Impact of Cardiopulmonary Bypass on Neurogenesis and Cortical Maturation.


Journal

Annals of neurology
ISSN: 1531-8249
Titre abrégé: Ann Neurol
Pays: United States
ID NLM: 7707449

Informations de publication

Date de publication:
12 2021
Historique:
revised: 22 09 2021
received: 21 06 2021
accepted: 26 09 2021
pubmed: 1 10 2021
medline: 15 12 2021
entrez: 30 9 2021
Statut: ppublish

Résumé

Neurodevelopmental delays and frontal lobe cortical dysmaturation are widespread among children with congenital heart disease (CHD). The subventricular zone (SVZ) is the largest pool of neural stem/progenitor cells in the postnatal brain. Our aim is to determine the effects of cardiopulmonary bypass (CPB) on neurogenesis and cortical maturation in piglets whose SVZ development is similar to human infants. Three-week-old piglets (n = 29) were randomly assigned to control (no surgery), mild-CPB (34°C full flow for 60 minutes) and severe-CPB groups (25°C circulatory-arrest for 60 minutes). The SVZ and frontal lobe were analyzed with immunohistochemistry 3 days and 4 weeks postoperatively. MRI of the frontal lobe was used to assess cortical development. SVZ neurogenic activity was reduced up to 4 weeks after both mild and severe CPB-induced insults. CPB also induced decreased migration of young neurons to the frontal lobe, demonstrating that CPB impairs postnatal neurogenesis. MRI 4 weeks after CPB displayed a decrease in gyrification index and cortical volume of the frontal lobe. Cortical fractional anisotropy was increased after severe CPB injury, indicating a prolonged deleterious impact of CPB on cortical maturation. Both CPB-induced insults displayed a significant change in densities of three major inhibitory neurons, suggesting excitatory-inhibitory imbalance in the frontal cortex. In addition, different CPB insults altered different subpopulations of inhibitory neurons. Our results provide novel insights into cellular mechanisms contributing to CHD-induced neurological impairments. Further refinement of CPB hardware and techniques is necessary to improve long-term frontal cortical dysmaturation observed in children with CHD. ANN NEUROL 2021;90:913-926.

Identifiants

pubmed: 34590341
doi: 10.1002/ana.26235
pmc: PMC8639674
mid: NIHMS1744637
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

913-926

Subventions

Organisme : NIMHD NIH HHS
ID : U54MD007597
Pays : United States
Organisme : Foundation for the National Institutes of Health
ID : R01HL139712
Organisme : Foundation for the National Institutes of Health
ID : U54HD090257
Organisme : NIMHD NIH HHS
ID : U54 MD007597
Pays : United States
Organisme : NIMHD NIH HHS
ID : U24 MD015970
Pays : United States
Organisme : NICHD NIH HHS
ID : P50 HD105328
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL146670
Pays : United States
Organisme : DoD Peer Reviewed Medical Research Program
ID : W81XWH2010199
Organisme : Foundation for the National Institutes of Health
ID : R01HL146670
Organisme : NICHD NIH HHS
ID : U54 HD090257
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL139712
Pays : United States

Informations de copyright

© 2021 American Neurological Association.

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Auteurs

Zaenab Dhari (Z)

Children's National Heart Institute, Center for Neuroscience Research, Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Hospital, Washington, DC.

Camille Leonetti (C)

Children's National Heart Institute, Center for Neuroscience Research, Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Hospital, Washington, DC.

Stephen Lin (S)

Department of Radiology, Howard University, Washington, DC.

Arianna Prince (A)

Children's National Heart Institute, Center for Neuroscience Research, Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Hospital, Washington, DC.
George Washington University School of Medicine and Health Science, Washington, DC.

James Howick (J)

Children's National Heart Institute, Center for Neuroscience Research, Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Hospital, Washington, DC.

David Zurakowski (D)

Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA.

Paul C Wang (PC)

Department of Radiology, Howard University, Washington, DC.
Department of Electrical Engineering, Fu Jen Catholic University, New Taipei City, Taiwan.

Richard A Jonas (RA)

Children's National Heart Institute, Center for Neuroscience Research, Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Hospital, Washington, DC.
George Washington University School of Medicine and Health Science, Washington, DC.

Nobuyuki Ishibashi (N)

Children's National Heart Institute, Center for Neuroscience Research, Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Hospital, Washington, DC.
George Washington University School of Medicine and Health Science, Washington, DC.

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Classifications MeSH