as well as in PC12 cells. Melatonin treatment also significantly increased the GAP43 in the cortex. In conclusion, melatonin treatment reduced neonatal rat brain injury after HI, and this appeared to be related to inhibiting autophagy as well as reducing apoptotic cell death. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Evaluation of Neonatal Lung Volume Growth by Pulmonary Magnetic Resonance Imaging in Patients with Congenital Diaphragmatic Hernia.

    Science.gov (United States)

    Schopper, Melissa A; Walkup, Laura L; Tkach, Jean A; Higano, Nara S; Lim, Foong Yen; Haberman, Beth; Woods, Jason C; Kingma, Paul S

    2017-09-01

    To evaluate postnatal lung volume in infants with congenital diaphragmatic hernia (CDH) and determine if a compensatory increase in lung volume occurs during the postnatal period. Using a novel pulmonary magnetic resonance imaging method for imaging neonatal lungs, the postnatal lung volumes in infants with CDH were determined and compared with prenatal lung volumes obtained via late gestation magnetic resonance imaging. Infants with left-sided CDH (2 mild, 9 moderate, and 1 severe) were evaluated. The total lung volume increased in all infants, with the contralateral lung increasing faster than the ipsilateral lung (mean ± SD: 4.9 ± 3.0 mL/week vs 3.4 ± 2.1 mL/week, P = .005). In contrast to prenatal studies, the volume of lungs of infants with more severe CDH grew faster than the lungs of infants with more mild CDH (Spearman's ρ=-0.086, P = .01). Although the contralateral lung volume grew faster in both mild and moderate groups, the majority of total lung volume growth in moderate CDH came from increased volume of the ipsilateral lung (42% of total lung volume increase in the moderate group vs 32% of total lung volume increase in the mild group, P = .09). Analysis of multiple clinical variables suggests that increased weight gain was associated with increased compensatory ipsilateral lung volume growth (ρ = 0.57, P = .05). These results suggest a potential for postnatal catch-up growth in infants with pulmonary hypoplasia and suggest that weight gain may increase the volume growth of the more severely affected lung. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. The common antitussive agent dextromethorphan protects against hyperoxia-induced cell death in established in vivo and in vitro models of neonatal brain injury.

    Science.gov (United States)

    Posod, A; Pinzer, K; Urbanek, M; Wegleiter, K; Keller, M; Kiechl-Kohlendorfer, U; Griesmaier, E

    2014-08-22

    Preterm infants are prematurely subjected to relatively high oxygen concentrations, even when supplemental oxygen is not administered. There is increasing evidence to show that an excess of oxygen is toxic to the developing brain. Dextromethorphan (DM), a frequently used antitussive agent with pleiotropic mechanisms of action, has been shown to be neuroprotective in various models of central nervous system pathology. Due to its numerous beneficial properties, it might also be able to counteract detrimental effects of a neonatal oxygen insult. The aim of the current study was to evaluate its therapeutic potential in established cell culture and rodent models of hyperoxia-induced neonatal brain injury. For in vitro studies pre- and immature oligodendroglial (OLN-93) cells were subjected to hyperoxic conditions for 48 h after pre-treatment with increasing doses of DM. For in vivo studies 6-day-old Wistar rat pups received a single intraperitoneal injection of DM in two different dosages prior to being exposed to hyperoxia for 24h. Cell viability and caspase-3 activation were assessed as outcome parameters at the end of exposure. DM significantly increased cell viability in immature oligodendroglial cells subjected to hyperoxia. In pre-oligodendroglial cells cell viability was not significantly affected by DM treatment. In vivo caspase-3 activation induced by hyperoxic exposure was significantly lower after administration of DM in gray and white matter areas. In control animals kept under normoxic conditions DM did not significantly influence caspase-3-dependent apoptosis. The present results indicate that DM is a promising and safe treatment strategy for neonatal hyperoxia-induced brain injury that merits further investigation. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. Third Trimester Brain Growth in Preterm Infants Compared With In Utero Healthy Fetuses.

    Science.gov (United States)

    Bouyssi-Kobar, Marine; du Plessis, Adré J; McCarter, Robert; Brossard-Racine, Marie; Murnick, Jonathan; Tinkleman, Laura; Robertson, Richard L; Limperopoulos, Catherine

    2016-11-01

    Compared with term infants, preterm infants have impaired brain development at term-equivalent age, even in the absence of structural brain injury. However, details regarding the onset and progression of impaired preterm brain development over the third trimester are unknown. Our primary objective was to compare third-trimester brain volumes and brain growth trajectories in ex utero preterm infants without structural brain injury and in healthy in utero fetuses. As a secondary objective, we examined risk factors associated with brain volumes in preterm infants over the third-trimester postconception. Preterm infants born before 32 weeks of gestational age (GA) and weighing <1500 g with no evidence of structural brain injury on conventional MRI and healthy pregnant women were prospectively recruited. Anatomic T2-weighted brain images of preterm infants and healthy fetuses were parcellated into the following regions: cerebrum, cerebellum, brainstem, and intracranial cavity. We studied 205 participants (75 preterm infants and 130 healthy control fetuses) between 27 and 39 weeks' GA. Third-trimester brain volumes were reduced and brain growth trajectories were slower in the ex utero preterm group compared with the in utero healthy fetuses in the cerebrum, cerebellum, brainstem, and intracranial cavity. Clinical risk factors associated with reduced brain volumes included dexamethasone treatment, the presence of extra-axial blood on brain MRI, confirmed sepsis, and duration of oxygen support. These preterm infants exhibited impaired third-trimester global and regional brain growth in the absence of cerebral/cerebellar parenchymal injury detected by using conventional MRI. Copyright © 2016 by the American Academy of Pediatrics.

  7. Giant Parietal Encephalocele with Massive Brain Herniation and Suboccipital Encephalocele in a Neonate: An Unusual Form of Double Encephalocele.

    Science.gov (United States)

    Menekse, Guner; Celik, Haydar; Bayar, Mehmet Akif

    2017-02-01

    Double encephalocele is extremely rare. We present an unusual form of double encephalocele including giant supratentorial and small infratentorial encephalocele in a neonate. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Neonatal Diagnostics: Towards Dynamic Growth Charts of Neuro-motor control

    Directory of Open Access Journals (Sweden)

    Elizabeth B Torres

    2016-11-01

    Full Text Available Current rise of neurodevelopmental disorders, poses a critical need to detect risk early in order to rapidly intervene. One of the tools Pediatricians use to track development is the standard Growth Chart. The Growth Charts are somewhat limited in predicting possible neurodevelopmental issues. They rely on linear models and assumptions of normality for physical growth data —obscuring key statistical information about possible neurodevelopmental risk in growth data that actually has accelerated, non-linear rates-of-change and variability encompassing skewed distributions. Here we use new analytics to profile growth data from 36 newborn babies that were tracked longitudinally for 5 months. By switching to incremental (velocity-based growth charts and combining these dynamic changes with underlying fluctuations in motor performance—as they transition from spontaneous random noise to a systematic signal— we demonstrate a method to detect very early stunting in the development of voluntary neuro-motor control and to flag risk of neurodevelopmental derail.

  9. No improvement of neuronal metabolism in the reperfusion phase with melatonin treatment after hypoxic-ischemic brain injury in the neonatal rat.

    Science.gov (United States)

    Berger, Hester R; Morken, Tora Sund; Vettukattil, Riyas; Brubakk, Ann-Mari; Sonnewald, Ursula; Widerøe, Marius

    2016-01-01

    Mitochondrial impairment is a key feature underlying neonatal hypoxic-ischemic (HI) brain injury and melatonin is potentially neuroprotective through its effects on mitochondria. In this study, we have used (1) H and (13) C NMR spectroscopy after injection of [1-(13) C]glucose and [1,2-(13) C]acetate to examine neuronal and astrocytic metabolism in the early reperfusion phase after unilateral HI brain injury in 7-day-old rat pups, exploring the effects of HI on mitochondrial function and the potential protective effects of melatonin on brain metabolism. One hour after hypoxia-ischemia, astrocytic metabolism was recovered and glycolysis was normalized, whereas mitochondrial metabolism in neurons was clearly impaired. Pyruvate carboxylation was also lower in both hemispheres after HI. The transfer of glutamate from neurons to astrocytes was higher whereas the transfer of glutamine from astrocytes to neurons was lower 1 h after HI in the contralateral hemisphere. Neuronal metabolism was equally affected in pups treated with melatonin (10 mg/kg) immediately after HI as in vehicle treated pups indicating that the given dose of melatonin was not capable of protecting the neuronal mitochondria in this early phase after HI brain injury. However, any beneficial effects of melatonin might have been masked by modulatory effects of the solvent dimethyl sulfoxide on cerebral metabolism. Neuronal and astrocytic metabolism was examined by (13) C and (1) H NMR spectroscopy in the early reperfusion phase after unilateral hypoxic-ischemic brain injury and melatonin treatment in neonatal rats. One hour after hypoxia-ischemia astrocytic mitochondrial metabolism had recovered and glycolysis was normalized, whereas mitochondrial metabolism in neurons was impaired. Melatonin treatment did not show a protective effect on neuronal metabolism. © 2015 International Society for Neurochemistry.

  10. Nerve growth factor mRNA in brain: localization by in situ hybridization

    International Nuclear Information System (INIS)

    Rennert, P.D.; Heinrich, G.

    1986-01-01

    Nerve Growth Factor is a 118 amino acid polypeptide that plays an important role in the differentiation and survival of neurons. The recent discovery that a mRNA that encodes beta Nerve Growth Factor is present in brain suggests that the Nerve Growth Factor gene may not only regulate gene expression of peripheral but also of central neurons. To identify the site(s) of Nerve Growth Factor mRNA production in the brain and to determine which cells express the Nerve Growth Factor gene, the technique of in situ hybridization was employed. A 32P-labeled RNA probe complementary to Nerve Growth Factor mRNA hybridized to cells in the stratum granulosum of the dentate gyrus and the stratum pyramidale of the hippocampus. These observations identify for the first time cellular sites of Nerve Growth Factor gene expression in the central nervous system, and suggest that Nerve Growth Factor mRNA is produced by neurons

  11. [Effect of antepartum taurine supplementation in regulating the activity of Rho family factors and promoting the proliferation of neural stem cells in neonatal rats with fetal growth restriction].

    Science.gov (United States)

    Li, Xiang-Wen; Li, Fang; Liu, Jing; Wang, Yan; Fu, Wei

    2016-11-01

    To study the possible effect of antepartum taurine supplementation in regulating the activity of Rho family factors and promoting the proliferation of neural stem cells in neonatal rats with fetal growth restriction (FGR), and to provide a basis for antepartum taurine supplementation to promote brain development in children with FGR. A total of 24 pregnant Sprague-Dawley rats were randomly divided into three groups: control, FGR, and taurine (n=8 each ). A rat model of FGR was established by food restriction throughout pregnancy. RT-PCR, immunohistochemistry, and Western blot were used to measure the expression of the specific intracellular markers for neural stem cells fatty acid binding protein 7 (FABP7), Rho-associated coiled-coil containing protein kinase 2 (ROCK2), ras homolog gene family, member A (RhoA), and Ras-related C3 botulinum toxin substrate (Rac). The FGR group had significantly lower OD value of FABP7-positive cells and mRNA and protein expression of FABP7 than the control group, and the taurine group had significantly higher OD value of FABP7-positive cells and mRNA and protein expression of FABP7 than the FGR group (Ptaurine group had significantly higher mRNA expression of RhoA and ROCK2 than the control group and significantly lower expression than the FGR group (Ptaurine group had significantly higher mRNA expression of Rac than the FGR and control groups (Ptaurine group had significantly lower protein expression of RhoA and ROCK2 than the FGR group (Ptaurine supplementation can promote the proliferation of neural stem cells in rats with FGR, and its mechanism may be related to the regulation of the activity of Rho family factors.

  12. Neonatal hypoglycemia.

    Science.gov (United States)

    Straussman, Sharon; Levitsky, Lynne L

    2010-02-01

    Hypoglycemia in the newborn may be associated with both acute decompensation and long-term neuronal loss. Studies of the cause of hypoglycemic brain damage and the relationship of hypoglycemia to disorders associated with hyperinsulinism have aided in our understanding of this common clinical finding. A recent consensus workshop concluded that there has been little progress toward a precise numerical definition of neonatal hypoglycemia. Nonetheless, newer brain imaging modalities have provided insight into the relationship between neuronal energy deficiency and central nervous system damage. Laboratory studies have begun to reveal the mechanism of hypoglycemic damage. In addition, there is new information about hyperinsulinemic hypoglycemia of genetic, environmental, and iatrogenic origin. The quantitative definition of hypoglycemia in the newborn remains elusive because it is a surrogate marker for central nervous system energy deficiency. Nonetheless, the recognition that hyperinsulinemic hypoglycemia, which produces profound central nervous system energy deficiency, is most likely to lead to long-term central nervous system damage, has altered management of children with hypoglycemia. In addition, imaging studies on neonates and laboratory evaluation in animal models have provided insight into the mechanism of neuronal damage.

  13. Brain reorganization in an experimental model of intrauterine growth restriction

    OpenAIRE

    Eixarch Roca, Elisenda

    2011-01-01

    1) INTRODUCCIÓ La restricció del creixement intrauterí (RCIU) secundaria a la insuficiència placentària afecta un 5-10% de tots els embarassos. Aquesta condició es considera un factor de risc important per el dany cerebral neonatal i els problemes cognitius en la infantesa. El coneixement de les vies fisiopatològiques que condueixen a aquest mal resultat és limitat i per aquest motiu, l’ús dels models animals es essencial per avançar en aquest coneixement. 2) OBJECTIU Desenvolupa...

  14. The effect of colostral immunoglobulin supplement on the passive immunity, growth and health of neonatal calves

    Directory of Open Access Journals (Sweden)

    Juha Nousiainen

    1994-09-01

    Full Text Available Neonatal dairy calves were randomly allotted to three colostrum feeding regimens with increasing intakes of immunoglobulins (Ig on the first day of life. The control group was fed one litre of pooled colostrum (Ig intake 19.5 g. In two experimental groups, the pooled colostrum was supplemented with 0.5 or 1.5 litres of commercial Ig-concentrate, giving a total Ig intake of 52.7 and 119.0 g, respectively. Serum IgG, IgM and IgA levels increased linearly (p < 0.001 on day 2 post partum with the increasing Ig intake. The calculated mean Ig-absorption rate was 61% and decreased linearly for IgM (p = 0.051 and IgG (p = 0.078 with increasing Ig intake. At the highest Ig intake, serum IgG remained above 10 g/l during 30 days post partum. In the experimental groups, serum IgM and IgA decreased sharply during the first week of life and were relatively constant thereafter. In the control group, however, there was an increase in serum IgM after one week post partum, perhaps due to the in situ production of Ig. With the increasing Ig intake there was a small and non-significant tendency for better live weight gain (p = 0.286 and a lower incidence of diarrhoea (p = 0.421 during the first four weeks of life. It is concluded that the Ig-product tested is well absorbed during 24 hours post partum and it can be used either as a supplement to maternal colostrum when its quality is poor, or as a substitute when colostrum is not available.

  15. Maternal milk consumption, fetal growth, and the risks of neonatal complications: The Generation R Study

    NARCIS (Netherlands)

    D.H.M. Heppe (Denise); R.M. van Dam (Rob); S.P. Willemsen (Sten); H. den Breeijen (Hanneke); H. Raat (Hein); A. Hofman (Albert); E.A.P. Steegers (Eric); V.W.V. Jaddoe (Vincent)

    2011-01-01

    textabstractBackground: Maternal cow-milk consumption may increase birth weight. Previous studies did not assess the association of maternal milk consumption with trimester-specific fetal growth. Objective: The objective was to assess associations of first-trimester maternal milk consumption with

  16. Modeling Early Postnatal Brain Growth and Development with CT: Changes in the Brain Radiodensity Histogram from Birth to 2 Years.

    Science.gov (United States)

    Cauley, K A; Hu, Y; Och, J; Yorks, P J; Fielden, S W

    2018-04-01

    The majority of brain growth and development occur in the first 2 years of life. This study investigated these changes by analysis of the brain radiodensity histogram of head CT scans from the clinical population, 0-2 years of age. One hundred twenty consecutive head CTs with normal findings meeting the inclusion criteria from children from birth to 2 years were retrospectively identified from 3 different CT scan platforms. Histogram analysis was performed on brain-extracted images, and histogram mean, mode, full width at half maximum, skewness, kurtosis, and SD were correlated with subject age. The effects of scan platform were investigated. Normative curves were fitted by polynomial regression analysis. Average total brain volume was 360 cm 3 at birth, 948 cm 3 at 1 year, and 1072 cm 3 at 2 years. Total brain tissue density showed an 11% increase in mean density at 1 year and 19% at 2 years. Brain radiodensity histogram skewness was positive at birth, declining logarithmically in the first 200 days of life. The histogram kurtosis also decreased in the first 200 days to approach a normal distribution. Direct segmentation of CT images showed that changes in brain radiodensity histogram skewness correlated with, and can be explained by, a relative increase in gray matter volume and an increase in gray and white matter tissue density that occurs during this period of brain maturation. Normative metrics of the brain radiodensity histogram derived from routine clinical head CT images can be used to develop a model of normal brain development. © 2018 by American Journal of Neuroradiology.

  17. [Effects of electric stimulation at the cerebellar fastigial nucleus on astrocytes in the hippocampus of neonatal rats with hypoxic-ischemic brain damage].

    Science.gov (United States)

    Li, Xiao-Li; Jia, Tian-Ming; Luan, Bin; Liu, Tao; Yuan, Yan

    2011-04-01

    To study the effects of electric stimulation at the cerebellar fastigial nucleus on astrocytes in the hippocampus of neonatal rats with hypoxic-ischemic brain damage (HIBD) and the possible mechanism. One hundred and eighty 7-day-old neonatal Sprague-Dawley rats were randomly divided into three groups: sham-operation (control group) and HIBD with and without electric stimulation (n=60 each). The HIBD model of neonatal rats was prepared by the Rice-Vennucci method. Electric stimulation at the cerebellar fastigial nucleus was given 24 hrs after the operation in the electric stimulation group once daily and lasted for 30 minutes each time. The other two groups were not subjected to electric stimulation but captured to fix in corresponding periods. Rats were sacrificed 3, 7, 14 and 21 days after stimulations to observe the glial fibrillary acidic protein (GFAP) expression by immunohistochemisty and the ultrastructural changes of astrocytes in the hippocampus under an electron microscope. Immunohistochemical analysis showed the expression of GFAP in the HIBD groups with and without electric stimulation increased significantly compared with the control group on day 3, reached the peak on day 7, and the increased expression remained till to day 21. The GFAP expression in the electric stimulation group was significantly lower than that in the untreated HIBD group at all time points. Under the electron microscope, the astrocytes in the untreated HIBD group were swollen and the amount of organelles was reduced, while the swelling of astrocytes was alleviated and the organelles remained in integrity in the electric stimulation group. The electric stimulation at the cerebellar fastigial nucleus can inhibit the excessive proliferation of astrocytes and relieve the structural damage of astrocytes in neonatal rats following HIBD.

  18. Mechanisms of Neuroprotection from Hypoxia-Ischemia (HI) Brain Injury by Up-regulation of Cytoglobin (CYGB) in a Neonatal Rat Model*

    Science.gov (United States)

    Tian, Shu-Feng; Yang, Han-Hua; Xiao, Dan-Ping; Huang, Yue-Jun; He, Gu-Yu; Ma, Hai-Ran; Xia, Fang; Shi, Xue-Chuan

    2013-01-01

    This study was designed to investigate the expression profile of CYGB, its potential neuroprotective function, and underlying molecular mechanisms using a model of neonatal hypoxia-ischemia (HI) brain injury. Cygb mRNA and protein expression were evaluated within the first 36 h after the HI model was induced using RT-PCR and Western blotting. Cygb mRNA expression was increased at 18 h in a time-dependent manner, and its level of protein expression increased progressively in 24 h. To verify the neuroprotective effect of CYGB, a gene transfection technique was employed. Cygb cDNA and shRNA delivery adenovirus systems were established (Cygb-cDNA-ADV and Cygb-shRNA-ADV, respectively) and injected into the brains of 3-day-old rats 4 days before they were induced with HI treatment. Rats from different groups were euthanized 24 h post-HI, and brain samples were harvested. 2,3,5-Triphenyltetrazolium chloride, TUNEL, and Nissl staining indicated that an up-regulation of CYGB resulted in reduced acute brain injury. The superoxide dismutase level was found to be dependent on expression of CYGB. The Morris water maze test in 28-day-old rats demonstrated that CYGB expression was associated with improvement of long term cognitive impairment. Studies also demonstrated that CYGB can up-regulate mRNA and protein levels of VEGF and increase both the density and diameter of the microvessels but inhibits activation of caspase-2 and -3. Thus, this is the first in vivo study focusing on the neuroprotective role of CYGB. The reduction of neonatal HI injury by CYGB may be due in part to antioxidant and antiapoptotic mechanisms and by promoting angiogenesis. PMID:23585565

  19. The neuroblast and angioblast chemotaxic factor SDF-1 (CXCL12 expression is briefly up regulated by reactive astrocytes in brain following neonatal hypoxic-ischemic injury

    Directory of Open Access Journals (Sweden)

    Walker Aisha L

    2005-10-01

    Full Text Available Abstract Background Stromal cell-derived factor 1 (SDF-1 or CXCL12 is chemotaxic for CXCR4 expressing bone marrow-derived cells. It functions in brain embryonic development and in response to ischemic injury in helping guide neuroblast migration and vasculogenesis. In experimental adult stroke models SDF-1 is expressed perivascularly in the injured region up to 30 days after the injury, suggesting it could be a therapeutic target for tissue repair strategies. We hypothesized that SDF-1 would be expressed in similar temporal and spatial patterns following hypoxic-ischemic (HI injury in neonatal brain. Results Twenty-five 7-day-old C57BL/J mice underwent HI injury. SDF-1 expression was up regulated up to 7 days after the injury but not at the later time points. The chief sites of SDF-1 up regulation were astrocytes, their foot processes along blood vessels and endothelial cells. Conclusion The localization of SDF-1 along blood vessels in the HI injury zone suggests that these perivascular areas are where chemotaxic signaling for cellular recruitment originates and that reactive astrocytes are major mediators of this process. The associated endothelium is likely to be the site for vascular attachment and diapedesis of CXCR4 receptor expressing cells to enter the injured tissue. Here we show that, relative to adults, neonates have a significantly smaller window of opportunity for SDF-1 based vascular chemotaxic recruitment of bone marrow-derived cells. Therefore, without modification, following neonatal HI injury there is only a narrow period of time for endogenous SDF-1 mediated chemotaxis and recruitment of reparative cells, including exogenously administered stem/progenitor cells.

  20. Exogenous hydrogen sulfide (H2S protects alveolar growth in experimental O2-induced neonatal lung injury.

    Directory of Open Access Journals (Sweden)

    Arul Vadivel

    Full Text Available Bronchopulmonary dysplasia (BPD, the chronic lung disease of prematurity, remains a major health problem. BPD is characterized by impaired alveolar development and complicated by pulmonary hypertension (PHT. Currently there is no specific treatment for BPD. Hydrogen sulfide (H2S, carbon monoxide and nitric oxide (NO, belong to a class of endogenously synthesized gaseous molecules referred to as gasotransmitters. While inhaled NO is already used for the treatment of neonatal PHT and currently tested for the prevention of BPD, H2S has until recently been regarded exclusively as a toxic gas. Recent evidence suggests that endogenous H2S exerts beneficial biological effects, including cytoprotection and vasodilatation. We hypothesized that H2S preserves normal alveolar development and prevents PHT in experimental BPD.We took advantage of a recently described slow-releasing H2S donor, GYY4137 (morpholin-4-ium-4-methoxyphenyl(morpholino phosphinodithioate to study its lung protective potential in vitro and in vivo.In vitro, GYY4137 promoted capillary-like network formation, viability and reduced reactive oxygen species in hyperoxia-exposed human pulmonary artery endothelial cells. GYY4137 also protected mitochondrial function in alveolar epithelial cells. In vivo, GYY4137 preserved and restored normal alveolar growth in rat pups exposed from birth for 2 weeks to hyperoxia. GYY4137 also attenuated PHT as determined by improved pulmonary arterial acceleration time on echo-Doppler, pulmonary artery remodeling and right ventricular hypertrophy. GYY4137 also prevented pulmonary artery smooth muscle cell proliferation.H2S protects from impaired alveolar growth and PHT in experimental O2-induced lung injury. H2S warrants further investigation as a new therapeutic target for alveolar damage and PHT.

  1. Experimentally Induced Gluten Enteropathy and Protective Effect of Epidermal Growth Factor in Artificially Fed Neonatal Rats

    Czech Academy of Sciences Publication Activity Database

    Štěpánková, Renata; Kofroňová, Olga; Tučková, Ludmila; Kozáková, Hana; Cebra, J. J.; Tlaskalová, Helena

    2003-01-01

    Roč. 36, - (2003), s. 96-104 ISSN 0277-2116 R&D Projects: GA ČR GA303/00/1370; GA ČR GA310/00/1373; GA ČR GA303/01/1380; GA ČR GA310/01/0933; GA AV ČR IAA5020210; GA AV ČR IBS5020203; GA AV ČR IAA5020101 Institutional research plan: CEZ:AV0Z5020903 Keywords : epidermal growth factor * celiac disease Subject RIV: EE - Microbiology, Virology Impact factor: 1.402, year: 2003

  2. Differences in neonatal neurotoxicity of brominated flame retardants, PBDE 99 and TBBPA, in mice

    International Nuclear Information System (INIS)

    Viberg, Henrik; Eriksson, Per

    2011-01-01

    Highlights: → Neonatal exposure to PBDE 99, but not TBBPA, causes changes in the neonatal brain. → CaMKII increases in neonatal hippocampus after PBDE 99 exposure. → CaMKII, GAP-43 and synaptophysin increase in neonatal cortex after PBDE 99 exposure. → CaMKII increase in hippocampus has earlier been seen to proceed behavioral changes. → Neonatal exposure to PBDE 99, but not TBBPA, is known to cause behavioral deficits. -- Abstract: Flame retardants such as polybrominated diphenyl ethers (PBDE) and tetrabromobisphenol A are used as flame retardants and detected in the environmental, wildlife species and human tissues. Exposure to PBDEs during the neonatal development of the brain has been shown to affect behavior and learning and memory in adult mice, while neonatal exposure to TBBPA (another brominated flame retardant) did not affect behavioral variables in the adult. In this study, we hypothesized that the effects of these compounds could be reflected by changes in biochemical substrates and cholinergic receptors and have examined the levels of four proteins involved in maturation of the brain, neuronal growth and synaptogenesis and the densities of both muscarinic and nicotinic cholinergic receptors. We measured the levels of radioactivity in the brain after administration of 14 C-labelled TBBPA at different time points and saw that levels of TBBA peaked earlier and decreased faster than the earlier reported levels of PBDE 99. The protein analysis in the neonatal brain showed changes in the levels of calcium/calmodulin-dependent protein kinase II (CaMKII), growth associated protein-43 (GAP-43) and synaptophysin following neonatal exposure to PBDE 99 (21 μmol/kg body weight), but not following exposure TBBPA. Furthermore, neonatal exposure to PBDE 99 and TBBPA caused a decrease in binding sites of the nicotinic ligand cytisine in frontal cortex. These results confirm earlier reported data that PBDE 99 can act as a developmental neurotoxicant, possibly

  3. A neonatal piglet model for investigating brain and cognitive development in small for gestational age human infants.

    Directory of Open Access Journals (Sweden)

    Emily C Radlowski

    Full Text Available The piglet was investigated as a potential model for studying brain and cognitive deficits associated with being born small for gestational age (SGA. Naturally farrowed SGA (0.7-1.0 kg BW and average for gestational age (AGA, 1.3-1.6 kg BW piglets were obtained on postnatal day (PD 2, placed in individual cages, and provided a nutritionally adequate milk replacer diet (285 ml/kg/d. Beginning at PD14, performance in a spatial T-maze task was assessed. At PD28, piglets were anesthetized for magnetic resonance (MR imaging to assess brain structure (voxel-based morphometry, connectivity (diffusion-tensor imaging and metabolites in the hippocampus and corpus callosum (proton MR spectroscopy. Piglets born SGA showed compensatory growth such that BW of SGA and AGA piglets was similar (P>0.05, by PD15. Birth weight affected maze performance, with SGA piglets taking longer to reach criterion than AGA piglets (p<0.01. Total brain volume of SGA and AGA piglets was similar (P<0.05, but overall, SGA piglets had less gray matter than AGA piglets (p<0.01 and tended to have a smaller internal capsule (p = 0.07. Group comparisons between SGA and AGA piglets defined 9 areas (≥ 20 clusters where SGA piglets had less white matter (p<0.01; 2 areas where SGA piglets had more white matter (p<0.01; and 3 areas where SGA piglets had more gray matter (p<0.01. The impact of being born SGA on white matter was supported by a lower (p<0.04 fractional anisotropy value for SGA piglets, suggesting reduced white matter development and connectivity. None of the metabolites measured were different between groups. Collectively, the results show that SGA piglets have spatial learning deficits and abnormal development of white matter. As learning deficits and abnormalities in white matter are common in SGA human infants, the piglet is a tractable translational model that can be used to investigate SGA-associated cognitive deficits and potential interventions.

