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Transient Improvement of Cerebellar Oligodendroglial Development in a Neonatal Hyperoxia Model by PDGFA Treatment

Till Scheuer1, Luisa Sophie Klein1, Christoph Bührer1

  • 1Department for Neonatology, Charité University Medical Center, Berlin, Germany.

Developmental Neurobiology
|January 24, 2019
PubMed

Insights

High oxygen exposure in preterm infants damages cerebellar white matter. Platelet-derived growth factor-A (PDGFA) transiently improved oligodendrocyte proliferation and myelination in a rat model, but benefits were not long-lasting.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Neonatal Research

Background:

  • Preterm birth can lead to cerebellar white matter damage due to altered oxygen levels.
  • Hyperoxia exposure in neonatal rats mimics increased arterial oxygen tension, impacting cerebellar development.
  • Growth factor (GF) synthesis in cerebellar astrocytes and oligodendrocyte progenitor cell (OPC) function are critical for white matter development.

Purpose of the Study:

  • To investigate the effects of hyperoxia on GF synthesis in cerebellar astrocytes.
  • To analyze OPC function following hyperoxia exposure.
  • To evaluate the therapeutic potential of PDGFA in protecting oligodendroglia and promoting myelination in a neonatal hyperoxia model.

Main Methods:

  • Hyperoxia exposure (80% O2 for 24h) in a rat model from postnatal day 6 (P6) to P7.
  • Magnetic-activated cell sorting (MACS) isolation of cerebellar astrocytes and OPCs for ex vivo and in vitro analysis.
  • Assessment of GF expression (Pdgfa, Fgf2, Bdnf) in astrocytes and gene expression (Olig1, Olig2, Sox9, Sox10, Cnp) in OPCs.
  • Nasal administration of PDGFA from P6 to P11 to assess its protective effects on oligodendroglia and myelination (MBP expression).

Main Results:

  • Hyperoxia significantly reduced the expression of Pdgfa, Fgf2, and Bdnf in cerebellar astrocytes.
  • Gene expression of key oligodendrocyte markers (Olig1, Olig2, Sox9, Sox10, Cnp) was decreased in OPCs following hyperoxia.
  • Nasal PDGFA administration transiently improved oligodendroglial proliferation and attenuated impaired myelin basic protein (MBP) expression, but these effects diminished after treatment cessation.

Conclusions:

  • Neonatal cerebellar injury due to hyperoxia impairs astrocyte growth factor synthesis and oligodendrocyte development.
  • PDGFA treatment shows promise for improving oligodendroglial proliferation and myelination in the short term.
  • The therapeutic benefits of PDGFA are not sustained long-term, highlighting the need for further research into sustained treatment strategies for neonatal cerebellar white matter injury.

Keywords:
astrogliacerebellumhyperoxiaoligodendrogliapreterm birth

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