The brain of fetuses with congenital diaphragmatic hernia shows signs of hypoxic injury with loss of progenitor cells, neurons, and oligodendrocytes.
Cerebral perfusion
Congenital diaphragmatic hernia
Hypoxia
Intrathoracic compression
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
13 06 2024
13 06 2024
Historique:
received:
28
01
2024
accepted:
08
06
2024
medline:
14
6
2024
pubmed:
14
6
2024
entrez:
13
6
2024
Statut:
epublish
Résumé
Congenital diaphragmatic hernia (CDH) is a birth defect characterized by incomplete closure of the diaphragm, herniation of abdominal organs into the chest, and compression of the lungs and the heart. Besides complications related to pulmonary hypoplasia, 1 in 4 survivors develop neurodevelopmental impairment, whose etiology remains unclear. Using a fetal rat model of CDH, we demonstrated that the compression exerted by herniated organs on the mediastinal structures results in decreased brain perfusion on ultrafast ultrasound, cerebral hypoxia with compensatory angiogenesis, mature neuron and oligodendrocyte loss, and activated microglia. In CDH fetuses, apoptosis was prominent in the subventricular and subgranular zones, areas that are key for neurogenesis. We validated these findings in the autopsy samples of four human fetuses with CDH compared to age- and sex-matched controls. This study reveals the molecular mechanisms and cellular changes that occur in the brain of fetuses with CDH and creates opportunities for therapeutic targets.
Identifiants
pubmed: 38871804
doi: 10.1038/s41598-024-64412-x
pii: 10.1038/s41598-024-64412-x
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
13680Subventions
Organisme : Natural Sciences and Engineering Research Council of Canada (NSERC)
ID : RGPIN-2021-03539
Organisme : Canadian Institutes of Health Research (CIHR) Project Grant
ID : 175300
Organisme : SickKids Congenital Diaphragmatic Hernia Fund
ID : R00DH00000
Informations de copyright
© 2024. The Author(s).
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