  4. Icotinib combined whole brain radiotherapy for patients with brain metastasis from lung adenocarcinoma harboring epidermal growth factor receptor mutation.

    Science.gov (United States)

    Li, Jin-Rui; Zhang, Ye; Zheng, Jia-Lian

    2016-07-01

    The brain is a metastatic organ that is most prone to lung adenocarcinoma (LAC). However, the prognosis of patients with brain metastasis remains very poor. In this study, we evaluated the efficacy of icotinib plus whole brain radiation therapy (WBRT) for treating patients with brain metastasis from epidermal growth factor receptor (EGFR)-mutated LAC. All patients received standard WBRT administered to the whole brain in 30 Gy in 10 daily fractions. Each patient was also instructed to take 125 mg icotinib thrice per day beginning from the first day of the WBRT. After completing the WBRT, maintenance icotinib was administered until the disease progressed or intolerable adverse effects were observed. Cranial progression-free survival (CPFS) and overall survival (OS) times were the primary endpoints. A total of 43 patients were enrolled in this study. Two patients (4.7%) presented a complete response (CR), whereas 20 patients (46.5%) presented a partial response (PR). The median CPFS and OS times were 11.0 and 15.0 months, respectively. The one-year CPFS rate was 40.0% for the patients harboring EGFR exon 19 deletion and 16.7% for the patients with EGFR exon 21 L858R (P=0.027). The concurrent administration of icotinib and WBRT exhibited favorable effects on the patients with brain metastasis. EGFR exon 19 deletion was predictive of a long CPFS following icotinib plus WBRT.

  5. Xanthine oxidase activity regulates human embryonic brain cells growth

    Directory of Open Access Journals (Sweden)

    Kevorkian G. A.

    2011-10-01

    Full Text Available Aim. Involvement of Xanthine Oxidase (XO; EC1.1.3.22 in cellular proliferation and differentiation has been suggested by the numerous investigations. We have proposed that XO might have undoubtedly important role during the development, maturation as well as the death of human embryos brain cells. Methods. Human abortion material was utilized for the cultivation of brain cells (E90. XO activity was measured by the formation of uric acid in tissue. Cell death was detected by the utility of Trypan Blue dye. Results. Allopurinol suppressed the XO activity in the brain tissue (0.12 ± 0.02; 0.20 ± 0.03 resp., p < 0.05. On day 12th the number of cells in the culture treated with the Allopurinol at the early stage of development was higher in comparison with the Control (2350.1 ± 199.0 vs 2123 ± 96 and higher in comparison with the late period of treatment (1479.6 ± 103.8, p < < 0.05. In all groups, the number of the dead cells was less than in Control, indicating the protective nature of Allopurinol as an inhibitor of XO. Conclusions. Allopurinol initiates cells proliferation in case of the early treatment of the human brain derived cell culture whereas at the late stages it has an opposite effect.

  6. Prenatal exposure to a maternal LP diet decreases BDNF expression in the brains of the neonatal offspring

    Science.gov (United States)

    Maternal low protein (LP) diets during gestation cause learning and mernmy impai1ment as well as cognitive deficits in the neonatal and adult offsp1ing. The cellular and molecular mechanism that mediate the deleterious effects of prenatal exposure to a maternal LP diet on cognitive function is egreg...

  7. A competitive advantage by neonatally engrafted human glial progenitors yields mice whose brains are chimeric for human glia

    DEFF Research Database (Denmark)

    Windrem, Martha S; Schanz, Steven J; Morrow, Carolyn

    2014-01-01

    Neonatally transplanted human glial progenitor cells (hGPCs) densely engraft and myelinate the hypomyelinated shiverer mouse. We found that, in hGPC-xenografted mice, the human donor cells continue to expand throughout the forebrain, systematically replacing the host murine glia. The differentiat...

  8. Measurement of Lactate Content and Amide Proton Transfer Values in the Basal Ganglia of a Neonatal Piglet Hypoxic-Ischemic Brain Injury Model Using MRI.

    Science.gov (United States)

    Zheng, Y; Wang, X-M

    2017-04-01

    As amide proton transfer imaging is sensitive to protein content and intracellular pH, it has been widely used in the nervous system, including brain tumors and stroke. This work aimed to measure the lactate content and amide proton transfer values in the basal ganglia of a neonatal piglet hypoxic-ischemic brain injury model by using MR spectroscopy and amide proton transfer imaging. From 58 healthy neonatal piglets (3-5 days after birth; weight, 1-1.5 kg) selected initially, 9 piglets remained in the control group and 43 piglets, in the hypoxic-ischemic brain injury group. Single-section amide proton transfer imaging was performed at the coronal level of the basal ganglia. Amide proton transfer values of the bilateral basal ganglia were measured in all piglets. The ROI of MR spectroscopy imaging was the right basal ganglia, and the postprocessing was completed with LCModel software. After hypoxic-ischemic insult, the amide proton transfer values immediately decreased, and at 0-2 hours, they remained at their lowest level. Thereafter, they gradually increased and finally exceeded those of the control group at 48-72 hours. After hypoxic-ischemic insult, the lactate content increased immediately, was maximal at 2-6 hours, and then gradually decreased to the level of the control group. The amide proton transfer values were negatively correlated with lactate content ( r = -0.79, P < .05). This observation suggests that after hypoxic-ischemic insult, the recovery of pH was faster than that of lactate homeostasis. © 2017 by American Journal of Neuroradiology.

  9. Postnatal brain and skull growth in an Apert syndrome mouse model

    Science.gov (United States)

    Hill, Cheryl A.; Martínez-Abadías, Neus; Motch, Susan M.; Austin, Jordan R.; Wang, Yingli; Jabs, Ethylin Wang; Richtsmeier, Joan T.; Aldridge, Kristina

    2012-01-01

    Craniofacial and neural tissues develop in concert throughout pre- and postnatal growth. FGFR-related craniosynostosis syndromes, such as Apert syndrome (AS), are associated with specific phenotypes involving both the skull and the brain. We analyzed the effects of the FGFR P253R mutation for Apert syndrome using the Fgfr2+/P253R mouse to evaluate the effects of this mutation on these two tissues over the course of development from day of birth (P0) to postnatal day 2 (P2). Three-dimensional magnetic resonance microscopy and computed tomography images were acquired from Fgfr2+/P253R mice and unaffected littermates at P0 (N=28) and P2 (N=23). 3D coordinate data for 23 skull and 15 brain landmarks were statistically compared between groups. Results demonstrate that the Fgfr2+/P253R mice show reduced growth in the facial skeleton and the cerebrum, while the height and width of the neurocranium and caudal regions of the brain show increased growth relative to unaffected littermates. This localized correspondence of differential growth patterns in skull and brain point to their continued interaction through development and suggest that both tissues display divergent postnatal growth patterns relative to unaffected littermates. However, the change in the skull-brain relationship from P0 to P2 implies that each tissue affected by the mutation retains a degree of independence, rather than one tissue directing the development of the other. PMID:23495236

  10. Refeeding syndrome in very-low-birth-weight intrauterine growth-restricted neonates.

    Science.gov (United States)

    Ross, J R; Finch, C; Ebeling, M; Taylor, S N

    2013-09-01

    Determine the incidence of refeeding syndrome, defined by the presence of hypophosphatemia in very-low-birth-weight (VLBW) infants with intrauterine growth restriction (IUGR) compared with those without IUGR. In this retrospective cohort study, VLBW infants admitted over a 10-year period (271 IUGR and 1982 non-IUGR) were evaluated for specific electrolyte abnormalities in the first postnatal week. IUGR infants were significantly more likely to have hypophosphatemia (41% vs 8.9%, relative risk (95% confidence interval: 7.25 (5.45, 9.65)) and severe hypophosphatemia (11.4% vs 1%, 12.06 (6.82, 21.33)) in the first postnatal week. The incidence of hypophosphatemia was significantly associated with the presence of maternal preeclampsia in all VLBW infants (odds ratio (OR): 2.58 (1.96, 3.40)) when controlling for birth weight and gestational age. Refeeding syndrome occurs in VLBW infants with IUGR and born to mothers with preeclampsia. Close monitoring of electrolytes, especially phosphorus, is warranted in this population.

  11. Structural growth trajectories and rates of change in the first 3 months of infant brain development.

    Science.gov (United States)

    Holland, Dominic; Chang, Linda; Ernst, Thomas M; Curran, Megan; Buchthal, Steven D; Alicata, Daniel; Skranes, Jon; Johansen, Heather; Hernandez, Antonette; Yamakawa, Robyn; Kuperman, Joshua M; Dale, Anders M

    2014-10-01

    The very early postnatal period witnesses extraordinary rates of growth, but structural brain development in this period has largely not been explored longitudinally. Such assessment may be key in detecting and treating the earliest signs of neurodevelopmental disorders. To assess structural growth trajectories and rates of change in the whole brain and regions of interest in infants during the first 3 months after birth. Serial structural T1-weighted and/or T2-weighted magnetic resonance images were obtained for 211 time points from 87 healthy term-born or term-equivalent preterm-born infants, aged 2 to 90 days, between October 5, 2007, and June 12, 2013. We segmented whole-brain and multiple subcortical regions of interest using a novel application of Bayesian-based methods. We modeled growth and rate of growth trajectories nonparametrically and assessed left-right asymmetries and sexual dimorphisms. Whole-brain volume at birth was approximately one-third of healthy elderly brain volume, and did not differ significantly between male and female infants (347 388 mm3 and 335 509 mm3, respectively, P = .12). The growth rate was approximately 1%/d, slowing to 0.4%/d by the end of the first 3 months, when the brain reached just more than half of elderly adult brain volume. Overall growth in the first 90 days was 64%. There was a significant age-by-sex effect leading to widening separation in brain sizes with age between male and female infants (with male infants growing faster than females by 200.4 mm3/d, SE = 67.2, P = .003). Longer gestation was associated with larger brain size (2215 mm3/d, SE = 284, P = 4×10-13). The expected brain size of an infant born one week earlier than average was 5% smaller than average; at 90 days it will not have caught up, being 2% smaller than average. The cerebellum grew at the highest rate, more than doubling in 90 days, and the hippocampus grew at the slowest rate, increasing by 47% in 90 days. There was left

  12. Toll-like receptor 4 mediates microglial activation and production of inflammatory mediators in neonatal rat brain following hypoxia: role of TLR4 in hypoxic microglia

    Science.gov (United States)

    2013-01-01

    Background Hypoxia induces microglial activation which causes damage to the developing brain. Microglia derived inflammatory mediators may contribute to this process. Toll-like receptor 4 (TLR4) has been reported to induce microglial activation and cytokines production in brain injuries; however, its role in hypoxic injury remains uncertain. We investigate here TLR4 expression and its roles in neuroinflammation in neonatal rats following hypoxic injury. Methods One day old Wistar rats were subjected to hypoxia for 2 h. Primary cultured microglia and BV-2 cells were subjected to hypoxia for different durations. TLR4 expression in microglia was determined by RT-PCR, western blot and immunofluorescence staining. Small interfering RNA (siRNA) transfection and antibody neutralization were employed to downregulate TLR4 in BV-2 and primary culture. mRNA and protein expression of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and inducible nitric oxide synthase (iNOS) was assessed. Reactive oxygen species (ROS), nitric oxide (NO) and NF-κB levels were determined by flow cytometry, colorimetric and ELISA assays respectively. Hypoxia-inducible factor-1 alpha (HIF-1α) mRNA and protein expression was quantified and where necessary, the protein expression was depleted by antibody neutralization. In vivo inhibition of TLR4 with CLI-095 injection was carried out followed by investigation of inflammatory mediators expression via double immunofluorescence staining. Results TLR4 immunofluorescence and protein expression in the corpus callosum and cerebellum in neonatal microglia were markedly enhanced post-hypoxia. In vitro, TLR4 protein expression was significantly increased in both primary microglia and BV-2 cells post-hypoxia. TLR4 neutralization in primary cultured microglia attenuated the hypoxia-induced expression of TNF-α, IL-1β and iNOS. siRNA knockdown of TLR4 reduced hypoxia-induced upregulation of TNF-α, IL-1β, iNOS, ROS and NO in BV-2 cells. TLR4

  13. Atomoxetine, a selective norepinephrine reuptake inhibitor, improves short-term histological outcomes after hypoxic-ischemic brain injury in the neonatal male rat.

    Science.gov (United States)

    Toshimitsu, Masatake; Kamei, Yoshimasa; Ichinose, Mari; Seyama, Takahiro; Imada, Shinya; Iriyama, Takayuki; Fujii, Tomoyuki

    2018-03-30

    Despite the recent progress of perinatal medicine, perinatal hypoxic-ischemic (HI) insult remains an important cause of brain injury in neonates, and is pathologically characterized by neuronal loss and the presence of microglia. Neurotransmitters, such as norepinephrine (NE) and glutamate, are involved in the pathogenesis of hypoxic-ischemic encephalopathy via the interaction between neurons and microglia. Although it is well known that the monoamine neurotransmitter NE acts as an anti-inflammatory agent in the brain under pathological conditions, its effects on perinatal HI insult remains elusive. Atomoxetine, a selective NE reuptake inhibitor, has been used clinically for the treatment of attention-deficit hyperactivity disorder in children. Here, we investigated whether the enhancement of endogenous NE by administration of atomoxetine could protect neonates against HI insult by using the neonatal male rat model. We also examined the involvement of microglia in this process. Unilateral HI brain injury was induced by the combination of left carotid artery dissection followed by ligation and hypoxia (8% O 2 , 2 h) in postnatal day 7 (P7) male rat pups. The pups were randomized into three groups: the atomoxetine treatment immediately after HI insult, the atomoxetine treatment at 3 h after HI insult, or the vehicle treatment group. The pups were euthanized on P8 and P14, and the brain regions including the cortex, striatum, hippocampus, and thalamus were evaluated by immunohistochemistry. HI insult resulted in severe brain damage in the ipsilateral hemisphere at P14. Atomoxetine treatment immediately after HI insult significantly increased NE levels in the ipsilateral hemisphere at 1 h after HI insult and reduced the neuronal damage via the increased phosphorylation of cAMP response element-binding protein (pCREB) in all brain regions examined. In addition, the number of microglia was maintained under atomoxetine treatment compared with that of the vehicle

  14. p53 is required for brain growth but is dispensable for resistance to nutrient restriction during Drosophila larval development.

    Science.gov (United States)

    Contreras, Esteban G; Sierralta, Jimena; Glavic, Alvaro

    2018-01-01

    Animal growth is influenced by the genetic background and the environmental circumstances. How genes promote growth and coordinate adaptation to nutrient availability is still an open question. p53 is a transcription factor that commands the cellular response to different types of stresses. In adult Drosophila melanogaster, p53 regulates the metabolic adaptation to nutrient restriction that supports fly viability. Furthermore, the larval brain is protected from nutrient restriction in a phenomenon called 'brain sparing'. Therefore, we hypothesised that p53 may regulate brain growth and show a protective role over brain development under nutrient restriction. Here, we studied the function of p53 during brain growth in normal conditions and in animals subjected to developmental nutrient restriction. We showed that p53 loss of function reduced animal growth and larval brain size. Endogenous p53 was expressed in larval neural stem cells, but its levels and activity were not affected by nutritional stress. Interestingly, p53 knockdown only in neural stem cells was sufficient to decrease larval brain growth. Finally, we showed that in p53 mutant larvae under nutrient restriction, the energy storage levels were not altered, and these larvae generated adults with brains of similar size than wild-type animals. Using genetic approaches, we demonstrate that p53 is required for proper growth of the larval brain. This developmental role of p53 does not have an impact on animal resistance to nutritional stress since brain growth in p53 mutants under nutrient restriction is similar to control animals.

  15. Imaging diagnosis and clinical findings of cerebral venous thrombosis in full-term neonates without brain damage: a ten-year review

    International Nuclear Information System (INIS)

    Monteiro, Alexandra Maria Vieira; Lima, Claudio Marcio Amaral de Oliveira; Ribeiro, Erica Barreiros; Lins, Maria Cristina; Miranda, Silvia; Miranda, Luis Eduardo

    2010-01-01

    Objective: to describe and compare imaging methods and clinical findings of cerebral venous thrombosis in four full-term neonates without brain damage, admitted to a neonatal intensive care unit. Materials and methods: ten-year review of four cases diagnosed with cerebral venous thrombosis by transfontanellar ultrasonography associated with Doppler fluxometry and confirmed by magnetic resonance imaging/magnetic resonance angiography in correlation with clinical findings and neurological progression. Results: ultrasonography presented normal results in 75% of cases and magnetic resonance imaging in 100%. Doppler fluxometry and magnetic resonance angiography were abnormal in 100% of cases. Hypoxia (100%) and early seizures (100%) were predominant among clinical findings with evoked potential changes in 50% of cases. In the assessment of the neuro development all the areas remained within normality parameters up to the conclusion of the present study. Conclusion: ultrasonography in association with Doppler can identify changes related to cerebral venous thrombosis and should be complemented with magnetic resonance imaging that is the gold standard for diagnosis in these cases. (author)

  16. Endogenous IL-6 of mesenchymal stem cell improves behavioral outcome of hypoxic-ischemic brain damage neonatal rats by supressing apoptosis in astrocyte.

    Science.gov (United States)

    Gu, Yan; He, Mulan; Zhou, Xiaoqin; Liu, Jinngjing; Hou, Nali; Bin, Tan; Zhang, Yun; Li, Tingyu; Chen, Jie

    2016-01-14

    Mesenchymal stem cell (MSC) transplantation reduces the neurological impairment caused by hypoxic-ischemic brain damage (HIBD) via immunomodulation. In the current study, we found that MSC transplantation improved learning and memory function and enhanced long-term potentiation in neonatal rats subjected to HIBD and the amount of IL-6 released from MSCs was far greater than that of other cytokines. However, the neuroprotective effect of MSCs infected with siIL-6-transduced recombinant lentivirus (siIL-6 MSCs) was significantly weakened in the behavioural tests and electrophysiological analysis. Meanwhile, the hippocampal IL-6 levels were decreased following siIL-6 MSC transplantation. In vitro, the levels of IL-6 release and the levels of IL-6R and STAT3 expression were increased in both primary neurons and astrocytes subjected to oxygen and glucose deprivation (OGD) following MSCs co-culture. The anti-apoptotic protein Bcl-2 was upregulated and the pro-apoptotic protein Bax was downregulated in OGD-injured astrocytes co-cultured with MSCs. However, the siIL-6 MSCs suppressed ratio of Bcl-2/Bax in the injured astrocytes and induced apoptosis number of the injured astrocytes. Taken together, these data suggest that the neuroprotective effect of MSC transplantation in neonatal HIBD rats is partly mediated by IL-6 to enhance anti-apoptosis of injured astrocytes via the IL-6/STAT3 signaling pathway.

  17. Stromal Cell-Derived Factor-1α Plays a Crucial Role Based on Neuroprotective Role in Neonatal Brain Injury in Rats

    Directory of Open Access Journals (Sweden)

    Miki Mori

    2015-08-01

    Full Text Available Owing to progress in perinatal medicine, the survival of preterm newborns has markedly increased. However, the incidence of cerebral palsy has risen in association with increased preterm birth. Cerebral palsy is largely caused by cerebral hypoxic ischemia (HI, for which there are no effective medical treatments. We evaluated the effects of stromal cell-derived factor-1α (SDF-1α on neonatal brain damage in rats. Left common carotid (LCC arteries of seven-day-old Wistar rat pups were ligated, and animals were exposed to hypoxic gas to cause cerebral HI. Behavioral tests revealed that the memory and spatial perception abilities were disturbed in HI animals, and that SDF-1α treatment improved these cognitive functions. Motor coordination was also impaired after HI but was unimproved by SDF-1α treatment. SDF-1α reduced intracranial inflammation and induced cerebral remyelination, as indicated by the immunohistochemistry results. These data suggest that SDF-1α specifically influences spatial perception abilities in neonatal HI encephalopathy.

  18. Evaluation of brain metabolism and hemodynamics in neonates; Exploration du metabolisme et de l`hemodynamique du cerveau du nouveau-ne

    Energy Technology Data Exchange (ETDEWEB)

    Messer, J. [Centre Hospitalier Universitaire, 67 - Strasbourg (France); Haddad, J.

    1996-09-01

    Evaluation of brain metabolism and hemodynamics has become a necessity in the neonatal period. Cerebral perfusion, oxygen consumption, and/or metabolism can be studied. Doppler, near-infrared tissual spectroscopy, and magnetic resonance spectroscopy are noninvasive techniques that can be used at the bedside. Available techniques for investigating the central nervous system are reviewed, with emphasis on their usefulness for establishing a diagnosis and a prognosis and for making therapeutic decisions. In perinatal asphyxia, these techniques are often useful for guiding therapeutic decisions. It may be appropriate to discuss discontinuation of therapy in patients with cerebral hyperemia, loss of vaso-reactivity to CO{sub 2}, and failure of oxidative phosphorylations responsible for a decrease in the PCr/Pi ratio, an increase in lactate levels, and a decrease in ATP levels. In other situations, these investigations can shed light on pathophysiologic mechanisms in preterm infants. Use of these techniques varies across neonatal units. Each unit should select the techniques that provide the best yields under the conditions prevailing in that unit. (authors). 31 refs., 2 tabs.

  19. Postnatal growth velocity modulates alterations of proteins involved in metabolism and neuronal plasticity in neonatal hypothalamus in rats born with intrauterine growth restriction.

    Science.gov (United States)

    Alexandre-Gouabau, Marie-Cécile F; Bailly, Emilie; Moyon, Thomas L; Grit, Isabelle C; Coupé, Bérengère; Le Drean, Gwenola; Rogniaux, Hélène J; Parnet, Patricia

    2012-02-01

    Intrauterine growth restriction (IUGR) due to maternal protein restriction is associated in rats with an alteration in hypothalamic centers involved in feeding behaviour. In order to gain insight into the mechanism of perinatal maternal undernutrition in the brain, we used proteomics approach to identify hypothalamic proteins that are altered in their expression following protein restriction in utero. We used an animal model in which restriction of the protein intake of pregnant rats (8% vs. 20%) produces IUGR pups which were randomized to a nursing regimen leading to either rapid or slow catch-up growth. We identified several proteins which allowed, by multivariate analysis, a very good discrimination of the three groups according to their perinatal nutrition. These proteins were related to energy-sensing pathways (Eno 1, E(2)PDH, Acot 1 and Fabp5), redox status (Bcs 1L, PrdX3 and 14-3-3 protein) or amino acid pathway (Acy1) as well as neurodevelopment (DRPs, MAP2, Snca). In addition, the differential expressions of several key proteins suggested possible shunts towards ketone-body metabolism and lipid oxidation, providing the energy and carbon skeletons necessary to lipogenesis. Our results show that maternal protein deprivation during pregnancy only (IUGR with rapid catch-up growth) or pregnancy and lactation (IUGR with slow postnatal growth) modulates numerous metabolic pathways resulting in alterations of hypothalamic energy supply. As several of these pathways are involved in signalling, it remains to be determined whether hypothalamic proteome adaptation of IUGR rats in response to different postnatal growth rates could also interfere with cerebral plasticity or neuronal maturation. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Neonatal levels of neurotrophic factors and risk of autism spectrum disorders

    DEFF Research Database (Denmark)

    Abdallah, Morsi; Mortensen, E L; Greaves-Lord, K

    2013-01-01

    To examine levels of 3 neurotrophic factors (NTFs): Brain derived neurotrophic factor (BDNF), Neurotrophin-4 (NT-4), and transforming growth factor-β (TGF-β) in dried blood spot samples of neonates diagnosed with autism spectrum disorders (ASD) later in life and frequency-matched controls....

  1. Neonatal domoic acid increases receptor density of α2 adrenoceptors and GABAA α5 receptors in limbic brain regions of adult rats

    DEFF Research Database (Denmark)

    Thomsen, Majken; Lillethorup, Thea Pinholt; Wegener, Gregers

    Background: The presymptomatic events involved in neurological disorders such as epilepsy remain elusive but represent an opportunity to understand disease development and stop the pathogenic processes leading to chronic epilepsy. Previous studies using Western blot and immunohistochemistry have...... found increased levels of α2 adrenoceptors in the hippocampal membrane of adult rats treated neonatally with low-dose domoic acid (DOM) along with decreased levels of both isoforms of glutamic acid decarboxylase (GAD), a catalyst of the decarboxylation of glutamate to GABA, indicating a reduction...... in GABAergic interneurons. Objectives: The aim of the present study was to investigate the expression of GABAA α5 and α2 adrenoceptors in limbic brain regions in a DOM rat model of epilepsy using autoradiography. Methods: Male Sprague-Dawley rats (N=3) were injected (s.c.) daily from postnatal day 8...

  2. Two-hit model of schizophrenia induced by neonatal immune activation and peripubertal stress in rats: Study of sex differences and brain oxidative alterations.

