Preeclampsia and neurodevelopmental outcomes: Potential pathogenic roles for inflammation and oxidative stress?

dc.contributor.authorBarron, Aaron
dc.contributor.authorMcCarthy, Cathal
dc.contributor.authorO'Keeffe, Gerard W.
dc.contributor.funderIrish Research Councilen
dc.contributor.funderHealth Research Boarden
dc.contributor.funderScience Foundation Irelanden
dc.date.accessioned2021-02-09T10:08:00Z
dc.date.available2021-02-09T10:08:00Z
dc.date.issued2021-01-25
dc.date.updated2021-02-09T09:49:10Z
dc.description.abstractPreeclampsia (PE) is a common and serious hypertensive disorder of pregnancy that occurs in approximately 3–5% of first-time pregnancies and is a well-known leading cause of maternal and neonatal mortality and morbidity. In recent years, there has been accumulating evidence that in utero exposure to PE acts as an environmental risk factor for various neurodevelopmental disorders, particularly autism spectrum disorder and ADHD. At present, the mechanism(s) mediating this relationship are uncertain. In this review, we outline the most recent evidence implicating a causal role for PE exposure in the aetiology of various neurodevelopmental disorders and provide a novel interpretation of neuroanatomical alterations in PE-exposed offspring and how these relate to their sub-optimal neurodevelopmental trajectory. We then postulate that inflammation and oxidative stress, two prominent features of the pathophysiology of PE, are likely to play a major role in mediating this association. The increased inflammation in the maternal circulation, placenta and fetal circulation in PE expose the offspring to both prenatal maternal immune activation—a risk factor for neurodevelopmental disorders, which has been well-characterised in animal models—and directly higher concentrations of pro-inflammatory cytokines, which adversely affect neuronal development. Similarly, the exaggerated oxidative stress in the mother, placenta and foetus induces the placenta to secrete factors deleterious to neurons, and exposes the fetal brain to directly elevated oxidative stress and thus adversely affects neurodevelopmental processes. Finally, we describe the interplay between inflammation and oxidative stress in PE, and how both systems interact to potentially alter neurodevelopmental trajectory in exposed offspring.en
dc.description.sponsorshipIrish Research Council (GOIPG/2019/4400); Health Research Board (HRB-EIA-2017-021)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationBarron, A., McCarthy, C. and O'Keeffe, G. W. (2021) 'Preeclampsia and neurodevelopmental outcomes: Potential pathogenic roles for inflammation and oxidative stress?', Molecular Neurobiology. doi: 10.1007/s12035-021-02290-4en
dc.identifier.doi10.1007/s12035-021-02290-4en
dc.identifier.eissn1559-1182
dc.identifier.issn0893-7648
dc.identifier.journaltitleMolecular Neurobiologyen
dc.identifier.urihttps://hdl.handle.net/10468/11048
dc.language.isoenen
dc.publisherSpringer Nature Switzerland AGen
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Career Development Award/15/CDA/3498/IE/Development of GDF5 neurotrophic factor therapy for Parkinson_s disease./en
dc.rights© 2021, the Authors, under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature. This is a post-peer-review, pre-copyedit version of an article published in Molecular Neurobiology. The final authenticated version is available online at: https://doi.org/10.1007/s12035-021-02290-4en
dc.subjectPreeclampsiaen
dc.subjectNeurodevelopmental disorderen
dc.subjectAutism Spectrum disorderen
dc.subjectAttention-deficit hyperactivity disorder Inflammationen
dc.subjectOxidative stressen
dc.titlePreeclampsia and neurodevelopmental outcomes: Potential pathogenic roles for inflammation and oxidative stress?en
dc.typeArticle (peer-reviewed)en
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