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

Jungner, Åsa LU ; Vallius Kvist, Suvi LU ; Romantsik, Olga LU ; Bruschettini, Matteo LU ; Ekström, Claes LU ; Bendix, Ivo ; Herz, Josephine ; Felderhoff-Mueser, Ursula ; Bibic, Adnan LU and In'T Zandt, René LU , et al. (2020) In Developmental Neuroscience
Abstract

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... (More)

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.

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keywords
Cardiopulmonary bypass, Cell-free hemoglobin, Hyperoxia, Oligodendrocyte, White matter
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Developmental Neuroscience
publisher
Karger
external identifiers
  • scopus:85078949672
  • pmid:31991415
ISSN
0378-5866
DOI
10.1159/000505206
language
English
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yes
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37b07f5e-c236-49ec-999e-ccedf8620bce
date added to LUP
2020-02-18 15:13:07
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2020-02-26 07:42:01
@article{37b07f5e-c236-49ec-999e-ccedf8620bce,
  abstract     = {<p>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 (f<sub>i</sub>O<sub>2</sub> = 0.8) or normoxia (f<sub>i</sub>O<sub>2</sub> = 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.</p>},
  author       = {Jungner, Åsa and Vallius Kvist, Suvi and Romantsik, Olga and Bruschettini, Matteo and Ekström, Claes and Bendix, Ivo and Herz, Josephine and Felderhoff-Mueser, Ursula and Bibic, Adnan and In'T Zandt, René and Gram, Magnus and Ley, David},
  issn         = {0378-5866},
  language     = {eng},
  publisher    = {Karger},
  series       = {Developmental Neuroscience},
  title        = {White Matter Brain Development after Exposure to Circulating Cell-Free Hemoglobin and Hyperoxia in a Rat Pup Model},
  url          = {http://dx.doi.org/10.1159/000505206},
  doi          = {10.1159/000505206},
  year         = {2020},
}