ArticleProceedings of the National Academy of Sciences of the United States of America2022
Prenatal disruption of blood-brain barrier formation via cyclooxygenase activation leads to lifelong brain inflammation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed.
- Maternal-fetal immune conflict contributes to male-specific impairments in a mouse model of neurodevelopmental disorders.Science advances · 2026Article
- Fibrinogen as a Driver of Oxidative Stress and Apoptosis in the Fetal Brain After Maternal Influenza.Research square · 2026Article
- Prenatal acoustic communication triggers adaptive vascular programming in the developing avian brain.The Journal of experimental biology · 2026Article
- Blood Serum From Obese Women Raises ROS Production by Neural Stem Cells.Developmental neurobiology · 2026Article
- Therapeutic potential ofIn silico pharmacology · 2026Article
- Maternal Obesity in Pregnancy: Risk Factor for Neurodevelopmental Outcomes in Offspring.Journal of neurochemistry · 2025Review
- Prostaglandin endoperoxide synthase 2 regulates neuroinflammation to mediate postoperative cognitive dysfunction in mice.Scientific reports · 2025Article
- CB1 and CB2 receptors differentially modulate the cognitive impact of maternal immune activation and perinatal cannabinoid exposure.Behavioural brain research · 2025Article
- Systemic Inflammatory Response Syndrome, Thromboinflammation, and Septic Shock in Fetuses and Neonates.International journal of molecular sciences · 2025Review
- PIWI-interacting RNA MIABEPIR regulates cerebral endothelial cell function via DAPK2 pathway in offspring following maternal immune activation.Clinical and translational medicine · 2025Article
- The microbiome as a modulator of neurological health across the maternal-offspring interface.The Journal of clinical investigation · 2025Review
- Prenatal Poly I:C exposure affects tryptophan-kynurenine metabolism associated with intestinal microbiome in female juvenile rats.Frontiers in immunology · 2025Article
- Pathophysiological associations between maternal immune activation and neurodevelopmental disorders in offspring: a comprehensive review.Frontiers in endocrinology · 2025Review
- Maternal immune activation by toll-like receptor 7 agonist during mid-gestation increases susceptibility to blood-brain barrier leakage after puberty.Brain behavior and immunity integrative · 2024Article
- Taprenepag restores maternal-fetal interface homeostasis for the treatment of neurodevelopmental disorders.Journal of neuroinflammation · 2024Article
- Blood-brain barrier disruption: a culprit of cognitive decline?Fluids and barriers of the CNS · 2024Review
- The neural and cardiovascular effects of exposure of gram-positive bacterial inflammation in preterm fetal sheep.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Gastrointestinal and brain barriers: unlocking gates of communication across the microbiota-gut-brain axis.Nature reviews. Gastroenterology & hepatology · 2024Review
- Stem cell-based approaches for developmental neurotoxicity testing.Frontiers in toxicology · 2024Review
- Network pharmacology- and molecular docking-based investigation on the mechanism of action of Si-ni San in the treatment of depression combined with anxiety and experimental verification in adolescent rats.Frontiers in psychiatry · 2024Article
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Abstract
Gestational maternal immune activation (MIA) in mice induces persistent brain microglial activation and a range of neuropathologies in the adult offspring. Although long-term phenotypes are well documented, how MIA in utero leads to persistent brain inflammation is not well understood. Here, we found that offspring of mothers treated with polyriboinosinic–polyribocytidylic acid [poly(I:C)] to induce MIA at gestational day 13 exhibit blood–brain barrier (BBB) dysfunction throughout life. Live MRI in utero revealed fetal BBB hyperpermeability 2 d after MIA. Decreased pericyte–endothelium coupling in cerebral blood vessels and increased microglial activation were found in fetal and 1- and 6-mo-old offspring brains. The long-lasting disruptions result from abnormal prenatal BBB formation, driven by increased proliferation of cyclooxygenase-2 (COX2; Ptgs2)-expressing microglia in fetal brain parenchyma and perivascular spaces. Targeted deletion of the Ptgs2 gene in fetal myeloid cells or treatment with the inhibitor celecoxib 24 h after immune activation prevented microglial proliferation and disruption of BBB formation and function, showing that prenatal COX2 activation is a causal pathway of MIA effects. Thus, gestational MIA disrupts fetal BBB formation, inducing persistent BBB dysfunction, which promotes microglial overactivation and behavioral alterations across the offspring life span. Taken together, the data suggest that gestational MIA disruption of BBB formation could be an etiological contributor to neuropsychiatric disorders.
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