Role of instrumented fetal sheep preparations in defining the pathogenesis of human periventricular white-matter injury
Role of instrumented fetal sheep preparations in defining the pathogenesis of human periventricular white-matter injury
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DOI：
10.1177/08830738060210070101
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发表时间：
2006-07-01
影响因子：
1.9
通讯作者：
Hohimer, A. Roger
中科院分区：
文献类型：
--
作者：
Back, Stephen A.;Riddle, Art;Hohimer, A. Roger
脑室周围白质损伤是与早产相关的脑损伤的主要形式，也是早产幸存者脑性瘫痪的主要原因。在了解脑室周围白质损伤的发病机制的进展，需要开发的动物模型，是相关的早产儿大脑的独特的生理和复制的主要神经病理特征的人类损伤。绵羊是研究最广泛的真正的胎儿准备。早产羊胎（妊娠0.65周）的神经发育与约24 - 28周的早产人相当。胎羊围栏的大小可以长期使用，因此可以通过可靠的脑白质血流和代谢测量来研究明确的损伤。我们在这里回顾了最近的进展，了解脑缺氧缺血和脆弱的少突胶质细胞祖细胞在未成熟的羊胎儿脑室周围白质损伤的发病机制中的作用。我们专注于高分辨率空间定义的脑血流测量在子宫内的最新发展。我们确定了绵羊的白质成熟90和120天的妊娠，少突胶质细胞谱系特异性抗体的免疫组织化学定位的定义。在未成熟的脑室周围白质中，少突胶质细胞的成熟存在相当大的空间和时间异质性。90- 105天胎羊的少突胶质细胞成熟与早产儿脑白质损伤高危期的人的少突胶质细胞成熟密切相关。因此，90- 105天胎儿脑室周围白质的不成熟状态是研究细胞成熟因子在白质损伤发病机制中的作用的最佳和动态的发育窗口。最后，我们回顾了仪器化胎羊的显著优势，以加速脑室周围白质损伤和脑瘫预防性治疗的进展。
Periventricular white-matter injury is the major form of brain injury associated with prematurity and the leading cause of cerebral palsy in survivors of premature birth. Progress in understanding the pathogenesis of periventricular white-matter injury requires the development of animal models that are relevant to the unique physiology of the preterm human brain and that replicate the major neuropathologic features of human injury. The sheep is the most extensively studied true fetal preparation. The neurodevelopment of the preterm sheep fetus (0.65 gestation) is comparable to that of the preterm human between approximately 24 and 28 weeks. The size of the fetal sheep pen-nits chronic instrumentation so that well-defined insults can be studied with reliable measurements of blood flow and metabolism in cerebral white-matter. We review here recent developments in the understanding of the role of cerebral hypoxia-ischemia and vulnerable oligodendrocyte progenitors in the pathogenesis of periventricular white-matter injury in the immature sheep fetus. We focus on recent developments in high-resolution spatially defined cerebral blood flow measurements in utero. We determined ovine white-matter maturation between 90 and 120 days' gestation, as defined by immunohistochemical localization of oligodendrocyte lineage-specific antibodies. There was considerable spatial and temporal heterogeneity in oligodendrocyte maturation in the immature periventricular white-matter. Oligodendrocyte maturation in the 90- to 105-day fetal sheep closely coincided with that of the preterm human during the high-risk period for white-matter injury. Hence, the immature state of the 90- to 105-day fetal periventricular white-matter is an optimal and dynamic developmental window to study the role of cellular-maturational factors in the pathogenesis of white-matter injury. We conclude with a review of the significant advantages of the instrumented fetal sheep to accelerate progress in the translation of preventive therapies for periventricular white-matter injury and cerebral palsy.