    Science.gov (United States)

    Monte, Aline Santos; Mello, Bruna Stefânia Ferreira; Borella, Vládia Célia Moreira; da Silva Araujo, Tatiane; da Silva, Francisco Eliclécio Rodrigues; Sousa, Francisca Cléa F de; de Oliveira, Antônio Carlos Pinheiro; Gama, Clarissa Severino; Seeman, Mary V; Vasconcelos, Silvânia Maria Mendes; Lucena, David Freitas De; Macêdo, Danielle

    2017-07-28

    Schizophrenia is considered to be a developmental disorder with distinctive sex differences. Aiming to simulate the vulnerability of the third trimester of human pregnancy to the developmental course of schizophrenia, an animal model was developed, using neonatal poly(I:C) as a first-hit, and peripubertal stress as a second-hit, i.e. a two-hit model. Since, to date, there have been no references to sex differences in the two-hit model, our study sought to determine sex influences on the development of behavior and brain oxidative change in adult rats submitted to neonatal exposure to poly(I:C) on postnatal days 5-7 as well as peripubertal unpredictable stress (PUS). Our results showed that adult two-hit rats present sex-specific behavioral alterations, with females showing more pronounced deficits in prepulse inhibition of the startle reflex and hyperlocomotion, while males showing more deficits in social interaction. Male and female animals exhibited similar working memory deficits. The levels of the endogenous antioxidant, reduced glutathione, were decreased in the prefrontal cortex (PFC) of both male and female animals exposed to both poly(I:C) and poly(I:C)+PUS. Only females presented decrements in GSH levels in the striatum. Nitrite levels were increased in the PFC of male and in the striatum of female poly(I:C)+PUS rats. Increased lipid peroxidation was observed in the PFC of females and in the striatum of males and females exposed to poly(I:C) and poly(I:C)+PUS. Thus, the present study presents evidence for sex differences in behavior and oxidative brain change induced by a two-hit model of schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Co-exposure to radiation and methyl mercury during a critical phase of neonatal brain development in mice enhances developmental neuro-behavioral effects

    International Nuclear Information System (INIS)

    Sundell-Bergman, Synnoeve; Eriksson, Per; Fredriksson, Anders; Fischer, Celia; Stenerloew, Bo

    2008-01-01

    Full text: Organisms, including man, are continuously exposed to low doses of ionizing radiation as well as persistent and non persistent chemicals in the environment. Hence, in the process of developing numerical limits for environmental protection, there is a strong need to consider interactive effects between radiation and other environmental stressors. It is known that ionizing radiation, as well as methyl mercury, can give rise to neuro-toxicological and neuro behavioural effects in mammals and that developmental neurotoxic effects can be seen after exposure during gestation. However, there is a lack of knowledge concerning effects and consequences from low-dose exposure during critical phases of perinatal and/or neonatal brain development and the combination of ionizing radiation and environmental chemicals. Epidemiological studies of patients with haemangioma have indicated that radiation exposures to the brain during infancy might deteriorate cognitive ability in adulthood. Ten-day old neonatal NMRI male mice were exposed to a single oral dose of MeHg (0.40 or 4.0 mg/kg bw). Four hours after the MeHg exposure the mice were irradiated with 60 Co gamma radiation at doses of 0,2 and 0,5 Gy. The animals were subjected to a spontaneous behaviour test at the ages of 2- and 4-months, and the water maze test at the age of 5 months. Neither the single dose of MeHg (0.4 mg/kg bw) nor the radiation dose of 0.2 Gy affected the spontaneous behavior, but the co-exposure to radiation and MeHg caused developmental neurotoxic effects. These effects were manifested as disrupted spontaneous behavior, lack of habituation, and impaired learning and memory functions. Studies are continuing to verify the effects ant to elucidate possible underlying mechanisms. (author)

  4. Predicting the Probability of Abnormal Stimulated Growth Hormone Response in Children After Radiotherapy for Brain Tumors

    International Nuclear Information System (INIS)

    Hua Chiaho; Wu Shengjie; Chemaitilly, Wassim; Lukose, Renin C.; Merchant, Thomas E.

    2012-01-01

    Purpose: To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. Methods and Materials: We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n = 72), low-grade glioma (n = 28) or craniopharyngioma (n = 6), who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test ≥7 ng/mL. Results: Independent predictor variables identified by multivariate logistic regression with high statistical significance (p < 0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Conclusions: Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency.

  5. Predicting the Probability of Abnormal Stimulated Growth Hormone Response in Children After Radiotherapy for Brain Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Hua Chiaho, E-mail: Chia-Ho.Hua@stjude.org [Department of Radiological Sciences, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Wu Shengjie [Department of Biostatistics, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Chemaitilly, Wassim [Division of Endocrinology, Department of Pediatric Medicine, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Lukose, Renin C.; Merchant, Thomas E. [Department of Radiological Sciences, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States)

    2012-11-15

    Purpose: To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. Methods and Materials: We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n = 72), low-grade glioma (n = 28) or craniopharyngioma (n = 6), who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test {>=}7 ng/mL. Results: Independent predictor variables identified by multivariate logistic regression with high statistical significance (p < 0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Conclusions: Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency.

  6. Body growth and brain development in premature babies: an MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Tzarouchi, Loukia C.; Zikou, Anastasia; Kosta, Paraskevi; Argyropoulou, Maria I. [University of Ioannina, Department of Radiology, Medical School, Ioannina (Greece); Drougia, Aikaterini; Andronikou, Styliani [University of Ioannina, Intensive Care Unit, Child Health Department, Medical School, Ioannina (Greece); Astrakas, Loukas G. [University of Ioannina, Department of Medical Physics, Medical School, Ioannina (Greece)

    2014-03-15

    Prematurity and intrauterine growth restriction are associated with neurodevelopmental disabilities. To assess the relationship between growth status and regional brain volume (rBV) and white matter microstructure in premature babies at around term-equivalent age. Premature infants (n= 27) of gestational age (GA): 29.8 ± 2.1 weeks, with normal brain MRI scans were studied at corrected age: 41.2 ± 1.4 weeks. The infants were divided into three groups: 1) appropriate for GA at birth and at the time of MRI (AGA), 2) small for GA at birth with catch-up growth at the time of MRI (SGA{sub a}) and 3) small for GA at birth with failure of catch-up growth at the time of MRI (SGA{sub b}). The T1-weighted images were segmented into 90 rBVs using the SPM8/IBASPM and differences among groups were assessed. Fractional anisotropy (FA) was measured bilaterally in 15 fiber tracts and its relationship to GA and somatometric measurements was explored. Lower rBV was observed in SGA{sub b} in superior and anterior brain areas. A positive correlation was demonstrated between FA and head circumference and body weight. Body weight was the only significant predictor for FA (P< 0.05). In premature babies, catch-up growth is associated with regional brain volume catch-up at around term-equivalent age, starting from the brain areas maturing first. Body weight seems to be a strong predictor associated with WM microstructure in brain areas related to attention, language, cognition, memory and executing functioning. (orig.)

  7. Body growth and brain development in premature babies: an MRI study

    International Nuclear Information System (INIS)

    Tzarouchi, Loukia C.; Zikou, Anastasia; Kosta, Paraskevi; Argyropoulou, Maria I.; Drougia, Aikaterini; Andronikou, Styliani; Astrakas, Loukas G.

    2014-01-01

    Prematurity and intrauterine growth restriction are associated with neurodevelopmental disabilities. To assess the relationship between growth status and regional brain volume (rBV) and white matter microstructure in premature babies at around term-equivalent age. Premature infants (n= 27) of gestational age (GA): 29.8 ± 2.1 weeks, with normal brain MRI scans were studied at corrected age: 41.2 ± 1.4 weeks. The infants were divided into three groups: 1) appropriate for GA at birth and at the time of MRI (AGA), 2) small for GA at birth with catch-up growth at the time of MRI (SGA a ) and 3) small for GA at birth with failure of catch-up growth at the time of MRI (SGA b ). The T1-weighted images were segmented into 90 rBVs using the SPM8/IBASPM and differences among groups were assessed. Fractional anisotropy (FA) was measured bilaterally in 15 fiber tracts and its relationship to GA and somatometric measurements was explored. Lower rBV was observed in SGA b in superior and anterior brain areas. A positive correlation was demonstrated between FA and head circumference and body weight. Body weight was the only significant predictor for FA (P< 0.05). In premature babies, catch-up growth is associated with regional brain volume catch-up at around term-equivalent age, starting from the brain areas maturing first. Body weight seems to be a strong predictor associated with WM microstructure in brain areas related to attention, language, cognition, memory and executing functioning. (orig.)

  8. Differences in brain functional connectivity at resting state in neonates born to healthy obese or normal-weight mothers

    Science.gov (United States)

    Recent studies have shown associations between maternal obesity at pre- or early pregnancy and long-term neurodevelopment in children, suggesting in utero effects of maternal obesity on offspring brain development. In this study, we examined whether brain functional connectivity to the prefrontal lo...

  9. GLUT3 gene expression is critical for embryonic growth, brain development and survival.

    Science.gov (United States)

    Carayannopoulos, Mary O; Xiong, Fuxia; Jensen, Penny; Rios-Galdamez, Yesenia; Huang, Haigen; Lin, Shuo; Devaskar, Sherin U

    2014-04-01

    Glucose is the primary energy source for eukaryotic cells and the predominant substrate for the brain. GLUT3 is essential for trans-placental glucose transport and highly expressed in the mammalian brain. To further elucidate the role of GLUT3 in embryonic development, we utilized the vertebrate whole animal model system of Danio rerio as a tractable system for defining the cellular and molecular mechanisms altered by impaired glucose transport and metabolism related to perturbed expression of GLUT3. The comparable orthologue of human GLUT3 was identified and the expression of this gene abrogated during early embryonic development. In a dose-dependent manner embryonic brain development was disrupted resulting in a phenotype of aberrant brain organogenesis, associated with embryonic growth restriction and increased cellular apoptosis. Rescue of the morphant phenotype was achieved by providing exogenous GLUT3 mRNA. We conclude that GLUT3 is critically important for brain organogenesis and embryonic growth. Disruption of GLUT3 is responsible for the phenotypic spectrum of embryonic growth restriction to demise and neural apoptosis with microcephaly. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    NARCIS (Netherlands)

    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

  11. Severe cell reduction in the future brain cortex in human growth-restricted fetuses and infants

    DEFF Research Database (Denmark)

    Samuelsen, Grethe B; Pakkenberg, Bente; Bogdanović, Nenad

    2007-01-01

    with controls. The daily increase in brain cells in the future cortex was only half of that of the controls. In the 3 other developmental zones, no significant differences in cell numbers could be demonstrated. CONCLUSIONS: IUGR in humans is associated with a severe reduction in cortical growth...

  12. Ultrasound evaluation of cortical brain development in fetuses with intrauterine growth restriction.

    Science.gov (United States)

    Businelli, Caterina; de Wit, Charlotte; Visser, Gerard H A; Pistorius, Lourens R

    2014-09-10

    Abstract Objective: We evaluated the ultrasound appearance of brain volume and cortical development in fetuses with early growth restriction and placental insufficiency. Methods: We examined a cohort of 20 fetuses with severe intrauterine growth restriction (IUGR) and evidence of placental insufficiency by three-dimensional (3D) ultrasound between 24 and 34 weeks. We graded cortical development and measured the supratentorial intracranial volume. The cortical grading and volume were compared to data obtained from a reference population of 28 adequate for gestational age (AGA) fetuses. Results: Ultrasound examinations were performed in 20 fetuses with IUGR. The biometry and brain volume were significantly reduced in IUGR fetuses. There was evidence of accelerated cortical development in IUGR fetuses. Conclusion: This study confirms that the smaller brain volume in IUGR fetuses, with normal or accelerated cortical maturation as previously depicted with postnatal MRI examination, can be demonstrated by prenatal 3D ultrasound.

  13. Mitochondrial Optic Atrophy (OPA) 1 Processing Is Altered in Response to Neonatal Hypoxic-Ischemic Brain Injury

    Science.gov (United States)

    Baburamani, Ana A.; Hurling, Chloe; Stolp, Helen; Sobotka, Kristina; Gressens, Pierre; Hagberg, Henrik; Thornton, Claire

    2015-01-01

    Perturbation of mitochondrial function and subsequent induction of cell death pathways are key hallmarks in neonatal hypoxic-ischemic (HI) injury, both in animal models and in term infants. Mitoprotective therapies therefore offer a new avenue for intervention for the babies who suffer life-long disabilities as a result of birth asphyxia. Here we show that after oxygen-glucose deprivation in primary neurons or in a mouse model of HI, mitochondrial protein homeostasis is altered, manifesting as a change in mitochondrial morphology and functional impairment. Furthermore we find that the mitochondrial fusion and cristae regulatory protein, OPA1, is aberrantly cleaved to shorter forms. OPA1 cleavage is normally regulated by a balanced action of the proteases Yme1L and Oma1. However, in primary neurons or after HI in vivo, protein expression of YmelL is also reduced, whereas no change is observed in Oma1 expression. Our data strongly suggest that alterations in mitochondria-shaping proteins are an early event in the pathogenesis of neonatal HI injury. PMID:26393574

  14. Pulsatile delivery of a leucine supplement during long-term continuous enteral feeding enhances lean growth in term neonatal pigs

    Science.gov (United States)

    Neonatal pigs are used as a model to study and optimize the clinical treatment of infants who are unable to maintain oral feeding. Using this model, we have previously shown that pulsatile administration of leucine during continuous feeding over 24 h via orogastric tube enhanced protein synthesis in...

  15. Research Progress of Mechanism and Treatment of Neonatal Hypoxic-ischemic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Yu-fei NI

    2017-09-01

    Full Text Available Neonatal hypoxic-ischemic encephalopathy (HIE is a hypoxic-ischemic brain injury caused by hypoxia after perinatal asphyxia in neonates, and one of the major causes of neonatal death, lifelong neurological disability and cognitive dysfunction. Although the mechanisms of HIE are complex and still unclear, it generally holds that HIE has a relationship with acute inflammatory reaction and is regulated by multiple cytokines and neuromodulators. Presently, therapeutic hypothermia, in the light of the lower mortality and improvement of prognosis, becomes a standard of care in many medical institutes, but there are still neonates dead or disabled after treatment. Therefore, it is necessary to use hypothermia in combination with other new adjuvant therapies (such as anti-inflammatory cytokine to improve the prognosis of neonatal HIE. Besides, glutamate receptor antagonist, calcium channel blockers, erythropoietin, and nerve growth factors also have certain therapeutic effects on neonatal HIE. Therefore, this review mainly focused on the mechanisms and treatments of HIE. Based on this, we hold that the future studies should concentrate on how to attenuate early brain injury and to improve the growth and differentiation of neuronal cells and non-neuronal cells, which is of great signifcance to prolong the therapeutic window of neuroprotection, promote long-term neural restoration and improve the prognosis.

  16. Brain Metabolism Alterations Induced by Pregnancy Swimming Decreases Neurological Impairments Following Neonatal Hypoxia-Ischemia in Very Immature Rats

    Directory of Open Access Journals (Sweden)

    Eduardo F. Sanches

    2018-06-01

    Full Text Available Introduction: Prematurity, through brain injury and altered development is a major cause of neurological impairments and can result in motor, cognitive and behavioral deficits later in life. Presently, there are no well-established effective therapies for preterm brain injury and the search for new strategies is needed. Intra-uterine environment plays a decisive role in brain maturation and interventions using the gestational window have been shown to influence long-term health in the offspring. In this study, we investigated whether pregnancy swimming can prevent the neurochemical metabolic alterations and damage that result from postnatal hypoxic-ischemic brain injury (HI in very immature rats.Methods: Female pregnant Wistar rats were divided into swimming (SW or sedentary (SE groups. Following a period of adaptation before mating, swimming was performed during the entire gestation. At postnatal day (PND3, rat pups from SW and SE dams had right common carotid artery occluded, followed by systemic hypoxia. At PND4 (24 h after HI, the early neurochemical profile was measured by 1H-magnetic resonance spectroscopy. Astrogliosis, apoptosis and neurotrophins protein expression were assessed in the cortex and hippocampus. From PND45, behavioral testing was performed. Diffusion tensor imaging and neurite orientation dispersion and density imaging were used to evaluate brain microstructure and the levels of proteins were quantified.Results: Pregnancy swimming was able to prevent early metabolic changes induced by HI preserving the energetic balance, decreasing apoptotic cell death and astrogliosis as well as maintaining the levels of neurotrophins. At adult age, swimming preserved brain microstructure and improved the performance in the behavioral tests.Conclusion: Our study points out that swimming during gestation in rats could prevent prematurity related brain damage in progeny with high translational potential and possibly interesting cost

  17. Neuroprotection by the histone deacetylase inhibitor trichostatin A in a model of lipopolysaccharide-sensitised neonatal hypoxic-ischaemic brain injury

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    Fleiss Bobbi

    2012-04-01

    Full Text Available Abstract Background Perinatal brain injury is complex and often associated with both inflammation and hypoxia-ischaemia (HI. In adult inflammatory brain injury models, therapies to increase acetylation are efficacious in reducing inflammation and cerebral injury. Our aim in the present study was to examine the neuropathological and functional effects of the histone deacetylase inhibitor (HDACi trichostatin A (TSA in a model of neonatal lipopolysaccharide (LPS-sensitised HI. We hypothesised that, by decreasing inflammation, TSA would improve injury and behavioural outcome. Furthermore, TSA’s effects on oligodendrocyte development, which is acetylation-dependent, were investigated. Methods On postnatal day 8 (P8, male and female mice were exposed to LPS together with or without TSA. On P9 (14 hours after LPS, mice were exposed to HI (50 minutes at 10% O2. Neuropathology was assessed at 24 hours, 5 days and 27 days post-LPS/HI via immunohistochemistry and/or Western blot analysis for markers of grey matter (microtubule-associated protein 2, white matter (myelin basic protein and cell death (activated caspase-3. Effects of TSA on LPS or LPS/HI-induced inflammation (cytokines and microglia number were assessed by Luminex assay and immunohistochemistry. Expression of acetylation-dependent oligodendrocyte maturational corepressors was assessed with quantitative PCR 6 hours after LPS and at 24 hours and 27 days post-LPS/HI. Animal behaviour was monitored with the open-field and trace fear-conditioning paradigms at 25 days post-LPS/HI to identify functional implications of changes in neuropathology associated with TSA treatment. Results TSA induced increased Ac-H4 in females only after LPS exposure. Also only in females, TSA reduced grey matter and white matter injury at 5 days post-LPS/HI. Treatment altered animal behaviour in the open field and improved learning in the fear-conditioning test in females compared with LPS/HI-only females at

  18. Long-term reorganization of structural brain networks in a rabbit model of intrauterine growth restriction.

    Science.gov (United States)

    Batalle, Dafnis; Muñoz-Moreno, Emma; Arbat-Plana, Ariadna; Illa, Miriam; Figueras, Francesc; Eixarch, Elisenda; Gratacos, Eduard

    2014-10-15

    Characterization of brain changes produced by intrauterine growth restriction (IUGR) is among the main challenges of modern fetal medicine and pediatrics. This condition affects 5-10% of all pregnancies and is associated with a wide range of neurodevelopmental disorders. Better understanding of the brain reorganization produced by IUGR opens a window of opportunity to find potential imaging biomarkers in order to identify the infants with a high risk of having neurodevelopmental problems and apply therapies to improve their outcomes. Structural brain networks obtained from diffusion magnetic resonance imaging (MRI) is a promising tool to study brain reorganization and to be used as a biomarker of neurodevelopmental alterations. In the present study this technique is applied to a rabbit animal model of IUGR, which presents some advantages including a controlled environment and the possibility to obtain high quality MRI with long acquisition times. Using a Q-Ball diffusion model, and a previously published rabbit brain MRI atlas, structural brain networks of 15 IUGR and 14 control rabbits at 70 days of age (equivalent to pre-adolescence human age) were obtained. The analysis of graph theory features showed a decreased network infrastructure (degree and binary global efficiency) associated with IUGR condition and a set of generalized fractional anisotropy (GFA) weighted measures associated with abnormal neurobehavior. Interestingly, when assessing the brain network organization independently of network infrastructure by means of normalized networks, IUGR showed increased global and local efficiencies. We hypothesize that this effect could reflect a compensatory response to reduced infrastructure in IUGR. These results present new evidence on the long-term persistence of the brain reorganization produced by IUGR that could underlie behavioral and developmental alterations previously described. The described changes in network organization have the potential to be used

  19. Effect of hyperbaric oxygenation on mitochondrial function of neuronal cells in the cortex of neonatal rats after hypoxic-ischemic brain damage

    Directory of Open Access Journals (Sweden)

    L. Yang

    2016-01-01

    Full Text Available The timing and mechanisms of protection by hyperbaric oxygenation (HBO in hypoxic-ischemic brain damage (HIBD have only been partially elucidated. We monitored the effect of HBO on the mitochondrial function of neuronal cells in the cerebral cortex of neonatal rats after HIBD. Neonatal Sprague-Dawley rats (total of 360 of both genders were randomly divided into normal control, HIBD, and HIBD+HBO groups. The HBO treatment began immediately after hypoxia-ischemia (HI and continued once a day for 7 consecutive days. Animals were euthanized 0, 2, 4, 6, and 12 h post-HI to monitor the changes in mitochondrial membrane potential (ΔΨm occurring soon after a single dose of HBO treatment, as well as 2, 3, 4, 5, 6, and 7 days post-HI to study ΔΨm changes after a series of HBO treatments. Fluctuations in ΔΨm were observed in the ipsilateral cortex in both HIBD and HIBD+HBO groups. Within 2 to 12 h after HI insult, the ΔΨm of the HIBD and HIBD+HBO groups recovered to some extent. A secondary drop in ΔΨm was observed in both groups during the 1-4 days post-HI period, but was more severe in the HIBD+HBO group. There was a secondary recovery of ΔΨm observed in the HIBD+HBO group, but not in the HIBD group, during the 5-7 days period after HI insult. HBO therapy may not lead to improvement of neural cell mitochondrial function in the cerebral cortex in the early stage post-HI, but may improve it in the sub-acute stage post-HI.

  20. Experimental Evidence that In Vivo Intracerebral Administration of L-2-Hydroxyglutaric Acid to Neonatal Rats Provokes Disruption of Redox Status and Histopathological Abnormalities in the Brain.

    Science.gov (United States)

    Ribeiro, Rafael Teixeira; Zanatta, Ângela; Amaral, Alexandre Umpierrez; Leipnitz, Guilhian; de Oliveira, Francine Hehn; Seminotti, Bianca; Wajner, Moacir

    2018-04-01

    Tissue accumulation of L-2-hydroxyglutaric acid (L-2-HG) is the biochemical hallmark of L-2-hydroxyglutaric aciduria (L-2-HGA), a rare neurometabolic inherited disease characterized by neurological symptoms and brain white matter abnormalities whose pathogenesis is not yet well established. L-2-HG was intracerebrally administered to rat pups at postnatal day 1 (P1) to induce a rise of L-2-HG levels in the central nervous system (CNS). Thereafter, we investigated whether L-2-HG in vivo administration could disturb redox homeostasis and induce brain histopathological alterations in the cerebral cortex and striatum of neonatal rats. L-2-HG markedly induced the generation of reactive oxygen species (increase of 2',7'-dichloroflurescein-DCFH-oxidation), lipid peroxidation (increase of malondialdehyde concentrations), and protein oxidation (increase of carbonyl formation and decrease of sulfhydryl content), besides decreasing the antioxidant defenses (reduced glutathione-GSH) and sulfhydryl content in the cerebral cortex. Alterations of the activities of various antioxidant enzymes were also observed in the cerebral cortex and striatum following L-2-HG administration. Furthermore, L-2-HG-induced lipid peroxidation and GSH decrease in the cerebral cortex were prevented by the antioxidant melatonin and by the classical antagonist of NMDA glutamate receptor MK-801, suggesting the involvement of reactive species and of overstimulation of NMDA receptor in these effects. Finally, L-2-HG provoked significant vacuolation and edema particularly in the cerebral cortex with less intense alterations in the striatum that were possibly associated with the unbalanced redox homeostasis caused by this metabolite. Taken together, it is presumed that these pathomechanisms may underlie the neurological symptoms and brain abnormalities observed in the affected patients.

  1. Sex differences in behavioral outcome following neonatal hypoxia ischemia: insights from a clinical meta-analysis and a rodent model of induced hypoxic ischemic brain injury.

    Science.gov (United States)

    Smith, Amanda L; Alexander, Michelle; Rosenkrantz, Ted S; Sadek, Mona Lisa; Fitch, R Holly

    2014-04-01

    Hypoxia ischemia (HI; reduced oxygen and/or blood flow to the brain) is one of the most common injuries among preterm infants and term infants with birth complications. Both populations show cognitive/behavioral deficits, including impairments in sensory, learning/memory, and attention domains. Clinical data suggests a sex difference in HI outcomes, with males exhibiting more severe cognitive/behavioral deficits relative to matched females. Our laboratory has also reported more severe behavioral deficits among male rats with induced HI relative to females with comparable injury (Hill et al., 2011a,b). The current study initially examined published clinical studies from the past 20years where long-term IQ outcome scores for matched groups of male and female premature infants were reported separately (IQ being the most common outcome measure). A meta-analysis revealed a female "advantage," as indicated by significantly better scores on performance and full scale IQ (but not verbal IQ) for premature females. We then utilized a rodent model of neonatal HI injury to assess sham and postnatal day 7 (P7) HI male and female rats on a battery of behavioral tasks. Results showed expected deficits in HI male rats, but also showed task-dependent sex differences, with HI males having significantly larger deficits than HI females on some tasks but equivalent deficits on other tasks. In contrast to behavioral results, post mortem neuropathology associated with HI was comparable across sex. These findings suggest: 1) neonatal female "protection" in some behavioral domains, as indexed by superior outcome following early injury relative to males; and 2) female protection may entail sex-specific plasticity or compensation, rather than a reduction in gross neuropathology. Further exploration of the mechanisms underlying this sex effect could aid in neuroprotection efforts for at-risk neonates in general, and males in particular. Moreover, our current report of comparable anatomical

  2. The role of feeding regimens in the growth of neonate broad-banded water snakes, Nerodia fasciata confluens, and possible effects on reproduction.

    Science.gov (United States)

    Scudder, R M; Burghardt, G M

    1985-05-01

    The effect of different feeding regimens on the growth pattern of Nerodia fasciata confluens was tested using a litter of 18 captive-born neonates. The snakes were divided among three feeding groups: one group fed once per week, another fed twice per week, and the third fed on alternate days. The once per week and the twice per week groups were offered the same weight of food each week, while the alternate-day group was offered food in excess of ingestion levels during each feeding session. The results indicate that there is a shift in the allocation of energy for growth in weight, snout-vent length, and tail length with a change in the feeding regimen. Females were affected more than the males. The results are discussed in relation to their possible effect on reproduction.

  3. Foetal and neonatal thyroid disorders.

    Science.gov (United States)

    Radetti, G; Zavallone, A; Gentili, L; Beck-Peccoz, P; Bona, G

    2002-10-01

    Thyroid hormones have been shown to be absolutely necessary for early brain development. During pregnancy, both maternal and foetal thyroid hormones contribute to foetal brain development and maternal supply explains why most of the athyreotic newborns usually do not show any signs of hypothyroidism at birth. Foetal and/or neonatal hypothyroidism is a rare disorder. Its incidence, as indicated by neonatal screening, is about 1:4000. Abnormal thyroid development (i.e. agenesia, ectopic gland, hypoplasia) or inborn errors in thyroid hormone biosynthesis are the most common causes of permanent congenital hypothyroidism. Recent studies reported that mutations involving Thyroid Transcriptor Factors (TTF) such as TTF-1, TTF-2, PAX-8 play an important role in altered foetal thyroid development. Deficiency of transcriptor factor (Pit-1, Prop-1, LHX-3) both in mother and in the foetus represents another rare cause of foetal hypothyroidism. At birth clinical picture may be not always so obvious and typical signs appear only after several weeks but a delayed diagnosis could have severe consequences consisting of delayed physical and mental development. Even if substitutive therapy is promptly started some learning difficulties might still arise suggesting that intrauterine adequate levels of thyroid hormones are absolutely necessary for a normal neurological development. Placental transfer of maternal antithyroid antibodies inhibiting fetal thyroid function can cause transient hypothyroidism at birth. If the mother with thyroid autoimmune disease is also hypothyroid during pregnancy and she doesn't receive substitutive therapy, a worse neurological outcome may be expected for her foetus. Foetal and/or neonatal hyperthyroidism is a rare condition and its incidence has been estimated around 1:4000-40000, according to various authors. The most common causes are maternal thyroid autoimmune disorders, such as Graves' disease and Hashimoto's thyroiditis. Rarer non autoimmune causes

  4. Brain IGF-1 receptors control mammalian growth and lifespan through a neuroendocrine mechanism.

    Directory of Open Access Journals (Sweden)

    Laurent Kappeler

    2008-10-01

    Full Text Available Mutations that decrease insulin-like growth factor (IGF and growth hormone signaling limit body size and prolong lifespan in mice. In vertebrates, these somatotropic hormones are controlled by the neuroendocrine brain. Hormone-like regulations discovered in nematodes and flies suggest that IGF signals in the nervous system can determine lifespan, but it is unknown whether this applies to higher organisms. Using conditional mutagenesis in the mouse, we show that brain IGF receptors (IGF-1R efficiently regulate somatotropic development. Partial inactivation of IGF-1R in the embryonic brain selectively inhibited GH and IGF-I pathways after birth. This caused growth retardation, smaller adult size, and metabolic alterations, and led to delayed mortality and longer mean lifespan. Thus, early changes in neuroendocrine development can durably modify the life trajectory in mammals. The underlying mechanism appears to be an adaptive plasticity of somatotropic functions allowing individuals to decelerate growth and preserve resources, and thereby improve fitness in challenging environments. Our results also suggest that tonic somatotropic signaling entails the risk of shortened lifespan.

