title: Abnormal neurogenesis and cortical growth in congenital heart disease.
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.
authors.affiliation: Center for Neuroscience Research, Children's National Health System, Washington, DC 20010, USA.|Children's National Heart Institute, Children's National Health System, Washington, DC 20010, USA.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Morton
authors.affiliation: Center for Neuroscience Research, Children's National Health System, Washington, DC 20010, USA.|Children's National Heart Institute, Children's National Health System, Washington, DC 20010, USA.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Korotcova
authors.affiliation: Frank Laboratory and Laboratory of Diagnostic Radiology Research, Department of Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Bobbi K
authors.initials: BK
authors.lastname: Lewis
authors.affiliation: Center for Genetic Medicine Research, Children's National Health System, Washington, DC 20010, USA.
authors.forename: Shivaprasad
authors.initials: S
authors.lastname: Bhuvanendran
authors.affiliation: Center for Neuroscience Research, Children's National Health System, Washington, DC 20010, USA.|Children's National Heart Institute, Children's National Health System, Washington, DC 20010, USA.
authors.forename: Shruti D
authors.initials: SD
authors.lastname: Ramachandra
authors.affiliation: Departments of Anesthesia and Surgery, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: David
authors.initials: D
authors.lastname: Zurakowski
authors.affiliation: Department of Biomedical Engineering and The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Jiangyang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering and The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Susumu
authors.initials: S
authors.lastname: Mori
authors.affiliation: Frank Laboratory and Laboratory of Diagnostic Radiology Research, Department of Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD 20892, USA.|Intramural Research Program, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Frank
authors.affiliation: Center for Neuroscience Research, Children's National Health System, Washington, DC 20010, USA. vgallo@childrensnational.org nishibas@childrensnational.org rjonas@childrensnational.org.|Children's National Heart Institute, Children's National Health System, Washington, DC 20010, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Jonas
authors.affiliation: Center for Neuroscience Research, Children's National Health System, Washington, DC 20010, USA. vgallo@childrensnational.org nishibas@childrensnational.org rjonas@childrensnational.org.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Gallo
authors.affiliation: Center for Neuroscience Research, Children's National Health System, Washington, DC 20010, USA. vgallo@childrensnational.org nishibas@childrensnational.org rjonas@childrensnational.org.|Children's National Heart Institute, Children's National Health System, Washington, DC 20010, USA.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Ishibashi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002465:Cell Movement; D005625:Frontal Lobe / Q000254:growth & development / Q000473:pathology*; D006333:Heart Failure / Q000151:congenital / Q000473:pathology*; D000860:Hypoxia / Q000473:pathology; D007395:Interneurons / Q000166:cytology; D058953:Neural Stem Cells / Q000166:cytology; D055495:Neurogenesis; D009457:Neuroglia / Q000166:cytology; D009474:Neurons / Q000166:cytology; D055153:Stem Cell Niche; D013234:Stem Cells / Q000166:cytology; D013552:Swine