Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Jun;289(12):3374-3392.
doi: 10.1111/febs.16020. Epub 2021 May 26.

Neurological consequences of neurovascular unit and brain vasculature damages: potential risks for pregnancy infections and COVID-19-babies

Marco Rasile  1   2 , Eliana Lauranzano  2 , Filippo Mirabella  1 , Michela Matteoli  2   3
Affiliations
Review

Neurological consequences of neurovascular unit and brain vasculature damages: potential risks for pregnancy infections and COVID-19-babies

Marco Rasile et al. FEBS J. 2022 Jun.

Abstract

Intragravidic and perinatal infections, acting through either direct viral effect or immune-mediated responses, are recognized causes of liability for neurodevelopmental disorders in the progeny. The large amounts of epidemiological data and the wealth of information deriving from animal models of gestational infections have contributed to delineate, in the last years, possible underpinning mechanisms for this phenomenon, including defects in neuronal migration, impaired spine and synaptic development, and altered activation of microglia. Recently, dysfunctions of the neurovascular unit and anomalies of the brain vasculature have unexpectedly emerged as potential causes at the origin of behavioral abnormalities and psychiatric disorders consequent to prenatal and perinatal infections. This review aims to discuss the up-to-date literature evidence pointing to the neurovascular unit and brain vasculature damages as the etiological mechanisms in neurodevelopmental syndromes. We focus on the inflammatory events consequent to intragravidic viral infections as well as on the direct viral effects as the potential primary triggers. These authors hope that a timely review of the literature will help to envision promising research directions, also relevant for the present and future COVID-19 longitudinal studies.

Keywords: COVID-19; blood-brain barrier; cytokines; hemorrhage; inflammation; long-COVID; maternal immune activation; neurovascular unit; prenatal viral infection; synapse.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Schematic representation of how viral infections affect the fetal NVU and the brain vasculature during pregnancy. Viruses can influence vessel development by both direct (i.e., congenital infection) and immune‐mediated (i.e., inflammatory state) processes.
Fig. 2
Fig. 2
Research tools for the study of behavioral phenotypes consequent to the NVU dysfunctions. Pericyte paucity and reduced vascular coverage, hemorrhages, downregulation of the tight junction protein claudin‐5, and lack of BCAAs into the brain parenchyma result in ASD‐ and schizophrenia‐like behaviors, as well as depression and dementia.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Brown AS & Susser ES (2008) Prenatal nutritional deficiency and risk of adult schizophrenia. Schizophr Bull 34, 1054–1063. - PMC - PubMed
    1. Stein AD & Lumey LH (2000) The relationship between maternal and offspring birth weights after maternal prenatal famine exposure: the Dutch Famine Birth Cohort Study. Hum Biol 72, 641–654. - PubMed
    1. Kępińska AP, Iyegbe CO, Vernon AC, Yolken R, Murray RM & Pollak TA (2020) Schizophrenia and influenza at the centenary of the 1918–1919 Spanish influenza pandemic: mechanisms of psychosis risk. Front psychiatry 11, 72. - PMC - PubMed
    1. Torrey EF, Miller J, Rawlings R & Yolken RH (1997) Seasonality of births in schizophrenia and bipolar disorder: a review of the literature. Schizophr Res 28, 1–38. - PubMed
    1. Brown AS & Derkits EJ (2010) Prenatal infection and schizophrenia: a review of epidemiologic and translational studies. Am J Psychiatry 167, 261–280. - PMC - PubMed

Publication types