  5. Abnormal cortical development after premature birth shown by altered allometric scaling of brain growth.

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    Olga Kapellou

    2006-08-01

    Full Text Available We postulated that during ontogenesis cortical surface area and cerebral volume are related by a scaling law whose exponent gives a quantitative measure of cortical development. We used this approach to investigate the hypothesis that premature termination of the intrauterine environment by preterm birth reduces cortical development in a dose-dependent manner, providing a neural substrate for functional impairment.We analyzed 274 magnetic resonance images that recorded brain growth from 23 to 48 wk of gestation in 113 extremely preterm infants born at 22 to 29 wk of gestation, 63 of whom underwent neurodevelopmental assessment at a median age of 2 y. Cortical surface area was related to cerebral volume by a scaling law with an exponent of 1.29 (95% confidence interval, 1.25-1.33, which was proportional to later neurodevelopmental impairment. Increasing prematurity and male gender were associated with a lower scaling exponent (p < 0.0001 independent of intrauterine or postnatal somatic growth.Human brain growth obeys an allometric scaling relation that is disrupted by preterm birth in a dose-dependent, sexually dimorphic fashion that directly parallels the incidence of neurodevelopmental impairments in preterm infants. This result focuses attention on brain growth and cortical development during the weeks following preterm delivery as a neural substrate for neurodevelopmental impairment after premature delivery.

  6. Disruption of the blood-brain interface in neonatal rat neocortex induces a transient expression of metallothionein in reactive astrocytes

    DEFF Research Database (Denmark)

    Penkowa, M; Moos, T

    1995-01-01

    rats were subjected to a localized freeze lesion of the neocortex of the right temporal cortex. This lesion results in a disrupted blood-brain interface, leading to extravasation of plasma proteins. From 16 h, reactive astrocytosis, defined as an increase in the number and size of cells expressing GFAP...

  7. Involvement of neuronal IL-1β in acquired brain lesions in a rat model of neonatal encephalopathy.

    Science.gov (United States)

    Savard, Alexandre; Lavoie, Karine; Brochu, Marie-Elsa; Grbic, Djordje; Lepage, Martin; Gris, Denis; Sebire, Guillaume

    2013-09-05

    Infection-inflammation combined with hypoxia-ischemia (HI) is the most prevalent pathological scenario involved in perinatal brain damage leading to life-long neurological disabilities. Following lipopolysaccharide (LPS) and/or HI aggression, different patterns of inflammatory responses have been uncovered according to the brain differentiation stage. In fact, LPS pre-exposure has been reported to aggravate HI brain lesions in post-natal day 1 (P1) and P7 rat models that are respectively equivalent - in terms of brain development - to early and late human preterm newborns. However, little is known about the innate immune response in LPS plus HI-induced lesions of the full-term newborn forebrain and the associated neuropathological and neurobehavioral outcomes. An original preclinical rat model has been previously documented for the innate neuroimmune response at different post-natal ages. It was used in the present study to investigate the neuroinflammatory mechanisms that underline neurological impairments after pathogen-induced inflammation and HI in term newborns. LPS and HI exerted a synergistic detrimental effect on rat brain. Their effect led to a peculiar pattern of parasagittal cortical-subcortical infarcts mimicking those in the human full-term newborn with subsequent severe neurodevelopmental impairments. An increased IL-1β response in neocortical and basal gray neurons was demonstrated at 4 h after LPS + HI-exposure and preceded other neuroinflammatory responses such as microglial and astroglial cell activation. Neurological deficits were observed during the acute phase of injury followed by a recovery, then by a delayed onset of profound motor behavior impairment, reminiscent of the delayed clinical onset of motor system impairments observed in humans. Interleukin-1 receptor antagonist (IL-1ra) reduced the extent of brain lesions confirming the involvement of IL-1β response in their pathophysiology. In rat pups at a neurodevelopmental age

  8. Maternal or neonatal infection: association with neonatal encephalopathy outcomes.

    Science.gov (United States)

    Jenster, Meike; Bonifacio, Sonia L; Ruel, Theodore; Rogers, Elizabeth E; Tam, Emily W; Partridge, John Colin; Barkovich, Anthony James; Ferriero, Donna M; Glass, Hannah C

    2014-07-01

    Perinatal infection may potentiate brain injury among children born preterm. The objective of this study was to examine whether maternal and/or neonatal infection are associated with adverse outcomes among term neonates with encephalopathy. This study is a cohort study of 258 term newborns with encephalopathy whose clinical records were examined for signs of maternal infection (chorioamnionitis) and infant infection (sepsis). Multivariate regression was used to assess associations between infection, pattern, and severity of injury on neonatal magnetic resonance imaging, as well as neurodevelopment at 30 mo (neuromotor examination, or Bayley Scales of Infant Development, second edition mental development index encephalopathy, chorioamnionitis was associated with a lower risk of brain injury and adverse outcomes, whereas signs of neonatal sepsis carried an elevated risk. The etiology of encephalopathy and timing of infection and its associated inflammatory response may influence whether infection potentiates or mitigates injury in term newborns.

  9. Influence of intracerebral exposure to enriched uranium on neutron specific enolase and interleukin-1 β content in neonatal rats

    International Nuclear Information System (INIS)

    Gu Guixiong; Zhu Shoupeng; Wang Liuyi; Yang Shuqin; Zhu Lingli

    2001-01-01

    Objective: To examine biochemically the injurious effects of enriched uranium 235 U on developing brain of neonatal rats. Methods: Neonatal rats were irradiated with single injection of 2 μl enriched uranium into the left lateral ventricle of the brain at postnatal day 1 ( 235 U, respectively. The micro-autoradiographic tracing was performed, somatic growth and neuro-behavior development of neonatal rats were examined by determination of multiple parameters, and the neuron specific enolase (NSE) and interleukin-1 β(IL-1 β) levels in brains were determined with radioimmunoassay. Results: The radionuclides were mainly accumulated in the neuronal nucleus, and autoradiographic tracks appeared in the cytoplasm and inter- cellular space. Neonatal rats showed delayed growth and abnormal neuro-behavior. The changes of NSE, IL-1 β in cerebellum, cerebral cortex, hippocampus, diencephalons showed a dose-dependent relationship that when the dose of irradiation was increased, the levels of NSE was decreased and the IL-1 β was increased. Conclusion: The nerve cell of developing brain of neonatal rats is sensitive, fragile and compensable to injurious effects of α-irradiation from enriched uranium

  10. The challenges of neonatal magnetic resonance imaging

    International Nuclear Information System (INIS)

    Arthurs, Owen J.; Graves, Martin J.; Lomas, David J.; Edwards, Andrea; Austin, Topun

    2012-01-01

    Improved neonatal survival rates and antenatal diagnostic imaging is generating a growing demand for postnatal MRI examinations. Neonatal brain MRI is now becoming standard clinical care in many settings, but with the exception of some research centres, the technique has not been optimised for imaging neonates and small children. Here, we review some of the challenges involved in neonatal MRI, including recent advances in overall MR practicality and nursing practice, to address some of the ways in which the MR experience could be made more neonate-friendly. (orig.)

  11. Complete adrenocorticotropin deficiency after radiation therapy for brain tumor with a normal growth hormone reserve

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, Haruna; Yoshioka, Katsunobu; Yamagami, Keiko [Osaka City General Hospital (Japan)] (and others)

    2002-06-01

    A 34-year-old man with neurofibromatosis type 1, who had received radiation therapy after the excision of a brain tumor 5 years earlier, was admitted to our hospital with vomiting and weight loss. Cortisol and adrenocorticotropin (ACTH) were undetectable before and after administration of 100 {mu}g corticotropin releasing hormone. The level of growth hormone without stimulation was 24.7 ng/ml. We diagnosed him to have complete ACTH deficiency attributable to radiation therapy. This is the first known case of a patient with complete ACTH deficiency after radiation therapy and a growth hormone reserve that remained normal. (author)

  12. Complete adrenocorticotropin deficiency after radiation therapy for brain tumor with a normal growth hormone reserve

    International Nuclear Information System (INIS)

    Sakai, Haruna; Yoshioka, Katsunobu; Yamagami, Keiko

    2002-01-01

    A 34-year-old man with neurofibromatosis type 1, who had received radiation therapy after the excision of a brain tumor 5 years earlier, was admitted to our hospital with vomiting and weight loss. Cortisol and adrenocorticotropin (ACTH) were undetectable before and after administration of 100 μg corticotropin releasing hormone. The level of growth hormone without stimulation was 24.7 ng/ml. We diagnosed him to have complete ACTH deficiency attributable to radiation therapy. This is the first known case of a patient with complete ACTH deficiency after radiation therapy and a growth hormone reserve that remained normal. (author)

  13. Detecting brain growth patterns in normal children using tensor-based morphometry.

    Science.gov (United States)

    Hua, Xue; Leow, Alex D; Levitt, Jennifer G; Caplan, Rochelle; Thompson, Paul M; Toga, Arthur W

    2009-01-01

    Previous magnetic resonance imaging (MRI)-based volumetric studies have shown age-related increases in the volume of total white matter and decreases in the volume of total gray matter of normal children. Recent adaptations of image analysis strategies enable the detection of human brain growth with improved spatial resolution. In this article, we further explore the spatio-temporal complexity of adolescent brain maturation with tensor-based morphometry. By utilizing a novel non-linear elastic intensity-based registration algorithm on the serial structural MRI scans of 13 healthy children, individual Jacobian growth maps are generated and then registered to a common anatomical space. Statistical analyses reveal significant tissue growth in cerebral white matter, contrasted with gray matter loss in parietal, temporal, and occipital lobe. In addition, a linear regression with age and gender suggests a slowing down of the growth rate in regions with the greatest white matter growth. We demonstrate that a tensor-based Jacobian map is a sensitive and reliable method to detect regional tissue changes during development. (c) 2007 Wiley-Liss, Inc.

  14. Expanding the mind: insulin-like growth factor I and brain development.

    Science.gov (United States)

    Joseph D'Ercole, A; Ye, Ping

    2008-12-01

    Signaling through the type 1 IGF receptor (IGF1R) after interaction with IGF-I is crucial to the normal brain development. Manipulations of the mouse genome leading to changes in the expression of IGF-I or IGF1R significantly alters brain growth, such that IGF-I overexpression leads to brain overgrowth, whereas null mutations in either IGF-I or the IGF1R result in brain growth retardation. IGF-I signaling stimulates the proliferation, survival, and differentiation of each of the major neural lineages, neurons, oligodendrocytes, and astrocytes, as well as possibly influencing neural stem cells. During embryonic life, IGF-I stimulates neuron progenitor proliferation, whereas later it promotes neuron survival, neuritic outgrowth, and synaptogenesis. IGF-I also stimulates oligodendrocyte progenitor proliferation although inhibiting apoptosis in oligodendrocyte lineage cells and stimulating myelin production. These pleiotropic IGF-I activities indicate that other factors provide instructive signals for specific cellular events and that IGF-I acts to facilitate them. Studies of the few humans with IGF-I and/or IGF1R gene mutations indicate that IGF-I serves a similar role in man.

  15. Differential regional brain growth and rotation of the prenatal human tentorium cerebelli.

    Science.gov (United States)

    Jeffery, Nathan

    2002-02-01

    Folds of dura mater, the falx cerebri and tentorium cerebelli, traverse the vertebrate endocranial cavity and compartmentalize the brain. Previous studies suggest that the tentorial fold has adopted an increasingly important role in supporting the increased load of the cerebrum during human evolution, brought about by encephalization and an adaptation to bipedal posture. Ontogenetic studies of the fetal tentorium suggest that its midline profile rotates inferoposteriorly towards the foramen magnum in response to disproportionate growth of the cerebrum. This study tests the hypothesis that differential growth of the cerebral and cerebellar components of the brain underlies the inferoposterior rotation of the tentorium cerebelli during human fetal development. Brain volumes and tentorial angles were taken from high-resolution magnetic resonance images of 46 human fetuses ranging from 10 to 29 gestational weeks. Apart from the expected increases of both supratentorial and infratentorial brain volumes with age, the results confirm previous studies showing a significant relative enlargement of the supratentorial volume. Correlated with this enlargement was a rotation of the midline section of the tentorium towards the posterior cranial base. These findings support the concept that increases of supratentorial volume relative to infratentorial volume affect an inferoposterior rotation of the human fetal tentorium cerebelli. These results are discussed in the context of the role played by the tentorium cerebelli during human evolution and underline implications for phylogenetic and ontogenetic models of encephalization.

  16. Halofuginone Inhibits Angiogenesis and Growth in Implanted Metastatic Rat Brain Tumor Model-an MRI Study

    Directory of Open Access Journals (Sweden)

    Rinat Abramovitch

    2004-09-01

    Full Text Available Tumor growth and metastasis depend on angiogenesis; therefore, efforts are made to develop specific angiogenic inhibitors. Halofuginone (HF is a potent inhibitor of collagen type α1(I. In solid tumor models, HF has a potent antitumor and antiangiogenic effect in vivo, but its effect on brain tumors has not yet been evaluated. By employing magnetic resonance imaging (MRI, we monitored the effect of HF on tumor progression and vascularization by utilizing an implanted malignant fibrous histiocytoma metastatic rat brain tumor model. Here we demonstrate that treatment with HF effectively and dose-dependently reduced tumor growth and angiogenesis. On day 13, HF-treated tumors were fivefold smaller than control (P < .001. Treatment with HF significantly prolonged survival of treated animals (142%; P = .001. In HF-treated rats, tumor vascularization was inhibited by 30% on day 13 and by 37% on day 19 (P < .05. Additionally, HF treatment inhibited vessel maturation (P = .03. Finally, in HF-treated rats, we noticed the appearance of a few clusters of satellite tumors, which were distinct from the primary tumor and usually contained vessel cores. This phenomenon was relatively moderate when compared to previous reports of other antiangiogenic agents used to treat brain tumors. We therefore conclude that HF is effective for treatment of metastatic brain tumors.

  17. Radiologic findings of neonatal sepsis

    International Nuclear Information System (INIS)

    Kim, Sam Soo; Han, Dae Hee; Choi, Guk Myeong; Jung, Hye Won; Yoon, Hye Kyung; Han, Bokyung Kim; Lee, Nam Yong

    1997-01-01

    To review the simple radiographic and sonographic findings in infants with neonatal sepsis. We retrospectively analyzed simple chest and abdominal radiographs, and brain sonograms in 36 newborn infants (preterm : term=23 :13). With neonatal sepsis diagnosed by blood culture and clinical manifestations. Pulmonary parenchymal infiltrate excluding respiratory distress syndrome and pulmonary edema or atelectasis was found in 22 infants (61%). Paralytic ileus, hepatosplenomegaly, and necrotizing enterocolitis were present in 18(50%), 9(25%), and 1(3%) infants, respectively, while skeletal changes suggesting osteomyelitis were found in three. Brain sonography was performed in 29 infants and in four, abnormalities were seen ; these comprised three germinal matrix hemorrhages and one intraparenchymal hemorrhage. In six patients(17%) radiologic examinations revealed no abnormality. In patients with neonatal sepsis, pulmonary infiltrates and paralytic ileus were common abnormalities. Although these were nonspecific, radiologic findings may be used to supplement clinical and laboratory findings in diagnosing neonatal sepsis and planning its treatment

  18. Radiologic findings of neonatal sepsis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sam Soo; Han, Dae Hee; Choi, Guk Myeong; Jung, Hye Won [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of); Yoon, Hye Kyung; Han, Bokyung Kim; Lee, Nam Yong [Sansung Medical Center, Seoul (Korea, Republic of)

    1997-06-01

    To review the simple radiographic and sonographic findings in infants with neonatal sepsis. We retrospectively analyzed simple chest and abdominal radiographs, and brain sonograms in 36 newborn infants (preterm : term=23 :13). With neonatal sepsis diagnosed by blood culture and clinical manifestations. Pulmonary parenchymal infiltrate excluding respiratory distress syndrome and pulmonary edema or atelectasis was found in 22 infants (61%). Paralytic ileus, hepatosplenomegaly, and necrotizing enterocolitis were present in 18(50%), 9(25%), and 1(3%) infants, respectively, while skeletal changes suggesting osteomyelitis were found in three. Brain sonography was performed in 29 infants and in four, abnormalities were seen ; these comprised three germinal matrix hemorrhages and one intraparenchymal hemorrhage. In six patients(17%) radiologic examinations revealed no abnormality. In patients with neonatal sepsis, pulmonary infiltrates and paralytic ileus were common abnormalities. Although these were nonspecific, radiologic findings may be used to supplement clinical and laboratory findings in diagnosing neonatal sepsis and planning its treatment.

  19. Regional alterations of brain biogenic amines and GABA/glutamate levels in rats following chronic lead exposure during neonatal development

    Energy Technology Data Exchange (ETDEWEB)

    Shailesh Kumar, M V; Desiraju, T [National Inst. of Mental Health and Neuro Sciences, Bangalore (India). Dept. of Neurophysiology

    1990-06-01

    Wistar rat pups were administered either a high dose of lead acetate (400 {mu}g lead-g body weight/day) or a low dose (100 {mu}g lead/g body weight/day) by gastric intubation, from 2 days through 60 days of age. The rats on both these doses exhibited statistically significant decreases in body and brain weights throughout the lead treatment period. A group of rats on high dose was also rehabilitated by discontinuing the lead from 60 days of age. In these rats, at 160 days of age, the body weight but not the brain weight recovered to normal levels. During the lead intake, the rats on high dose revealed significant elevations in the levels of noradrenaline (NA) in the hippocampus (HI), cerebellum (CE), hypothalamus (HY), brainstem (BS), and accumbens-striatum (SA). The elevated levels in all the above regions except in the HY persisted even after rehabilitation. The dopamine (DA) levels changed significantly in opposite directions in HY (elevation) and BS (reduction) during the lead treatment, and the HY recovered after rehabilitation. Under lead, the serotonin (5HT) levels were elevated significantly in the HI, BS and MC (motor cortex), while after rehabilitation the abnormality persisted only in the MC. Low dose lead treatment was also effective on the same areas of brain. In the low dose group, estimation of the levels of GABA and glutamate were also done, and a significant decrease of GABA in CE and glutamate in MC was observed. The differences observed in the neurotoxic effects (none or significant) of lead in the different regions for each of the transmitters (NA, DA, 5HT) supports the interesting conclusion that the vulnerability of the axon terminals of any given type is dependent on some regional factors, although the projections of the different regions originate from an apparently similar category of neurons in the brain stem. (orig.).

  20. Minocycline Attenuates Neonatal Germinal-Matrix-Hemorrhage-Induced Neuroinflammation and Brain Edema by Activating Cannabinoid Receptor 2.

    Science.gov (United States)

    Tang, Jun; Chen, Qianwei; Guo, Jing; Yang, Liming; Tao, Yihao; Li, Lin; Miao, Hongping; Feng, Hua; Chen, Zhi; Zhu, Gang

    2016-04-01

    Germinal matrix hemorrhage (GMH) is the most common neurological disease of premature newborns leading to detrimental neurological sequelae. Minocycline has been reported to play a key role in neurological inflammatory diseases by controlling some mechanisms that involve cannabinoid receptor 2 (CB2R). The current study investigated whether minocycline reduces neuroinflammation and protects the brain from injury in a rat model of collagenase-induced GMH by regulating CB2R activity. To test this hypothesis, the effects of minocycline and a CB2R antagonist (AM630) were evaluated in male rat pups that were post-natal day 7 (P7) after GMH. We found that minocycline can lead to increased CB2R mRNA expression and protein expression in microglia. Minocycline significantly reduced GMH-induced brain edema, microglial activation, and lateral ventricular volume. Additionally, minocycline enhanced cortical thickness after injury. All of these neuroprotective effects of minocycline were prevented by AM630. A cannabinoid CB2 agonist (JWH133) was used to strengthen the hypothesis, which showed the identical neuroprotective effects of minocycline. Our study demonstrates, for the first time, that minocycline attenuates neuroinflammation and brain injury in a rat model of GMH, and activation of CBR2 was partially involved in these processes.

  1. Recombinant EPF/chaperonin 10 promotes the survival of O4-positive pro-oligodendrocytes prepared from neonatal rat brain.

    Science.gov (United States)

    McCombe, P A

    2008-12-01

    Chaperonin 10 (cpn 10) is a small heat-shock protein that is usually intracellular. Early pregnancy factor (EPF), a biologically active protein that was first described in the serum of pregnant mammals, is homologous to cpn 10. EPF/cpn 10 has been reported to have effects on immunomodulation and cell survival and to inhibit activation of toll-like receptors by lipopolysaccharide. We found that recombinant EPF/cpn 10 was able to suppress experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, which is a disease causing inflammation and demyelination of the brain and spinal cord. This beneficial effect could be due to anti-inflammatory and/or cell survival properties of EPF/cpn 10. We aimed to assess the effects of cpn 10 on cells of the oligodendrocyte lineage because oligodendrocytes are the brain cells that produce myelin and that are depleted in multiple sclerosis. Two forms of recombinant EPF/cpn 10 were prepared in the pGEX expression system and in the baculovirus expression system. Purified O4(+) pro-oligodendrocytes were prepared from the brains of day-old Wistar rats and isolated by cell sorting with flow cytometry. Single cells were dispensed into micro-well plates and tested for survival in the presence of a range of concentrations of the two forms of cpn 10. We also studied the effects of bFGF, PDGF, IGF-1 and insulin as controls. With cpn 10 present, there was enhanced survival of O4(+) cells.

  2. Neonatal nutrition and metabolism

    National Research Council Canada - National Science Library

    Thureen, Patti J; Hay, William W

    2006-01-01

    ..., the volume highlights the important longterm effects of fetal and neonatal growth on health in later life. In addition, there are very practical chapters on methods and techniques for assessing nutritional status, body composition, and evaluating metabolic function. Written by an authoritative, international team of cont...

  3. Intracranial complications of Serratia marcescens infection in neonates.

    Science.gov (United States)

    Madide, Ayanda; Smith, Johan

    2016-03-15

    Even though Serratia marcescens is not one of the most common causes of infection in neonates, it is associated with grave morbidity and mortality. We describe the evolution of brain parenchymal affectation observed in association with S. marcescens infection in neonates. This retrospective case series details brain ultrasound findings of five neonates with hospital-acquired S. marcescens infection. Neonatal S. marcescens infection with or without associated meningitis can be complicated by brain parenchymal affectation, leading to cerebral abscess formation. It is recommended that all neonates with this infection should undergo neuro-imaging more than once before discharge from hospital; this can be achieved using bedside ultrasonography.

  4. Antenatal taurine reduces cerebral cell apoptosis in fetal rats with intrauterine growth restriction.

    Science.gov (United States)

    Liu, Jing; Wang, Xiaofeng; Liu, Ying; Yang, Na; Xu, Jing; Ren, Xiaotun

    2013-08-15

    From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12(th) day of pregnancy, 300 mg/kg rine was daily added to food until spontaneous delivery occurred. Brain tissues from normal neonatal rats at 6 hours after delivery, neonatal rats with intrauterine growth restriction, and neonatal rats with intrauterine growth restriction undergoing taurine supplement were obtained for further experiments. The terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling assay revealed that the number of apoptotic cells in the brain tissue of neonatal rats with intrauterine growth restriction significantly increased. Taurine supplement in pregnant rats reduced cell apoptosis in brain tissue from neonatal rats with intrauterine growth restriction. nohistochemical staining revealed that taurine supplement increased glial cell line-derived neurotrophic factor expression and decreased caspase-3 expression in the cerebral cortex of intrauterine growth-restricted fetal rats. These results indicate that taurine supplement reduces cell apoptosis through the glial cell line-derived neurotrophic factor-caspase-3 signaling pathway, resulting in a protective effect on the intrauterine growth-restricted fetal rat brain.

  5. Vascular endothelial growth factors enhance the permeability of the mouse blood-brain barrier.

    Directory of Open Access Journals (Sweden)

    Shize Jiang

    Full Text Available The blood-brain barrier (BBB impedes entry of many drugs into the brain, limiting clinical efficacy. A safe and efficient method for reversibly increasing BBB permeability would greatly facilitate central nervous system (CNS drug delivery and expand the range of possible therapeutics to include water soluble compounds, proteins, nucleotides, and other large molecules. We examined the effect of vascular endothelial growth factor (VEGF on BBB permeability in Kunming (KM mice. Human VEGF165 was administered to treatment groups at two concentrations (1.6 or 3.0 µg/mouse, while controls received equal-volume saline. Changes in BBB permeability were measured by parenchymal accumulation of the contrast agent Gd-DTPA as assessed by 7 T magnetic resonance imaging (MRI. Mice were then injected with Evans blue, sacrificed 0.5 h later, and perfused transcardially. Brains were removed, fixed, and sectioned for histological study. Both VEGF groups exhibited a significantly greater signal intensity from the cerebral cortex and basal ganglia than controls (P<0.001. Evans blue fluorescence intensity was higher in the parenchyma and lower in the cerebrovasculature of VEGF-treated animals compared to controls. No significant brain edema was observed by diffusion weighted MRI (DWI or histological staining. Exogenous application of VEGF can increase the permeability of the BBB without causing brain edema. Pretreatment with VEGF may be a feasible method to facilitate drug delivery into the CNS.

  6. Brain metastasis in human epidermal growth factor receptor 2-positive breast cancer: from biology to treatment

    Energy Technology Data Exchange (ETDEWEB)

    Koo, Tae Ryool [Dept. of Radiation Oncology, Hallym University Chuncheon Sacred Heart Hospital, Chuncheon (Korea, Republic of); Kim, In Ah [Dept. of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of)

    2016-03-15

    Overexpression of human epidermal growth factor receptor 2 (HER2) is found in about 20% of breast cancer patients. With treatment using trastuzumab, an anti-HER2 monoclonal antibody, systemic control is improved. Nonetheless, the incidence of brain metastasis does not be improved, rather seems to be increased in HER2-positive breast cancer. The mainstay treatment for brain metastases is radiotherapy. According to the number of metastatic lesions and performance status of patients, radiosurgery or whole brain radiotherapy can be performed. The concurrent use of a radiosensitizer further improves intracranial control. Due to its large molecular weight, trastuzumab has a limited ability to cross the blood-brain barrier. However, small tyrosine kinase inhibitors such as lapatinib, has been noted to be a promising agent that can be used as a radiosensitizer to affect HER2-positive breast cancer. This review will outline general management of brain metastases and will focus on preclinical findings regarding the radiosensitizing effect of small molecule HER2 targeting agents.

  7. Immature rat brain slices exposed to oxygen-glucose deprivation as an in vitro model of neonatal hypoxic-ischemic encephalopathy.

    Science.gov (United States)

    Fernández-López, David; Martínez-Orgado, José; Casanova, Ignacio; Bonet, Bartolomé; Leza, Juan Carlos; Lorenzo, Pedro; Moro, Maria Angeles; Lizasoain, Ignacio

    2005-06-30

    To analyze whether exposure to oxygen-glucose deprivation (OGD) of immature rat brain slices might reproduce the main pathophysiologic events leading to neuronal death in neonatal hypoxic-ischemic encephalopathy (NHIE), 500 microm-thick brain slices were obtained from 7-day-old Wistar rats, and incubated in oxygenated physiological solution. In OGD group, oxygen and glucose were removed from the medium for 10-30 min (n = 25); then, slices were re-incubated in normal medium. In control group the medium composition remained unchanged (CG, n = 30). Medium samples were obtained every 30 min for 3 h. To analyze neuronal damage, slices were stained with Nissl and CA1 area of hippocampus and cortex were observed under microscopy. In addition, neuronal death was quantified as LDH released to the medium determined by spectrophotometry. Additionally, medium glutamate (Glu) levels were determined by HPLC and those of TNFalpha by ELISA, whereas inducible nitric oxide synthase expression was determined by Western blot performed on slices homogenate. Optimal OGD time was established in 20 min. After OGD, a significant decrease in the number of neurones in hippocampus and cortex was observed. LDH release was maximal at 30 min, when it was five-fold greater than in CG. Furthermore, medium Glu concentrations were 200 times greater than CG levels at the end of OGD period. A linear relationship between Glu and LDH release was demonstrated. Finally, 3 h after OGD a significant induction of iNOS as well as an increase in TNFalpha release were observed. In conclusion, OGD appears as a feasible and reproducible in vitro model, leading to a neuronal damage, which is physiopathologically similar to that found in NHIE.

