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

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.

• Authors: Daniela Hoeber, Marco Sifringer, Yohan van de Looij, Josephine Herz, Stéphane V Sizonenko, Karina Kempe, Meray Serdar, Joanna Palasz, Martin Hadamitzky, Stefanie Endesfelder, Joachim Fandrey, Ursula Felderhoff-Müser, Ivo Bendix
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2016 Pg. 9247493 ( 2016) ISSN: 1942-0994 [Electronic] United States
• PMID: 27493706 (Publication Type: Journal Article)

Chemical References

• Myelin Basic Protein
• Neuregulin-1
• Neuroprotective Agents
• Synaptophysin
• Erythropoietin
• Neuropilin-1

Topics

• Animals
• Animals, Newborn
• Behavior, Animal (drug effects)
• Brain Injuries (etiology, metabolism, pathology)
• Cell Survival (drug effects)
• Cognition (drug effects)
• Diffusion Tensor Imaging
• Disease Models, Animal
• Down-Regulation (drug effects)
• Erythropoietin (pharmacology)
• Hyperoxia
• Immunohistochemistry
• Microscopy, Confocal
• Mitochondria (metabolism)
• Myelin Basic Protein (metabolism)
• Neuregulin-1 (genetics, metabolism)
• Neuronal Plasticity (drug effects)
• Neuropilin-1 (genetics, metabolism)
• Neuroprotective Agents (pharmacology)
• Oligodendroglia (cytology, drug effects, metabolism)
• Rats
• Rats, Wistar
• Synaptophysin (genetics, metabolism)
• White Matter (drug effects, metabolism)