Project

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From cortex to classroom: enhancing brain development for premature infants

English title From cortex to classroom: enhancing brain development for premature infants
Applicant Hüppi Petra
Number 124101
Funding scheme SPUM
Research institution Service de Développement et Croissance Département de Pédiatrie Hôpital des Enfants - HUG
Institution of higher education University of Geneva - GE
Main discipline Neurology, Psychiatry
Start/End 01.10.2009 - 30.09.2012
Approved amount 2'892'192.00
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Keywords (15)

prematurity; brain development; learning disabilities; cortex; magnetic resonance imaging; neuro-electrophysiology; animal models; brain damage; neuroprotection; developmental neuroscience; prematurity ; perinatal brain damage ; long-term developmental disabilities; functional brain development; neurprotection

Lay Summary (English)

Lead
From cortex to classroom is a multidisciplinary reserach program aimed at enhancing brain development for premature infants
Lay summary
Currently the rate for prematurity is the highest it has been in over 20 years. Long-term survival for premature infants has become an almost expected outcome over the past two decades due to improved neonatal care, but unfortunately often associated with perinatal brain damage and long-term developmental disabilities,such as cerebral palsy, mental retardation and a wide spectrum of learning disabilities. A critical feature of neonatal brain damage is that, in addition to the acute damage, neuronal circuits pursue developmental processes with a significant cell loss. This could lead to disruption of normal developmental processes and even more dramatic deterioration of brain functions. The key issue is to understand how, where and when these changes take place and to understand the cellular and molecular mechanisms of these processes. This will be important for developing new strategies to improve tissue repair and the subsequent development of preserved cortical circuits. The Cortex to Classroom programme is a specific targeted programme including research projects dedicated to young clinician scientists,and designed to (1) understand the effects of prematurity on long-term structural and functional brain development, (2) identify early markers of perinatal brain damage and its underlying mechanism and (3) target endogenous and exogenous molecules for potential neuroprotective and neuroregenerative intervention (e.g. Erythropoietin). One important objective of the project will be to use and to develop animal models of functional recovery which will represent a point of convergence between clinicians and basic scientists and simultaneously allow for addressing issues of medical relevance and testing molecular hypotheses, with a study design which uses methodology, such as magnetic resonance imaging and neuro-electrophysiology, that allows translation from animal to human and vice-versa. The current research is aimed at finding new strategies to help reduce the enormous individual, familial, and societal burden that perinatal brain damage in premature infants represents. It is this consortiums goal to contribute to an improvement of this situation for future generations.
Direct link to Lay Summary Last update: 24.05.2016

