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Sci Transl Med. 2017 Jan 25;9(374). pii: eaah7029. doi: 10.1126/scitranslmed.aah7029.

Abnormal neurogenesis and cortical growth in congenital heart disease.

Author information

1
Center for Neuroscience Research, Children's National Health System, Washington, DC 20010, USA.
2
Children's National Heart Institute, Children's National Health System, Washington, DC 20010, USA.
3
Frank Laboratory and Laboratory of Diagnostic Radiology Research, Department of Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD 20892, USA.
4
Center for Genetic Medicine Research, Children's National Health System, Washington, DC 20010, USA.
5
Departments of Anesthesia and Surgery, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
6
Department of Biomedical Engineering and The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
7
Intramural Research Program, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, USA.
8
Center for Neuroscience Research, Children's National Health System, Washington, DC 20010, USA. vgallo@childrensnational.org nishibas@childrensnational.org rjonas@childrensnational.org.

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.

PMID:
28123074
PMCID:
PMC5467873
DOI:
10.1126/scitranslmed.aah7029
[Indexed for MEDLINE]
Free PMC Article

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