Subventricular zone stem cell niche injury is associated with intestinal perforation in preterm infants and predicts future motor impairment

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.

Keywords: cerebral palsy; cranial ultrasound; ependymal; inflammasome; intestinal perforation; necrotizing enterocolitis; neonatal brain injury; neural stem cell; neurodevelopmental outcome; niche; preterm infant; subventricular zone; white matter injury.

MeSH terms

  • Animals
  • Brain Injuries* / complications
  • Brain Injuries* / diagnostic imaging
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Infant, Premature
  • Intestinal Perforation* / complications
  • Lateral Ventricles
  • Mice
  • Motor Disorders* / complications
  • Premature Birth*
  • Stem Cell Niche