Responsible applicant and co-applicants

Employees

Publications

Publication
Delayed cyclic activity development on early amplitude-integrated eeg in the preterm infant with brain lesions
Natalucci G, Rousson V, Bucher HU, Bernet V, Hagmann C, Latal B (2013), Delayed cyclic activity development on early amplitude-integrated eeg in the preterm infant with brain lesions, in Neonatology, 103(2), 134-140.
Determinants of plasma copeptin: A systematic investigation in a pediatric mechanical ventilation model
L'Abate P, Wiegert S, Struck J, Wellmann S, Cannizzaro V (2013), Determinants of plasma copeptin: A systematic investigation in a pediatric mechanical ventilation model, in Respiratory Physiology and Neurobiology, 185(2), 222-227.
Self-perceived health status and mental health outcomes in young adults born with less than 1000 g
Natalucci G, Becker J, Becher K, Bickle GM, Landolt MA, Bucher HU (2013), Self-perceived health status and mental health outcomes in young adults born with less than 1000 g, in Acta Paediatrica, International Journal of Paediatrics, 102(3), 294-299.
Outcome at two years of age in a Swiss national cohort of extremely preterm infants born between 2000 and 2008
Schlapbach LJ, Adams M, Proietti E, Aebischer M, Grunt S, Borradori-Tolsa C, Bickle-Graz M, Bucher HU, Latal B, Natalucci G (2012), Outcome at two years of age in a Swiss national cohort of extremely preterm infants born between 2000 and 2008, in BMC Pediatrics, 12, 1.
Perinatal and early postnatal reorganization of the subplate and related cellular compartments in the human cerebral wall as revealed by histological and MRI approaches
Kostović I, Jovanov-Milošević N, Radoš M, Sedmak G, Benjak V, Kostović-Srzentić M, Vasung L, Čuljat M, Radoš M, Hüppi P, Judaš M (2012), Perinatal and early postnatal reorganization of the subplate and related cellular compartments in the human cerebral wall as revealed by histological and MRI approaches, in Brain Structure and Function, 1-23.
Copeptin: a marker for stress reaction in fetuses with intrauterine growth restriction
Burkhardt T, Schwabe S, Morgenthaler NG, Natalucci G, Zimmermann R, Wellmann S (2012), Copeptin: a marker for stress reaction in fetuses with intrauterine growth restriction, in AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY, 207(6), 497.
Morphology-driven automatic segmentation of MR images of the neonatal brain
Gui L, Lisowski R, Faundez T, Huppi PS, Lazeyras F, Kocher M (2012), Morphology-driven automatic segmentation of MR images of the neonatal brain, in MEDICAL IMAGE ANALYSIS, 16(8), 1565-1579.
Plasma C-Terminal Pro-Endothelin-1 and the Natriuretic Pro-Peptides NT-proBNP and MR-proANP in Very Preterm Infants with Patent Ductus Arteriosus
Letzner J, Berger F, Schwabe S, Benzing J, Morgenthaler NG, Bucher HU, Buhrer C, Arlettaz R, Wellmann S (2012), Plasma C-Terminal Pro-Endothelin-1 and the Natriuretic Pro-Peptides NT-proBNP and MR-proANP in Very Preterm Infants with Patent Ductus Arteriosus, in NEONATOLOGY, 101(2), 116-124.
Subfield-specific neurovascular remodeling in the entorhino-hippocampal-organotypic slice culture as a response to oxygen-glucose deprivation and excitotoxic cell death.
Chip S (2012), Subfield-specific neurovascular remodeling in the entorhino-hippocampal-organotypic slice culture as a response to oxygen-glucose deprivation and excitotoxic cell death., in J Cereb Blood Flow Metab., 1-11.
Health-Related Quality of Life and Behavior of Triplets at Adolescent Age
Natalucci Giancarlo, Iten Manuela, Hofmann Julia, Bucher Hans U., Arlettaz Romaine, Molinari Luciano, Latal Beatrice, Landolt Markus A. (2012), Health-Related Quality of Life and Behavior of Triplets at Adolescent Age, in JOURNAL OF PEDIATRICS, 161(3), 495-495.
Plasma midregional proadrenomedullin in newborn infants: impact of prematurity and perinatal infection
Admaty D, Benzing J, Burkhardt T, Lapaire O, Hegi L, Szinnai G, Morgenthaler NG, Bucher HU, Buhrer C, Wellmann S (2012), Plasma midregional proadrenomedullin in newborn infants: impact of prematurity and perinatal infection, in PEDIATRIC RESEARCH, 72(1), 70-76.
High-field diffusion tensor imaging characterization of cerebral white matter injury in LPS-exposed fetal sheep.
van de Looij Yohan, Lodygensky Gregory A, Dean Justin, Lazeyras François, Hagberg Henrik, Kjellmer Ingemar, Mallard Carina, Hüppi Petra S, Sizonenko Stéphane V (2012), High-field diffusion tensor imaging characterization of cerebral white matter injury in LPS-exposed fetal sheep., in Pediatric research, 72, 285-292.
Who plays the strings in newborn analgesia at birth, vasopressin or oxytocin?
Wellmann S, Bührer Christoph (2012), Who plays the strings in newborn analgesia at birth, vasopressin or oxytocin?, in Front Neurosci, 6, 78.
Plasma Pro-Endothelin-1 and Respiratory Distress in Newborn Infants
Benzing J, Stabile O, Szinnai G, Morgenthaler NG, Schulzke SM, Buhrer C, Wellmann S (2012), Plasma Pro-Endothelin-1 and Respiratory Distress in Newborn Infants, in JOURNAL OF PEDIATRICS, 160(3), 517-519.
