Brain sparing and the blood brain barrier—bridging the preclinical to clinical gap

Commentary Article on Gestational hypoxia increases blood-brain barrier permeability in the neonatal cerebral cortex of guinea pigs, by E. Figueroa et al.The brain, and particularly the fetal brain, is the most highly metabolically active and energy-expensive organ in the body, with the developing fetal brain reliant on oxygen and nutrients supplied across the placenta. 1Pathological reductions in fetal oxygen supply during pregnancy are relatively common, caused by acute stress such as during labor and contractions, or induced chronically secondary to placental insufficiency.In the case of placental insufficiency and chronic fetal hypoxemia, the fetus decreases fetal growth, resulting in fetal growth restriction (FGR).The fetus also mounts a physiological response to hypoxemia, redistributing blood flow towards the brain at the expense of nonessential tissue beds-this adaptation is called brain sparing. 2 This brain sparing response is considered a survival mechanism, ensuring adequate oxygen supply to the brain during fetal compromise and, indeed when prolonged, this adaptation protects brain growth relative to other organs resulting in asymmetric FGR (the head is relatively larger than other organs). 2,3Clinically, fetal brain sparing is detected via Doppler ultrasound as vasodilatation of the middle cerebral artery (MCA) and/or a reduction in the cerebroplacental ratio (CPR). 4,5Accumulating evidence indicates that brain sparing may be associated with elevated risk of adverse neurodevelopmental outcome, 4,5 yet the pathophysiology linking prolonged cerebral vasodilation, brain sparing and altered brain development at the cellular level remains largely uncharacterized.Here we provide a commentary on the work of Figueroa et al. 6 who examined how chronic fetal hypoxia and brain sparing affect cerebrovascular development.