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_iO₂ = 0.8) or normoxia (f_iO₂ = 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.
Dev Neurosci 2019;41:234–246

中文翻译：

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暴露于大鼠幼犬模型中的循环无细胞血红蛋白和高氧血症后，白色物质的大脑发育。

患有严重先天性心脏缺陷的新生儿有弥漫性白质损伤和神经发育障碍的风险。这项研究旨在确定在体外循环中存在的无细胞血红蛋白和高氧循环对白质脑发育的影响。产后第6天的幼鼠腹膜内注射无细胞的Hb或载体，并暴露于高氧血症（f _i O ₂ = 0.8）或常氧（f _i O ₂= 0.21）24小时。我们通过免疫组织化学，基因和蛋白质分析以及体内扩散张量磁共振成像（MRI）评估了凋亡，髓鞘形成和少突胶质细胞成熟。与以前的研究一致，我们发现通过高氧暴露后白质，皮层，丘脑和海马的Olig2 +细胞中TUNEL +染色可确定少突胶质细胞的凋亡增加，而无细胞Hb则无其他影响。联合暴露于无细胞的Hb和高氧后，在6小时时观察到细胞间粘附分子1的mRNA表达瞬时增加。通过免疫组化，Western印迹和扩散张量MRI确定，在损伤，单独递送或联合给药后均未观察到少突胶质细胞成熟延迟或髓鞘减少的迹象。在我们的模型中
Dev Neurosci 2019; 41：234–246