Pediatr Res. 2025 Sep 9. doi: 10.1038/s41390-025-04345-x. Online ahead of print.
ABSTRACT
BACKGROUND: Fetal growth restriction (FGR) causes an adaptive redistribution of the cardiac output towards sustained cerebral vasodilation. However, the consequences of FGR and cerebral vasodilatation due to fetal hypoxia on the blood-brain barrier (BBB) are still poorly studied. This study assesses BBB permeability in the neonatal cortex of pups gestated under intrauterine hypobaric hypoxia.
METHODS: 15 Guinea pig (Cavia porcellus) newborns were used in this study; 8 were gestated in normoxia (Nx), and 7 were gestated under chronic hypobaric hypoxia (Hx). Fetal examinations by ultrasound were assessed. At birth, pups were euthanized, and the cerebral cortex was collected to determine gene and protein expression. The permeability was quantified by immunolocalization of perivascular albumin in the prefrontal cortex BBB.
RESULT: The brain-sparing phenotype was associated with increased medial cerebral artery vasodilation during gestation and carotid endothelial vasodilation at birth. Additionally, gestational hypoxia decreased the protein levels of claudin-5 and claudin-12 in the neonatal cortex. Finally, albumin-immunopositive areas significantly increased in the brain parenchyma in the Hx neonatal cortex.
CONCLUSION: Our findings demonstrate that gestational hypoxia is associated with changes in the expression of genes and proteins related to the paracellular permeability of the BBB, which appears relevant to normal neurodevelopmental processes in perinatal life.
IMPACT: Gestational hypoxia generated a redistribution of flow (brain-sparing effects) associated with an increase in the cerebroplacental index and a growth restriction at birth using guinea pigs as an FGR model. The brain-sparing phenotype is associated with a decrease in the expression of claudins in the cerebral vasculature and increased BBB permeability in newborns gestated in hypobaric hypoxia. The observed permeability of the BBB in the neonatal cortex resembles the permeability phenotypes of postnatal hypoxia models, such as those of cerebral infarction or neonatal ischemic encephalopathy.
PMID:40925994 | DOI:10.1038/s41390-025-04345-x
