The neurovascular unit (NVU) is a relatively recent concept in neuroscience that broadly describes the relationship between brain cells and their blood vessels. The NVU incorporates cellular and extracellular components involved in regulating cerebral blood flow and blood-brain barrier function. The NVU within the adult brain has attracted strong research interest and its structure and function is well described, however, the NVU in the developing brain over the fetal and neonatal period remains much less well known. One area of particular interest in perinatal brain development is the impact of known neuropathological insults on the NVU. The aim of this review is to synthesize existing literature to describe structure and function of the NVU in the developing brain, with a particular emphasis on exploring the effects of perinatal insults. Accordingly, a brief overview of NVU components and function is provided, before discussion of NVU development and how this may be affected by perinatal pathologies. We have focused this discussion around three common perinatal insults: prematurity, acute hypoxia, and chronic hypoxia. A greater understanding of processes affecting the NVU in the perinatal period may enable application of targeted therapies, as well as providing a useful basis for research as it expands further into this area.

Background Fetal growth restriction (FGR) is associated with deficits in the developing brain, including neurovascular unit (NVU) dysfunction. Endothelial colony forming cells (ECFC) can mediate improved vascular stability, and have demonstrated potential to enhance vascular development and protection. This investigation examined whether ECFCs from human umbilical cord blood (UCB) enhanced NVU development in FGR and appropriate for gestational age (AGA) fetal sheep. Methods Twin-bearing ewes had surgery performed at 88–90 days’ gestation, inducing FGR in one fetus. At 113 days, ECFCs (1 × 107 cells) cultured from human UCB were administered intravenously to fetal sheep in utero. At 127 days, ewes and their fetuses were euthanised, fetal brains collected, and NVU components analysed by immunohistochemistry. Results Twenty-four fetal lambs, arranged in four groups: AGA (n = 7), FGR (n = 5), AGA + ECFC (n = 6), and FGR + ECFC (n = 6), were included in analyses. FGR resulted in lower body weight than AGA (P = 0.002) with higher brain/body weight ratio (P = 0.003). ECFC treatment was associated with increased vascular density throughout the brain in both AGA + ECFC and FGR + ECFC groups, as well as increased vascular–astrocyte coverage and VEGF expression in the cortex (P = 0.003, P = 0.0006, respectively) and in the subcortical white matter (P = 0.01, P = 0.0002, respectively) when compared with the untreated groups. Conclusions ECFC administration enhanced development of NVU components in both the AGA and FGR fetal brain. Further investigation is required to assess how to optimise the enhanced angiogenic capabilities of ECFCs to provide a therapeutic strategy to protect the developing NVU against vulnerabilities associated with FGR.