Early ultrastructural changes in blood-brain barrier vessels of the rat embryo

The blood-brain barrier (BBB) in fetal rat brain has been shown by others to be more permeable to a variety of blood-borne solutes than the BBB in adults. We used ultrastructural morphometric methods to measured the density of putative vascular pores between the ages of embryonic day (E) 11 and birth to determine the structural basis for this relatively high permeability. We found that fenestrations, that are frequent at E11, declined rapidly and were last seen at E13 in intraparenchymal vessels and at E17 in pial vessels. Interendothelial junctions in fetal brain contained expanded clefts suggestive of paracellular channels at all ages examined, although they disappear after birth. Both of these features likely contribute to high fetal BBB permeability, but endothelial vesicles probably do not. The central nervous system is vascularized by ingrowth of capillary sprouts from the perineurial vascular plexus. Invading capillaries express BBB features in response to inductive signals from the surrounding neural tissue. We compared early ultrastructural changes in perineurial vessels, which are separated from neural tissue by a sizeable perivascular space, with those in intraneural vessels, which are totally enveloped by neural tissue, to determine whether the inductive interaction requires close cellular contact. For the most part, the perineurial and intraneural vessels matured in parallel. Furthermore, cerebellar vessels developed in parallel with cerebral vessels, even though they did not invade neural tissue until a comparatively late stage. These results suggest that intimate contact between neural tissue and vessel walls is not a requirement for BBB expression.