  8. Impact of perinatal systemic hypoxic-ischemic injury on the brain of male offspring rats: an improved model of neonatal hypoxic-ischemic encephalopathy in early preterm newborns.

    Directory of Open Access Journals (Sweden)

    Yuejun Huang

    Full Text Available In this study, we attempted to design a model using Sprague-Dawley rats to better reproduce perinatal systemic hypoxic-ischemic encephalopathy (HIE in early preterm newborns. On day 21 of gestation, the uterus of pregnant rats were exposed and the blood supply to the fetuses of neonatal HIE groups were thoroughly abscised by hemostatic clamp for 5, 10 or 15 min. Thereafter, fetuses were moved from the uterus and manually stimulated to initiate breathing in an incubator at 37 °C for 1 hr in air. We showed that survival rates of offspring rats were decreased with longer hypoxic time. TUNEL staining showed that apoptotic cells were significant increased in the brains of offspring rats from the 10 min and 15 min HIE groups as compared to the offspring rats in the control group at postnatal day (PND 1, but there was no statistical difference between the offspring rats in the 5 min HIE and control groups. The perinatal hypoxic treatment resulted in decreased neurons and increased cleaved caspase-3 protein levels in the offspring rats from all HIE groups at PND 1. Platform crossing times and the percentage of the time spent in the target quadrant of Morris Water Maze test were significantly reduced in the offspring rats of all HIE groups at PND 30, which were associated with decreased brain-derived neurotrophic factor levels and neuronal cells in the hippocampus of offspring rats at PND 35. These data demonstrated that perinatal ischemic injury led to the death of neuronal cells and long-lasting impairment of memory. This model reproduced hypoxic ischemic encephalopathy in early preterm newborns and may be appropriate for investigating therapeutic interventions.

  9. Impact of Perinatal Systemic Hypoxic–Ischemic Injury on the Brain of Male Offspring Rats: An Improved Model of Neonatal Hypoxic–Ischemic Encephalopathy in Early Preterm Newborns

    Science.gov (United States)

    Xu, Hongwu; Wu, Weizhao; Lai, Xiulan; Ho, Guyu; Ma, Lian; Chen, Yunbin

    2013-01-01

    In this study, we attempted to design a model using Sprague-Dawley rats to better reproduce perinatal systemic hypoxic-ischemic encephalopathy (HIE) in early preterm newborns. On day 21 of gestation, the uterus of pregnant rats were exposed and the blood supply to the fetuses of neonatal HIE groups were thoroughly abscised by hemostatic clamp for 5, 10 or 15 min. Thereafter, fetuses were moved from the uterus and manually stimulated to initiate breathing in an incubator at 37 °C for 1 hr in air. We showed that survival rates of offspring rats were decreased with longer hypoxic time. TUNEL staining showed that apoptotic cells were significant increased in the brains of offspring rats from the 10 min and 15 min HIE groups as compared to the offspring rats in the control group at postnatal day (PND) 1, but there was no statistical difference between the offspring rats in the 5 min HIE and control groups. The perinatal hypoxic treatment resulted in decreased neurons and increased cleaved caspase-3 protein levels in the offspring rats from all HIE groups at PND 1. Platform crossing times and the percentage of the time spent in the target quadrant of Morris Water Maze test were significantly reduced in the offspring rats of all HIE groups at PND 30, which were associated with decreased brain-derived neurotrophic factor levels and neuronal cells in the hippocampus of offspring rats at PND 35. These data demonstrated that perinatal ischemic injury led to the death of neuronal cells and long-lasting impairment of memory. This model reproduced hypoxic ischemic encephalopathy in early preterm newborns and may be appropriate for investigating therapeutic interventions. PMID:24324800

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

    Directory of Open Access Journals (Sweden)

    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

  11. Relationship of maternal mean platelet volume with fetal Doppler parameters and neonatal complications in pregnancies with and without intrauterine growth restriction.

    Science.gov (United States)

    Ureyen, Isin; Ozyuncu, Ozgur; Sahin-Uysal, Nihal; Kara, Ozgur; Basaran, Derman; Turgal, Mert; Deren, Ozgur

    2017-02-01

    In this study, we investigated the relationship of mean platelet volume (MPV) with the presence and the severity of intrauterine growth restriction (IUGR) and with neonatal complications. The pregnancies with and without IUGR, that were followed-up in our hospital between 2003 and 2009 were analyzed retrospectively. Pregnancies which resulted in birth of a newborn with a birthweight less than 10th percentile for the gestational age were selected for IUGR group. IUGR cases were divided into three groups according to the Doppler parameters. There was no significant difference between the MPV values in the groups. There was no association between MPV and Doppler parameters that can be used in predicting the severity of IUGR. There was no significant relation between MPV and the perinatal complications such as intracranial hemorrhage (ICH), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), the development of sepsis, postpartum exitus (PPEX) and intrauterine exitus (IUEX). Higher MPV values were associated with hospitalization in the neonatal intensive care unit (NICU) and respiratory distress syndrome (RDS) in the IUGR group. Analysis of MPV is a simple and readily available laboratory test. Prospective researches employing standard measurement technics are required to clarify the relationship between MPV and IUGR.

  12. Relationship between relative cerebral blood flow, relative cerebral blood volume, and relative cerebral metabolic rate of oxygen in the preterm neonatal brain.

    Science.gov (United States)

    Nourhashemi, Mina; Kongolo, Guy; Mahmoudzadeh, Mahdi; Goudjil, Sabrina; Wallois, Fabrice

    2017-04-01

    The mechanisms responsible for coupling between relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), and relative cerebral metabolic rate of oxygen ([Formula: see text]), an important function of the microcirculation in preterm infants, remain unclear. Identification of a causal relationship between rCBF-rCBV and [Formula: see text] in preterms may, therefore, help to elucidate the principles of cortical hemodynamics during development. We simultaneously recorded rCBF and rCBV and estimated [Formula: see text] by two independent acquisition systems: diffuse correlation spectroscopy and near-infrared spectroscopy, respectively, in 10 preterms aged between 28 and 35 weeks of gestational age. Transfer entropy was calculated in order to determine the directionality between rCBF-rCBV and [Formula: see text]. The surrogate method was applied to determine statistical significance. The results show that rCBV and [Formula: see text] have a predominant driving influence on rCBF at the resting state in the preterm neonatal brain. Statistical analysis robustly detected the correct directionality of rCBV on rCBF and [Formula: see text] on rCBF. This study helps to clarify the early organization of the rCBV-rCBF and [Formula: see text] inter-relationship in the immature cortex.

  13. STATISTICAL GROWTH MODELING OF LONGITUDINAL DT-MRI FOR REGIONAL CHARACTERIZATION OF EARLY BRAIN DEVELOPMENT.

    Science.gov (United States)

    Sadeghi, Neda; Prastawa, Marcel; Fletcher, P Thomas; Gilmore, John H; Lin, Weili; Gerig, Guido

    2012-01-01

    A population growth model that represents the growth trajectories of individual subjects is critical to study and understand neurodevelopment. This paper presents a framework for jointly estimating and modeling individual and population growth trajectories, and determining significant regional differences in growth pattern characteristics applied to longitudinal neuroimaging data. We use non-linear mixed effect modeling where temporal change is modeled by the Gompertz function. The Gompertz function uses intuitive parameters related to delay, rate of change, and expected asymptotic value; all descriptive measures which can answer clinical questions related to growth. Our proposed framework combines nonlinear modeling of individual trajectories, population analysis, and testing for regional differences. We apply this framework to the study of early maturation in white matter regions as measured with diffusion tensor imaging (DTI). Regional differences between anatomical regions of interest that are known to mature differently are analyzed and quantified. Experiments with image data from a large ongoing clinical study show that our framework provides descriptive, quantitative information on growth trajectories that can be directly interpreted by clinicians. To our knowledge, this is the first longitudinal analysis of growth functions to explain the trajectory of early brain maturation as it is represented in DTI.

  14. Tuberculosis neonatal

    OpenAIRE

    Pastor Durán, Xavier

    1986-01-01

    PROTOCOLOS TERAPEUTICOS. TUBERCULOSIS NEONATAL 1. CONCEPTO La tuberculosis neonatal es la infección del recién nacido producida por el bacilo de Koch. Es una situación rara pero grave que requiere un diagnóstico precoz y un tratamiento enérgico..

  15. Neonatal erythropoietin mitigates impaired gait, social interaction and diffusion tensor imaging abnormalities in a rat model of prenatal brain injury.

    Science.gov (United States)

    Robinson, Shenandoah; Corbett, Christopher J; Winer, Jesse L; Chan, Lindsay A S; Maxwell, Jessie R; Anstine, Christopher V; Yellowhair, Tracylyn R; Andrews, Nicholas A; Yang, Yirong; Sillerud, Laurel O; Jantzie, Lauren L

    2018-04-01

    Children who are born preterm are at risk for encephalopathy of prematurity, a leading cause of cerebral palsy, cognitive delay and behavioral disorders. Current interventions are limited and none have been shown to reverse cognitive and behavioral impairments, a primary determinant of poor quality of life for these children. Moreover, the mechanisms of perinatal brain injury that result in functional deficits and imaging abnormalities in the mature brain are poorly defined, limiting the potential to target interventions to those who may benefit most. To determine whether impairments are reversible after a prenatal insult, we investigated a spectrum of functional deficits and diffusion tensor imaging (DTI) abnormalities in young adult animals. We hypothesized that prenatal transient systemic hypoxia-ischemia (TSHI) would induce multiple functional deficits concomitant with reduced microstructural white and gray matter integrity, and tested whether these abnormalities could be ameliorated using postnatal erythropoietin (EPO), an emerging neurorestorative intervention. On embryonic day 18 uterine arteries were transiently occluded for 60min via laparotomy. Shams underwent anesthesia and laparotomy for 60min. Pups were born and TSHI pups were randomized to receive EPO or vehicle via intraperitoneal injection on postnatal days 1 to 5. Gait, social interaction, olfaction and open field testing was performed from postnatal day 25-35 before brains underwent ex vivo DTI to measure fractional anisotropy, axial diffusivity and radial diffusivity. Prenatal TSHI injury causes hyperactivity, impaired gait and poor social interaction in young adult rats that mimic the spectrum of deficits observed in children born preterm. Collectively, these data show for the first time in a model of encephalopathy of prematurity that postnatal EPO treatment mitigates impairments in social interaction, in addition to gait deficits. EPO also normalizes TSHI-induced microstructural abnormalities

  16. Posttraumatic growth following acquired brain injury: A systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Elaine Louise Kinsella

    2015-08-01

    Full Text Available The idea that acquired brain injury (ABI caused by stroke, haemorrhage, infection or traumatic insult to the brain can result in posttraumatic growth (PTG for individuals is increasingly attracting psychological attention. However PTG also attracts controversy as a result of ambiguous empirical findings. The extent that demographic variables, injury factors, subjective beliefs, and psychological health are associated with PTG following ABI is not clear. Consequently, this systematic review and meta-analysis explores the correlates of variables within these four broad areas and PTG. From a total of 744 published studies addressing PTG in people with ABI, eight studies met inclusion criteria for detailed examination. Meta-analysis of these studies indicated that growth was related to employment, longer education, subjective beliefs about change post-injury, relationship status, older age, longer time since injury, and lower levels of depression. Results from homogeneity analyses indicated significant inter-study heterogeneity across variables. There is general support for the idea that people with ABI can experience growth, and that various demographics, injury-related variables, subjective beliefs and psychological health are related to growth. The contribution of social integration and the forming of new identities post-ABI to the experience of PTG is explored. These meta-analytic findings are however constrained by methodological limitations prevalent in the literature. Clinical and research implications are discussed with specific reference to community and collective factors that enable PTG.

  17. Differential effect of maternal diet supplementation with α-Linolenic adcid or n-3 long-chain polyunsaturated fatty acids on glial cell phosphatidylethanolamine and phosphatidylserine fatty acid profile in neonate rat brains

    Directory of Open Access Journals (Sweden)

    Cruz-Hernandez Cristina

    2010-01-01

    Full Text Available Abstract Background Dietary long-chain polyunsaturated fatty acids (LC-PUFA are of crucial importance for the development of neural tissues. The aim of this study was to evaluate the impact of a dietary supplementation in n-3 fatty acids in female rats during gestation and lactation on fatty acid pattern in brain glial cells phosphatidylethanolamine (PE and phosphatidylserine (PS in the neonates. Methods Sprague-Dawley rats were fed during the whole gestation and lactation period with a diet containing either docosahexaenoic acid (DHA, 0.55% and eicosapentaenoic acid (EPA, 0.75% of total fatty acids or α-linolenic acid (ALA, 2.90%. At two weeks of age, gastric content and brain glial cell PE and PS of rat neonates were analyzed for their fatty acid and dimethylacetal (DMA profile. Data were analyzed by bivariate and multivariate statistics. Results In the neonates from the group fed with n-3 LC-PUFA, the DHA level in gastric content (+65%, P Conclusion The present study confirms that early supplementation of maternal diet with n-3 fatty acids supplied as LC-PUFA is more efficient in increasing n-3 in brain glial cell PE and PS in the neonate than ALA. Negative correlation between n-6 DPA, a conventional marker of DHA deficiency, and DMA in PE suggests n-6 DPA that potentially be considered as a marker of tissue ethanolamine plasmalogen status. The combination of multivariate and bivariate statistics allowed to underline that the accretion pattern of n-3 LC-PUFA in PE and PS differ.

  18. Effects of Antenatal Maternal Depressive Symptoms and Socio-Economic Status on Neonatal Brain Development are Modulated by Genetic Risk.

    Science.gov (United States)

    Qiu, Anqi; Shen, Mojun; Buss, Claudia; Chong, Yap-Seng; Kwek, Kenneth; Saw, Seang-Mei; Gluckman, Peter D; Wadhwa, Pathik D; Entringer, Sonja; Styner, Martin; Karnani, Neerja; Heim, Christine M; O'Donnell, Kieran J; Holbrook, Joanna D; Fortier, Marielle V; Meaney, Michael J

    2017-05-01

    This study included 168 and 85 mother-infant dyads from Asian and United States of America cohorts to examine whether a genomic profile risk score for major depressive disorder (GPRSMDD) moderates the association between antenatal maternal depressive symptoms (or socio-economic status, SES) and fetal neurodevelopment, and to identify candidate biological processes underlying such association. Both cohorts showed a significant interaction between antenatal maternal depressive symptoms and infant GPRSMDD on the right amygdala volume. The Asian cohort also showed such interaction on the right hippocampal volume and shape, thickness of the orbitofrontal and ventromedial prefrontal cortex. Likewise, a significant interaction between SES and infant GPRSMDD was on the right amygdala and hippocampal volumes and shapes. After controlling for each other, the interaction effect of antenatal maternal depressive symptoms and GPRSMDD was mainly shown on the right amygdala, while the interaction effect of SES and GPRSMDD was mainly shown on the right hippocampus. Bioinformatic analyses suggested neurotransmitter/neurotrophic signaling, SNAp REceptor complex, and glutamate receptor activity as common biological processes underlying the influence of antenatal maternal depressive symptoms on fetal cortico-limbic development. These findings suggest gene-environment interdependence in the fetal development of brain regions implicated in cognitive-emotional function. Candidate biological mechanisms involve a range of brain region-specific signaling pathways that converge on common processes of synaptic development. © The Author 2017. Published by Oxford University Press.

  19. Effects of brain-derived neurotrophic factor (BDNF) on the cochlear nucleus in cats deafened as neonates.

    Science.gov (United States)

    Kandathil, Cherian K; Stakhovskaya, Olga; Leake, Patricia A

    2016-12-01

    Many previous studies have shown significant neurotrophic effects of intracochlear delivery of BDNF in preventing degeneration of cochlear spiral ganglion (SG) neurons after deafness in rodents and our laboratory has shown similar results in developing cats deafened prior to hearing onset. This study examined the morphology of the cochlear nucleus (CN) in a group of neonatally deafened cats from a previous study in which infusion of BDNF elicited a significant improvement in survival of the SG neurons. Five cats were deafened by systemic injections of neomycin sulfate (60 mg/kg, SQ, SID) starting one day after birth, and continuing for 16-18 days until auditory brainstem response (ABR) testing demonstrated profound bilateral hearing loss. The animals were implanted unilaterally at about 1 month of age using custom-designed electrodes with a drug-delivery cannula connected to an osmotic pump. BDNF (94 μg/ml; 0.25 μl/hr) was delivered for 10 weeks. The animals were euthanized and studied at 14-23 weeks of age. Consistent with the neurotrophic effects of BDNF on SG survival, the total CN volume in these animals was significantly larger on the BDNF-treated side than on the contralateral side. However, total CN volume, both ipsi- and contralateral to the implants in these deafened juvenile animals, was markedly smaller than the CN in normal adult animals, reflecting the severe effects of deafness on the central auditory system during development. Data from the individual major CN subdivisions (DCN, Dorsal Cochlear Nucleus; PVCN, Posteroventral Cochlear Nucleus; AVCN, Anteroventral Cochlear Nucleus) also were analyzed. A significant difference was observed between the BDNF-treated and control sides only in the AVCN. Measurements of the cross-sectional areas of spherical cells showed that cells were significantly larger in the AVCN ipsilateral to the implant than on the contralateral side. Further, the numerical density of spherical cells was significantly lower in

  20. Human blood-brain barrier insulin-like growth factor receptor

    International Nuclear Information System (INIS)

    Duffy, K.R.; Pardridge, W.M.; Rosenfeld, R.G.

    1988-01-01

    Insulin-like growth factor (IGF)-1 and IGF-2, may be important regulatory molecules in the CNS. Possible origins of IGFs in brain include either de novo synthesis or transport of circulating IGFs from blood into brain via receptor mediated transcytosis mechanisms at the brain capillary endothelial wall, ie, the blood-brain barrier (BBB). In the present studies, isolated human brain capillaries are used as an in vitro model system of the human BBB and the characteristics of IGF-1 or IGF-2 binding to this preparation were assessed. The total binding of IGF-2 at 37 degrees C exceeded 130% per mg protein and was threefold greater than the total binding for IGF-1. However, at 37 degrees C nonsaturable binding equaled total binding, suggesting that endocytosis is rate limiting at physiologic temperatures. Binding studies performed at 4 degrees C slowed endocytosis to a greater extent than membrane binding, and specific binding of either IGF-1 or IGF-2 was detectable. Scatchard plots for either peptide were linear and the molar dissociation constant of IGF-1 and IGF-2 binding was 2.1 +/- 0.4 and 1.1 +/- 0.1 nmol/L, respectively. Superphysiologic concentrations of porcine insulin inhibited the binding of both IGF-1 (ED50 = 2 micrograms/mL) and IGF-2 (ED50 = 0.5 microgram/mL). Affinity cross linking of 125 I-IGF-1, 125 I-IGF-2, and 125 I-insulin to isolated human brain capillaries was performed using disuccinimidylsuberate (DSS). These studies revealed a 141 kd binding site for both IGF-1 and IGF-2, and a 133 kd binding site for insulin

  1. Mathematical modeling of human glioma growth based on brain topological structures: study of two clinical cases.

    Directory of Open Access Journals (Sweden)

    Cecilia Suarez

    Full Text Available Gliomas are the most common primary brain tumors and yet almost incurable due mainly to their great invasion capability. This represents a challenge to present clinical oncology. Here, we introduce a mathematical model aiming to improve tumor spreading capability definition. The model consists in a time dependent reaction-diffusion equation in a three-dimensional spatial domain that distinguishes between different brain topological structures. The model uses a series of digitized images from brain slices covering the whole human brain. The Talairach atlas included in the model describes brain structures at different levels. Also, the inclusion of the Brodmann areas allows prediction of the brain functions affected during tumor evolution and the estimation of correlated symptoms. The model is solved numerically using patient-specific parametrization and finite differences. Simulations consider an initial state with cellular proliferation alone (benign tumor, and an advanced state when infiltration starts (malign tumor. Survival time is estimated on the basis of tumor size and location. The model is used to predict tumor evolution in two clinical cases. In the first case, predictions show that real infiltrative areas are underestimated by current diagnostic imaging. In the second case, tumor spreading predictions were shown to be more accurate than those derived from previous models in the literature. Our results suggest that the inclusion of differential migration in glioma growth models constitutes another step towards a better prediction of tumor infiltration at the moment of surgical or radiosurgical target definition. Also, the addition of physiological/psychological considerations to classical anatomical models will provide a better and integral understanding of the patient disease at the moment of deciding therapeutic options, taking into account not only survival but also life quality.

  2. Mesenchymal stem cells support neuronal fiber growth in an organotypic brain slice co-culture model.

    Science.gov (United States)

    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.

  3. Growth hormone treatment and risk of recurrence or progression of brain tumors in children: a review.

    Science.gov (United States)

    Bogarin, Roberto; Steinbok, Paul

    2009-03-01

    Brain tumors are one of the most common types of solid neoplasm in children. As life expectancy of these patients has increased with new and improved therapies, the morbidities associated with the treatments and the tumor itself have become more important. One of the most common morbidities is growth hormone deficiency, and since recombinant growth hormone (GH) became available, its use has increased exponentially. There is concern that in the population of children with brain tumors, GH treatment might increase the risk of tumor recurrence or progression or the appearance of a second neoplasm. In the light of this ongoing concern, the current literature has been reviewed to provide an update on the risk of tumor recurrence, tumor progression, or new intracranial tumor formation when GH is used to treat GH deficiency in children, who have had or have intracranial tumors. On the basis of this review, the authors conclude that the use of GH in patients with brain tumor is safe. GH therapy is not associated with an increased risk of central nervous system tumor progression or recurrence, leukemia (de novo or relapse), or extracranial non-leukemic neoplasms.

  4. Insulin and insulin-like growth factor receptors in the brain: physiological and pathological aspects.

    Science.gov (United States)

    Werner, Haim; LeRoith, Derek

    2014-12-01

    The involvement of insulin, the insulin-like growth factors (IGF1, IGF2) and their receptors in central nervous system development and function has been the focus of scientific interest for more than 30 years. The insulin-like peptides, both locally-produced proteins as well as those transported from the circulation into the brain via the blood-brain barrier, are involved in a myriad of biological activities. These actions include, among others, neuronal survival, neurogenes, angiogenesis, excitatory and inhibitory neurotransmission, regulation of food intake, and cognition. In recent years, a linkage between brain insulin/IGF1 and certain neuropathologies has been identified. Epidemiological studies have demonstrated a correlation between diabetes (mainly type 2) and Alzheimer׳s disease. In addition, an aberrant decline in IGF1 values was suggested to play a role in the development of Alzheimer׳s disease. The present review focuses on the expression and function of insulin, IGFs and their receptors in the brain in physiological and pathological conditions. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  5. Neonatal hypertension.

    Science.gov (United States)

    Sharma, Deepak; Farahbakhsh, Nazanin; Shastri, Sweta; Sharma, Pradeep

    2017-03-01

    Neonatal hypertension (HT) is a frequently under reported condition and is seen uncommonly in the intensive care unit. Neonatal HT has defined arbitrarily as blood pressure more than 2 standard deviations above the base as per the age or defined as systolic BP more than 95% for infants of similar size, gestational age and postnatal age. It has been diagnosed long back but still is the least studied field in neonatology. There is still lack of universally accepted normotensive data for neonates as per gestational age, weight and post-natal age. Neonatal HT is an important morbidity that needs timely detection and appropriate management, as it can lead to devastating short-term effect on various organs and also poor long-term adverse outcomes. There is no consensus yet about the treatment guidelines and majority of treatment protocols are based on the expert opinion. Neonate with HT should be evaluated in detail starting from antenatal, perinatal, post-natal history, and drug intake by neonate and mother. This review article covers multiple aspects of neonatal hypertension like definition, normotensive data, various etiologies and methods of BP measurement, clinical features, diagnosis and management.

  6. Neonatal retinoblastoma

    Directory of Open Access Journals (Sweden)

    Tero T Kivelä

    2017-01-01

    Full Text Available From 7% to 10% of all retinoblastomas and from 44% to 71% of familial retinoblastomas in developed countries are diagnosed in the neonatal period, usually through pre- or post-natal screening prompted by a positive family history and sometimes serendipitously during screening for retinopathy of prematurity or other reasons. In developing countries, neonatal diagnosis of retinoblastoma has been less common. Neonatal retinoblastoma generally develops from a germline mutation of RB1, the retinoblastoma gene, even when the family history is negative and is thus usually hereditary. At least one-half of infants with neonatal retinoblastoma have unilateral tumors when the diagnosis is made, typically the International Intraocular Retinoblastoma Classification (Murphree Group B or higher, but most germline mutation carriers will progress to bilateral involvement, typically Group A in the fellow eye. Neonatal leukokoria usually leads to the diagnosis in children without a family history of retinoblastoma, and a Group C tumor or higher is typical in the more advanced involved eye. Almost all infants with neonatal retinoblastoma have at least one eye with a tumor in proximity to the foveola, but the macula of the fellow eye is frequently spared. Consequently, loss of reading vision from both eyes is exceptional. A primary ectopic intracranial neuroblastic tumor known as trilateral retinoblastoma is no more common after neonatal than other retinoblastoma. For many reasons, neonatal retinoblastoma may be a challenge to eradicate, and the early age at diagnosis and relatively small tumors do not guarantee the preservation of both eyes of every involved child. Oncology nurses can be instrumental in contributing to better outcomes by ensuring that hereditary retinoblastoma survivors receive genetic counseling, by referring families of survivors to early screening programs when they are planning for a baby, and by providing psychological and practical support

  7. Implanting Glioblastoma Spheroids into Rat Brains and Monitoring Tumor Growth by MRI Volumetry.

    Science.gov (United States)

    Löhr, Mario; Linsenmann, Thomas; Jawork, Anna; Kessler, Almuth F; Timmermann, Nils; Homola, György A; Ernestus, Ralf-Ingo; Hagemann, Carsten

    2017-01-01

    The outcome of patients suffering from glioblastoma multiforme (GBM) remains poor with a median survival of less than 15 months. To establish innovative therapeutical approaches or to analyze the effect of protein overexpression or protein knockdown by RNA interference in vivo, animal models are mandatory. Here, we describe the implantation of C6 glioma spheroids into the rats' brain and how to follow tumor growth by MRI scans. We show that C6 cells grown in Sprague-Dawley rats share several morphologic features of human glioblastoma like pleomorphic cells, areas of necrosis, vascular proliferation, and tumor cell invasion into the surrounding brain tissue. In addition, we describe a method for tumor volumetry utilizing the CISS 3D- or contrast-enhanced T1-weighted 3D sequence and freely available post-processing software.

  8. The mating brain: early maturing sneaker males maintain investment into the brain also under fast body growth in Atlantic salmon (Salmo salar).

    Science.gov (United States)

    Kotrschal, Alexander; Trombley, Susanne; Rogell, Björn; Brannström, Ioana; Foconi, Eric; Schmitz, Monika; Kolm, Niclas

    It has been suggested that mating behaviours require high levels of cognitive ability. However, since investment into mating and the brain both are costly features, their relationship is likely characterized by energetic trade-offs. Empirical data on the subject remains equivocal. We investigated if early sexual maturation was associated with brain development in Atlantic salmon ( Salmo salar ), in which males can either stay in the river and sexually mature at a small size (sneaker males) or migrate to the sea and delay sexual maturation until they have grown much larger (anadromous males). Specifically, we tested how sexual maturation may induce plastic changes in brain development by rearing juveniles on either natural or ad libitum feeding levels. After their first season we compared brain size and brain region volumes across both types of male mating tactics and females. Body growth increased greatly across both male mating tactics and females during ad libitum feeding as compared to natural feeding levels. However, despite similar relative increases in body size, early maturing sneaker males maintained larger relative brain size during ad libitum feeding levels as compared to anadromous males and females. We also detected several differences in the relative size of separate brain regions across feeding treatments, sexes and mating strategies. For instance, the relative size of the cognitive centre of the brain, the telencephalon, was largest in sneaker males. Our data support that a large relative brain size is maintained in individuals that start reproduction early also during fast body growth. We propose that the cognitive demands during complex mating behaviours maintain a high level of investment into brain development in reproducing individuals.

