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Pediatr Res. 2013 Dec;74(6):658-67. doi: 10.1038/pr.2013.155. Epub 2013 Sep 3.

Erythropoietin signaling promotes oligodendrocyte development following prenatal systemic hypoxic-ischemic brain injury.

Author information

1
Departments of Neurosurgery and Neurology, F.M. Kirby Center for Neurobiology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
2
Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio.

Abstract

BACKGROUND:

Brain injury from preterm birth causes white matter injury (WMI), and it leads to chronic neurological deficits including cerebral palsy, epilepsy, cognitive, and behavioral delay. Immature O4+ oligodendrocytes are particularly vulnerable to WMI. Understanding how the developing brain recovers after injury is essential to finding more effective therapeutic strategies. Erythropoietin (EPO) promotes neuronal recovery after injury; however, its role in enhancing oligodendroglial lineage recovery is unclear. Previously, we found that recombinant EPO (rEPO) treatment enhances myelin basic protein (MBP) expression and functional recovery in adult rats after prenatal transient systemic hypoxia-ischemia (TSHI). We hypothesized that after injury, rEPO would enhance oligodendroglial lineage cell genesis, survival, maturation, and myelination.

METHODS:

In vitro assays were used to define how rEPO contributes to specific stages of oligodendrocyte development and recovery after TSHI.

RESULTS:

After prenatal TSHI injury, rEPO promotes genesis of oligodendrocyte progenitors from oligodendrospheres, survival of oligodendrocyte precursor cells (OPCs) and O4+ immature oligodendrocytes, O4+ cell process extension, and MBP expression. rEPO did not alter OPC proliferation.

CONCLUSION:

Together, these studies demonstrate that EPO signaling promotes critical stages of oligodendroglial lineage development and recovery after prenatal TSHI injury. EPO treatment may be beneficial to preterm and other infant patient populations with developmental brain injury hallmarked by WMI.

PMID:
24108187
PMCID:
PMC3865073
DOI:
10.1038/pr.2013.155
[Indexed for MEDLINE]
Free PMC Article

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