Are the Cognitive Alterations Present in Children Born From Preeclamptic Pregnancies the Result of Impaired Angiogenesis? Focus on the Potential Role of the VEGF Family

Abstract

Evidence from clinical studies has proposed that children born from preeclamptic women have a higher risk of suffering neurological, psychological, or behavioral alterations. However, to date, the mechanisms behind these outcomes are poorly understood. Here, we speculate that the neurodevelopmental alterations in the children of preeclamptic pregnancies result from impaired angiogenesis. The pro-angiogenic factors vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) are key regulators of both vascular and neurological development, and it has been widely demonstrated that umbilical blood of preeclamptic pregnancies contains high levels of soluble VEGF receptor type 1 (sFlt-1), a decoy receptor of VEGF. As a consequence, this anti-angiogenic state could lead to long-lasting neurological outcomes. In this non-systematic review, we propose that alterations in the circulating concentrations of VEGF, PlGF, and sFlt-1 in preeclamptic pregnancies will affect both fetal cerebrovascular function and neurodevelopment, which in turn may cause cognitive alterations in post-natal life.

Prenatal intake of omega‐3 promotes Wnt/β‐catenin signaling pathway, and preserves integrity of the blood–brain barrier in preeclamptic rats

“…Concordant with our results, previous studies have also illustrated that decreased VEGF together with increased expression of sFlt-1 are the cardinal factors of endothelial dysfunction in preeclampsia. There is additional experimental evidence that the interference with VEGF signaling could mediate endothelial dysfunction in preeclampsia (Maynard & Karumanchi, 2011) and that the cognitive alterations present in children born from preeclamptic pregnancies are attributed to impaired cerebral VEGF and angiogenesis (Lara et al, 2018).…”

Development of the Neuro-Immune-Vascular Plexus in the Ventricular Zone of the Prenatal Rat Neocortex

“…Indeed, we have found that Zika administration to fetal rhesus monkeys produced abnormalities in microglial cell and Tbr2 + cell distribution, blood vessel morphology, and is correlated with thinner cortical gray matter (Tarantal et al 2020). Other conditions including schizophrenia, hydrocephaly, and children born of pre-eclamptic pregnancies have also been correlated with vascular abnormalities (Webster et al 2001;Lara et al 2018;Fehnel et al 2019). Cortical gray matter reduction in schizophrenia has been associated with both neuroinflammation (Zhang et al 2016) and altered levels of the vascular growth factor VEGF (Pillai et al 2016).…”

Pre-eclampsia Complicated With Maternal Renal Dysfunction Is Associated With Poor Neurological Development at 3 Years Old in Children Born Before 34 Weeks of Gestation

“…The specific character of sFlt-1 in adapting neuroanatomical and vascular construction and circulatory characteristics at the central nervous system level are unclear ( 50 ). sFlt-1 high levels are related to adult psychiatric and neurological alterations ( 51 , 52 ).…”