Department of Pediatrics, Division of Neonatology, Duke University School of Medicine, Durham, NC, USA.
Department of Radiology, Duke University School of Medicine, Durham, NC, USA.
Cell Stem Cell. 2024 Apr 4;31(4):467-483.e6. doi: 10.1016/j.stem.2024.03.001. Epub 2024 Mar 26.
Brain injury is highly associated with preterm birth. Complications of prematurity, including spontaneous or necrotizing enterocolitis (NEC)-associated intestinal perforations, are linked to lifelong neurologic impairment, yet the mechanisms are poorly understood. Early diagnosis of preterm brain injuries remains a significant challenge. Here, we identified subventricular zone echogenicity (SVE) on cranial ultrasound in preterm infants following intestinal perforations. The development of SVE was significantly associated with motor impairment at 2 years. SVE was replicated in a neonatal mouse model of intestinal perforation. Examination of the murine echogenic subventricular zone (SVZ) revealed NLRP3-inflammasome assembly in multiciliated FoxJ1 ependymal cells and a loss of the ependymal border in this postnatal stem cell niche. These data suggest a mechanism of preterm brain injury localized to the SVZ that has not been adequately considered. Ultrasound detection of SVE may serve as an early biomarker for neurodevelopmental impairment after inflammatory disease in preterm infants.
脑损伤与早产儿高度相关。早产儿的并发症，包括自发性或坏死性小肠结肠炎（NEC）相关的肠穿孔，与终身神经功能障碍有关，但机制尚不清楚。早产儿脑损伤的早期诊断仍然是一个重大挑战。在这里，我们在肠穿孔后的早产儿头颅超声中发现了侧脑室下区回声增强（SVE）。SVE 的发展与 2 岁时的运动障碍显著相关。SVE 在肠穿孔的新生小鼠模型中得到了复制。对具有回声的鼠侧脑室下区（SVZ）的检查显示，多纤毛 FoxJ1 室管膜细胞中 NLRP3 炎性小体的组装，以及在这个出生后干细胞龛中的室管膜边界丧失。这些数据表明，一种局限于 SVZ 的早产儿脑损伤机制尚未得到充分考虑。SVE 的超声检测可能成为早产儿炎症性疾病后神经发育障碍的早期生物标志物。