  9. Neonatal domoic acid decreases in vivo binding of [11C]yohimbine to α2 adrenoceptors in adult rat brain

    DEFF Research Database (Denmark)

    Thomsen, Majken; Lillethorup, Thea Pinholt; Jakobsen, Steen

    -quantitative analysis. MicroPET images were analyzed using PMOD software and registered to an average Sprague-Dawley rat MRI brain atlas to acquire data in limbic and cortical regions of interest. Results: In behavioural testing DOM60, and to a lesser extent DOM20 rats, spent more time in the periphery during the open......-Dawley rats (n=6-7 per group) were injected (s.c.) daily from postnatal day 8-14 with saline or one of two low sub-convulsive doses, 20µg/kg [DOM20] or 60µg/kg [DOM60] of DOM, an AMPA/kainate receptor agonist. The behaviour of the rats was observed in an open field test, a social interaction test...... and the forced swim test at day 50, 75 and 98, respectively. At ~120 days of age 3-4 rats per group were injected with [11C]yohimbine, an α2 adrenergic receptor antagonist, and scanned in a Mediso micro positron emission tomography (PET) scanner, to measure α2 adrenoceptor binding. The volume of distribution (VT...

  10. Neonatal hypocalcemia, neonatal seizures, and intellectual disability in 22q11.2 deletion syndrome

    Science.gov (United States)

    Cheung, Evelyn Ning Man; George, Susan R.; Andrade, Danielle M.; Chow, Eva W. C.; Silversides, Candice K.; Bassett, Anne S.

    2015-01-01

    Purpose Hypocalcemia is a common endocrinological condition in 22q11.2 deletion syndrome. Neonatal hypocalcemia may affect neurodevelopment. We hypothesized that neonatal hypocalcemia would be associated with rare, more severe forms of intellectual disability in 22q11.2 deletion syndrome. Methods We used a logistic regression model to investigate potential predictors of intellectual disability severity, including neonatal hypocalcemia, neonatal seizures, and complex congenital heart disease, e.g., interrupted aortic arch, in 149 adults with 22q11.2 deletion syndrome. Ten subjects had moderate-to-severe intellectual disability. Results The model was highly significant (P < 0.0001), showing neonatal seizures (P = 0.0018) and neonatal hypocalcemia (P = 0.047) to be significant predictors of a more severe level of intellectual disability. Neonatal seizures were significantly associated with neonatal hypocalcemia in the entire sample (P < 0.0001), regardless of intellectual level. There was no evidence for the association of moderate- to-severe intellectual disability with other factors such as major structural brain malformations in this sample. Conclusion The results suggest that neonatal seizures may increase the risk for more severe intellectual deficits in 22q11.2 deletion syndrome, likely mediated by neonatal hypocalcemia. Neonatal hypocalcemia often remains unrecognized until the postseizure period, when damage to neurons may already have occurred. These findings support the importance of early recognition and treatment of neonatal hypocalcemia and potentially neonatal screening for 22q11.2 deletions. PMID:23765047

  11. Effect of enteral IGF-1 supplementation on feeding tolerance, growth, and gut permeability in enterally fed premature neonates

    NARCIS (Netherlands)

    Corpeleijn, Willemijn E.; van Vliet, Ineke; de Gast-Bakker, Dana-Anne H.; van der Schoor, Sophie R. D.; Alles, Martine S.; Hoijer, Maarten; Tibboel, Dick; van Goudoever, Johannes B.

    2008-01-01

    The gastrointestinal tract of the premature newborn functions suboptimally with regard to digestion, absorption, and feeding tolerance. Human milk contains trophic factors, such as insulin-like growth factor-1 (IGF-1), that are believed to stimulate gut growth and function. The objective of this

  12. Comparison of the effects of radiation and hyperthermia on prenatal retardation of brain growth of guinea-pigs

    International Nuclear Information System (INIS)

    Wanner, R.A.; Edwards, M.J.

    1983-01-01

    On day 21 of pregnancy guinea-pigs were exposed to hyperthermia or #betta# radiation. The effects on prenatal growth and especially brain growth of offspring were compared. Doses of 0.04-0.99 Gy of radiation produced a dose-dependent and irreversible reduction of brainweight in the offspring, but had little effect on body weight. Treatment with hyperthermia resulting in maternal temperatures of 41.8-43.9 0 C after exposure in a heated incubator for an hour also produced a dose-related micrencephaly in the offspring. Comparison of the two agents showed that a dose increment of 0.525 Gy of radiation produced a deficit in brain weight equivalent to an elevation of 1 0 C in maternal temperature. Using this guinea-pig brain weight assay system a threshold was detected of between 0.05 and 0.10 Gy for retardation of brain growth. (author)

  13. Cerebral oxygenation in the preterm neonate

    NARCIS (Netherlands)

    Dix, L.M.L.

    2017-01-01

    Although survival rates of preterm infants are improving, preterm birth is still associated with significant morbidity.The brain is one of the most vulnerable organs in preterm infants. Neonatal brain injury can have a large impact on the quality of life. Monitoring the immature brain is therefore

  14. Vascular endothelial growth factor-A determines detectability of experimental melanoma brain metastasis in GD-DTPA-enhanced MRI.

    NARCIS (Netherlands)

    Leenders, W.P.J.; Kusters, B.; Pikkemaat, J.A.; Wesseling, P.; Ruiter, D.J.; Heerschap, A.; Barentsz, J.O.; Waal, R.M.W. de

    2003-01-01

    We have previously shown that the dense vascular network in mouse brain allows for growth of human melanoma xenografts (Mel57) by co-option of preexisting vessels. Overexpression of recombinant vascular endothelial growth factor-A (VEGF-A) by such xenografts induced functional and morphologic

  15. Neonatal Nursing

    OpenAIRE

    Crawford, Doreen; Morris, Maryke

    1994-01-01

    "Neonatal Nursing" offers a systematic approach to the nursing care of the sick newborn baby. Nursing actions and responsibilities are the focus of the text with relevant research findings, clinical applications, anatomy, physiology and pathology provided where necessary. This comprehensive text covers all areas of neonatal nursing including ethics, continuing care in the community, intranatal care, statistics and pharmokinetics so that holistic care of the infant is described. This book shou...

  16. Identification of Transmembrane Protease Serine 2 and Forkhead Box A1 As the Potential Bisphenol A Responsive Genes in the Neonatal Male Rat Brain

    Directory of Open Access Journals (Sweden)

    Takayoshi Ubuka

    2018-03-01

    Full Text Available Perinatal exposure of Bisphenol A (BPA to rodents modifies their behavior in later life. To understand how BPA modifies their neurodevelopmental process, we first searched for BPA responsive genes from androgen and estrogen receptor signaling target genes by polymerase chain reaction array in the neonatal male rat brain. We used a transgenic strain of Wistar rats carrying enhanced green fluorescent protein tagged to gonadotropin-inhibitory hormone (GnIH promoter to investigate the possible interaction of BPA responsive genes and GnIH neurons. We found upregulation of transmembrane protease serine 2 (Tmprss2, an androgen receptor signaling target gene, and downregulation of Forkhead box A1 (Foxa1, an ER signaling target gene, in the medial amygdala of male rats that were subcutaneously administered with BPA from day 1 to 3. Tmprss2-immunoreactive (ir cells were distributed in the olfactory bulb, cerebral cortex, hippocampus, amygdala, and hypothalamus in 3 days old but not in 1-month-old male rats. Density of Tmprss2-ir cells in the medial amygdala was increased by daily administration of BPA from day 1 to 3. Tmprss2 immunoreactivity was observed in 26.5% of GnIH neurons clustered from the ventral region of the ventromedial hypothalamic nucleus to the dorsal region of the arcuate nucleus of 3-day-old male rat hypothalamus. However, Tmprss2 mRNA expression significantly decreased in the amygdala and hypothalamus of 1-month-old male rats. Foxa1 mRNA expression was higher in the hypothalamus than the amygdala in 3 days old male rats. Intense Foxa1-ir cells were only found in the peduncular part of lateral hypothalamus of 3-day-old male rats. Density of Foxa1-ir cells in the hypothalamus was decreased by daily administration of BPA from day 1 to 3. Foxa1 mRNA expression in the hypothalamus also significantly decreased at 1 month. These results suggest that BPA disturbs the neurodevelopmental process and behavior of rats later in their life by

  17. Visual-motor integration and fine motor skills at 6½ years of age and associations with neonatal brain volumes in children born extremely preterm in Sweden: a population-based cohort study.

    Science.gov (United States)

    Bolk, Jenny; Padilla, Nelly; Forsman, Lea; Broström, Lina; Hellgren, Kerstin; Åden, Ulrika

    2018-02-17

    This exploratory study aimed to investigate associations between neonatal brain volumes and visual-motor integration (VMI) and fine motor skills in children born extremely preterm (EPT) when they reached 6½ years of age. Prospective population-based cohort study in Stockholm, Sweden, during 3 years. All children born before gestational age, 27 weeks, during 2004-2007 in Stockholm, without major morbidities and impairments, and who underwent MRI at term-equivalent age. Brain volumes were calculated using morphometric analyses in regions known to be involved in VMI and fine motor functions. VMI was assessed with The Beery-Buktenica Developmental Test of Visual-Motor Integration-sixth edition and fine motor skills were assessed with the manual dexterity subtest from the Movement Assessment Battery for Children-second edition, at 6½ years. Associations between the brain volumes and VMI and fine motor skills were evaluated using partial correlation, adjusted for total cerebral parenchyma and sex. Out of 107 children born at gestational age skills (r=0.54, P=0.01). Associations were also seen between fine motor skills and the volume of the cerebellum (r=0.42, P=0.02), brainstem (r=0.47, P=0.008) and grey matter (r=-0.38, P=0.04). Neonatal brain volumes in areas known to be involved in VMI and fine motor skills were associated with scores for these two functions when children born EPT without major brain lesions or cerebral palsy were evaluated at 6½ years of age. Establishing clear associations between early brain volume alterations and later VMI and/or fine motor skills could make early interventions possible. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. Visual–motor integration and fine motor skills at 6½ years of age and associations with neonatal brain volumes in children born extremely preterm in Sweden: a population-based cohort study

    Science.gov (United States)

    Padilla, Nelly; Forsman, Lea; Broström, Lina; Hellgren, Kerstin; Åden, Ulrika

    2018-01-01

    Objectives This exploratory study aimed to investigate associations between neonatal brain volumes and visual–motor integration (VMI) and fine motor skills in children born extremely preterm (EPT) when they reached 6½ years of age. Setting Prospective population-based cohort study in Stockholm, Sweden, during 3 years. Participants All children born before gestational age, 27 weeks, during 2004–2007 in Stockholm, without major morbidities and impairments, and who underwent MRI at term-equivalent age. Main outcome measures Brain volumes were calculated using morphometric analyses in regions known to be involved in VMI and fine motor functions. VMI was assessed with The Beery-Buktenica Developmental Test of Visual–Motor Integration—sixth edition and fine motor skills were assessed with the manual dexterity subtest from the Movement Assessment Battery for Children—second edition, at 6½ years. Associations between the brain volumes and VMI and fine motor skills were evaluated using partial correlation, adjusted for total cerebral parenchyma and sex. Results Out of 107 children born at gestational age motor skills (r=0.54, P=0.01). Associations were also seen between fine motor skills and the volume of the cerebellum (r=0.42, P=0.02), brainstem (r=0.47, P=0.008) and grey matter (r=−0.38, P=0.04). Conclusions Neonatal brain volumes in areas known to be involved in VMI and fine motor skills were associated with scores for these two functions when children born EPT without major brain lesions or cerebral palsy were evaluated at 6½ years of age. Establishing clear associations between early brain volume alterations and later VMI and/or fine motor skills could make early interventions possible. PMID:29455171

  19. Sestrin2 induced by hypoxia inducible factor1 alpha protects the blood-brain barrier via inhibiting VEGF after severe hypoxic-ischemic injury in neonatal rats.

    Science.gov (United States)

    Shi, Xudan; Doycheva, Desislava Met; Xu, Liang; Tang, Jiping; Yan, Min; Zhang, John H

    2016-11-01

    Hypoxic ischemic (HI) encephalopathy remains the leading cause of perinatal brain injury resulting in long term disabilities. Stabilization of blood brain barrier (BBB) after HI is an important target, therefore, in this study we aim to determine the role of sestrin2, a stress inducible protein which is elevated after various insults, on BBB stabilization after moderate and severe HI injuries. Rat pups underwent common carotid artery ligation followed by either 150min (severe model) or 100min (moderate model) of hypoxia. 1h post HI, rats were intranasally administered with recombinant human sestrin2 (rh-sestrin2) and sacrificed for infarct area, brain water content, righting reflex and geotaxis reflex. Sestrin2 was silenced using siRNA and an activator/inhibitor of hypoxia inducible factor1α (HIF1α) was used to examine their roles on BBB permeability. Rats subjected to severe HI exhibited larger infarct area and higher sestrin2 expression compared to rats in the moderate HI group. rh-sestrin2 attenuated brain infarct and edema, while silencing sestrin2 reversed these protective effects after severe HI. HIF1α induced sestrin2 activation in severe HI but not in moderate HI groups. A HIF1a agonist was shown to increase permeability of the BBB via vascular endothelial growth factor (VEGF) after moderate HI. However, after severe HI, HIF1α activated both VEGF and sestrin2. But HIF1α dependent sestrin2 activation was the predominant pathway after severe HI which inhibited VEGF and attenuated BBB permeability. rh-sestrin2 attenuated BBB permeability via upregulation of endogenous sestrin2 which was induced by HIF1α after severe HI. However, HIF1α's effects as a prodeath or prosurvival signal were influenced by the severity of HI injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Insulin-like growth factors act synergistically with basic fibroblast growth factor and nerve growth factor to promote chromaffin cell proliferation

    DEFF Research Database (Denmark)

    Frödin, M; Gammeltoft, S

    1994-01-01

    We have investigated the effects of insulin-like growth factors (IGFs), basic fibroblast growth factor (bFGF), and nerve growth factor (NGF) on DNA synthesis in cultured chromaffin cells from fetal, neonatal, and adult rats by using 5-bromo-2'-deoxyuridine (BrdUrd) pulse labeling for 24 or 48 h...... implications for improving the survival of chromaffin cell implants in diseased human brain....

  1. Association of cord blood chemokines and other biomarkers with neonatal complications following intrauterine inflammation.

    Directory of Open Access Journals (Sweden)

    Yoshikazu Otsubo

    Full Text Available Intrauterine inflammation has been associated with preterm birth and neonatal complications. Few reports have comprehensively investigated multiple cytokine profiles in cord blood and precisely identified surrogate markers for intrauterine inflammation.To identify the cytokines and surrogate markers associated with intrauterine inflammation and subsequent neonatal complications.We analyzed cord blood samples from 135 patients admitted to the neonatal intensive care unit at Sasebo City General Hospital. We retrospectively determined the associations between the presence of neonatal complications and cord blood cytokines, prenatal factors, and laboratory data at birth. A total of 27 cytokines in the cord blood were measured using a bead-based array sandwich immunoassay.Both Th1 and Th2 cytokine levels were low, whereas the levels of growth factors and chemokines were high. In particular, chemokines IL-8, MCP-1, and MIP-1α were significantly higher in very premature neonates when compared with more mature neonates. In addition, some have been shown to be associated with multiple neonatal complications, including patent ductus arteriosus (PDA, respiratory distress syndrome (RDS, and chronic lung disease (CLD. Similarly, the levels of N-terminal pro-brain natriuretic peptide, nucleated RBC, and urinary β2-microglobulin were associated with these complications and chemokine levels.Our results suggest the association of inflammatory chemokines IL-8, MCP-1, and MIP-1α with intrauterine inflammation, premature birth, and neonatal complications in these perinatal subjects. Furthermore, the association of the aforementioned biomarkers with PDA, RDS, and CLD may help establish early diagnostic measures to predict such neonatal complications following intrauterine inflammation.

  2. Analysis of trophic responses in lesioned brain: focus on basic fibroblast growth factor mechanisms

    Directory of Open Access Journals (Sweden)

    Chadi G.

    1998-01-01

    Full Text Available The actions of fibroblast growth factors (FGFs, particularly the basic form (bFGF, have been described in a large number of cells and include mitogenicity, angiogenicity and wound repair. The present review discusses the presence of the bFGF protein and messenger RNA as well as the presence of the FGF receptor messenger RNA in the rodent brain by means of semiquantitative radioactive in situ hybridization in combination with immunohistochemistry. Chemical and mechanical injuries to the brain trigger a reduction in neurotransmitter synthesis and neuronal death which are accompanied by astroglial reaction. The altered synthesis of bFGF following brain lesions or stimulation was analyzed. Lesions of the central nervous system trigger bFGF gene expression by neurons and/or activated astrocytes, depending on the type of lesion and time post-manipulation. The changes in bFGF messenger RNA are frequently accompanied by a subsequent increase of bFGF immunoreactivity in astrocytes in the lesioned pathway. The reactive astrocytes and injured neurons synthesize increased amount of bFGF, which may act as a paracrine/autocrine factor, protecting neurons from death and also stimulating neuronal plasticity and tissue repair

  3. Neuroprotective Role of Nerve Growth Factor in Hypoxic-Ischemic Brain Injury

    Directory of Open Access Journals (Sweden)

    Antonio Chiaretti

    2013-06-01

    Full Text Available Hypoxic-ischemic brain injuries (HIBI in childhood are frequently associated with poor clinical and neurological outcome. Unfortunately, there is currently no effective therapy to restore neuronal loss and to determine substantial clinical improvement. Several neurotrophins, such as Nerve Growth Factor (NGF, Brain-Derived Neurotrophic Factor (BDNF, and Glial Derived Neurotrophic Factor (GDNF, play a key role in the development, differentiation, and survival of the neurons of the peripheral and central nervous system. Experimental animal studies demonstrated their neuroprotective role in HIBI, while only a few studies examined the neuroprotective mechanisms in patients with severe HIBI. We report two cases of children with HIBI and prolonged comatose state who showed a significant improvement after intraventricular NGF administration characterized by amelioration of electroencephalogram (EEG and cerebral perfusion at single-photon emission computed tomography (SPECT. The improvement in motor and cognitive functions of these children could be related to the neuroprotective role exerted by NGF in residual viable cholinergic neurons, leading to the restoration of neuronal networks in the damaged brain.

  4. Inhibition of type I insulin-like growth factor receptor signaling attenuates the development of breast cancer brain metastasis.

    Science.gov (United States)

    Saldana, Sandra M; Lee, Heng-Huan; Lowery, Frank J; Khotskaya, Yekaterina B; Xia, Weiya; Zhang, Chenyu; Chang, Shih-Shin; Chou, Chao-Kai; Steeg, Patricia S; Yu, Dihua; Hung, Mien-Chie

    2013-01-01

    Brain metastasis is a common cause of mortality in cancer patients, yet potential therapeutic targets remain largely unknown. The type I insulin-like growth factor receptor (IGF-IR) is known to play a role in the progression of breast cancer and is currently being investigated in the clinical setting for various types of cancer. The present study demonstrates that IGF-IR is constitutively autophosphorylated in brain-seeking breast cancer sublines. Knockdown of IGF-IR results in a decrease of phospho-AKT and phospho-p70s6k, as well as decreased migration and invasion of MDA-MB-231Br brain-seeking cells. In addition, transient ablation of IGFBP3, which is overexpressed in brain-seeking cells, blocks IGF-IR activation. Using an in vivo experimental brain metastasis model, we show that IGF-IR knockdown brain-seeking cells have reduced potential to establish brain metastases. Finally, we demonstrate that the malignancy of brain-seeking cells is attenuated by pharmacological inhibition with picropodophyllin, an IGF-IR-specific tyrosine kinase inhibitor. Together, our data suggest that the IGF-IR is an important mediator of brain metastasis and its ablation delays the onset of brain metastases in our model system.

  5. White matter hyperintensities, systemic inflammation, brain growth, and cognitive functions in children exposed to air pollution.

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Mora-Tiscareño, Antonieta; Styner, Martin; Gómez-Garza, Gilberto; Zhu, Hongtu; Torres-Jardón, Ricardo; Carlos, Esperanza; Solorio-López, Edelmira; Medina-Cortina, Humberto; Kavanaugh, Michael; D'Angiulli, Amedeo

    2012-01-01

    Air pollution exposures are linked to neuroinflammation and neuropathology in young urbanites. Forty percent of exposed children and young adults exhibit frontal tau hyperphosphorylation and 51% have amyloid-β diffuse plaques compared to 0% in low pollution controls. In older adults, white matter hyperintensities (WMH) are associated with cognitive deficits while inflammatory markers correlate with greater atrophy than expected for age. We investigated patterns of WMH, magnetic resonance imaging (MRI) volume growth, blood inflammatory mediators, and cognition in matched children from two urban cohorts: one severely and one minimally exposed to air pollution. Baseline and one year follow-up measurements of cognitive abilities, brain MRI volumes, and blood were collected in 20 Mexico City (MC) children (10 with WMH+, and 10 without WMH-) and 10 matched controls (WMH-). MC WMH- children display the profile of classical pro-inflammatory defensive responses: high interleukin 12, production of powerful pro-inflammatory cytokines, and low concentrations of key cytokines and chemokines associated with neuroprotection. MC WMH+ children exhibit a response involved in resolution of inflammation, immunoregulation, and tissue remodeling. The MC WMH+ group responded to the air pollution-associated brain volumetric alterations with white and grey matter volume increases in temporal, parietal, and frontal regions and better cognitive performance compared to MC WMH-. We conclude that complex modulation of cytokines and chemokines influences children's central nervous system structural and volumetric responses and cognitive correlates resulting from environmental pollution exposures. Identification of biomarkers associating systemic inflammation to brain growth is critical for detecting children at higher risk for cognitive deficits and neurodegeneration, thereby warranting early implementation of neuroprotective measures.

  6. Mechano growth factor, a splice variant of IGF-1, promotes neurogenesis in the aging mouse brain.

    Science.gov (United States)

    Tang, Jason J; Podratz, Jewel L; Lange, Miranda; Scrable, Heidi J; Jang, Mi-Hyeon; Windebank, Anthony J

    2017-07-07

    Mechano growth factor (MGF) is a splice variant of IGF-1 first described in skeletal muscle. MGF induces muscle cell proliferation in response to muscle stress and injury. In control mice we found endogenous expression of MGF in neurogenic areas of the brain and these levels declined with age. To better understand the role of MGF in the brain, we used transgenic mice that constitutively overexpressed MGF from birth. MGF overexpression significantly increased the number of BrdU+ proliferative cells in the dentate gyrus (DG) of the hippocampus and subventricular zone (SVG). Although MGF overexpression increased the overall rate of adult hippocampal neurogenesis at the proliferation stage it did not alter the distribution of neurons at post-mitotic maturation stages. We then used the lac-operon system to conditionally overexpress MGF in the mouse brain beginning at 1, 3 and 12 months with histological and behavioral observation at 24 months of age. With conditional overexpression there was an increase of BrdU+ proliferating cells and BrdU+ differentiated mature neurons in the olfactory bulbs at 24 months when overexpression was induced from 1 and 3 months of age but not when started at 12 months. This was associated with preserved olfactory function. In vitro, MGF increased the size and number of neurospheres harvested from SVZ-derived neural stem cells (NSCs). These findings indicate that MGF overexpression increases the number of neural progenitor cells and promotes neurogenesis but does not alter the distribution of adult newborn neurons at post-mitotic stages. Maintaining youthful levels of MGF may be important in reversing age-related neuronal loss and brain dysfunction.

  7. Brain metabolite alterations in infants born preterm with intrauterine growth restriction: association with structural changes and neurodevelopmental outcome.

    Science.gov (United States)

    Simões, Rui V; Muñoz-Moreno, Emma; Cruz-Lemini, Mónica; Eixarch, Elisenda; Bargalló, Núria; Sanz-Cortés, Magdalena; Gratacós, Eduard

    2017-01-01

    Intrauterine growth restriction and premature birth represent 2 independent problems that may occur simultaneously and contribute to impaired neurodevelopment. The objective of the study was to assess changes in the frontal lobe metabolic profiles of 1 year old intrauterine growth restriction infants born prematurely and adequate-for-gestational-age controls, both premature and term adequate for gestational age and their association with brain structural and biophysical parameters and neurodevelopmental outcome at 2 years. A total of 26 prematurely born intrauterine growth restriction infants (birthweight intrauterine growth restriction infants had slightly smaller brain volumes and increased frontal lobe white matter mean diffusivity compared with both prematurely born but adequate for gestational age and term adequate for gestational age controls. Frontal lobe N-acetylaspartate levels were significantly lower in prematurely born intrauterine growth restriction than in prematurely born but adequate for gestational age infants but increased in prematurely born but adequate for gestational age compared with term adequate-for-gestational-age infants. The prematurely born intrauterine growth restriction group also showed slightly lower choline compounds, borderline decrements of estimated glutathione levels, and increased myoinositol to choline ratios, compared with prematurely born but adequate for gestational age controls. These specific metabolite changes were locally correlated to lower gray matter content and increased mean diffusivity and reduced white matter fraction and fractional anisotropy. Prematurely born intrauterine growth restriction infants also showed a tendency for poorer neurodevelopmental outcome at 2 years, associated with lower levels of frontal lobe N-acetylaspartate at 1 year within the preterm subset. Preterm intrauterine growth restriction infants showed altered brain metabolite profiles during a critical stage of brain maturation, which

  8. Survival Rate without Brain Abnormalities on Postnatal Ultrasonography among Monochorionic Twins after Fetoscopic Laser Photocoagulation for Selective Intrauterine Growth Restriction with Concomitant Oligohydramnios.

    Science.gov (United States)

    Ishii, Keisuke; Wada, Seiji; Takano, Mayumi; Nakata, Masahiko; Murakoshi, Takeshi; Sago, Haruhiko

    2018-02-20

    We aimed to clarify the survival rate without brain abnormalities (BA) after fetoscopic laser photoco-agulation (FLP) for monochorionic diamniotic twin gestations (MCDA) with selective intrauterine growth restriction (sIUGR) accompanied by abnormal umbilical artery (UA) Doppler waveforms and isolated oligohydramnios in the sIUGR twin. This retrospective study included 52 cases that underwent FLP. The main outcome was survival rate without BA of the twins at age 28 days. BA was defined as severe intraventricular hemorrhage and periventricular leukomalacia on postnatal ultrasonography. Median gestational age at FLP was 20 (16-24) weeks. Ten cases were classified as type III based on Doppler for the UA. For all cases, including 20 cases of anterior placenta, FLP was completed without major intraoperative complications. Amnioinfusion was required in 49 cases for better fetoscopic visualization. Fetal loss occurred in 29 sIUGR twins and two larger twins, whereas one larger twin experienced neonatal death. Survival rates without BA were 44% (n = 23) for sIUGR twins and 94% (n = 49) for the larger twins. FLP for MCDA with sIUGR presenting with oligohydramnios in the sIUGR twin might be considered a prenatal treatment option. © 2018 S. Karger AG, Basel.

