White Matter Brain Development after Exposure to Circulating Cell-Free Hemoglobin and Hyperoxia in a Rat Pup Model

Åsa Jungner, Suvi Vallius Kvist, Olga Romantsik, Matteo Bruschettini, Claes Ekström, Ivo Bendix, Josephine Herz, Ursula Felderhoff-Mueser, Adnan Bibic, René In'T Zandt, Magnus Gram, David Ley

Research output: Contribution to journalArticlepeer-review


Neonates born with critical congenital heart defects are at risk of diffuse white matter injuries and neurodevelopmental impairments. This study aimed to determine the impact of circulating cell-free hemoglobin and hyperoxia, both present during cardiopulmonary bypass circulation, on white matter brain development. Postnatal day 6 rat pups were injected intraperitoneally with cell-free Hb or vehicle and exposed to hyperoxia (fiO2 = 0.8) or normoxia (fiO2 = 0.21) for 24 h. We evaluated apoptosis, myelination, and oligodendrocyte maturation with immunohistochemistry, gene and protein analyses, and in vivo diffusion tensor magnetic resonance imaging (MRI). Consistent with previous studies, we found an increase in apoptosis of oligodendrocytes as determined by TUNEL+ staining in Olig2+ cells in white matter, cortex, thalamus, and hippocampus following exposure to hyperoxia with no additional effect of cell-free Hb. A transient increase in the mRNA expression of intercellular adhesion molecule 1 at 6 h was observed following combined exposure to cell-free Hb and hyperoxia. No indications of oligodendrocyte maturational delay or hypomyelination were observed after either insult, delivered separately or combined, as determined by immunohistochemistry, Western blot, and diffusion tensor MRI. In our model, exposure to circulatory cell-free Hb, with or without concomitant hyperoxia, did not significantly alter brain white matter development.

Original languageEnglish
Pages (from-to)234-246
Number of pages13
JournalDevelopmental Neuroscience
Issue number3-4
Early online date2020
Publication statusPublished - 2020 Feb

Subject classification (UKÄ)

  • Neurosciences
  • Cell and Molecular Biology

Free keywords

  • Cardiopulmonary bypass
  • Cell-free hemoglobin
  • Hyperoxia
  • Oligodendrocyte
  • White matter


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