Blood-Brain Barrier Disintegration in Growth-Restricted Fetuses with Brain Sparing Effect

Abstract

The endothelial cells of the blood-brain barrier adhere closely, which is provided by tight junctions (TJs). The aim of the study was to assess the damage to the endothelial TJs in pregnancy, complicated by fetal growth restriction (FGR) and circulatory centralization (brain-sparing effect, BS). The serum concentrations of NR1 subunit of the N-methyl-D-aspartate receptor (NR1), nucleoside diphosphate kinase A (NME1), S100 calcium-binding protein B (S100B), occludin (OCLN), claudin-5 (CLN5), and zonula occludens protein – 1 (zo-1), and the placental expressions of OCLN, claudin-4 (CLN4), CLN5, and zo-1 were assessed with ELISA. The significantly higher serum NME1 concentrations and the serum CLN5/zo-1 index were observed in FGR pregnancy with BS, as compared to the FGR group without BS. The FGR newborns with BS were about 20 times more likely to develop an intraventricular hemorrhage (IVH) than the FGR infants without BS. The cerebroplacental ratio (CPR) allowed to predict the IVH in growth-restricted fetuses. The significantly lower placental CLN4 expression was observed in the FGR group with BS and who postnatally developed an IVH, as compared to the growth-restricted infants with BS without IVH signs. Pregnancy complicated by FGR and BS is associated with the destabilization of the fetal blood-brain barrier. The IVH in newborns is reflected in the inhibition of the placental CLN4 expression, which may be a useful marker in the prediction of an IVH among growth-restricted fetuses.

Mass Spectrometry as a Quantitative Proteomic Analysis Tool for the Search for Temporal Lobe Epilepsy Biomarkers: A Systematic Review

“…There are data on the association of NME1 with the processes of neuronal development as a result of brain damage, confirmed in in vitro studies and in the study of experimental models [ 76 ]. NME1, as a component of the cytosol, can interact with components and regulators of the cytoskeleton: intermediate filaments, actin-binding proteins, adhesive junction proteins, and focal adhesion proteins [ 77 ]. In a study by Wright et al [ 78 ], it was found that NME1 is a growth stimulator of dorsal root ganglion neurites, since it may be active as a positive chemotactic signal.…”

Doppler Indices of the Uterine, Umbilical and Fetal Middle Cerebral Artery in Diabetic versus Non-Diabetic Pregnancy: Systematic Review and Meta-Analysis

“…Results of our meta-analysis presented no significant differences between the DM and non-DM groups in terms of fetal MCA Doppler parameters. It is known that long-term uncontrolled hyperglycemia, chronic hypertension, preeclampsia, and IUGR can lead to placental vascular dysfunction with changes even in fetal circulation [ 53 , 82 , 104 , 105 , 106 ]. But the effect of metabolic changes due to diabetes mellitus during pregnancy on the fetus may be acidemia without hypoxemia, thus that redistribution seen in fetal hypoxemia may not occur even in severely compromised fetuses; and, therefore, it is of huge importance not to misrepresent this state by apparently normal fetal Doppler results [ 80 ].…”

Does fetal growth restriction induce neuropathology within the developing brainstem?

“…Brain sparing is considered a common consequence of placental insufficiency and FGR, and both preclinical and clinical studies have shown an association between brain sparing and disruption to the BBB (Castillo‐Melendez et al., 2015 ; Misan et al., 2022 ). Human data show evidence that brain sparing and asymmetric growth is associated with increased rates of intraventricular haemorrhage (Misan et al., 2022 ), and also an increased risk of abnormal neurological function including reduced neuro‐behavioural scores across the motor system, social‐interactive, and attentional domains (Figueras et al., 2011 ).…”

“…The fetus detects hypoxaemia via the carotid and central chemoreceptors, providing signals to the brainstem that result in redistribution of the fetal combined cardiac output to maximise oxygenation of vital organs, especially the brain – called brain sparing (Giussani, 2016 ). Although brain sparing is a protective mechanism, this response does not protect the developing brain from neuropathology, with both physiological and functional deficits shown to be associated with brain sparing (Figueras et al., 2011 ; Misan et al., 2022 ). Hence the terminology of cerebrovascular compensation may be more apt to describe this fetal defence to hypoxaemia.…”