  9. Neonatal pain

    Science.gov (United States)

    Walker, Suellen M

    2014-01-01

    Effective management of procedural and postoperative pain in neonates is required to minimize acute physiological and behavioral distress and may also improve acute and long-term outcomes. Painful stimuli activate nociceptive pathways, from the periphery to the cortex, in neonates and behavioral responses form the basis for validated pain assessment tools. However, there is an increasing awareness of the need to not only reduce acute behavioral responses to pain in neonates, but also to protect the developing nervous system from persistent sensitization of pain pathways and potential damaging effects of altered neural activity on central nervous system development. Analgesic requirements are influenced by age-related changes in both pharmacokinetic and pharmacodynamic response, and increasing data are available to guide safe and effective dosing with opioids and paracetamol. Regional analgesic techniques provide effective perioperative analgesia, but higher complication rates in neonates emphasize the importance of monitoring and choice of the most appropriate drug and dose. There have been significant improvements in the understanding and management of neonatal pain, but additional research evidence will further reduce the need to extrapolate data from older age groups. Translation into improved clinical care will continue to depend on an integrated approach to implementation that encompasses assessment and titration against individual response, education and training, and audit and feedback. PMID:24330444

  10. The impact of prenatal and neonatal infection on neurodevelopmental outcomes in very preterm infants

    OpenAIRE

    Lee, Iris; Neil, Jeffrey J.; Huettner, Phyllis C.; Smyser, Christopher D.; Rogers, Cynthia E.; Shimony, Joshua S.; Kidokoro, Hiroyuki; Mysorekar, Indira U.; Inder, Terrie E.

    2014-01-01

    Objective Determine the association of prenatal and neonatal infections with neurodevelopmental outcomes in very preterm infants. Study Design Secondary retrospective analysis of 155 very preterm infants at a single tertiary referral center. General linear or logistic regression models were used to evaluate the association with hospital factors; brain injury, growth, and development; and neurobehavioral outcome. Result Necrotizing enterocolitis with sepsis was associated with reduced transcer...

  11. Neonatal umbilical inflammatory myofibroblastic tumor

    African Journals Online (AJOL)

    antenatal scan. The preferred treatment option is resection of the tumor. Spontaneous regression has been described. Ann Pediatr Surg 13:160–162 c 2017 Annals of Pediatric. Surgery. ... Keywords: inflammatory myofibroblastic tumor, neonatal tumor, surgical resection ... Other anatomical regions were the brain, the.

  12. Cisatracurium, but not mivacurium, inhibits survival and axonal growth of neonatal and adult rat peripheral neurons in vitro

    NARCIS (Netherlands)

    Lirk, Philipp; Longato, Stefano; Rieder, Josef; Klimaschewski, Lars

    2004-01-01

    Cisatracurium and mivacurium are widely used neuromuscular blocking drugs. Previous reports have indicated growth-inhibitory effects of cisatracurium, but not mivacurium, on two human cell lines in vitro. These effects were ascribed to oxidative stress elicited by acrylate esters formed during

  13. Evaluation of body growth and myoenteric neurons of Wistar rats after neonatal treatment with monosodium glutamate = Avaliação do crescimento corporal e dos neurônios mioentéricos de ratos Wistar após tratamento neonatal com glutamato monossódico

    OpenAIRE

    Fernando Carlos Sousa; Maria Montserrat Diaz Pedrosa Furlan; Rosana Torrezan; Josy Fraccaro de Marins; Melina Rizzato Vismara

    2007-01-01

    This work aimed at evaluating how the neonatal treatment withmonosodium glutamate reflects on body parameters and on myoenteric neurons of Wistar rats. Male rats were injected with monosodium glutamate during the first five postnatal days. Body growth was recorded until the age of 90 days, when the animals were killed.Fasting plasma glucose, caloric density and weight of organs were assayed. Gastric and duodenal whole-mounts stained with NADH diaphorase were observed for neuronal numbers and ...

  14. Ictericia Neonatal

    OpenAIRE

    Blanco de la Fuente, María Isabel

    2014-01-01

    El motivo que ha llevado a la realización de este trabajo fin de grado sobre el tema de la ICTERICIA NEONATAL se debe a la elevada frecuencia de su aparición en la población. Un porcentaje elevado de RN la padecen al nacer siendo, en la mayor parte de los casos, un proceso fisiológico resuelto con facilidad debido a una inmadurez del sistema hepático y a una hiperproducción de bilirrubina. La ictericia neonatal es la pigmentación de color amarillo de la piel y mucosas en ...

  15. Improving Brain Magnetic Resonance Image (MRI Segmentation via a Novel Algorithm based on Genetic and Regional Growth

    Directory of Open Access Journals (Sweden)

    Javadpour A.

    2016-06-01

    Full Text Available Background: Regarding the importance of right diagnosis in medical applications, various methods have been exploited for processing medical images solar. The method of segmentation is used to analyze anal to miscall structures in medical imaging. Objective: This study describes a new method for brain Magnetic Resonance Image (MRI segmentation via a novel algorithm based on genetic and regional growth. Methods: Among medical imaging methods, brains MRI segmentation is important due to high contrast of non-intrusive soft tissue and high spatial resolution. Size variations of brain tissues are often accompanied by various diseases such as Alzheimer’s disease. As our knowledge about the relation between various brain diseases and deviation of brain anatomy increases, MRI segmentation is exploited as the first step in early diagnosis. In this paper, regional growth method and auto-mate selection of initial points by genetic algorithm is used to introduce a new method for MRI segmentation. Primary pixels and similarity criterion are automatically by genetic algorithms to maximize the accuracy and validity in image segmentation. Results: By using genetic algorithms and defining the fixed function of image segmentation, the initial points for the algorithm were found. The proposed algorithms are applied to the images and results are manually selected by regional growth in which the initial points were compared. The results showed that the proposed algorithm could reduce segmentation error effectively. Conclusion: The study concluded that the proposed algorithm could reduce segmentation error effectively and help us to diagnose brain diseases.

  16. Neonatal immune activation during early and late postnatal brain development differently influences depression-related behaviors in adolescent and adult C57BL/6 mice

    Directory of Open Access Journals (Sweden)

    Jafar Majidi-Zolbanin

    2014-06-01

    Full Text Available Aim: Immune challenge during early and late neonatal periods can induce robust alterations in physiological and behavioral functions, resulting in greater risk for the development of neuropsychiatric disorders, such as anxiety and depression, later in life. In addition, previous studies concluded that increasing age correlates with increased depression behaviors in humans and rodents. This study aimed to investigate for the first time whether immune challenge with a viral mimic, synthetic double-stranded ribonucleic acid (Poly I: C during different neonatal periods can differently affect depression-related behaviors in adolescent and adult mice. Methods: Male C57BL/6 mice were treated with either saline or Poly I:C (1 mg/kg and 4 mg/kg on postnatal days (PND 3-5 (early neonatal phase or PND 14-16 (late neonatal phase, and then subjected to behavioral tests, including tail suspension test and forced swimming test, during adolescence (PND 35 or 40 and adulthood (PND 85 or 90. Results: The results demonstrated that early neonatal immune activation increases depression-related behaviors in both adolescent and adult mice, but late neonatal immune activation only increases depression in adult mice. In other words, these findings indicated that the nature of the offspring's neuropathology can depend on the severity of the insult, the pup's age at the time of the insult, and offspring age at the time of behavioral testing. Conclusion: These findings suggest that dose and timing of neonatal insult and offspring age may be important factors for evaluating neuropsychiatric disorders in adults who experienced early life infection.

  17. Three-dimensional brain growth abnormalities in childhood-onset schizophrenia visualized by using tensor-based morphometry.

    Science.gov (United States)

    Gogtay, Nitin; Lu, Allen; Leow, Alex D; Klunder, Andrea D; Lee, Agatha D; Chavez, Alex; Greenstein, Deanna; Giedd, Jay N; Toga, Arthur W; Rapoport, Judith L; Thompson, Paul M

    2008-10-14

    Earlier studies revealed progressive cortical gray matter (GM) loss in childhood-onset schizophrenia (COS) across both lateral and medial surfaces of the developing brain. Here, we use tensor-based morphometry to visualize white matter (WM) growth abnormalities in COS throughout the brain. Using high-dimensional elastic image registration, we compared 3D maps of local WM growth rates in COS patients and healthy children over a 5-year period, based on analyzing longitudinal brain MRIs from 12 COS patients and 12 healthy controls matched for age, gender, and scan interval. COS patients showed up to 2.2% slower growth rates per year than healthy controls in WM (P = 0.02, all P values corrected). The greatest differences were in the right hemisphere (P = 0.006). This asymmetry was attributable to a right slower than left hemisphere growth rate mapped in COS patients (P = 0.037) but not in healthy controls. WM growth rates reached 2.6% per year in healthy controls (P = 0.0002). COS patients showed only a 1.3% per year trend for growth in the left hemisphere (P = 0.066). In COS, WM growth rates were associated with improvement in the Children's Global Assessment Scale (R = 0.64, P = 0.029). Growth rates were reduced throughout the brain in COS, but this process appeared to progress in a front-to-back (frontal-parietal) fashion, and this effect was not attributable to lower IQ. Growth rates were correlated with functional prognosis and were visualized as detailed 3D maps. Finally, these findings also confirm that the progressive GM deficits seen in schizophrenia are not the result of WM overgrowth.

  18. Evolution of growth hormone neurosecretory disturbance after cranial irradiation for childhood brain tumours: a prospective study

    International Nuclear Information System (INIS)

    Spoudeas, H.A.; Hindmarsh, P.C.; Brook, C.G.D.; Matthews, D.R.

    1996-01-01

    To determine the aetiopathology of post-irradiation growth hormone (GH) deficiency, we performed a mixed longitudinal analysis of 56 24 h serum GH concentration profiles and 45 paired insulin-induced hypoglycaemia tests (ITT) in 35 prepubertal children, aged 1.5-11.8 years, with brain tumours in the posterior foss (n = 25) or cerebral hemispheres (n 10). Assessments were made before (n = 16), 1 year (n = 25) and 2 to 5 years (n = 15) after a cranial irradiation (DXR) dose of at least 30 Gy. Fourier transforms, occupancy percentage, first-order derivatives (FOD) and mean concentrations were determined from the GH profiles taken after neurosurgery but before radiotherapy (n = 16) and in three treatment groups: Group 1: neurosurgery only without DXR 9n 9); Group 2: ≥ 30 Gy DXR only (n = 22); Group 3: ≥ 30 Gy DXR with additional chemotherapy (n = 9). Results were compared with those from 26 short normally growing (SN) children. (author)

  19. Vascular endothelial growth factor A protein level and gene expression in intracranial meningiomas with brain edema

    DEFF Research Database (Denmark)

    Nassehi, Damoun; Dyrbye, Henrik; Andresen, Morten

    2011-01-01

    Meningiomas are the second most common primary intracranial tumors in adults. Although meningiomas are mostly benign, more than 50% of patients with meningioma develop peritumoral brain edema (PTBE), which may be fatal because of increased intracranial pressure. Vascular endothelial growth factor....... Forty-three patients had primary, solitary, supratentorial meningiomas with PTBE. In these, correlations in PTBE, edema index, VEGF-A protein, VEGF gene expression, capillary length, and tumor water content were investigated. DNA-branched hybridization was used for measuring VEGF gene expression...... in tissue homogenates prepared from frozen tissue samples. The method for VEGF-A analysis resembled an ELISA assay, but was based on chemiluminescence. The edema index was positively correlated to VEGF-A protein (p = 0.014) and VEGF gene expression (p

  20. Correlation between Nerve Growth Factor (NGF with Brain Derived Neurotropic Factor (BDNF in Ischemic Stroke Patient

    Directory of Open Access Journals (Sweden)

    Joko Widodo

    2016-05-01

    Full Text Available Background: The neurotrophins nerve growth factor (NGF and brain-derived neurotrophic factor (BDNF is a family of polypeptides that play critical role during neuronal development, appear to mediate protective role on neurorepair in ischemic stroke. Naturally in adult brain neurorepair process consist of: angiogenesis, neurogenesis, and neuronal plasticity, it can also be stimulated by endogenous neurorepair. In this study we observed correlation between NGF and BDNF ischemic stroke patient’s onset: 7-30 and over 30 days. Methods: This is cross sectional study on 46 subjects aged 38 – 74 years old with ischemic stroke from The Indonesian Central Hospital of Army Gatot Subroto Jakarta. Diagnosis of ischemic stroke was made using clinical examination and magnetic resonance imaging (MRI by neurologist. Subjects were divided into 2 groups based on stroke onset: 7 – 30 days (Group A: 19 subjects and > 30 days (Group B: 27 Subjects. Serum NGF levels were measured with ELISA method and BDNF levels were measured using multiplex method with Luminex Magpix. Results: Levels of NGF and BDNF were significantly different between onset group A and B (NGF p= 0.022, and BDNF p=0.008, with mean levels NGF in group A higher than group B, indicating that BDNF levels is lower in group A than group B. There was no significant correlation between NGF and BDNF levels in all groups. Conclusion: The variations in neurotrophic factor levels reflect an endogenous attempt at neuroprotection against biochemical and molecular changes after ischemic stroke. NGF represents an early marker of brain injury while BDNF recovery is most prominent during the first 14 days after onsite but continuous for more than 30 days. There is no significant correlation between NGF and BDNF in each group.  

  1. Gonadotropin-releasing hormone receptor (Gnrhr gene knock out: Normal growth and development of sensory, motor and spatial orientation behavior but altered metabolism in neonatal and prepubertal mice.

    Directory of Open Access Journals (Sweden)

    Ellen R Busby

    Full Text Available Gonadotropin-releasing hormone (GnRH is important in the control of reproduction, but its actions in non-reproductive processes are less well known. In this study we examined the effect of disrupting the GnRH receptor in mice to determine if growth, metabolism or behaviors that are not associated with reproduction were affected. To minimize the effects of other hormones such as FSH, LH and sex steroids, the neonatal-prepubertal period of 2 to 28 days of age was selected. The study shows that regardless of sex or phenotype in the Gnrhr gene knockout line, there was no significant difference in the daily development of motor control, sensory detection or spatial orientation among the wildtype, heterozygous or null mice. This included a series of behavioral tests for touch, vision, hearing, spatial orientation, locomotory behavior and muscle strength. Neither the daily body weight nor the final weight on day 28 of the kidney, liver and thymus relative to body weight varied significantly in any group. However by day 28, metabolic changes in the GnRH null females compared with wildtype females showed a significant reduction in inguinal fat pad weight normalized to body weight; this was accompanied by an increase in glucose compared with wildtype females shown by Student-Newman-Keuls Multiple Comparison test and Student's unpaired t tests. Our studies show that the GnRH-GnRHR system is not essential for growth or motor/sensory/orientation behavior during the first month of life prior to puberty onset. The lack of the GnRH-GnRHR axis, however, did affect females resulting in reduced subcutaneous inguinal fat pad weight and increased glucose with possible insulin resistance; the loss of the normal rise of estradiol at postnatal days 15-28 may account for the altered metabolism in the prepubertal female pups.

  2. [Factors impacting the growth and nutritional status of cystic fibrosis patients younger than 10 years of age who did not undergo neonatal screening].

    Science.gov (United States)

    Hortencio, Taís Daiene Russo; Nogueira, Roberto José Negrão; Marson, Fernando Augusto de Lima; Hessel, Gabriel; Ribeiro, José Dirceu; Ribeiro, Antônio Fernando

    2015-01-01

    The aim of this study was to evaluate by clinical and laboratory parameters how cystic fibrosis (CF) affects growth and nutritional status of children who were undergoing CF treatment but did not receive newborn screening. A historical cohort study of 52 CF patients younger than 10 years of age were followed in a reference center in Campinas, Southeast Brazil. Anthropometric measurements were abstracted from medical records until March/2010, when neonatal screening program was implemented. Between September/2009 and March/2010, parental height of the 52 CF patients were also measured. Regarding nutritional status, four patients had Z-scores ≤ -2 for height/age (H/A) and body mass index/age (BMI/A). The following variables were associated with improved H/A ratio: fewer hospitalizations, longer time from first appointment to diagnosis, longer time from birth to diagnosis and later onset of respiratory disease. Forced vital capacity [FVC(%)], forced expiratory flow between 25-75% of FVC [FEF25-75(%)], forced expiratory volume in the first second [FEV1(%)], gestational age, birth weight and early respiratory symptoms were associated with IMC/A. Greater number of hospitalizations, diagnosis delay and early onset of respiratory disease had a negative impact on growth. Lower spirometric values, lower gestational age, lower birth weight, and early onset of respiratory symptoms had negative impact on nutritional status. Malnutrition was observed in 7.7% of cases, but 23% of children had nutritional risk. Copyright © 2014 Associação de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  3. Neonatal Jaundice

    DEFF Research Database (Denmark)

    Maimburg, Rikke Damkjær; Væth, Michael; Schendel, Diana

    2008-01-01

    In a previous study, we found that infants transferred to a neonatal ward after delivery had an almost twofold increased risk of being diagnosed with infantile autism later in childhood in spite of extensive controlling of obstetric risk factors. We therefore decided to investigate other reasons ...

  4. Some growth factors in neoplastic tissues of brain tumors of different histological structure

    Directory of Open Access Journals (Sweden)

    O. I. Kit

    2016-01-01

    Full Text Available Introduction. Pathologic angiogenesis is typical for angiogenic diseases including tumor growth. Vascular endothelial growth factor (VEGF, fibroblast growth factor (FGF, transforming growth factor alpha and beta (which are also known as “triggers” of angiogenesis, and other factors (Gacche, Meshram, 2013; Nijaguna et al., 2015 play a special role in its development. Evaluation of the important mechanisms of angiogenesis in physiological and pathological conditions remains to be a subject of heightened interest for the past 30 years. It is known that VEGF A is the main trigger of growing blood vessels into the tumor tissue. This is specific mitogen signal for endothelial cells that triggers the mechanisms of cell division and migration. VEGF-induced tumor vasculature has a number of structural and functional features that provide growth and progression of tumors, including increased permeability of blood vessels and their chaotic arrangement.Objective: to study in comparative aspect the level of certain growth factors in the following tissues: glioblastomas, brain metastasis of the breast cancer, meningiomas as well as corresponding peritumoral areas.Materials and methods. Tissue samples were obtained from 56 patients admitted to the surgical treatment in Rostov Research Institute of Oncology: 24 patients had glioblastomas, 19 patients had brain metastasis of the breast cancer, 13 patients with meningiomas without peritumoral edema. Histological control was carried out in all cases. Age of patients ranged from 35 to 72 years. The level of growth factor was detected in the samples of tumor tissue and regions immediately adjacent to the tumor foci (peritumoral area by the method of immunoassay and using standard test systems. The following growth factor were detected: VEGF-A and its receptors VEGF-R1 (BenderMedSystem, Austria, VEGF-C and its receptor VEGF-R3 (BenderMedSystem, Austria, EGF (Biosource, USA, IFR-1 and IFR-2 (Mediagnost, USA, TGF

  5. Occurrence of DNET and other brain tumors in Noonan syndrome warrants caution with growth hormone therapy.

    Science.gov (United States)

    McWilliams, Geoffrey D; SantaCruz, Karen; Hart, Blaine; Clericuzio, Carol

    2016-01-01

    Noonan syndrome (NS) is an autosomal dominant developmental disorder caused by mutations in the RAS-MAPK signaling pathway that is well known for its relationship with oncogenesis. An 8.1-fold increased risk of cancer in Noonan syndrome has been reported, including childhood leukemia and solid tumors. The same study found a patient with a dysembryoplastic neuroepithelial tumor (DNET) and suggested that DNET tumors are associated with NS. Herein we report an 8-year-old boy with genetically confirmed NS and a DNET. Literature review identified eight other reports, supporting the association between NS and DNETs. The review also ascertained 13 non-DNET brain tumors in individuals with NS, bringing to 22 the total number of NS patients with brain tumors. Tumor growth while receiving growth hormone (GH) occurred in our patient and one other patient. It is unknown whether the development or progression of tumors is augmented by GH therapy, however there is concern based on epidemiological, animal and in vitro studies. This issue was addressed in a 2015 Pediatric Endocrine Society report noting there is not enough data available to assess the safety of GH therapy in children with neoplasia-predisposition syndromes. The authors recommend that GH use in children with such disorders, including NS, be undertaken with appropriate surveillance for malignancies. Our case report and literature review underscore the association of NS with CNS tumors, particularly DNET, and call attention to the recommendation that clinicians treating NS patients with GH do so with awareness of the possibility of increased neoplasia risk. © 2015 Wiley Periodicals, Inc.

  6. Review: Neuroinflammation in intrauterine growth restriction.

    Science.gov (United States)

    Wixey, Julie A; Chand, Kirat K; Colditz, Paul B; Bjorkman, S Tracey

    2017-06-01

    Disruption to the maternal environment during pregnancy from events such as hypoxia, stress, toxins, inflammation, and reduced placental blood flow can affect fetal development. Intrauterine growth restriction (IUGR) is commonly caused by chronic placental insufficiency, interrupting supply of oxygen and nutrients to the fetus resulting in abnormal fetal growth. IUGR is a major cause of perinatal morbidity and mortality, occurring in approximately 5-10% of pregnancies. The fetal brain is particularly vulnerable in IUGR and there is an increased risk of long-term neurological disorders including cerebral palsy, epilepsy, learning difficulties, behavioural difficulties and psychiatric diagnoses. Few studies have focused on how growth restriction interferes with normal brain development in the IUGR neonate but recent studies in growth restricted animal models demonstrate increased neuroinflammation. This review describes the role of neuroinflammation in the progression of brain injury in growth restricted neonates. Identifying the mediators responsible for alterations in brain development in the IUGR infant is key to prevention and treatment of brain injury in these infants. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Inhibitory effects of brain-derived neurotrophic factor precursor on viability and neurite growth of murine hippocampal neurons

    Directory of Open Access Journals (Sweden)

    Jia CHEN

    2014-10-01

    Full Text Available Objective To explore the mediation effect of p75 neurotrophin receptor (p75NTR in the effect of brainderived neurotrophic factor precursor (proBDNF on viability and neurite growth of murine hippocampal neurons. Methods  Hippocampal neurons were obtained from p75NTR+/+ and p75NTR-/- 18-day mice and primarily cultured. For p75NTR+/+ neurons, three experimental groups were set, i.e. control, proBDNF (30ng/ml, and proBDNF (30ng/ml+p75/Fc (30µg/ml groups. For p75NTR-/- neurons, two experimental groups were set, i.e. control and proBDNF (30ng/ml groups. MTT assays were performed after 24h to examine the viability of neonatal primary neurons. Immunofluorescent staining was conducted after 72h to investigate the neurite length. Results With MAP2 and DAPI double fluorescent staining it was identified that the neonatal hippocampal neurons were successfully cultured in vitro with high purity. For viability assay of p75NTR+/+ neurons, it was found that the absorbance value at 570nm (A570 in proBDNF group was significantly lower than that in control group (P0.05. With neurite growth assay of p75NTR+/+ neurons, it was found that the neurite length in proBDNF group was significantly shorter than that in control group (P0.05. With neurite growth assay of p75NTR-/- neurons, no difference in neurite length was observed between proBDNF group and control group. Conclusion proBDNF may inhibit the neuronal viability and neurite growth via p75NTR. DOI: 10.11855/j.issn.0577-7402.2014.09.03

  8. Differential effects of vascular endothelial growth factor A isoforms in a mouse brain metastasis model of human melanoma.

    NARCIS (Netherlands)

    Kusters, B.; Waal, R.M.W. de; Wesseling, P.; Verrijp, K.; Maass, C.N.; Heerschap, A.; Barentsz, J.O.; Sweep, C.G.J.; Ruiter, D.J.; Leenders, W.P.J.

    2003-01-01

    We reported previously that vascular endothelial growth factor isoform A (VEGF-A) expression by Mel57 human melanoma cells led to tumor progression in a murine brain metastasis model in an angiogenesis-independent fashion by dilation of co-opted, pre-existing vessels and concomitant enhanced blood

  9. Higher neonatal growth rate and body condition score at 7 months are predictive factors of obesity in adult female Beagle dogs.

    Science.gov (United States)

    Leclerc, Lucie; Thorin, Chantal; Flanagan, John; Biourge, Vincent; Serisier, Samuel; Nguyen, Patrick

    2017-04-13

    The risks during early growth on becoming overweight in adulthood are widely studied in humans. However, early-life predictive factors for canine adult overweight and obesity have not yet been studied. To identify factors that may help explain the development of overweight and obesity at adulthood in dogs, a longitudinal study of 2 years was conducted in 24 female Beagle dogs of the same age, sexual status, and raised under identical environmental conditions. By means of a hierarchical classification on principal components with the following quantitative values: fat-free mass (FFM), percentage fat mass and pelvic circumference at 2 years of age, three groups of dogs were established and were nominally named: ideal weight (IW, n = 9), slightly overweight (OW1, n = 6) and overweight (OW2, n = 9). With the aim of identifying predictive factors of development of obesity at adulthood parental characteristics, growth pattern, energy balance and plasma factors were analysed by logistic regression analysis. At 24 months, the group compositions were in line with the body condition scores (BCS 1-9) values of the IW (5 or 6/9), the OW1 (6/9) and the OW2 (7 or 8/9) groups. Logistic regression analysis permitted the identification of neonatal growth rate during the first 2 weeks of life (GR 2W ) and BCS at 7 months as predictors for the development of obesity at adulthood. Seventy percent of dogs with either GR 2W >125% or with BCS > 6/9 at 7 months belonged to the OW2 group. Results from energy intake and expenditure, corrected for FFM, showed that there was a greater positive energy imbalance between 7 and 10 months for the OW2, compared to the IW group. This study expands the understanding of previously reported risk factors for being overweight or obese in dogs, establishing that (i) 15 out of 24 of the studied dogs became overweight and (ii) GR 2W and BCS at 7 months of age could be used as predictive factors as overweight adult dogs in the OW2

  10. Bayesian automated cortical segmentation for neonatal MRI

    Science.gov (United States)

    Chou, Zane; Paquette, Natacha; Ganesh, Bhavana; Wang, Yalin; Ceschin, Rafael; Nelson, Marvin D.; Macyszyn, Luke; Gaonkar, Bilwaj; Panigrahy, Ashok; Lepore, Natasha

    2017-11-01

    Several attempts have been made in the past few years to develop and implement an automated segmentation of neonatal brain structural MRI. However, accurate automated MRI segmentation remains challenging in this population because of the low signal-to-noise ratio, large partial volume effects and inter-individual anatomical variability of the neonatal brain. In this paper, we propose a learning method for segmenting the whole brain cortical grey matter on neonatal T2-weighted images. We trained our algorithm using a neonatal dataset composed of 3 fullterm and 4 preterm infants scanned at term equivalent age. Our segmentation pipeline combines the FAST algorithm from the FSL library software and a Bayesian segmentation approach to create a threshold matrix that minimizes the error of mislabeling brain tissue types. Our method shows promising results with our pilot training set. In both preterm and full-term neonates, automated Bayesian segmentation generates a smoother and more consistent parcellation compared to FAST, while successfully removing the subcortical structure and cleaning the edges of the cortical grey matter. This method show promising refinement of the FAST segmentation by considerably reducing manual input and editing required from the user, and further improving reliability and processing time of neonatal MR images. Further improvement will include a larger dataset of training images acquired from different manufacturers.

  11. [Neonatal cholestasis

    Science.gov (United States)

    Roquete, M L

    2000-07-01

    OBJECTIVE: To warn pediatricians about the early recognition of cholestasis in newborns and infants. METHODS: A bibliographic research about cholestasis was performed using Medline, and emphasizing the most relevant publications of the last 30 years. RESULTS: The concept of cholestasis and the causes of cholestatic tendency in newborns and infants are described. Several causes of intra and extrahepatic cholestasis are reported as well. In this review, only the diseases with diagnostic, therapeutic or prognostic peculiarities are commented, including extrahepatic biliary atresia, idiopathic neonatal hepatitis, galactosemia, and Alagille s syndrome. Furthermore, several resources are discussed for the diagnosis of cholestasis. CONCLUSIONS: The establishment of the diagnosis of cholestasis through the detection of hyperbilirubinemia in newborns who present jaundice after 14 days of life is a goal that could change the prognosis of several diseases responsible for neonatal cholestasis.

