Children's National Heart Institute, Children's National Health System, Washington, DC.
Center for Neuroscience Research, Children's National Health System, Washington, DC.
J Am Heart Assoc. 2017 Aug 15;6(8):e005997. doi: 10.1161/JAHA.117.005997.
Newly developed white matter (WM) injury is common after cardiopulmonary bypass (CPB) in severe/complex congenital heart disease. Fractional anisotropy (FA) allows measurement of macroscopic organization of WM pathology but has rarely been applied after CPB. The aims of our animal study were to define CPB-induced FA alterations and to determine correlations between these changes and cellular events after congenital heart disease surgery.
Normal porcine WM development was first assessed between 3 and 7 weeks of age: 3-week-old piglets were randomly assigned to 1 of 3 CPB-induced insults. FA was analyzed in 31 WM structures. WM oligodendrocytes, astrocytes, and microglia were assessed immunohistologically. Normal porcine WM development resembles human WM development in early infancy. We found region-specific WM vulnerability to insults associated with CPB. FA changes after CPB were also insult dependent. Within various WM areas, WM within the frontal cortex was susceptible, suggesting that FA in the frontal cortex should be a biomarker for WM injury after CPB. FA increases occur parallel to cellular processes of WM maturation during normal development; however, they are altered following surgery. CPB-induced oligodendrocyte dysmaturation, astrogliosis, and microglial expansion affect these changes. FA enabled capturing CPB-induced cellular events 4 weeks postoperatively. Regions most resilient to CPB-induced FA reduction were those that maintained mature oligodendrocytes.
Reducing alterations of oligodendrocyte development in the frontal cortex can be both a metric and a goal to improve neurodevelopmental impairment in the congenital heart disease population. Studies using this model can provide important data needed to better interpret human imaging studies.
体外循环（CPB）后，严重/复杂先天性心脏病患者常出现新的脑白质损伤。各向异性分数（FA）可用于测量脑白质病变的宏观组织结构，但在 CPB 后很少应用。本动物研究的目的是确定 CPB 引起的 FA 改变，并确定这些改变与先天性心脏病手术后的细胞事件之间的相关性。
首先评估了 3 至 7 周龄正常猪脑白质的发育情况：3 周龄仔猪被随机分配到 3 种 CPB 诱导损伤中的 1 种。在 31 个脑白质结构中分析 FA。通过免疫组织化学评估脑白质少突胶质细胞、星形胶质细胞和小胶质细胞。正常猪脑白质的发育与人类婴儿早期的脑白质发育相似。我们发现 CPB 相关损伤具有特定区域的脑白质易损性。CPB 后 FA 的改变也与损伤有关。在各种脑白质区域中，额叶脑白质易受影响，这表明 CPB 后额叶脑白质的 FA 应该是脑白质损伤的生物标志物。CPB 诱导的少突胶质细胞发育不良、星形胶质细胞增生和小胶质细胞扩张影响了这些变化。FA 可捕获 CPB 术后 4 周的细胞事件。对 CPB 诱导的 FA 降低最具抵抗力的区域是那些保持成熟少突胶质细胞的区域。
减少 CPB 诱导的额叶脑白质少突胶质细胞发育改变既可以作为一种指标，也可以作为改善先天性心脏病患者神经发育障碍的目标。使用该模型的研究可以提供更好地解释人类影像学研究所需的重要数据。
