Systems approach to the study of brain damage in the very preterm newborn.
BACKGROUND
A systems approach to the study of brain damage in very preterm newborns has been lacking.


METHODS
In this perspective piece, we offer encephalopathy of prematurity as an example of the complexity and interrelatedness of brain-damaging molecular processes that can be initiated inflammatory phenomena.


RESULTS
Using three transcription factors, nuclear factor-kappa B (NF-κB), Notch-1, and nuclear factor erythroid 2 related factor 2 (NRF2), we show the inter-connectedness of signaling pathways activated by some antecedents of encephalopathy of prematurity.


CONCLUSIONS
We hope that as biomarkers of exposures and processes leading to brain damage in the most immature newborns become more readily available, those who apply a systems approach to the study of neuroscience can be persuaded to study the pathogenesis of brain disorders in the very preterm newborn.
Neuroepidemiology Unit, Boston Children's Hospital Boston, MA, USA ; Department of Neurology, Harvard Medical School Boston, MA, USA.
Alan
A
Leviton
Inserm, U1141 Paris, France ; Department of Perinatal Imaging and Health, Department of Division of Imaging Sciences and Biomedical Engineering, King's College London, King's Health Partners, St. Thomas' Hospital London, UK.
Pierre
P
Gressens
Department of Systems Biology and Bioinformatics, University of Rostock Rostock, Germany ; Stellenbosch Institute for Advanced Study (STIAS) Stellenbosch, South Africa.
Olaf
O
Wolkenhauer
Department of Public Health and Community Medicine, Tufts University School of Medicine Boston, MA, USA ; Perinatal Epidemiology Unit, Department of Gynecology and Obstetrics, Hannover Medical School Hannover, Germany.
Olaf
O
Dammann
Notch-1; brain; epigenetic; inflammation; nuclear factor erythroid 2 related factor 2 (NRF2); nuclear factor-kappa B (NF-κB); prematurity; systems biology