In vivo assessment of myelination by phase imaging at high magnetic field
Lodygensky GA, Marques JP, Maddage R, Perroud E, Sizonenko SV, Huppi PS, Gruetter R (2012), In vivo assessment of myelination by phase imaging at high magnetic field, in NEUROIMAGE, 59(3), 1979-1987.
Early Postnatal Migration and Development of Layer II Pyramidal Neurons in the Rodent Cingulate/Retrosplenial Cortex
Zgraggen Eloisa, Boitard Michael, Roman Inge, Kanemitsu Michiko, Potter Gael, Salmon Patrick, Vutskits Laszlo, Dayer Alexandre G., Kiss Jozsef Z. (2012), Early Postnatal Migration and Development of Layer II Pyramidal Neurons in the Rodent Cingulate/Retrosplenial Cortex, in CEREBRAL CORTEX, 22(1), 144-157.
Impact of sepsis on neurodevelopmental outcome in a swiss national cohort of extremely premature infants
Schlapbach LJ, Aebischer M, Adams M, Natalucci G, Bonhoeffer J, Latzin P, Nelle M, Bucher HU, Latal B, Zeilinger G, Capone A, Glanzmann R, Weber P, Steinlin M, Grunt S, Bär W, Keller E, Killer Ch, Tolsa J-F, Bickle-Graz M, Pfister RE, Huppi PS, Borradori-Tolsa C, Berger TM, Schmitt-Mechelke T (2011), Impact of sepsis on neurodevelopmental outcome in a swiss national cohort of extremely premature infants, in Pediatrics, 128(2), e348-e357.
The role of birthweight discordance in the intellectual and motor outcome for triplets at early school age
Natalucci G, Seitz J, von Siebenthal K, Bucher HU, Molinari L, Jenni OG, Latal B (2011), The role of birthweight discordance in the intellectual and motor outcome for triplets at early school age, in Developmental Medicine and Child Neurology, 53(9), 822-828.
Delayed cortical impairment following lipopolysaccharide exposure in preterm fetal sheep.
Dean Justin M, van de Looij Yohan, Sizonenko Stephane V, Lodygensky Gregory A, Lazeyras Francois, Bolouri Hayde, Kjellmer Ingemar, Huppi Petra S, Hagberg Henrik, Mallard Carina (2011), Delayed cortical impairment following lipopolysaccharide exposure in preterm fetal sheep., in Annals of neurology, 70(5), 846-56.
The RNA-binding protein RBM3 is involved in hypothermia induced neuroprotection
Chip S, Zelmer A, Ogunshola OO, Felderhoff-Mueser U, Nitsch C, Buhrer C, Wellmann S (2011), The RNA-binding protein RBM3 is involved in hypothermia induced neuroprotection, in NEUROBIOLOGY OF DISEASE, 43(2), 388-396.
Plasma Copeptin in Preterm Infants: A Highly Sensitive Marker of Fetal and Neonatal Stress
Benzing J, Wellmann S, Achini F, Letzner J, Burkhardt T, Beinder E, Morgenthaler NG, Haagen U, Bucher HU, Buhrer C, Lapaire O, Szinnai G (2011), Plasma Copeptin in Preterm Infants: A Highly Sensitive Marker of Fetal and Neonatal Stress, in JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 96(6), 982-985.
Functional Development of Large-Scale Sensorimotor Cortical Networks in the Brain
Quairiaux Charles, Megevand Pierre, Kiss Jozsef Z., Michel Christoph M. (2011), Functional Development of Large-Scale Sensorimotor Cortical Networks in the Brain, in JOURNAL OF NEUROSCIENCE, 31(26), 9574-9584.
Longitudinal MR Assessment of Hypoxic Ischemic Injury in the Immature Rat Brain
van de Looij Y, Chatagner A, Huppi PS, Gruetter R, Sizonenko SV (2011), Longitudinal MR Assessment of Hypoxic Ischemic Injury in the Immature Rat Brain, in MAGNETIC RESONANCE IN MEDICINE, 65(2), 305-312.
High Copeptin Concentrations in Umbilical Cord Blood after Vaginal Delivery and Birth Acidosis
Wellmann S, Benzing J, Cippa G, Admaty D, Creutzfeldt R, Mieth RA, Beinder E, Lapaire O, Morgenthaler NG, Haagen U, Szinnai G, Buhrer C, Bucher HU (2010), High Copeptin Concentrations in Umbilical Cord Blood after Vaginal Delivery and Birth Acidosis, in JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 95(11), 5091-5096.
Neuroimaging of cortical development and brain connectivity in human newborns and animal models
Lodygensky GA, Vasung L, Sizonenko SV, Huppi PS (2010), Neuroimaging of cortical development and brain connectivity in human newborns and animal models, in JOURNAL OF ANATOMY, 217(4), 418-428.
Effect of Sedation and Analgesia on Postoperative Amplitude-Integrated EEG in Newborn Cardiac Patients
Bernet Vera, Latal Beatrice, Natalucci Giancarlo, Doell Carsten, Ziegler Anna, Wohlrab Gabriele (2010), Effect of Sedation and Analgesia on Postoperative Amplitude-Integrated EEG in Newborn Cardiac Patients, in PEDIATRIC RESEARCH, 67(6), 650-655.
Érythropoïétine et neuroprotection
Chatagner A (2010), Érythropoïétine et neuroprotection, in Archives de Pédiatrie, 17, 78-84.
Functional brain maturation assessed during early life correlates with anatomical brain maturation at term equivalent age in preterm infants
Natalucci G, Leuchter RH, Ulrich Bucher H, Latal B, Koller B, Hüppi PS, Hagmann C, Functional brain maturation assessed during early life correlates with anatomical brain maturation at term equivalent age in preterm infants, in Pediatr Res, 0.

