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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 140334
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 01.10.2012 - 31.12.2016
Approved amount 2'988'556.00
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All Disciplines (2)

Discipline
Neurology, Psychiatry
Pathophysiology

Keywords (10)

Extracellular matrix; mechanism of cell death; premature infants; wnt signalling; imaging biomarker; brain development; neuroprotection; electrophysiology biomarker; cortex; erythropoietin

Lay Summary (English)

Lead
From Cortex to Classroom: Enhancing Brain Development for Premature InfantsLay summary; Research aim and project
Lay summary

Perinatal injury could lead to disruption of normal developmental processes and deterioration of brain functions. The Cortex to Classroom programme is a specific targeted programme including research projects 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.
One important objective of the initial project and its prolongation is to use and to develop animal models of functional recovery. This will represent the translational part between clinicians and basic scientists. This approach further allows for simultaneously addressing issues of medical relevance and testing molecular hypotheses using an animal study design that includes similar methodology as that for human studies, such as imaging, electro-physiology, behavioral testing and serum markers.
As a whole, the project will incorporate both animal studies (basic neuroscience) and applied research in human newborns (neuroimaging, EEG and clinical neurodevelopment) in order to identify new approaches for early diagnosis of brain damage and therapy to enhance brain development.

Direct link to Lay Summary Last update: 13.03.2015

Responsible applicant and co-applicants

Employees

Associated projects

Number Title Start Funding scheme
189096 Erythropoietin for the repair of cerebral injury in very preterm infants (EpoRepair) 01.01.2020 Project funding (Div. I-III)
124101 From cortex to classroom: enhancing brain development for premature infants 01.10.2009 SPUM
169848 Erythropoietin for the repair of cerebral injury in very preterm infants (EpoRepair) 01.01.2017 Project funding (Div. I-III)
159705 Temporal dynamics of whole-brain neuronal networks 01.05.2015 Project funding (Div. I-III)
124101 From cortex to classroom: enhancing brain development for premature infants 01.10.2009 SPUM
169848 Erythropoietin for the repair of cerebral injury in very preterm infants (EpoRepair) 01.01.2017 Project funding (Div. I-III)
173677 ROPROP 01.12.2018 ERA-NET
150828 Development of Advanced Translational High-Field MRI 12.05.2014 R'EQUIP

Abstract

The majority of premature infants is expected to survive the neonatal period due to improved neonatal care, but unfortunately outcome is often associated with long-term developmental disabilities, such as cerebral palsy, mental retardation, a wide spectrum of learning disabilities and a higher risk for neuro-psychiatric disorders. Current research goals focus on finding new strategies to help reduce the enormous individual, familial, and societal burden that perinatal brain damage and subsequent neurodevelopmental impairement in premature infants pose. This can be achieved either by preventing brain injury or by facilitating injury recovery following neonatal brain damage. Prevention of brain injury is a difficult task as the timing and involved mechanisms are not yet fully understood. Recovery of functions, on the other hand, represents a major challenge for current clinical and basic research. The data available from human and animal studies indicate that some capacity for functional recovery exists after perinatal injury, which relies on a limited regeneration and reorganization of preserved circuits. A critical feature of neonatal brain damage is that, in addition to the acute damage, neuronal circuits pursue developmental processes with significant cell loss and altered neuro-environment. This could lead to disruption of normal developmental processes and deterioration of brain functions. The key issue therefore is to understand how, where and when brain injury and neuronal circuit disruption take place and to delineate the cellular and molecular mechanisms of these processes. A better understanding will be critical 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. One important objective of the initial project and its prolongation is to use and to develop animal models of functional recovery. This will represent the translational part between clinicians and basic scientists. This approach further allows for simultaneously addressing issues of medical relevance and testing molecular hypotheses using an animal study design that includes similar methodology as that for human studies, such as imaging, electro-physiology, behavioral testing and serum markers.In the initial project we focussed on mechanisms of perinatal hypoxic/ischemic and inflammatory damage to the white and grey matter and the brain’s potential for regeneration through progenitor cells that arise from the subventricular zone. In the second part of the project, we will focus on effects of conditions such as intraventricular hemorrhage and intrauterine growth restriction on the brain development and repair. The project will incorporate both animal studies (basic neuroscience) and applied research in human new-borns (neuroimaging, EEG and clinical neurodevelopment) in order to identify new approaches for early diagnosis of brain damage and therapy to enhance brain development. Erythropoietin as a potential neuroprotective agent is tested both in the animal model as in clinical human trials. With this approach that covers both basic and clinical research we can fulfil this call’s requirement to put emphasis on translational research aimed at bringing basic knowledge through to clinical practice.This program project will enhance the state-of-the-art by• Initiating perinatal translational (bench-to-bedside) research in defining perinatal brain injury and repair • Enabling early detection by biomarker profiles of neonatal brain damage and repair and characterising differences between different causal pathways (infection/inflammation vs hypoxia-ischemia, intraventricular hemorrhage and intrauterine growth restriction) and the response to regeneration and repair• Providing new neuroprotective (EPO) and brain development enhancing strategies in newborns and addressing the key question of the role of stimulating endogenous neurogenesis in reversing functional deficits after neonatal brain damage• Developing marketable tools (biomarker & neuroimaging & EEG) to bring these goals into clinical neonatal intensive care practice•Establishing high risk well-documented cohorts of premature infants which will provide long-term neurocognitive outcome data to measure efficiency of neuro-enhancing therapies (clinical platform)•Introducing young clinician scientists to translational clinical research aimed at enhancing early brain development.
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