  12. Neonatal Kraniefraktur

    DEFF Research Database (Denmark)

    Johannesen, Katrine Marie Harries; Stantchev, Hristo

    2015-01-01

    During the latest decades the incidence of birth traumas has decreased significantly. Even so the traumas still contribute to an increased mortality and morbidity. We present a case of spontaneous neonatal skull fracture following a normal vaginal delivery. Abnormal facial structure was seen, and......, and the fracture was identified with an MRI. The fractures healed without neurosurgical intervention. Case reports show that even in uncomplicated vaginal deliveries skull fractures can be seen and should be suspected in children with facial abnormalities....

  13. Insulin-like growth factor II messenger ribonucleic acids are synthesized in the choroid plexus of the rat brain

    International Nuclear Information System (INIS)

    Hynes, M.A.; Brooks, P.J.; Van Wyk, J.J.; Lund, P.K.

    1988-01-01

    Previous studies demonstrating the presence of immunoreactive insulin-like growth factors (IGFs) and their receptors in the brain suggest a role of the IGFs in the central nervous system. IGF-II has been implicated as the predominant IGF in brain of mature animals based on studies of immunoreactive peptide and of IGF-II mRNAs. To obtain information about the sites of synthesis of IGF-II in adult rat brain, a 32 P-labeled 31 base long synthetic oligodeoxyribonucleotide complementary in sequence to trailer peptide coding sequences in rat IGF-II mRNA (IGF-II 31 mer) was hybridized with coronal sections of fixed rat brain. The IGF-II 31 mer showed specific hybridization with the choroid plexus throughout rat brain, whereas in other brain regions, structures or cells, hybridization was not discernibly above background. These findings suggest that the choroid plexus is a primary site of synthesis of IGF-II, a probable source of IGF-II in cerebrospinal fluid, and a potential source of IGF-II for actions on target cells within the adult rat brain

  14. Brain Tumors

    Science.gov (United States)

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  15. [The contribution of the clinical examination, electroencephalogram, and brain MRI in assessing the prognosis in term newborns with neonatal encephalopathy. A cohort of 30 newborns before the introduction of treatment with hypothermia].

    Science.gov (United States)

    Jadas, V; Brasseur-Daudruy, M; Chollat, C; Pellerin, L; Devaux, A M; Marret, S

    2014-02-01

    Perinatal asphyxia complicated by hypoxic ischemic brain injury remains a source of neurological lesions. A major aim of neonatologists is to evaluate the severity of neonatal encephalopathy (NE) and to evaluate prognosis. The purpose of this study was to determine the contribution of brain MRI compared to electroencephalogram (EEG) and clinical data in assessing patients' prognosis. Thirty newborns from the pediatric resuscitation unit at Rouen university hospital were enrolled in a retrospective study between January 2006 and December 2008, prior to introduction of hypothermia treatment. All 30 newborns had at least two anamnestic criteria of perinatal asphyxia, one brain MRI in the first 5 days of life and another after 7 days of life as well as an early EEG in the first 2 days of life. Then, the infants were seen in consultation to assess neurodevelopment. This study showed a relation between NE stage and prognosis. During stage 1, prognosis was good, whereas stage 3 was associated with poor neurodevelopment outcome. Normal clinical examination before the 8th day of life was a good prognostic factor in this study. There was a relationship between severity of EEG after the 5th day of life and poor outcome. During stage 2, EEG patterns varied in severity, and brain MRI provided a better prognosis. Lesions of the basal ganglia and a decreased or absent signal of the posterior limb of the internal capsule were poor prognostic factors during brain MRI. These lesions were underestimated during standard MRI in the first days of life but were visible with diffusion sequences. Cognitive impairment affected 40% of surviving children, justifying extended pediatric follow-up. This study confirms the usefulness of brain MRI as a diagnostic tool in hypoxic ischemic encephalopathy in association with clinical data and EEG tracings. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  16. Developmental exposure to terbutaline alters cell signaling in mature rat brain regions and augments the effects of subsequent neonatal exposure to the organophosphorus insecticide chlorpyrifos

    International Nuclear Information System (INIS)

    Meyer, Armando; Seidler, Frederic J.; Aldridge, Justin E.; Slotkin, Theodore A.

    2005-01-01

    Exposure to apparently unrelated neurotoxicants can nevertheless converge on common neurodevelopmental events. We examined the long-term effects of developmental exposure of rats to terbutaline, a β-adrenoceptor agonist used to arrest preterm labor, and the organophosphorus insecticide chlorpyrifos (CPF) separately and together. Treatments mimicked the appropriate neurodevelopmental stages for human exposures: terbutaline on postnatal days (PN) 2-5 and CPF on PN11-14, with assessments conducted on PN45. Although neither treatment affected growth or viability, each elicited alterations in CNS cell signaling mediated by adenylyl cyclase (AC), a transduction pathway shared by numerous neuronal and hormonal signals. Terbutaline altered signaling in the brainstem and cerebellum, with gender differences particularly notable in the cerebellum (enhanced AC in males, suppressed in females). By itself, CPF exposure elicited deficits in AC signaling in the midbrain, brainstem, and striatum. However, sequential exposure to terbutaline followed by CPF produced larger alterations and involved a wider spectrum of brain regions than were obtained with either agent alone. In the cerebral cortex, adverse effects of the combined treatment intensified between PN45 and PN60, suggesting that exposures alter the long-term program for development of synaptic communication, leading to alterations in AC signaling that emerge even after adolescence. These findings indicate that terbutaline, like CPF, is a developmental neurotoxicant, and reinforce the idea that its use in preterm labor may create a subpopulation that is sensitized to long-term CNS effects of organophosphorus insecticides

  17. Ventricular shape and relative position abnormalities in preterm neonates

    Directory of Open Access Journals (Sweden)

    N. Paquette

    2017-01-01

    Full Text Available Recent neuroimaging findings have highlighted the impact of premature birth on subcortical development and morphological changes in the deep grey nuclei and ventricular system. To help characterize subcortical microstructural changes in preterm neonates, we recently implemented a multivariate tensor-based method (mTBM. This method allows to precisely measure local surface deformation of brain structures in infants. Here, we investigated ventricular abnormalities and their spatial relationships with surrounding subcortical structures in preterm neonates. We performed regional group comparisons on the surface morphometry and relative position of the lateral ventricles between 19 full-term and 17 preterm born neonates at term-equivalent age. Furthermore, a relative pose analysis was used to detect individual differences in translation, rotation, and scale of a given brain structure with respect to an average. Our mTBM results revealed broad areas of alterations on the frontal horn and body of the left ventricle, and narrower areas of differences on the temporal horn of the right ventricle. A significant shift in the rotation of the left ventricle was also found in preterm neonates. Furthermore, we located significant correlations between morphology and pose parameters of the lateral ventricles and that of the putamen and thalamus. These results show that regional abnormalities on the surface and pose of the ventricles are also associated with alterations on the putamen and thalamus. The complementarity of the information provided by the surface and pose analysis may help to identify abnormal white and grey matter growth, hinting toward a pattern of neural and cellular dysmaturation.

  18. Perinatal brain damage : The term infant

    NARCIS (Netherlands)

    Hagberg, Henrik; David Edwards, A.; Groenendaal, Floris

    2016-01-01

    Perinatal brain injury at term is common and often manifests with neonatal encephalopathy including seizures. The most common aetiologies are hypoxic–ischaemic encephalopathy, intracranial haemorrhage and neonatal stroke. Besides clinical and biochemical assessment the diagnostic evaluation rely

  19. The Methanol Extract of Angelica sinensis Induces Cell Apoptosis and Suppresses Tumor Growth in Human Malignant Brain Tumors

    Directory of Open Access Journals (Sweden)

    Yu-Ling Lin

    2013-01-01

    Full Text Available Glioblastoma multiforme (GBM is a highly vascularized and invasive neoplasm. The methanol extract of Angelica sinensis (AS-M is commonly used in traditional Chinese medicine to treat several diseases, such as gastric mucosal damage, hepatic injury, menopausal symptoms, and chronic glomerulonephritis. AS-M also displays potency in suppressing the growth of malignant brain tumor cells. The growth suppression of malignant brain tumor cells by AS-M results from cell cycle arrest and apoptosis. AS-M upregulates expression of cyclin kinase inhibitors, including p16, to decrease the phosphorylation of Rb proteins, resulting in arrest at the G0-G1 phase. The expression of the p53 protein is increased by AS-M and correlates with activation of apoptosis-associated proteins. Therefore, the apoptosis of cancer cells induced by AS-M may be triggered through the p53 pathway. In in vivo studies, AS-M not only suppresses the growth of human malignant brain tumors but also significantly prolongs patient survival. In addition, AS-M has potent anticancer effects involving cell cycle arrest, apoptosis, and antiangiogenesis. The in vitro and in vivo anticancer effects of AS-M indicate that this extract warrants further investigation and potential development as a new antibrain tumor agent, providing new hope for the chemotherapy of malignant brain cancer.

  20. Neonatal immune activation during early and late postnatal brain development differently influences depression-related behaviors in adolescent and adult C57BL/6 mice

    OpenAIRE

    Jafar Majidi-Zolbanin; Mohammad-Hossein Doosti; Behzad Baradaran; Mohammad Amani; Maryam Azarfarin; Ali-Akbar Salari

    2014-01-01

    Aim: Immune challenge during early and late neonatal periods can induce robust alterations in physiological and behavioral functions, resulting in greater risk for the development of neuropsychiatric disorders, such as anxiety and depression, later in life. In addition, previous studies concluded that increasing age correlates with increased depression behaviors in humans and rodents. This study aimed to investigate for the first time whether immune challenge with a viral mimic, synthetic dou...

  1. Vascular endothelial growth factor is upregulated by l-dopa in the parkinsonian brain: implications for the development of dyskinesia

    Science.gov (United States)

    Francardo, Veronica; Lindgren, Hanna S.; Sillivan, Stephanie E.; O’Sullivan, Sean S.; Luksik, Andrew S.; Vassoler, Fair M.; Lees, Andrew J.; Konradi, Christine

    2011-01-01

    Angiogenesis and increased permeability of the blood–brain barrier have been reported to occur in animal models of Parkinson’s disease and l-dopa-induced dyskinesia, but the significance of these phenomena has remained unclear. Using a validated rat model of l-dopa-induced dyskinesia, this study demonstrates that chronic treatment with l-dopa dose dependently induces the expression of vascular endothelial growth factor in the basal ganglia nuclei. Vascular endothelial growth factor was abundantly expressed in astrocytes and astrocytic processes in the proximity of blood vessels. When co-administered with l-dopa, a small molecule inhibitor of vascular endothelial growth factor signalling significantly attenuated the development of dyskinesia and completely blocked the angiogenic response and associated increase in blood–brain barrier permeability induced by the treatment. The occurrence of angiogenesis and vascular endothelial growth factor upregulation was verified in post-mortem basal ganglia tissue from patients with Parkinson’s disease with a history of dyskinesia, who exhibited increased microvascular density, microvascular nestin expression and an upregulation of vascular endothelial growth factor messenger ribonucleic acid. These congruent findings in the rat model and human patients indicate that vascular endothelial growth factor is implicated in the pathophysiology of l-dopa-induced dyskinesia and emphasize an involvement of the microvascular compartment in the adverse effects of l-dopa pharmacotherapy in Parkinson’s disease. PMID:21771855

  2. CT findings in neonatal hypothermia

    International Nuclear Information System (INIS)

    Schulman, H.; Laufer, L.; Berginer, J.; Hertzanu, Y.; Hershkowitz, E.; Berenstein, T.; Sofer, S.; Maor, E.

    1998-01-01

    Background. Newborn infants are particularly prone to hypothermia, a condition with a high mortality. Objective. To study the CT brain patterns in infants with hypothermia and neurological symptoms. Materials and methods. We reviewed the brain CT of nine infants with neonatal hypothermia, multiple organ failure, seizures and coma. Results. Two infants had normal CT scans, acutely and at follow-up, and were clinically normal at follow-up. In seven infants, CT showed diffuse cerebral oedema, with reversal of the normal density relationship between grey and white matter and a relative increased density of the thalami, brainstem and cerebellum - the 'reversal sign'. In six surviving infants with severe developmental delay, follow-up CT revealed cerebral atrophy with multicystic encephalomalacia. Conclusions. The 'reversal sign' has been described in the abused child, birth asphyxia and anoxia due to drowning. Neonatal hypothermia is offered as a further cause. (orig.)

  3. CT findings in neonatal hypothermia

    Energy Technology Data Exchange (ETDEWEB)

    Schulman, H.; Laufer, L.; Berginer, J.; Hertzanu, Y. [Department of Radiology, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, P. O. Box 151, Beer-Sheva 84101 (Israel); Hershkowitz, E.; Berenstein, T.; Sofer, S. [Pediatric Intensive Care Unit, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva (Israel); Maor, E. [Department of Pathology, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva (Israel)

    1998-06-01

    Background. Newborn infants are particularly prone to hypothermia, a condition with a high mortality. Objective. To study the CT brain patterns in infants with hypothermia and neurological symptoms. Materials and methods. We reviewed the brain CT of nine infants with neonatal hypothermia, multiple organ failure, seizures and coma. Results. Two infants had normal CT scans, acutely and at follow-up, and were clinically normal at follow-up. In seven infants, CT showed diffuse cerebral oedema, with reversal of the normal density relationship between grey and white matter and a relative increased density of the thalami, brainstem and cerebellum - the `reversal sign`. In six surviving infants with severe developmental delay, follow-up CT revealed cerebral atrophy with multicystic encephalomalacia. Conclusions. The `reversal sign` has been described in the abused child, birth asphyxia and anoxia due to drowning. Neonatal hypothermia is offered as a further cause. (orig.) With 6 figs., 1 tab., 13 refs.

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

    Science.gov (United States)

    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.

  5. In Vivo Detection of Perinatal Brain Metabolite Changes in a Rabbit Model of Intrauterine Growth Restriction (IUGR.

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    Rui V Simões

    Full Text Available Intrauterine growth restriction (IUGR is a risk factor for abnormal neurodevelopment. We studied a rabbit model of IUGR by magnetic resonance imaging (MRI and spectroscopy (MRS, to assess in vivo brain structural and metabolic consequences, and identify potential metabolic biomarkers for clinical translation.IUGR was induced in 3 pregnant rabbits at gestational day 25, by 40-50% uteroplacental vessel ligation in one horn; the contralateral horn was used as control. Fetuses were delivered at day 30 and weighted. A total of 6 controls and 5 IUGR pups underwent T2-w MRI and localized proton MRS within the first 8 hours of life, at 7T. Changes in brain tissue volumes and respective contributions to each MRS voxel were estimated by semi-automated registration of MRI images with a digital atlas of the rabbit brain. MRS data were used for: (i absolute metabolite quantifications, using linear fitting; (ii local temperature estimations, based on the water chemical shift; and (iii classification, using spectral pattern analysis.Lower birth weight was associated with (i smaller brain sizes, (ii slightly lower brain temperatures, and (iii differential metabolite profile changes in specific regions of the brain parenchyma. Specifically, we found estimated lower levels of aspartate and N-acetylaspartate (NAA in the cerebral cortex and hippocampus (suggesting neuronal impairment, and higher glycine levels in the striatum (possible marker of brain injury. Our results also suggest that the metabolic changes in cortical regions are more prevalent than those detected in hippocampus and striatum.IUGR was associated with brain metabolic changes in vivo, which correlate well with the neurostructural changes and neurodevelopment problems described in IUGR. Metabolic parameters could constitute non invasive biomarkers for the diagnosis and abnormal neurodevelopment of perinatal origin.

  6. Developmental exposure to terbutaline and chlorpyrifos: pharmacotherapy of preterm labor and an environmental neurotoxicant converge on serotonergic systems in neonatal rat brain regions

    International Nuclear Information System (INIS)

    Aldridge, Justin E.; Meyer, Armando; Seidler, Frederic J.; Slotkin, Theodore A.

    2005-01-01

    Developmental exposure to unrelated neurotoxicants can nevertheless produce similar neurobehavioral outcomes. We examined the effects of developmental exposure to terbutaline, a tocolytic β 2 -adrenoceptor agonist used to arrest preterm labor, and chlorpyrifos (CPF), a widely used organophosphate pesticide, on serotonin (5HT) systems. Treatments were chosen to parallel periods typical of human developmental exposures, terbutaline (10 mg/kg) on postnatal days (PN) 2-5 and CPF (5 mg/kg) on PN11-14, with assessments conducted on PN45, comparing each agent alone as well as sequential administration of both. Although neither treatment affected growth or viability, each elicited similar alterations in factors that are critical to the function of the 5HT synapse: 5HT 1A receptors, 5HT 2 receptors, and the presynaptic 5HT transporter (5HTT). Either agent elicited global increases in 5HT receptors and the 5HTT in brain regions possessing 5HT cell bodies (midbrain, brainstem) as well as in the hippocampus, which contains 5HT projections. For both terbutaline and CPF, males were affected more than females, although there were some regional disparities in the sex selectivity between the two agents. Both altered 5HT receptor-mediated cell signaling, suppressing stimulatory effects on adenylyl cyclase and enhancing inhibitory effects. When animals were exposed sequentially to both agents, the outcomes were no more than additive and, for many effects, less than additive, suggesting convergence of the two agents on a common set of developmental mechanisms. Our results indicate that 5HT systems represent a target for otherwise unrelated neuroteratogens

  7. Increased expression of vascular endothelial growth factor attenuates contusion necrosis without influencing contusion edema after traumatic brain injury in rats.

    Science.gov (United States)

    Tado, Masahiro; Mori, Tatsuro; Fukushima, Masamichi; Oshima, Hideki; Maeda, Takeshi; Yoshino, Atsuo; Aizawa, Shin; Katayama, Yoichi

    2014-04-01

    To clarify the role of vascular endothelial growth factor (VEGF) in the formation of contusion edema and necrosis after traumatic brain injury, we examined the time course of changes in the VEGF expression (enzyme-linked immunosorbent assay), cerebrovascular permeability (extravasation of Evans blue), and water content (dry-wet weight method) of the contused brain tissue in a cortical impact injury model using rats. In addition, we tested the effects of administration of bevacizumab (VEGF monoclonal antibody) on changes in the cerebrovascular permeability and water content of the contused brain tissue, as well as the neurological deficits (rota rod test) and volume of contusion necrosis. Increased VEGF expression was maximal at 72 h after injury (pnecrosis at 21 days (pnecrosis. This is probably because of an increased angiogenesis and improved microcirculation in the areas surrounding the core of contusion.

  8. Neonatal Infections

    Science.gov (United States)

    ... can cause serious problems such as heart disease, brain damage, deafness, visual impairment, or even miscarriage. Infection later in the pregnancy may lead to less severe effects on the fetus but can still cause problems ...

  9. Failure to thrive among neonates, associated factors and early neonatal outcome

    International Nuclear Information System (INIS)

    Thomas, Erica; Manji, Karim; Mpembeni Rose

    2005-01-01

    Failure to thrive or growth failure is an important feature of problems prevalent in the neonate. It remains one of the greatest challenges for the practicing pediatrician and it is a common pathway or outcome of several different underlaying infant and maternal conditions. To determine the prevalence, possible causes and early neonatal outcome of failure to thrive among young infants admitted to the Neonatal Unit in this hospital. A cross-sectional descriptive hospital based study, was carried for 10 months from April 2001 to January 2002 at the Neonatal Unit at Muhimbili National Hospital. (author)

  10. Standardisation of neonatal clinical practice.

    Science.gov (United States)

    Bhutta, Z A; Giuliani, F; Haroon, A; Knight, H E; Albernaz, E; Batra, M; Bhat, B; Bertino, E; McCormick, K; Ochieng, R; Rajan, V; Ruyan, P; Cheikh Ismail, L; Paul, V

    2013-09-01

    The International Fetal and Newborn Growth Consortium for the 21(st) Century (INTERGROWTH-21(st) ) is a large-scale, population-based, multicentre project involving health institutions from eight geographically diverse countries, which aims to assess fetal, newborn and preterm growth under optimal conditions. Given the multicentre nature of the project and the expected number of preterm births, it is vital that all centres follow the same standardised clinical care protocols to assess and manage preterm infants, so as to ensure maximum validity of the resulting standards as indicators of growth and nutrition with minimal confounding. Moreover, it is well known that evidence-based clinical practice guidelines can reduce the delivery of inappropriate care and support the introduction of new knowledge into clinical practice. The INTERGROWTH-21(st) Neonatal Group produced an operations manual, which reflects the consensus reached by members of the group regarding standardised definitions of neonatal morbidities and the minimum standards of care to be provided by all centres taking part in the project. The operational definitions and summary management protocols were developed by consensus through a Delphi process based on systematic reviews of relevant guidelines and management protocols by authoritative bodies. This paper describes the process of developing the Basic Neonatal Care Manual, as well as the morbidity definitions and standardised neonatal care protocols applied across all the INTERGROWTH-21(st) participating centres. Finally, thoughts about implementation strategies are presented. © 2013 Royal College of Obstetricians and Gynaecologists.

  11. The neuroprotective effects of intramuscular insulin-like growth factor-I treatment in brain ischemic rats.

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    Heng-Chih Chang

    Full Text Available Brain ischemia leads to muscle inactivity-induced atrophy and may exacerbate motor function deficits. Intramuscular insulin-like growth factor I (IGF-I injection has been shown to alleviate the brain ischemia-induced muscle atrophy and thus improve the motor function. Motor function is normally gauged by the integrity and coordination of the central nervous system and peripheral muscles. Whether brain ischemic regions are adaptively changed by the intramuscular IGF-I injection is not well understood. In this study, the effect of intramuscular IGF-I injection was examined on the central nervous system of brain ischemic rats. Rats were divided into 4 groups: sham control, brain ischemia control, brain ischemia with IGF-I treatment, and brain ischemia with IGF-I plus IGF-I receptor inhibitor treatment. Brain ischemia was induced by right middle cerebral artery occlusion. IGF-I and an IGF-1 receptor inhibitor were injected into the affected calf and anterior tibialis muscles of the treated rats for 4 times. There was an interval of 2 days between each injection. Motor function was examined and measured at the 24 hours and 7 days following a brain ischemia. The affected hind-limb muscles, sciatic nerve, lumbar spinal cord, and motor cortex were collected for examination after euthanizing the rats. IGF-I expression in the central nervous system and affected muscles were significantly decreased after brain ischemia. Intramuscular IGF-I injection increased the IGF-I expression in the affected muscles, sciatic nerve, lumbar spinal cord, and motor cortex. It also increased the p-Akt expression in the affected motor cortex. Furthermore, intramuscular IGF-I injection decreased the neuronal apoptosis and improved the motor function. However, co-administration of the IGF-I receptor inhibitor eliminated these effects. Intramuscular IGF-I injection after brain ischemia attenuated or reversed the decrease of IGF-I in both central and peripheral tissues, and

  12. Probabilistic maps of the white matter tracts with known associated functions on the neonatal brain atlas: Application to evaluate longitudinal developmental trajectories in term-born and preterm-born infants.

    Science.gov (United States)

    Akazawa, Kentaro; Chang, Linda; Yamakawa, Robyn; Hayama, Sara; Buchthal, Steven; Alicata, Daniel; Andres, Tamara; Castillo, Deborrah; Oishi, Kumiko; Skranes, Jon; Ernst, Thomas; Oishi, Kenichi

    2016-03-01

    Diffusion tensor imaging (DTI) has been widely used to investigate the development of the neonatal and infant brain, and deviations related to various diseases or medical conditions like preterm birth. In this study, we created a probabilistic map of fiber pathways with known associated functions, on a published neonatal multimodal atlas. The pathways-of-interest include the superficial white matter (SWM) fibers just beneath the specific cytoarchitectonically defined cortical areas, which were difficult to evaluate with existing DTI analysis methods. The Jülich cytoarchitectonic atlas was applied to define cortical areas related to specific brain functions, and the Dynamic Programming (DP) method was applied to delineate the white matter pathways traversing through the SWM. Probabilistic maps were created for pathways related to motor, somatosensory, auditory, visual, and limbic functions, as well as major white matter tracts, such as the corpus callosum, the inferior fronto-occipital fasciculus, and the middle cerebellar peduncle, by delineating these structures in eleven healthy term-born neonates. In order to characterize maturation-related changes in diffusivity measures of these pathways, the probabilistic maps were then applied to DTIs of 49 healthy infants who were longitudinally scanned at three time-points, approximately five weeks apart. First, we investigated the normal developmental pattern based on 19 term-born infants. Next, we analyzed 30 preterm-born infants to identify developmental patterns related to preterm birth. Last, we investigated the difference in diffusion measures between these groups to evaluate the effects of preterm birth on the development of these functional pathways. Term-born and preterm-born infants both demonstrated a time-dependent decrease in diffusivity, indicating postnatal maturation in these pathways, with laterality seen in the corticospinal tract and the optic radiation. The comparison between term- and preterm

  13. IGF-I: A key growth factor that regulates neurogenesis and synaptogenesis from embryonic to adult stages of the brain

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    Vanesa eNieto-Estévez

    2016-02-01

    Full Text Available The generation of neurons in the adult mammalian brain requires the activation of quiescent neural stem cells (NSCs. This activation and the sequential steps of neuron formation from NSCs are regulated by a number of stimuli, which include growth factors. Insulin-like growth factor-I (IGF-I exert pleiotropic effects, regulating multiple cellular processes depending on their concentration, cell type and the developmental stage of the animal. Although IGF-I expression is relatively high in the embryonic brain its levels drop sharply in the adult brain except in neurogenic regions, i.e., the hippocampus (HP and the subventricular zone-olfactory bulb (SVZ-OB. By contrast, the expression of IGF-IR remains relatively high in the brain irrespective of the age of the animal. Evidence indicates that IGF-I influences NSC proliferation and differentiation into neurons and glia as well as neuronal maturation including synapse formation. Furthermore, recent studies have shown that IGF-I not only promote adult neurogenesis by regulating NSC number and differentiation but also, by influencing neuronal positioning and migration as described during SVZ-OB neurogenesis. In this article we will revise and discuss the actions reported for IGF-I signaling in a variety of in vitro and in vivo models, focusing on the maintenance and proliferation of NSCs/progenitors, neurogenesis and neuron integration in synaptic circuits.

  14. IGF-I: A Key Growth Factor that Regulates Neurogenesis and Synaptogenesis from Embryonic to Adult Stages of the Brain

    Science.gov (United States)

    Nieto-Estévez, Vanesa; Defterali, Çağla; Vicario-Abejón, Carlos

    2016-01-01

    The generation of neurons in the adult mammalian brain requires the activation of quiescent neural stem cells (NSCs). This activation and the sequential steps of neuron formation from NSCs are regulated by a number of stimuli, which include growth factors. Insulin-like growth factor-I (IGF-I) exert pleiotropic effects, regulating multiple cellular processes depending on their concentration, cell type, and the developmental stage of the animal. Although IGF-I expression is relatively high in the embryonic brain its levels drop sharply in the adult brain except in neurogenic regions, i.e., the hippocampus (HP) and the subventricular zone-olfactory bulb (SVZ-OB). By contrast, the expression of IGF-IR remains relatively high in the brain irrespective of the age of the animal. Evidence indicates that IGF-I influences NSC proliferation and differentiation into neurons and glia as well as neuronal maturation including synapse formation. Furthermore, recent studies have shown that IGF-I not only promote adult neurogenesis by regulating NSC number and differentiation but also by influencing neuronal positioning and migration as described during SVZ-OB neurogenesis. In this article we will revise and discuss the actions reported for IGF-I signaling in a variety of in vitro and in vivo models, focusing on the maintenance and proliferation of NSCs/progenitors, neurogenesis, and neuron integration in synaptic circuits. PMID:26941597

  15. Thyroid Hormone-Dependent Formation of a Subcortical Band Heterotopia (SBH) in the Neonatal Brain is not Exacerbated Under Conditions of Low Dietary Iron

    Science.gov (United States)

    Thyroid hormones (TH) are critical for brain development. Modest TH insufficiency in pregnant rats induced by propylthiouracil (PTU) results in formation of a structural abnormality, a subcortical band heterotopia (SBH), in brains of offspring. PTU reduces TH by inhibiting the s...

  16. Effects of chronic aluminum exposure on learning and memory and brain-derived nerve growth factor in rats