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
ISMRM 2013 20.04.2013 Salt Lake City, USA
SPUM Symposium 21.02.2013 Zürich, CH
Preterm Brain 2013 21.02.2013 Zürich, switzerland
CIBM - Brain imaging meeting 12.02.2013 Lausanne, CH
SSN 2013 20.01.2013 Zürich
JFRN 2012 14.12.2012 Paris, France
EAPS 2012 17.10.2012 Istambul, Turkey
ESPR 2012 08.10.2012 Istanbul, Turkey
ESMRMB 2012 04.10.2012 Lisbon
GNPI 2012 13.09.2012 Hamburg
Hershey conference 07.06.2012 London, UK
SGP 2012 31.05.2012 Luzern
27th Intern. Workshop on Surfactant Repalcement 31.05.2012 Lisboa, Portugal
ISMRM 2012 05.05.2012 Melbourn, Australia
PAS 2012 01.05.2012 Boston, USA
SPR 2012 07.03.2012 Boston, USA
Wittener Perinatalkongress 2012 19.01.2012 Witten, Germany
Perinatale Medizin 2011 01.12.2011 Berlin
ESPR 2011 15.10.2011 Newcastle, GB
SGP, 2011 - Research Day 01.09.2011 Montreux, Switzerland
SGGG 2011 24.06.2011 Lugano, Switzerland
GNPI 2011 27.05.2011 Mannheim, Germany
ISMRM 2011 07.05.2011 Montréal, Canada
PAS 2011 30.04.2011 Denver - USA
American Neuroscience Meeting 2011 12.03.2011 Washington DC, USA
Annual Meeting of the Swiss Society of Neonatology 2011 18.01.2011 Bern, Switzerland
ESPR 2010 25.10.2010 Copenhagen, Denmark
GNPI 2010 19.06.2010 Saarbrücken, Germany
ISMRM 2010 03.05.2010 Stockholm, Sweden
Hershey conf on developmental brain injury 07.03.2010 Snowbird


Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
Opening of the SPUM project 28.02.2009 Lausane, Switzernland


Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions La semaine du cerveau Western Switzerland 12.03.2012
Media relations: radio, television Journal Journal 19:30 Western Switzerland 05.10.2011
Media relations: radio, television Le suivi des grands prématurés 36.9° Western Switzerland 16.11.2011
Media relations: radio, television Plongée dans le service de Néonatologie du CHUV Mise au point Western Switzerland 04.12.2011
Media relations: print media, online media The world in the Womb GEO International 01.04.2010

Awards

Title Year
Gottfried und Julia Bangerter-Rhyner-Stiftung 2012
SNF Project Basic Research 2012
Max Cloëtta 2011
Zurich Center for Integrative Human Physiology (ZIHP) 2011

Associated projects

Number Title Start Funding scheme
128015 Ectopic niche formation by grafted neural stem/progenitors in the ischemic cerebral cortex 01.01.2010 SCOPES
140334 From Cortex to Classroom: Enhancing Brain Development for Premature Infants 01.10.2012 SPUM
135581 Nutrition et lésion du cerveau en développement: Neuroprotection par la lactoferrin des lésions cérébrales du prématuré 01.08.2011 Project funding (Div. I-III)
135817 Development of Emotion and Cognition in Preterm Born Cohorts: Neurostructural and Neurofunctional Correlates from Birth to Early Adolescence 01.10.2011 Project funding (special)
163084 Building the path to resilience in preterm infants: a neuroimaging investigation of the impact of multisensory and neurocognitive interventions 01.02.2016 Project funding (special)
140334 From Cortex to Classroom: Enhancing Brain Development for Premature Infants 01.10.2012 SPUM
141007 Characterizing the role of the RNA-binding protein RBM3 in neuroprotection and neuronal cell differentiation 01.07.2012 Project funding (Div. I-III)
182832 Building the path to resilience after preterm birth: cortical development and network based interventions in longitudinal cohorts 01.02.2019 Project funding (Div. I-III)

Abstract

Currently the rate for prematurity is the highest it has been in over 20 years. Long-term survival for premature infants has become an almost expected outcome over the past two decades due to improved neonatal care, but unfortunately often associated with perinatal brain damage and long-term developmental disabilities,such as cerebral palsy, mental retardation and a wide spectrum of learning disabilities. A critical feature of neonatal brain damage is that, in addition to the acute damage, neuronal circuits pursue developmental processes with a significant cell loss. This could lead to disruption of normal developmental processes and even more dramatic deterioration of brain functions. The key issue is to understand how, where and when these changes take place and to understand the cellular and molecular mechanisms of these processes. This will be important for developing new strategies to improve tissue repair and the subsequent development of preserved cortical circuits. The Cortex to Classroom programme is a specific targeted programme including research projects dedicated to young clinician scientists,and designed to (1) understand the effects of prematurity on long-term structural and functional brain development, (2) identify early markers of perinatal brain damage and its underlying mechanism and (3) target endogenous and exogenous molecules for potential neuroprotective and neuroregenerative intervention (e.g. Erythropoietin). One important objective of the project will be to use and to develop animal models of functional recovery which will represent a point of convergence between clinicians and basic scientists and simultaneously allow for addressing issues of medical relevance and testing molecular hypotheses, with a study design which uses methodology, such as magnetic resonance imaging and neuro-electrophysiology, that allows translation from animal to human and vice-versa. The current research is aimed at finding new strategies to help reduce the enormous individual, familial, and societal burden that perinatal brain damage in premature infants represents. It is this consortiums goal to contribute to an improvement of this situation for future generations.
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