The brain of fetuses with congenital diaphragmatic hernia shows signs of hypoxic injury with loss of progenitor cells, neurons, and oligodendrocytes

Autor: George Biouss, Lina Antounians, Julien Aguet, Katarina Kopcalic, Nikan Fakhari, Jerome Baranger, Luc Mertens, Olivier Villemain, Augusto Zani
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Scientific Reports, Vol 14, Iss 1, Pp 1-15 (2024)
Druh dokumentu: article
ISSN: 2045-2322
41416090
DOI: 10.1038/s41598-024-64412-x
Popis: Abstract 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.
Databáze: Directory of Open Access Journals
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