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Erythropoietin Restores Long-Term Neurocognitive Function Involving Mechanisms of Neuronal Plasticity in a Model of Hyperoxia-Induced Preterm Brain Injury

Hoeber, Daniela
Sifringer, Marco
Herz, Josephine
Kempe, Karina
Serdar, Meray
Palasz, Joanna
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Published in Oxidative Medicine and Cellular Longevity. 2016, vol. 2016, 9247493
Abstract Cerebral white and grey matter injury is the leading cause of an adverse neurodevelopmental outcome in prematurely born infants. High oxygen concentrations have been shown to contribute to the pathogenesis of neonatal brain damage. Here, we focused on motor-cognitive outcome up to the adolescent and adult age in an experimental model of preterm brain injury. In search of the putative mechanisms of action we evaluated oligodendrocyte degeneration, myelination, and modulation of synaptic plasticity-related molecules. A single dose of erythropoietin (20,000 IU/kg) at the onset of hyperoxia (24 hours, 80% oxygen) in 6-day-old Wistar rats improved long-lasting neurocognitive development up to the adolescent and adult stage. Analysis of white matter structures revealed a reduction of acute oligodendrocyte degeneration. However, erythropoietin did not influence hypomyelination occurring a few days after injury or long-term microstructural white matter abnormalities detected in adult animals. Erythropoietin administration reverted hyperoxia-induced reduction of neuronal plasticity-related mRNA expression up to four months after injury. Thus, our findings highlight the importance of erythropoietin as a neuroregenerative treatment option in neonatal brain injury, leading to improved memory function in adolescent and adult rats which may be linked to increased neuronal network connectivity.
Keywords AnimalsAnimals, NewbornBehavior, Animal/drug effectsBrain Injuries/etiology/metabolism/pathologyCell Survival/drug effectsCognition/drug effectsDiffusion Tensor ImagingDisease Models, AnimalDown-Regulation/drug effectsErythropoietin/pharmacologyHyperoxiaImmunohistochemistryMicroscopy, ConfocalMitochondria/metabolismMyelin Basic Protein/metabolismNeuregulin-1/genetics/metabolismNeuronal Plasticity/drug effectsNeuropilin-1/genetics/metabolismNeuroprotective Agents/pharmacologyOligodendroglia/cytology/drug effects/metabolismRatsRats, WistarSynaptophysin/genetics/metabolismWhite Matter/drug effects/metabolism
PMID: 27493706
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HOEBER, Daniela et al. Erythropoietin Restores Long-Term Neurocognitive Function Involving Mechanisms of Neuronal Plasticity in a Model of Hyperoxia-Induced Preterm Brain Injury. In: Oxidative medicine and cellular longevity, 2016, vol. 2016, p. 9247493. doi: 10.1155/2016/9247493 https://archive-ouverte.unige.ch/unige:97108

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Deposited on : 2017-09-27

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