PDF(Pubmed)
Abstract：
Congenital diaphragmatic hernia (CDH) is a birth defect characterized by incomplete closure of the diaphragm, herniation of abdominal organs into the chest, and compression of the lungs and the heart. Besides complications related to pulmonary hypoplasia, 1 in 4 survivors develop neurodevelopmental impairment, whose etiology remains unclear. Using a fetal rat model of CDH, we demonstrated that the compression exerted by herniated organs on the mediastinal structures results in decreased brain perfusion on ultrafast ultrasound, cerebral hypoxia with compensatory angiogenesis, mature neuron and oligodendrocyte loss, and activated microglia. In CDH fetuses, apoptosis was prominent in the subventricular and subgranular zones, areas that are key for neurogenesis. We validated these findings in the autopsy samples of four human fetuses with CDH compared to age- and sex-matched controls. This study reveals the molecular mechanisms and cellular changes that occur in the brain of fetuses with CDH and creates opportunities for therapeutic targets.
摘要：
先天性膈疝（CDH）是一种以膈肌闭合不完全为特征的出生缺陷，腹部器官突出到胸部，还有肺和心脏的压迫.除了与肺发育不全相关的并发症，四分之一的幸存者出现神经发育障碍，其病因尚不清楚。使用胎鼠CDH模型，我们证明了由突出器官对纵隔结构的压迫导致超快超声的脑灌注减少，脑缺氧代偿性血管生成，成熟神经元和少突胶质细胞丢失，和激活的小胶质细胞。在CDH胎儿中，细胞凋亡在脑室下和颗粒下区域突出，是神经发生的关键区域。与年龄和性别匹配的对照相比，我们在四个患有CDH的人类胎儿的尸检样本中验证了这些发现。这项研究揭示了CDH胎儿大脑中发生的分子机制和细胞变化，并为治疗目标创造了机会。
