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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Standard

White Matter Brain Development after Exposure to Circulating Cell-Free Hemoglobin and Hyperoxia in a Rat Pup Model. / Jungner, Åsa; Vallius Kvist, Suvi; Romantsik, Olga; Bruschettini, Matteo; Ekström, Claes; Bendix, Ivo; Herz, Josephine; Felderhoff-Mueser, Ursula; Bibic, Adnan; In'T Zandt, René; Gram, Magnus; Ley, David.

I: Developmental Neuroscience, Vol. 41, Nr. 3-4, 02.2020, s. 234-246.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

APA

CBE

MLA

Vancouver

Author

RIS

TY - JOUR

T1 - White Matter Brain Development after Exposure to Circulating Cell-Free Hemoglobin and Hyperoxia in a Rat Pup Model

AU - Jungner, Åsa

AU - Vallius Kvist, Suvi

AU - Romantsik, Olga

AU - Bruschettini, Matteo

AU - Ekström, Claes

AU - Bendix, Ivo

AU - Herz, Josephine

AU - Felderhoff-Mueser, Ursula

AU - Bibic, Adnan

AU - In'T Zandt, René

AU - Gram, Magnus

AU - Ley, David

PY - 2020/2

Y1 - 2020/2

N2 - 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.

AB - 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.

KW - Cardiopulmonary bypass

KW - Cell-free hemoglobin

KW - Hyperoxia

KW - Oligodendrocyte

KW - White matter

U2 - 10.1159/000505206

DO - 10.1159/000505206

M3 - Article

C2 - 31991415

AN - SCOPUS:85078949672

VL - 41

SP - 234

EP - 246

JO - Developmental Neuroscience

JF - Developmental Neuroscience

SN - 1421-9859

IS - 3-4

ER -