Abnormal neurogenesis and cortical growth in congenital heart disease

Paul D. Morton, Ludmila Korotcova, Bobbi K. Lewis, Shivaprasad Bhuvanendran, Shruti D. Ramachandra, David Zurakowski, Jiangyang Zhang, Susumu Mori, Joseph A. Frank, Richard A. Jonas, Vittorio Gallo, Nobuyuki Ishibashi

Research output: Contribution to journalArticlepeer-review

Abstract

Long-term neurological deficits due to immature cortical development are emerging as a major challenge in congenital heart disease (CHD). However, cellular mechanisms underlying dysregulation of perinatal corticogenesis in CHD remain elusive. The subventricular zone (SVZ) represents the largest postnatal niche of neural stem/progenitor cells (NSPCs). We show that the piglet SVZ resembles its human counterpart and displays robust postnatal neurogenesis. We present evidence that SVZ NSPCs migrate to the frontal cortex and differentiate into interneurons in a region-specific manner. Hypoxic exposure of the gyrencephalic piglet brain recapitulates CHD-induced impaired cortical development. Hypoxia reduces proliferation and neurogenesis in the SVZ, which is accompanied by reduced cortical growth. We demonstrate a similar reduction in neuroblasts within the SVZ of human infants born with CHD. Our findings demonstrate that SVZ NSPCs contribute to perinatal corticogenesis and suggest that restoration of SVZ NSPCs' neurogenic potential is a candidate therapeutic target for improving cortical growth in CHD. 2017

Original languageEnglish (US)
Article numbereaah7029
JournalScience translational medicine
Volume9
Issue number374
DOIs
StatePublished - Jan 25 2017

ASJC Scopus subject areas

  • Medicine(all)

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