Baud Olivier, Daire Jean-Luc, Dalmaz Yvette, Fontaine Romain H, Krueger Richard C, Sebag Guy, Evrard Philippe, Gressens Pierre, Verney Catherine
Laboratoire de Neurobiologie du Développement, INSERM E9935, Service de Néonatologie et Service de Neurologie, Hôpital Robert Debré, Paris, France.
Brain Pathol. 2004 Jan;14(1):1-10. doi: 10.1111/j.1750-3639.2004.tb00492.x.
In the premature infant, periventricular leukomalacia, usually related to hypoxicischemic white matter damage, is the main cause of neurological impairment. We hypothesized that protracted prenatal hypoxia might induce white matter damage during the perinatal period. Pregnant Sprague-Dawley rats were placed in a chamber supplied with hypoxic gas (10% O2-90% N2) from embryonic day 5 (E5) to E20. Neonatal rat brains were investigated by histology, immunocytochemistry, western blotting, in situ hybridization, DNA fragmentation analysis, and in vivo magnetic resonance imaging (MRI). Body weight of pups subjected to prenatal hypoxia was 10 to 30% lower from P0 to P14 than in controls. Specific white matter cysts were detected between P0 and P7 in pups subjected to prenatal hypoxia, in addition to abnormal extra-cellular matrix, increased lipid peroxidation, white matter cell death detected by TUNEL, and increased activated macrophage counts in white matter. Subsequently, gliotic scars and delayed myelination primarily involving immature oligodendrocytes were seen. In vivo MRI with T1, T2, and diffusion sequences disclosed similar findings immediately after birth, showing strong correlations with histological abnormalities. We speculate that protracted prenatal hypoxia in rat induces white matter damage occurring through local inflammatory response and oxidative stress linked to re-oxygenation during the perinatal period.
在早产儿中，脑室周围白质软化通常与缺氧缺血性白质损伤有关，是神经功能障碍的主要原因。我们推测，长时间的产前缺氧可能在围产期诱发白质损伤。将怀孕的斯普拉格-道利大鼠从胚胎第5天（E5）至E20置于供应缺氧气体（10%氧气-90%氮气）的舱室中。通过组织学、免疫细胞化学、蛋白质印迹、原位杂交、DNA片段分析和体内磁共振成像（MRI）对新生大鼠脑进行研究。产前缺氧的幼崽从出生后第0天（P0）至P14的体重比对照组低10%至30%。除了细胞外基质异常、脂质过氧化增加、TUNEL检测到的白质细胞死亡以及白质中活化巨噬细胞计数增加外，在产前缺氧的幼崽中，在P0至P7期间还检测到特定的白质囊肿。随后，出现了主要累及未成熟少突胶质细胞的胶质瘢痕和髓鞘形成延迟。出生后立即进行的T1、T2和扩散序列的体内MRI显示了类似的结果，与组织学异常有很强的相关性。我们推测，大鼠长时间的产前缺氧会诱发白质损伤，其发生机制是通过围产期与再氧合相关的局部炎症反应和氧化应激。
